SCHOOL OF BIO & CHEMICAL ENGINEERING

DEPARTMENT OF BIOMEDICAL ENGINEERING

UNIT – I – BIOMEMS AND NANOTECHOLOGY – SBM1606

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 UNIT 1 – BIOMEMS AND NANOTECHNOLOGY

1 DEFINITION:
Microelectromechanical systems (MEMS), MicroElectroMechanical or microelectronic
and microelectromechanical systems and the related micromechatronics is the technology of
very small devices; it merges at the nano-scale into nanoelectromechanical systems (NEMS)
and nanotechnology.
MEMS are separate and distinct from the hypothetical vision of molecular nanotechnology
or molecular electronics. MEMS are made up of components between 1 to 100 micrometres
in size (i.e. 0.001 to 0.1 mm), and MEMS devices generally range in size from 20 micrometres
to a millimetre (i.e. 0.02 to 1.0 mm). They usually consist of a central unit that processes data
(the microprocessor) and several components that interact with the surroundings such as
microsensors. At these size scales, the standard constructs of classical physics are not
always useful. Because of the large surface area to volume ratio of MEMS, surface effects such
as electrostatics and wetting dominate over volume effects such as inertia or thermal
mass.
MEMS or Micro Electro Mechanical Systems are Semiconductor ICs that have combined the
electrical and mechanical property of Silicon. There are actual moving mass, springs, cavities,
dampers etc inside a MEMS structure. MEMS can detect motions such as acceleration, gravity,
angular motion, magnetic field and pressure etc. Typical MEMS is SIP (system in package) IC
consisting of two ICs. First IC senses the desired parameter and converts it into equivalent
capacitance. Second IC converts the capacitance into equivalent voltage or digitally onto I2C
bus.
Two principal components of MEMS:
A sensing or actuating element and a signal transduction unit. MEMS as a microsensor:
2 ORIGIN:
Manufactured on to semiconductor material.
Used to make sensors, actuators, accelerometer,switches and light.
Used in automobiles, aerospace, biomedical app wireless,optical communication.
(1) 1947-invention of the point contact transistor uses electrical current (or) a small amt
of voltage to control a larger change in current (or) voltage
-Transistor is a building blocks of computers, cellular phones other modern electronics .
(2) 1954-Discovery of the piezoresistive effect in silicon and germanium to sense air (or) H2O
pressure,better then metal.
Eg.Strain gauges, pressure sensor and accelerometer utilize piezoresistive effect in silicon
(3) 1958-First integrated circuit (IC). IC includes transistors, resistors, capacitors and wires.
(4) 1968-The resonant gate transistor patented this device . It joined a mechanical component
with an electronic element and is called a resonant gate. 1mm size, it serves as a frequency

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 filter in IC.
(5) 1971-Invention of µ processor.
Single chip microprocessor . -Paved the way for the personal computer
(6) 1979-HP micro machined inkjet nozzle thermal inkjet technology (TIJ).
TIJ-heats ink-creating tiny bubbles, tiny bubbles collapse – ink squirts through an array of
nozzle onto the paper
(7) 1982-LIGA process – manufacturing microstructure
(8) 1986-AFM – scans the surface of an atomic structure by measuring the force acting on the
tip of a micro scale cantilever
(9) 1992 – Grating light modulator .
-It is a micro opto electro mechanical system (mems)
-Graphic printing, lithography and optical communication. (10)1993-Multi user mems
processes (MUMPs) a three layer poly silicon surface micro machining process to create their
own design (1cm)
. (11)1993-First manufactured accelerometer. The automotive industry used this accelerometer
in automobiles for airbag deployment sensing, highly reliable, very small, inexpensive .
(12)1994-Deap reactive ion etching patened.
-DRIE – highly an isotropic etch process used to create deep,steep sided holes and
trenches in to H2o.
(13) Late 1990s early 2000 -biomem. -Scientist are combining sensors and actuators with
emerging biotechnology.
Application includes,
-Drug delivery system
-DNA array
-Insulin pump
-Lab – on – a – chip (LOC)
-Glucometers
-Neural probe arrays
-Microfluidics

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3 Summary
Mems devises measured things as pressure in engines and motion in cars mems are
controlling our communication network mems travel through human body to a monitor blood
pressure.
The application and growth of mems and memes are endless. Mems are even getting
smaller now have nano electro mechanical systems (nems).
4. TYPES:
4.1MATERIALS USED FOR MEMS MANUFACTURING
The fabrication of MEMS evolved from the process technology in semiconductor device
fabrication, i.e. the basic techniques are deposition of material layers, patterning by
photolithography and etching to produce the required shapes.
4.1.1Silicon
Silicon is the material used to create most integrated circuits used in consumer electronics
in the modern industry. The economies of scale, ready availability of cheap high -quality
materials and ability to incorporate electronic functionality make silicon attractive for a wide
variety of MEMS applications. Silicon also has significant advantages engendered through its
material properties.
In single crystal form, silicon is an almost perfect Hookean material, meaning that when it is
flexed there is virtually no hysteresis and hence almost no energy dissipation. As well as
making for highly repeatable motion, this also makes silicon very reliable as it suffers very
little fatigue and can have service lifetimes in the range of billions to trillions of cycles
without breaking.
4.1.2 Polymers
Even though the electronics industry provides an economy of scale for the silicon industry,
crystalline silicon is still a complex and relatively expensive material to be produced. Polymers
on the other hand can be produced in huge volumes, with a great variety of material
characteristics. MEMS devices can be made from polymers by processes such asinjection
molding, embossing or stereolithography and are especially well suited to microfluidic
applications such as disposable blood testing cartridges.
4.1.3 Metals
Metals can also be used to create MEMS elements. While metals do not have some of the
advantages displayed by silicon in terms of mechanical properties, when used within their
limitations, metals can exhibit very high degrees of reliability. Metals can be deposited by
electroplating, evaporation, and sputtering processes. Commonly used metals include gold,
nickel, aluminium, copper, chromium, titanium, tungsten, platinum, and silver.
4.1.4 Ceramics
The nitrides of silicon, aluminium and titanium as well as silicon carbide and other
ceramics are increasingly applied in MEMS fabrication due to advantageous combinations of
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material properties. AlN crystallizes in the wurtzite structure and thus shows pyroelectric
and piezoelectric properties enabling sensors, for instance, with sensitivity to normal and
shear forces. TiN, on the other hand, exhibits a high electrical conductivity and large
elastic modulus allowing to realize electrostatic MEMS actuation schemes with ultrathin
membranes. Moreover, the high resistance of TiN against biocorrosion qualifies the material
for applications in biogenic environments and in biosensors.
5. MEMS TECHNOLOGY:
Micro-Electro-Mechanical Systems, or MEMS, is a technology that in its most general form
can be defined as miniaturized mechanical and electro-mechanical elements (i.e., devices and
structures) that are made using the techniques of microfabrication. The critical physical
dimensions of MEMS devices can vary from well below one micron on the lower end of the
dimensional spectrum, all the way to several millimeters. Likewise, the types of MEMS
devices can vary from relatively simple structures having no moving elements, to extremely
complex electromechanical systems with multiple moving elements under the control of
integrated microelectronics. The one main criterion of MEMS is that there are at least some
elements having some sort of mechanical functionality whether or not these elements can
move. The term used to define MEMS varies in different parts of the world. In the United
States they are predominantly called MEMS, while in some other parts of the world they are
called
“Microsystems Technology” or “micromachined devices”.
While the functional elements of MEMS are miniaturized structures, sensors, actuators, and
microelectronics, the most notable (and perhaps most interesting) elements are the
microsensors and microactuators. Microsensors and microactuators are appropriately
categorized as
“transducers”, which aredefined as devices that convert energy from oneform to another. In the
case of microsensors, the device typically converts a measured mechanical signal into an
electrical signal.

Fig. 1.1 Components of MEMS

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Over the past several decades MEMS researchers and developers have demonstrated an
extremely large number of microsensors for almost every possible sensing modality including
temperature, pressure, inertial forces, chemical species, magnetic fields, radiation, etc.
Remarkably, many of these micromachined sensors have demonstrated performances
exceeding those of their macroscale counterparts. That is, the micromachined version of, for
example, a pressure transducer, usually outperforms a pressure sensor made using the most
precise macroscale level machining techniques. Not only is the performance of MEMS devices
exceptional, but their method of production leverages the same batch fabrication techniques
used in the integrated circuit industry – which can translate into low per-device production
costs, as well as many other benefits. Consequently, it is possible to not only achieve stellar
device performance, but to do so at a relatively low cost level. Not surprisingly, silicon based
discrete microsensors were quickly commercially exploited and the markets for these devices
continue to grow at a rapid rate.
More recently, the MEMS research and development community has demonstrated a number
of microactuators including: microvalves for control of gas and liquid flows; optical switches
and mirrors to redirect or modulate light beams; independently controlled micromirror arrays
for displays, microresonators for a number of different applications, micropumps to develop
positive fluid pressures, microflaps to modulate airstreams on airfoils, as well as many others.
Surprisingly, even though these microactuators are extremely small, they frequently can cause
effects at the macroscale level; that is, these tiny actuators can perform mechanical feats far
larger than their size would imply. For example, researchers have placed small microactuators
on the leading edge of airfoils of an aircraft and have been able to steer the aircraft using only
these microminiaturized devices.

Fig:1. 2. A surface micromachined electro-statically-actuated micromotor fabricated by

the MNX.
This device is an example of a MEMS-based microactuator.

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The real potential of MEMS starts to become fulfilled when these miniaturized sensors,
actuators, and structures can all be merged onto a common silicon substrate along with
integrated circuits (i.e., microelectronics). While the electronics are fabricated using integrated
circuit (IC) process sequences (e.g., CMOS, Bipolar, or BICMOS processes), the
micromechanical components are fabricated using compatible "micromachining" processes
that selectively etch away parts of the silicon wafer or add new structural layers to form the
mechanical and electromechanical devices. It is even more interesting if MEMS can be merged
not only with microelectronics, but with other technologies such as photonics, nanotechnology,
etc. This is sometimes called “heterogeneous integration.” Clearly, these technologies are
filled with numerous commercial market opportunities.
The present MEMS involves a single discrete microsensor, a single discrete microactuator, a
single microsensor integrated with electronics, a multiplicity of essentially identical
microsensors integrated with electronics, a single microactuator integrated with electronics, or
a multiplicity of essentially identical microactuators integrated with electronics.
This vision of MEMS whereby microsensors, microactuators and microelectronics and other
technologies, can be integrated onto a single microchip is expected to be one of the most
important technological breakthroughs of the future. This will enable the development of smart
products by augmenting the computational ability of microelectronics with the perception and
control capabilities of microsensors and microactuators. Microelectronic integrated circuits
can be thought of as the "brains" of a system and MEMS augments this decision-making
capability with "eyes" and "arms", to allow microsystems to sense and control the environment.
Sensors gather information from the environment through measuring mechanical, thermal,
biological, chemical, optical, and magnetic phenomena. The electronics then process the
information derived from the sensors and through some decision making capability direct the
actuators to respond by moving, positioning, regulating, pumping, and filtering, thereby
controlling the environment for some desired outcome or purpose. Furthermore, because
MEMS devices are manufactured using batch fabrication techniques, similar to ICs,
unprecedented levels of functionality, reliability, and sophistication can be placed on a small
silicon chip at a relatively low cost. MEMS technology is extremely diverse and fertile, both in
its expected application areas, as well as in how the devices are designed and manufactured.

Fig:1. 3 An array of sub-micron posts made using top-down nanotechnology fabrication

methods.
Although MEMS and Nanotechnology are sometimes cited as separate and distinct
technologies, in reality the distinction between the two is not so clear-cut. In fact, these two
technologies are highly dependent on one another. The well-known scanning tunneling-tip
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microscope (STM) which is used to detect individual atoms and molecules on the nanometer
scale is a MEMS device. Similarly the atomic force microscope (AFM) which is used to
manipulate the placement and position of individual atoms and molecules on the surface of a
substrate is a MEMS device as well. In fact, a variety of MEMS technologies are required in
order to interface with the nanoscale domain.
Likewise, many MEMS technologies are becoming dependent on nanotechnologies for
successful new products. For example, the crash airbag accelerometers that are manufactured
using MEMS technology can have their long-term reliability degraded due to dynamic in-use
stiction effects between the proof mass and the substrate. A nanotechnology called
Self-Assembled Monolayers (SAM) coatings are now routinely used to treat the surfaces of the
moving MEMS elements so as to prevent stiction effects from occurring over the product’s life.
6.MEMS IN HEALTH CARE
Healthcare has emerged as one the biggest and fastest growing Industry around the World. The
growing importance of Human life, increase in individual disposal income and awareness of
preventative measures are driving the growth of this Industry. Increase in life expectancy and
ageing of world population has made Healthcare as a very lucrative Industry.
MEMS has evolved as one of the most revolutionized Semiconductor components in personal
Healthcare. The advent of MEMS is opening new ventures of application in Healthcare. This
article will address some of the applications MEMS in medical electronics system design to
serve the healthcare needs. Semiconductor are used in core medical electronic Instruments
such as CT scan, X-ray machines, ECG, Ultrasound, Blood pressure and Glucose monitoring
etc. Semiconductor plays function such as sensing, signal conditioning, data conversion &
processing, controlling the machines & robots etc.
Bulky and centralized hospital equipments now have a new substitute – handheld personalized
healthcare equipments. As firsthand healthcare is shifting from Hospitals to individual, the
need of miniaturization, cost-effectiveness, robustness and battery operation has evolved. After
creating a new wave of revolution in consumer and mobile phone Industry, MEMS is all set to
give healthcare a new definition. Some typical applications of MEMS in Healthcare are
pedometer, blood pressure monitoring, ECG, hearing aids etc. MEMS can also be used in
complex procedures such as DNA Analysis.
Motions MEMS such as accelerometer have made it possible to accurately measure motion by
consuming minimal power with a very compact form factor. As MEMS can detect both linear
and angular motion in all 3-axis, a complete inertial state of body or body part can be detected.
MEMS can be used in not only wearable device such as pedometer or mobile ECG machine but
also penetrative gadgets such as blood pressure monitors or miniaturized robots.
6.1 APPLICATION OF MEMS
6.1.1.Pedometer
Pedometer is perhaps one of the simplest application yet very useful application of MEMS.
MEMS can detect the jerk body is facing while a user is running or walking at each step. The
jerk experienced by MEMS IC. This feature can be used to measure accurately number of steps
taken. MEMS can be used to calculate Step count, Speed, Distance, Calories. Some parameters
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such as step length, height and weight may be needed for calibration. Accurately Pedometer
can be developed keeping in mind the locations where user is wearing them (attached to belt,
shirt/pant pocket etc). A 3-axis accelerometer can detect acceleration in all the three axis so a
single MEMS can detect the change independent of the way pedometer is worn by the user.
MEMS can also be used to detect the swing in centre of gravity of person. This data can be used
by doctor to suggest the right posture or even wear right equipment to the patient.
6.1.2HearingAid
MEMS microphone has made it possible to make small size hearing aid with high sound
quality, reliability and affordability. MEMS microphones meet price points set by the
traditional electret condenser microphones (ECM), while boasting superior reliability and
robustness. MP45DT microphone is less susceptible to mechanical vibration, temperature
variations and electromagnetic interference. The sensing element, capable of detecting acoustic
waves, is manufactured using a specialized silicon micromachining process to produce audio
sensors. MEMS microphone based hearing aid can be designed in such a way that it becomes
invisible to external world thus avoiding apparent social issues.
6.1.3 Early Diagnosis of Glaucoma
MEMS microphone and a transmitter antenna when mounted on a 24-hour silicon disposable
lens can be used for early diagnosis of glaucoma. As the MEMS sensor is ultra miniaturized, it
can be mounted at the peripheral of lens without impacting normal viewing. Also a small
antenna will transmit relevant data to the receiving station. The Sensor is capable of measuring
cornea deformations due to Intra-Ocular-Pressure (IOP) variations. The IOP Sensor is a
wireless sensor that acts as a transducer, antenna and mechanical support for additional
read-out electronics. This information can be monitored and analyzed by Hospital to take
necessary action and diagnose glaucoma in its early stage.

Fig1.4. Early diagnosis of Glaucoma

6.1.4 Blood Pressure
The human circulatory system generates pressure which can be measured by miniaturized and
biocompatible BioMEMS. The generated pressure is complex and varies by a large value and
change by the current situation of human body so it require very specific MEMS to do the task.
The BioMEMS can be inserted into the body and moved to the specific places near the heart.
By measuring pressure gradients across heart valves, doctors can access valve disease. It will
be to diagnose and monitor heart failure and measuring cardiac output.
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6.1.5 Body Gateway
Body gateway is a wearable device used for measuring physiological parameters such as ECG,
heart rate, breathing rate etc. It can also detect person’s movement and if there is a abnormal
movement such as falling down on floor can be detected. The measured data or alarms can be
sent via Bluetooth to internet gateway device which can send the data to Hospital control
rooms. MEMS is the key enablers for this, it can detect person movement and change is blood
pressure to measure the breathing rate. The small size and ultra low power consumption has
made it possible. This application of MEMS can also lead to revolution of telemedicine where
hospitals can monitor patients in real time scenario and take necessary action remotely. It can
also reduce the cost of treatment drastically as patients no longer have to admit in Hospitals for
monitoring reliable information.

Fig1.5. Body Gateway

6.1.6 Lab on Chip
Lab-on-a-chip allows small amounts of bodily fluids to be tested in seconds. All chemical
reactions occur inside thebiochip’s buried channels or on its surface. And because the cartridge
that carries the chip is self-contained and disposable, the system strongly reduces the
cross-contamination risks of conventional multi-step protocols. The ST Lab-on-chip is
designed to handle micro fluidics and some of the knowledge is based on expertise in MEMS
inkjet printer chips. The Lab-on-chip can amplify or multiply DNA sample in approx 15
minutes thus requires very small amount of fluid, saves time and is economical.
7.INTEGRATED MEMS
The majority of microelectromechanical system (MEMS) devices must be combined with
integrated circuits (ICs) for operation in larger electronic systems. A MEMS device typically
interacts with a physical, chemical or optical quantity and has an electrical interface to the
outside world. For MEMS sensors, the electrical output signal correlates with the physical,
optical or chemical input quantity that is sensed. In the case of MEMS actuators, an electrical
input signal is used to control one or more physical, optical or chemical quantities. To enable
the MEMS transducer to perform useful functions, the electrical interface with the outside
world is, in most cases, realized through integrated circuits (ICs) that provide the system with
the necessary intelligence. ICs may provide signal conditioning functions such as
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analog-to-digital conversion, amplification, temperature compensation, storage or filtering as
well as system testing and logic and communication functions
MEMS and ICs can be integrated using two basic methods:
(1)In the general approach referred to here as a multi-chip solution, MEMS and IC
components are manufactured on separate substrates using dedicated MEMS and IC
processes and are subsequently hybridized in the final system. Two-dimensionally or
side-by-side integrated systems are often referred to as multi-chip modules. When chips
are vertically stacked in a package in this way, such a system is also referred to as a
system-in-package or a vertical multi-chip module2. Devices created through vertical
stacking of several IC chips are also referred to as three-dimensional integrated circuits
(3D ICs).
(2) In the general approach referred to here as a system-on-chip (SoC) solution, MEMS and IC
components are manufactured on the same substrate, using consecutive or interlaced
processing schemes.
8.MICROSYSTEMS
Microsystems are miniaturized (silicon or polymer) devices which perform non-electronic
functions: typically sensing and actuation. Typical microsystems have mechanical parts, like
microbridges in RF switches or bending cantilevers in atomic force microscopes (AFMs);
electrical parts like piezoresistors in airbag sensors or capacitors in pressure sensors; or
thermal, optical and fluidic structures like heaters and nozzles in inkjet printer or flow sensors.
In biomicrosystems (BioMEMS) cells or microbeads are handled by fluidic streams, magnetic
and electric fields, thermal gradients etc. In chemical microsystems operations like sample
pretreatment, separation and detection are built on microchips. This field is also known as
microfluidics or lab-on-a-chip. Today it is possible to build up microsystems without any
tooling needed by computer-aided direct parallel batch processing technologies called RMPD
Rapid Micro Product Development.
A microsystem is an engineering system that contains MEMS components that are designed to
perform specific engineering functions. 3 components : micro sensors, actuators, and a
processing unit.

Fig1. 6 Components of a Microsystem

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 Fig1.7 Microsystems
An intelligent microsystem incorporates signal processing and closed-loop feedback control
systems into a microsystem.
Examples – Micro gears, Micro mixer, Micro mirrors
TEXT / REFERENCE BOOKS
1. Tai-Ran Hsu, MEMS & Microsystem, Design and manufacture, Mc. Graw Hill 2002.
2. Malsch, NeelinaH., ed., Biomedical Nanotechnology, Washington, DC: CRC Press,
2005
3. 3. Marc J. Madou, Fundamentals of Microfabrication and Nanotechnology, 3rd
Edition, Three-Volume Set,CRC Press 2011.
4. Mohamed Gad-el-Hak, The MEMS Handbook, CRC Press, 2005
5. HocineYahia, Shape Memory Implants Springer Verlag 2000.

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 SCHOOL OF BIO & CHEMICAL ENGINEERING

DEPARTMENT OF BIOMEDICAL ENGINEERING

UNIT – II – Processing : Micro Machining Technology – SBM1606

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 UNIT 2

PROCESSING: MICRO MACHINING TECHNOLOGY

2.LITHOGRAPHY
Lithography in MEMS context is typically the transfer of a pattern into a photosensitive
material by selective exposure to a radiation source such as light. A photosensitive material is a
material that experiences a change in its physical properties when exposed to a radiation
source. If a photosensitive material is selectively exposed to radiation (e.g. by masking some of
the radiation) the pattern of the radiation on the material is transferred to the material exposed,
as the properties of the exposed and unexposed regions differ.
This exposed region can then be removed or treated providing a mask for the underlying
substrate. Photolithography is typically used with metal or other thin film deposition, wet
and dry etching.
2.1.1Electron beam lithography
Electron beam lithography (often abbreviated as e-beam lithography) is the practice of
scanning a beam of electrons in a patterned fashion across a surface covered with a film
(called the resist) ("exposing" the resist) and of selectively removing either exposed or
non-exposed regions of the resist ("developing"). The purpose, is to create very small
structures in the resist that can subsequently be transferred to the substrate material, often by
etching. It was developed for manufacturing integrated circuits, and is also used for creating
nanotechnology architectures.
The primary advantage of electron beam lithography is that it is one of the ways to beat the
diffraction limit of light and make features in the nanometer region. This form of maskless
lithography has found wide usage in photomask- making used in photolithography, low
-volume production of semiconductor components, and research & development.
The key limitation of electron beam lithography is throughput, i.e., the very long time it takes
to expose an entire silicon wafer or glass substrate. A long exposure time leaves the user
vulnerable to beam drift or instability which may occur during the exposure. Also, the
turn-around time for reworking or re-design is lengthened unnecessarily if the pattern is not
being changed the second time.
2.1.2Ion beam lithography
It is known that focused-ion-beam lithography has the capability of writing extremely fine lines
(less than 50 nm line and space has been achieved) without proximity effect. However, because
the writing field in ion-beam lithography is quite small, large area patterns must be created by
stitching together the small fields.
2.1.3Ion track technology
Ion track technology is a deep cutting tool with a resolution limit around 8 nm applicable to
radiation resistant minerals, glasses and polymers. It is capable to generate holes in thin films

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without any development process. Structural depth can be defined either by ion range or by
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material thickness. Aspect ratios up to several 10 can be reached. The technique can shape and
texture materials at a defined inclination angle. Random pattern, single-ion track structures and
aimed pattern consisting of individual single tracks can be generated.
2.1.4X-ray lithography
X-ray lithography, is a process used in electronic industry to selectively remove parts of a thin
film. It uses X-rays to transfer a geometric pattern from a mask to a light-sensitive chemical
photoresist, or simply "resist," on the substrate. A series of chemical treatments then engraves
the produced pattern into the material underneath the photoresist.
2.1.5Diamond patterning
A simple way to carve or create patterns on the surface of nanodiamonds without damaging
them could lead to a new photonic devices.
Diamond patterning is a method of forming diamond MEMS. It is achieved by the lithographic
application of diamond films to a substrate such as silicon. The patterns can be formed by
selective deposition through a silicon dioxide mask, or by deposition followed by
micromachining or focused ion beam milling.
2.2ETCHING:
Etching processes
There are two basic categories of etching processes: wet etching and dry etching. In the
former, the material is dissolved when immersed in a chemical solution. In the latter, the
material is sputtered or dissolved using reactive ions or a vapor phase etchant.
2.2.1Wet etching
Wet chemical etching consists in selective removal of material by dipping a substrate into a
solution that dissolves it. The chemical nature of this etching process provides a good
selectivity, which means the etching rate of the target material is considerably higher than the
mask material if selected carefully.
2.2.2Isotropic etching
Etching progresses at the same speed in all directions. Long and narrow holes in a mask will
produce v-shaped grooves in the silicon. The surface of these grooves can be atomically
smooth if the etch is carried out correctly, with dimensions and angles being extremely
accurate.
2.2.3Anisotropic etching
Some single crystal materials, such as silicon, will have different etching rates depending on
the crystallographic orientation of the substrate. This is known as anisotropic etching and one
of the most common examples is the etching of silicon in KOH (potassium hydroxide), where
Si <111>planes etch approximately 100 times slower than other planes (crystallographic
orientations) .Therefore, etching a rectangular hole in a (100)-Si wafer results in a pyramid
shaped etch pit with 54.7° walls, instead of a hole with curved sidewalls as with isotropic
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etching.
2.2.4HF etching
Hydrofluoric acid is commonly used as an aqueous etchant for silicon dioxide (SiO 2, also
known as BOX for SOI), usually in 49% concentrated form, 5:1, 10:1 or 20:1 BOE (buffered
oxide etchant) or BHF (Buffe red HF). They were first used in medieval times for glass etching.
It was used in IC fabrication for patterning the gate oxide until the process step was replaced by
RIE.
Hydrofluoric acid is considered one of the more dangerous acids in the cleanroom. It penet
rates the skin upon contact and it diffuses straight to the bone. Therefore, the damage is not felt
until it is too late.
2.2.5Electrochemical etching
Electrochemical etching (ECE) for dopant-selective removal of silicon is a common method to
automate and to selectively control etching. An active p-n diode junction is required, and
either type of dopant can be the etch-resistant ("etch-stop") material. Boron is the most
common etch-stop dopant. In combination with wet anisotropic etching as described above,
ECE has been used successfully for controlling silicon diaphragm thickness in commercial
piezoresistive silicon pressure sensors. Selectively doped regions can be created either by
implantation, diffusion, or epitaxial deposition of silicon.
2.3 Dry etching
2.3.1Vapor etching
Xenon difluoride -Xenondifluoride (XeF) is a dry vapor phase isotropic etch for silicon
originally applied for MEMS in 1995 at University of California, Los Angeles.Primarily used
for releasing metal and dielectric structures by undercutting silicon, XeF has the advantage of a
stiction-free release unlike wet etchants. Its etch selectivity to silicon is very high, allowing it to
work with photoresist, SiO , silicon nitride, and various metals for masking. Its reaction to
silicon is "plasmaless", is purely chemical and spontaneous and is often operated in pulsed
mode. Models of the etching action are available, and university laboratories and various
commercial tools offer solutions using this approach.
2.3.2Plasma etching
Modern VLSI processes avoid wet etching, and use plasma etching instead. Plasma etchers can
operate in several modes by adjusting the parameters of the plasma. Ordinary plasma etching
operates between 0.1 and 5 Torr. (This unit of pressure, commonly used in vacuum
engineering, equals approximately 133.3 pascals.) The plasma produces energetic free radicals,
neutrally charged, that react at the surface of the wafer. Since neutral particles attack the wafer
from all angles, this process is isotropic.
Plasma etching can be isotropic, i.e., exhibiting a lateral undercut rate on a patterned surface
approximately the same as its downward etch rate, or can be anisotropic, i.e., exhibiting a
smaller lateral undercut rate than its downward etch rate. Such anisotropy is maximized in deep
reactive ion etching. The use of the term anisotropy for plasma etching should not be conflated

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with the use of the same term when referring to orientation-dependent etching.
The source gas for the plasma usually contains small molecules rich in chlorine or fluorine. For
instance, carbon tetrachloride (CCl4) etches silicon and aluminium, and
trifluoromethaneetches silicon dioxide and silicon nitride. A plasma containing oxygen is used
to oxidize ("ash") photoresist and facilitate its removal.
Ion milling, or sputter etching, uses lower pressures, often as low as 10−4 Torr (10 mPa). It
bombards the wafer with energetic ions of noble gases, often Ar+, which knock atoms from the
substrate by transferring momentum. Because the etching is performed by ions, which
approach the wafer approximately from one direction, this process is highly anisotropic. On the
other hand, it tends to display poor selectivity. Reactive-ion etching (RIE) operates under
conditions intermediate between sputter and plasma etching (between 10–3 and 10−1 Torr).
Deep reactive-ion etching (DRIE) modifies the RIE technique to produce deep, narrow
features.
Sputtering
2.3.4 Reactive ion etching (RIE)
In reactive-ion etching (RIE), the substrate is placed inside a reactor, and several gases are
introduced. Plasma is struck in the gas mixture using an RF power source, which breaks the gas
molecules into ions. The ions accelerate towards, and react with, the surface of the material
being etched, forming another gaseous material. This is known as the chemical part of reactive
ion etching. There is also a physical part, which is similar to the sputtering deposition process.
If the ions have high enough energy, they can knock atoms out of the material to be etched
without a chemical reaction. It is a very complex task to develop dry etches processes that
balance chemical and physical etching, since there are many parameters to adjust. By changing
the balance it is possible to influence the anisotropy of the etching, since the chemical part is
isotropic and the physical part highly anisotropic the combination can form sidewalls that have
shapes from rounded to vertical.
Deep RIE (DRIE) is a special subclass of RIE that is growing in popularity. In this process,
etch depths of hundreds of micrometres are achieved with almost vertical sidewalls. The
primary technology is based on the so-called "Bosch process" named after the German
company Robert Bosch, which filed the original patent, where two different gas compositions
alternate in the reactor. Currently there are two variations of the DRIE. The first variation
consists of three distinct steps (the original Bosch process) while the second variation only
consists of two steps. In the first variation, the etch cycle is as follows:
(i) SF6 isotropic etch;
(ii) C4F8 passivation;
(iii) SF6 anisoptropic etch for floor cleaning. In the 2nd variation, steps (i) and (iii) are
combined.
Both variations operate similarly. The C4F8 creates a polymer on the surface of the substrate,
and the second gas composition (SF6 and O2) etches the substrate. The polymer is immediately
sputtered away by the physical part of the etching, but only on the horizontal surfaces and not
5
the sidewalls. Since the polymer only dissolves very slowly in the chemical part of the etching,
it builds up on the sidewalls and protects them from etching. As a result, etching aspect ratios
of 50 to 1 can be achieved. The process can easily be used to etch completely through a silicon
substrate, and etch rates are 3–6 times higher than wet etching.
2.4 ION IMPLANTAION
An ion-implantation material-modification technique was applied to a micro-electro
mechanical systems (MEMS) fabrication technique in order to enhance the functionality of
MEMS. Ion implantation, which is well known as doping technology in semiconductor and
surface modification technology, can alter the characteristics of a substrate by the addition of
ions. However, when the object is a microscale device such as MEMS, such implantation
involves metallurgy of the micro material, because size, depth, and area of the modified area
are on the same order as the size of the microscale device. When the characteristics that can be
controlled by ion implantation are combined with other properties, such mechanical, electrical,
optical, and chemical, a wide range of characteristics can be easily controlled simply by
changing the operating parameters, such as ion species, energy, dose, and substrate
temperature. By effectively utilizing region selectivity, which is an advantage of ion
implantation, the local physical properties of a micro device can be controlled. Consequently,
in the design of MEMS devices, material properties can be controlled to enhance the
functionality of the device. In this study, we used this ion implantation technique, which only
involved injection of ions and etching that changed the chemical property of the substrate
material, to fabricate a micro device, e.g., a microcantileverbeam, that has low elasticity and
electric conductance.
2.5 WAFER BONDING
Wafer bonding is a packaging technology on wafer- level for the fabrication of
microelectromechanical systems (MEMS), nanoelectromechanical systems (NEMS),
microelectronics and optoelectronics, ensuring a mechanically stable and hermetically sealed
encapsulation. The wafers' diameter range from 100 mm to 200 mm (4 inch to 8 inch) for
MEMS/NEMS and up to 300 mm (12 inch) for the production of microelectronic devices
In microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS),
the package protects the sensitive internal structures from environmental influences such as
temperature, moisture, high pressure and oxidizing species. The long-term stability and
reliability of the functional elements depend on the encapsulation process, as does the overall
device cost. The package has to fulfill the following requirements:

 protection against environmental influences

 heat dissipation
 integration of elements with different technologies
 compatibility with the surrounding periphery
 maintenance of energy and information flow
2.5.1TECHNIQUES:
6
The commonly used and developed bonding methods are as follows:
Direct bonding Plasma activated bonding Anodic bonding Eutectic bonding Glass
frit bonding Adhesive bonding Thermo compression bonding Reactive bonding
Transient liquid phase diffusion bonding
2.5.2REQUIREMENTS:
The bonding of wafers requires specific environmental conditions which can generally be
defined as follows:
1) substrate surface
 flatness
 smoothness
 cleanliness
2) bonding environment
 bond temperature
 ambient pressure
 applied force
3) materials

 substrate materials
 intermediate layer materials

The actual bond is an interaction of all those conditions and requirements. Hence, the applied
technology needs to be chosen in respect to the present substrate and defined specification like
max. bearable temperature, mechanical pressure or desired gaseous atmosphere.
2.5.3EVALUATION:
The bonded wafers are characterized in order to evaluate a technology's yield, bonding strength
and level of hermeticity either for fabricated devices or for the purpose of process
development. Therefore, several different approaches for the bond characterization have
emerged. On the one hand non-destructive optical methods to find cracks or interfacial voids
are used beside destructive techniques for the bond strength evaluation, like tensile or shear
testing. On the other hand the unique properties of carefully chosen gases or the pressure
depending vibration behavior of micro resonators are exploited for hermeticity testing.
2.6INTEGRATED PROCESSING
With the integrated process option the wafers are removed from the standard line and after the
addition of micromachining steps return to the standard line. The position of the additional
process steps is extremely important. In some cases the additional depositions are added after
the main thermal processing but before the aluminium. Depending on the sensitivity of the
7
electronics devices to thermal budget, a maximum thermal budget for the micromachining is
determined.

Fig2.1 integrated processing

2.7BULK MICROMACHINING
Bulk micromachining is the oldest paradigm of silicon based MEMS. The whole thickness of a
silicon wafer is used for building the micro-mechanical structures.Silicon is machined using
various etching processes. Anodic bonding of glass plates or additional silicon wafers is
used for adding features in the third dimension and for hermetic encapsulation. Bulk
micromachining has been essential in enabling high performance pressure sensors and
accelerometers.
The term bulk micromachining comes from the fact that this type of micromachining is used to
realize micromechanical structures within the bulk of a single-crystal silicon wafer by
selectively removing (‘etching’) wafer material. The microstructures fabricated using bulk
micromachining may cover the thickness range from submicron to full wafer thickness
(200–500 μm), and the lateral size range from submicron to the lateral dimensions of a full
wafer. Bulk micromachining technique allows to selectively remove significant amounts of
silicon from a substrate to form membranes on one side of a wafer, a variety of trenches, holes,
or other
Bulk micromachining technique can be divided into wet etching and dry etching of silicon
according to the phase of etchants. Liquid etchants, almost exclusively replying on aqueous
chemicals, are referred to as wet etching. Vapor and plasma etchants are referred to as dry
etching. For etching such thick silicon substrate, anisotropic wet etchants such as solutions of
potassium hydroxide (KOH), ethylene diamine and pyrocatechol (EDP),
tetramethylammonium hydroxide (TMAH), and hydrazine-water are used. These etchants
have different etch rates in different crystal orientation of the silicon . Wet etching in mostcase
is done from the back side of the wafer while the plasma etching is being applied to front
side.Etch process can be made selective by the use of dopants (heavily doped regions etch
slowly) or may even be halted electrochemically (e.g., etching stops upon encountering a
region of different polarity in a biased p–n junction). A region at which wet etching tends to
slow down or diminish is called an etch-stop. Wet etching occurs by dipping substrate into an
etching bath or spraying it with etchants that may be acid or alkaline. Wet etching can either be
isotropic etching or anisotropic etching depending on the structure of the materials or the
etchants used. If the material is amorphous or polycrystalline, wet etching is always isotropic
8
etching. During isotropic etching (etchants used are acid solution), resist is always undercut,
implying that the deep etching is not practical for MEMS.

Fig.2.2 Etched grooves using (a) anisotropic etchants, (b) isotropic etchants, (c) Reactive
Ion Etching (RIE)
2.7.1 Isotropic Etching
Isotropic etching uses very strong acids for attacking the Si, resulting in rounded patterns
grooved into the substrate material because of the equal etch rate in all directions. Rates of up
to 50 microns per minute can be achieved (about 100 times faster than anisotropic etching).
The rate depends on the concentration of the acid used and the processing temperature as well
as on the grade of agitation applied to the sample while etching. Because the etch rate depends
on agitation, difficulties occur when controlling the exact extend of the etched structure.
The most common etchants are mixtures of hydrofluoric acids (HF) and nitric acid (HNO3)
with either water or rather acetic acid being used as diluent. A solution of this kind is often
referred to as HNAsystem. Since the etch rate of SiO2 is high (300 to 800 Å/min), either thick
layers of oxide or alternative masking layers like silicon nitride (Si3N4) are needed when
etching deeper patterns into the substrate. Otherwise the accuracy of the mask could be affected
in a negative way, resulting in poor resolution of the etched profile.
Since the etchant attacks the Si equally in every direction, it takes away the material
horizontally as well, thus undercutting the masking layer on top. The longer the sample
remains in the etch bath, the stronger this effect, since the etch rate is all the same in every
direction, making masking a difficult task when etching isotropically.
A common means for cleaning a plain wafer before doing any kind of process is immersing it in
a piranha etch (H2O2:H2SO4, concentration varying between 1:1 and 4:1) to remove
impurities on top of the sample. The acid does not affect Si itself, developing a thin film of
oxide instead when brought in contact.
The BHF solution mentioned above for patterning the oxide mask also belongs to the category
of isotropic etchants.
2.7.2Anisotropic Etching
Anisotropic etching techniques were developed later than their isotropic relatives. The most
9
important attribute of anisotropic etch is their ability to control the lateral extensions of the
etched profile. In contrast to the isotropic etchants, anisotropic etchants attack the substrate
material depending on its crystalline structure, thus revealing very precise structures when
applied correctly. They were developed in the 1960s by Bell Laboratories.
Common chemicals used in anisotropic etching processes are:
Potassium hydroxide (KOH)/H2O solutions, sometimes with ispropyl alcohol (IPA) additive at
65-85°C
Ethylene diaminepyrocatechol (EDP), diluted with water at 115ºC
Tetramethylammmonium hydroxide (TMAH) and water at 90ºC
Hydrazine N2H4/H2O/IPA at 115ºC
The etchants differ with respect to their specifications regarding handling, toxicity, and
appropriate masking material. Again, the etch rate depends on the concentration of the solution
used, higher concentrations generally slow down the etching process, since the water is needed
in the etching process as an oxidizing agent for silicon.
KOH is the most popular etchant. It can be used in near saturated solutions with processing
temperatures of up to 80ºC; higher temperatures affect the etch uniformity and produce
unwanted fumes. A disadvantage of this chemical is the fact that its etch selectivity between Si
an SiO2 is too low, resulting in mask layers made of oxide being attacked quickly. Therefore,
for this process, alternative masking materials are needed, adding additional process steps to
the fabrication process. Like applying to the isotropic HNA etching system, Si3N4 is an
appropriate material for masking, staying untouched by the KOH etchant. While the etching is
in progress, the development of bubbles that consist of hydrogen set free by the reaction occurs.
When too great in numbers, these bubbles can prevent parts of the solution from keeping in
touch with the substrate's surface, leading to an increase in surface roughness. This especially
happens at long etch times when using solutions of high concentration. Agitation of the
immersed sample reduces this problem. KOH can cause blindness in contact with the eyes, but
is less hazardous than most of the other etching solutions.
TMAH is the newest of the etching solutions mentioned above. Being non-toxic, its handling is
easy compared to the other etchants. The appropriate concentration is chosen by weighing
surface smoothness against etch rate, since the first is better with more saturated solutions,
whereas the latter rises with the amount of water present in the solution. A value of
approximately 22 wt% is usually a reasonable compromise between these two factors. The
disadvantage of TMAH is its lower etch rate of Si, compared to the other chemicals.
Hydrazine was the first anisotropic etchant. It is explosive at concentrations of 50 % and above
in solution with water and very toxic (suspected to cause cancer). For this reason it is hardly in
use anymore, having been replaced by EDP in most cases which is less hazardous. The surface
quality of the produced structures is very good, depending on the water concentration and the
temperature of the solution. Silicon oxide nearly is not attacked and therefore often used as
masking material, as well as many metallic films.
The organic etchant EDP was developed to replace the hard to handle hydrazine, providing a
10
more stable and less toxic means for anisotropic etching processes. SiO2 can be used as
masking material, since with EDP the etch selectivity between Si and its oxide is very good.
Selectivity is also good between Si and various other materials, e. g., gold, chromium, silver,
copper or silicon nitride, making this etchant pretty flexible in this respect. But the solution is
toxic and has to be handled with great care. It ages fast, especially in the presence of oxide,
resulting in an optically denser liquid with considerably lower etch activity.
In general, etch rates of anisotropic etchants are considerably lower than those of isotropic
processes, mostly being slower than 1 µm/s. Etching deep structures of some 100 microns into
the bulk of a substrate material therefore is far more time consuming when using anisotropic
etchants, demanding processing times of several hours. This requires a careful choice of the
masking material to prevent the etched structure to get too imprecise due to the mask layer
being attacked to hard by the etchant. In some cases, surface roughness is too high, making a
short isotropic etch advisable after the anisotropic process for smoothing purposes.
For both isotropic and anisotropic etching proper protection of the backside of the wafer is
required. This can be done mechanically by keeping it in a special holder that prevents the
backside to get exposed to the liquid. Or, it is possible to coat it with a chemical protection
layer,
e. g., waxes.
2.8.SURFACE MICRO MACHINING
In contrast to the bulk micromachining described above, where three-dimensional structures
are etched into the substrate wafer, surface micromachining consists of building them by
layering thin films of new material onto the surface of the substrate. Usually, sacrificial spacer
layers are used to create freestanding structures like air-bridges; after depositing such a
sacrificial layer and patterning it using microlithographic steps described above, the material
for the final structure is deposited. Afterwards, the spacer layer is removed by an appropriate
etchant, freeing the desired structure.
Surface micromachining was invented in the late 1960s, when a cantilever beam was produced
by underetching the applied material on top of a sacrificial layer. The techniques used in this
area emerged in the early 1980s, using polysilicon as structural material. Many different
structures created using surface micromachining have been demonstrated, e. g., springs, gears,
sliders and sealed cavities. However, the first commercial application based on this process
was announced 1991 by Analog Devices (an accelerometer for the automobile industries).
Surface micromachining uses layers deposited on the surface of a substrate as the structural
materials, rather than using the substrate itself. Surface micromachining was created in the late
1980s to render micromachining of silicon more compatible with planar integrated circuit
technology, with the goal of combining MEMS and integrated circuits on the same silicon
wafer. The original surface micromachining concept was based on thin polycrystalline silicon
layers patterned as movable mechanical structures and released by sacrificial etching of the
underlying oxide layer. Interdigital comb electrodes were used to produce in-plane forces and
to detect in-plane movement capacitively. This MEMS paradigm has enabled the
manufacturing of low cost accelerometers for e.g. automotive air-bag systems and other
applications where low performance and/or high g-ranges are sufficient. Analog Devices has
11
pioneered the industrialization of surface micromachining and has realized the co-integration
of MEMS and integrated circuits.

Fig2.3 Basic surface micromachining process. (a) Spacer layer deposition. (b) Pattering
of the spacer layer. (c) Deposition of the microstructure layer. (d) Patterning of desired
structure.
2.8.1Stripping of the spacer layer resolves final structure.
The steps for producing the air-bridge are clearly visible. Different materials can be used for
the spacer layer, with photoresist being the simplest choice, reducing the steps necessary for
patterning. Photoresist can be exposed with an appropriate mask and simply developed,
revealing the structure needed for the following deposition of the microstructure layer. If a
metallic material is used for this purpose, often a seed layer is deposited in order to enable the
final structure to be applied via electrodeposition. This seed layer can be evaporated to a
thickness of ~100 Å; afterwards, the sample is electroplated for an appropriate time in order to
achieve the desired thickness of the final structure.
A variation of the standard surface micromachining process is called lift-off. Its aim is to apply
a (metallic in most cases) layer to the substrate only in specific areas. Therefore, a sacrificial
layer (usually photoresist) is applied and patterned, opening the regions that are to be covered
with the metal film. After deposition of the metal, it contacts the substrate only in those regions.
By removing the photoresist with a solvent that does not attack the metal layer, the material on
top of the sacrificial layer is "lifted off", leaving the metal only at the desired areas

12
 Fig. 2.4.Principle of the lift-off process
Important for the success of the lift-off procedure is the use of relatively thick photoresist in
order to provide a very thin metallic layer on the sidewalls of the opening. This allows the
lift-off to be completed without breaking the metallic film too easily. This is also the main
difference between lift-off and normal surface micromachining, where thicker sidewalls are
required in order to provide stability of the free structure.
The advantage of the lift-off procedure is the ability to work with metallic layers such as
platinum or gold that are difficult to pattern by etching directly.
2.9COATING TECHNOLOGY
Stiction is a major problem in MEMS devices. Stiction (i.e.,unintentional adhesion) occurs
when surface adhesion forces (viz., capillary, van derWaals and electrostatic) are higher than
the mechanical restoring force of the miniaturized surfaces of the structural components. As a
result of stiction, surfaces can permanently adhere to each other causing device failure-a
phenomenon known as in-use stiction.
The application of low-energy surface coatings would be required to eliminate or reduce
capillary, chemical bonding and electrostatic forces between the contacting microstructure
surfaces of the MEMS device.
Coatings should have the following characteristics.-
The coating should have excellent adhesion on the surfaces of the micro-components It
should be hydrophobic in nature and thin enough not to bridge structural features of the MEMS
device. The coating also has to permeate through microscopically small openings and
diffuse onto under surfaces. The coating film should have stability in MEMS operating
environments (viz. air and vacuum) It should retain its lubricating properties for longer
periods. This is specially critical in MEMS devices for biomedical applications.
2.9.1Techniques:
2.9.2Spin coating
Spin coating of photoresist is the standard coatingmethod for flat wafers in MEMS technology.
First, photoresist is flooded onto thewafer in order to cover the whole surface. A pause afterthe
dispense step allows additional time for the solutionto flow into the deep features. A slow
13
acceleration andspin speed is applied in the first step. This allows timefor the solution to flow
and spread prior to drying. Asecond step with a fast spin speed promotes the drying ofthe film
and reduces the further flowing of photoresistthat can result in non-uniformal coating.
2.9.3Spray Coating
The direct spray system includes an ultrasonic spray nozzle, which generates a distribution of
droplets of micrometer size. It can reduce the effect of fluid dynamics of photoresist on the
wafer as the resist droplets are supposed to stay where they are being deposited. The central
part of the aerosol is forwarded to the dispense nozzle which is constructed to reduce the carrier
gas pressure and to redirect the resist spray perpendicular to the substrate surface. During spray
coating, the wafer is rotated slowly while the swivel arm of the spray coating unit is moved
across the wafer. The low spinner speed (30-60rpm) is to minimize the centrifugal force. The
rotating also allows resist coverage in all the angle of the cavities. Photoresist AZ4562 diluted
with a solvent is used for this spray system as it results in good coverage and uniform layer
2.9.4Electrodeposition
It requires a special plating equipment and cataphoretic resist emulsion. To deposit a
photoresist layer, the wafer surface must be coated with an electrically conductive material.
The wafer to be coated faces an inert, planar stainless steel anode at a distance of 50 mm.
2.10CVD-LIGA PROCESS
The LIGA Fabrication process provides the possibility to produce micromechanical structures
with very high aspect ratios compared to other microelectromechanical technologies (up to
300:1). The height of the manufactured pieces can be 100 microns to a couple of millimeters.
By using molding, different materials (metal, ceramics as well as plastic) can be used to
produce the final structure.
LIGA is a German abbreviation and stands for Lithographie, Galvanoformung and Abformung
(lithography, electrodeposition and molding). The process was developed in the 1980s by the
Kernforschungszentrum Karlsruhe, Germany (KfK) to provide a technique for producing large
numbers of micron sized nozzles.
The principle of the LIGA process consists of depositing a relatively thick layer of a polymer
sensitive to X-rays on top of a conductive substrate or one covered with a conductive seed
layer. This can be done by applying multiple coats of photoresist during spinning the substrate
wafer for thicknesses of up to a few hundred microns. For thicker polymer layers (millimeters)
it is common to buy prefabricated plates of PMMA (polymethylmethacrylate, a polymer often
used as photoresist), attach them to the substrate plate and mill them back to the desired
thickness.
After exposure through an appropriate X-ray-mask, a developer removes either the exposed
(positive photoresist) or the unexposed (negative) areas of polymer, and metal layers are grown
by electroplating in the spaces now free from cover. Often the metal is grown higher than
needed and then milled back to the desired thickness together with the photoresist. Having
removed the unwanted areas of the polymer, the resulting metallic structure can be used. Free
mechanical structures can be manufactured by using a sacrificial layer between the wafer

14
substrate and the grown metal film and dissolving this layer, thus yielding the structure in the
end of the process; this technique is called sacrificial LIGA (SLIGA).

Fig2.5. LIGA process

For the purpose of mass production, the metal can serve as a mould or embossing tool for
pieces made of various materials such as metals, polymers, ceramics or glass.
The major advantages of the LIGA process are the high aspect ratios made possible and
therefore the larger heights of the pieces, very sharp vertical sidewalls as well as the possibility
to produce three-dimensional structures by using a sacrificial layer as described above.
The main disadvantage of LIGA is the need of high-energy X-rays that can only be achieved
with a synchrotron. This and the expensive X-ray masks needed for exposure make the cost for
the process high. On the other hand, the mass production of microstructures by using the
produced structures as mold for other materials becomes very inexpensive per produced
device, since the expensive exposure step only needs to be done once in the beginning of the
fabrication process.
To reduce the cost of LIGA, especially the investment costs for the synchrotron, the usage of
traditional lithography light sources in the UV range is being investigated in combination with
other photoresist materials (rather polyamides or standard photoresists than the polymers used
in X-ray lithography). Using these processes, structures of up to 80 microns in height can be
produced with this technique.

15
Alternatively companies providing the necessary tools for LIGA to multiple users can reduce
the production cost, too. MCNC in Research Triangle Park, NC offers LIGAMUMPs&trade;, a
"Multi-user MEMS Process that involves the fabrication of high aspect ratio MEMS in a
low-cost environment"

TEXT / REFERENCE BOOKS

1. Tai-Ran Hsu, MEMS & Microsystem, Design and manufacture, Mc. Graw Hill 2002.
2. Malsch, NeelinaH., ed., Biomedical Nanotechnology, Washington, DC: CRC Press,
2005
3. 3. Marc J. Madou, Fundamentals of Microfabrication and Nanotechnology, 3rd
Edition, Three-Volume Set,CRC Press 2011.
4. Mohamed Gad-el-Hak, The MEMS Handbook, CRC Press, 2005
5. HocineYahia, Shape Memory Implants Springer Verlag 2000.

16
 SCHOOL OF BIO & CHEMICAL ENGINEERING

DEPARTMENT OF BIOMEDICAL ENGINEERING

UNIT – III – MICROSYSTEMS AND MICROFLUIDS– SBM1302

1
 UNIT-3- MICROSYSTEMS AND MICROFLUIDS
3.1 Micro systems:
Microsystems are miniaturized (silicon or polymer) devices which perform non-electronic
functions typically sensing and actuation
3.1.1Microfluidics:
Microfluidics is a multidisciplinary field intersecting engineering, physics, chemistry,
biochemistry, nanotechnology, and biotechnology, with practical applications to the design of
systems in which low volumes of fluids are processed to achieve multiplexing, automation, and
high-throughput screening.
3.2.Microsensors
Sensors used in MEMS are termed microsensors. They have physical dimensions in the
submicrometer to millimeter range. They have lower manufacturing cost (mass-production,
less materials),wider exploitation of IC technology (integration),wider applicability to sensor
arrays, less weight.
Sensors in mems are classified as
3.2.1Acoustic wave sensor
These generally measure chemical composition in gas.
Generate acoustic wave by converting mechanical energy into electrical energy.
3.2.2Biomedical sensors
It has bio-sensors, bio-instruments, surgery tools and system for analysing quick,
accurate and low cost testing of biological substance.
They are used to measure biological substance as well as for diagnostic purpose.
Eg: glucose + O2gluconaldehyde +H2O2.
3.2.3Chemical sensors
Used to sense particular chemical compound Very simple
Eg: metals are vulnerable to oxidation when exposed to air for long, oxide on the metal change
in properties such as electrical resistance, based on this principle the microsensors are designed
and developed.
Chemi-resistors
Polymers used in this sensors can cause change in electrical conducting of metal
Eg:NH3
3.2.4Optical sensors
Principle of interaction between photons in light and electron in solid that receive the light have

2
been well developed to sense the intensity of light.
Solid state material that provide strong photon electron interaction are used as sensing material.
Selection of this material are based on the quantum efficiency.
3.2.5Pressure sensors:
They are generally used in automotive and aerospace industry.
Human body is a complex system of pumps, valves,vessels and interconnections.health
monitoring of a patient requires knowledge of blood pressure,bladder pressure and cerebral
spinal fluid pressure.
Pressure sensors are inserted in the human body to monitor the above, these sensors should be
small and ideally disposable.
Sensors are inserted to catheter and then to the arteries.
3.2.6Thermal sensors
Thermocouple are most common transducer used to sense heat.
The principle is when electromotive force produced at the open end of 2 dissimilar metallic
wires,the junction of the wire is heated. Temperature produced at junction due to heating can be
correlated to magnitude of produced emf or voltage.
3.3Actuators
An actuator is a type of motor that is responsible for moving or controlling a mechanism or
system.
It is operated by a source of energy, typically electric current, hydraulic fluid pressure,
or pneumatic pressure, and converts that energy into motion.
3.1Types:
There are four main types of actuators: Hydraulic, Pneumatic, Electric and Mechanical.
3.1.1Hydraulic actuator:
Hydraulic actuators consist of a cylinder or fluid motor that utilizes hydraulic power to
facilitate mechanical process. The mechanical motion gives an output in terms of linear, rotary
or oscillatory motion. Since liquids are nearly incompressible, they take longer to gain speed
and power and also slow back down, but they can exert great force. The hydraulic actuator also
allows for very precise control of the movement produced. In linear hydraulic actuators, a
typical set-up is made up of a hollow cylinder that contains a liquid, usually oil, and a piston
that is inserted in it. When pressure is applied onto the piston, objects can be moved by the
force produced. Hydraulic actuators can be operated manually, such as a hydraulic car jack, or
they can be operated through a hydraulic pump, which can be seen in construction equipment
such as cranes or excavators.
3.1.2Pneumatic actuator:

3
Pneumatic actuators work on the same concept as hydraulic actuators except compressed gas is
used instead of liquid. Energy, in the form of compressed gas, is converted into linear or rotary
motion, depending on the type of actuator. Pneumatic energy is more desirable for main engine
controls because it can quickly respond in starting and stopping as the power source does not
need to be stored in reserve for operation. Also, pneumatic actuators are preferred in places
where cleanliness is important, since the fluid in hydraulic actuators might leak and
contaminate the surroundings. However, pneumatic actuators are still likely to leak, making
them less efficient compared to mechanical actuators. Another downside is that they take up a
lot of space, create a lot of noise and are difficult to transport once installed in a place.
3.1.3Electric actuator:
Electric actuators are devices powered by motors that convert electrical energy to mechanical
torque. The electrical energy is used to create motion in equipment that require multi-turn
valves like gate or globe valves. Since no oil is involved, electrical actuators are considered to
be one of the cleanest and readily available forms of actuators. Electric actuators are typically
installed in engines, where they open and close different valves. There are many designs of
electric actuators and this depends on their function in the engine that they are installed in.
3.1.4Mechanical actuator:
Mechanical actuators function through converting rotary motion to linear motion.When a
rotary motion. Devices such as gears, rails, pulley, chain and others are used to help convert the
motion. Some of the simple mechanisms used to convert motion are screws, where the rotation
of the actuator's nut causes the screw shaft to move in a straight line, the wheel and axle, where
the rotating motion of a wheel causes a belt or something similar to move in a linear motion.
3.2Electrostatic Forces
Electrostatic force is the phenomenon that results from slow-moving or stationary electrical
charges. electrostatic force is the physical reaction that holds together the electromagnetic field
created by subatomic particles, such as electrons and protons.Electrostatic force between
electrons and protons is one of the strongest forces in the universe, even more powerful than
gravity. A hydrogen atom, which contains only one electron and one proton, has the
fundamental force of gravity keeping it together.As two surfaces come in contact with each
other, charge exchange occurs, resulting in the development of electrostatic forces.
3.3Intelligent/ Smart Materials
A smart material is one which reacts to its environment all by itself. The change is inherent to
the material and not a result of some electronics. The reaction may exhibit itself as a change in
volume, a change in colour or a change in viscosity and this may occur in response to a change
in temperature, stress, electrical current, or magnetic field.
These smart materials include shape memory alloys, piezoelectric materials, magneto-
rheological and electro-rheological materials, magnetostrictive materials and chromic
materials which change their colour in reaction to various stimuli.
A smart structure incorporates some form of actuator and sensor (which may be made from
smart materials) with control hardware and software to form a system which reacts to its
4
environment. Such a structure might be an aircraft wing which continuously alters its profile
during flight to give the optimum shape for the operating conditions at the time.

The current generation of smart structures featuring piezoelectric materials is generally

synthesized with polymeric fibrous composite laminates which readily accommodate
embedded piezoelectric actuators and sensors. Any external force applied on the structure will
set vibrations and cause deformations in the structure. These deformations will cause stresses
and strains in the structure. If the structure is embedded with smart crystals, the effects of the
vibration can be controlled using a feedback mechanism. Since piezoelectrics undergo surface
elongation when an electric field is applied and produce charge when surface strain is applied,
they can be used as both actuators and sensors. Some commonly used actuation materials are
lead zirconatetitanate (PZT) and polyvinylidenefluoride (PVDF). Some ceramic
electrostrictive materials are also used as actuation materials among them are lead magnesium
niobate(PMN),Terfenol, a rare earth magnetic like material and Nitinol (nickel titanium alloy).
They are available in the form of wires or sheets. These substances have the ability to change
the shape, natural frequency,damping or other mechanical characteristics in response to change
in environment.
3.3.1Shape Memory Alloys
Shape memory alloys (SMAs) are one of the most well known types of smart material. The
SME describes the process of a material changing shape or remembering a particular shape at a
specific temperature (i.e. its transformation or memory temperature).
Shape memory alloys have found a large number of uses in aerospace, medicine and the leisure
industry.
Medical applications- Nitinol is biocompatible, that is, it can be used in the body without an
adverse reaction, so it has found a number of medical uses. These include stents in which rings
of SMA wire hold open a polymer tube to open up a blocked vein, blood filters, and bone plates
which contract upon transformation to pull the two ends of the broken bone in to closer contact
and encourage more rapid healing. SMAs also find use in dentistry for orthodontic braces
which straighten teeth.
SMAs can be used as actuators. They can be used in cut out switches for kettles and other
devices, security door locks, fire protection devices such as smoke alarms and cooking safety
indicators.
3.3.2 Piezoelectric Materials
The piezoelectric effect and electrostriction are opposite phenomena and both relate a shape
change with voltage.
An electrical field is generated if a mechanical force is applied to the material to change its
shape. This is the piezoelectric effect. When a electric field is applied to the piezoelectric
material it changes its shape very rapidly and very precisely in accordance with the magnitude
of the field.

5
The piezoelectric effect was first observed in quartz and various other crystals such as
tourmaline. Barium titanate and cadmium sulphate have also been shown to demonstrate the
effect but by far the most commonly used piezoelectric ceramic today is lead zirconium titanate
(PZT).

The main use of piezoelectric ceramics is in actuators, in the microbiology field in microscopic
cell handling systems, in fibre optics and acoustics, in ink-jet printers where fine movement
control is necessary and for vibration damping. The most well known application is in the
sensors which deploy car airbags. The material changes in shape with the impact thus
generating a field which deploys the airbag. Ionic polymers work in a similar way to
piezoelectric ceramics, However they need to be wet to function. An electrical current is passed
through the polymer when it is wet to produce a change in its crystal structure and thus its
shape. Muscle fibres are essentially polymeric and operate in a similar way, so research in this
field has focussed on potential uses in medicine.
3.3.3Magnetostrictive Materials
Magnetostrictive materials are similar to piezoelectric and electrostrictive materials except the
change in shape are related to a magnetic field rather than an electrical field.
Magnetostrictive materials convert magnetic to mechanical energy or vice versa.
The most common magnetostrictive material today is called TERFENOL-D (terbium (TER),
iron (FE), Naval Ordanance Laboratory (NOL) and dysprosium (D)). This alloy of terbium,
iron and dysprosium shows a large magnetostrictive effect and is used in transducers and
actuators. Magnetic materials contain domains which can be likened to tiny magnets within the
material. When an external magnetic field is applied the domains rotate to align with this field
and this result in a shape change. Conversely if the material is squashed or stretched by means
of an external force the domains are forced to move and this causes a change in the
magnetisation. Magnetostrictive materials can be used as both actuators (where a magnetic
field is applied to cause a shape change) and sensors (which convert a movement into a
magnetic field).Ultrasonic magnetostrictive transducers have been used in ultrasonic cleaners
and surgical tools. Other applications include hearing aids, razorblade sharpeners, linear
motors, damping systems, positioning equipment, and sonar.
3.3.4Magneto- And Electro Rheological Materials
Electro-rheological (ER) materials change their properties with the application of an electrical
field and consist of insulating oil such as mineral oil containing a dispersion of solid particles.
Magnetorheological materials (MR) are again based on a mineral or silicone oil carrier but this
time the solid dispersed within the fluid is a magnetically soft material (such as iron) and the
properties of the fluid are altered by applying a magnetic field. In both cases the dispersed
particles are of the order of microns in size. In both cases the smart fluid changes from a fluid to
a solid with the application of the relevant field. The small particles in the fluid align and are
attracted to each other resulting in a dramatic change in viscosity.
The effect takes milliseconds to occur and is completely reversible by the removal of the field.
The first industries to identify uses were the automotive and aerospace industries where the
6
fluids are used in vibration damping and variable torque transmission. MR dampers are used to
control the suspension in cars to allow the feel of the ride to be varied. Dampers are also used in
prosthetic limbs to allow the patient to adapt to various movements for example the change
from running to walking.

7
3.4LAB ON CHIP
A s (LOC) is a device that integrates one or several laboratory functions on a single chip of only
millimeters to a few square centimeters to achieve automation and high-throughput screening.
LOCs deals with the handling of extremely small fluid volumes down to less than picoliters.
Lab-on-a-chip devices are a subset of Micro-electro-mechanical systems (MEMS) devices and
often indicated by "Micro Total Analysis Systems" (µTAS) as well. LOC is closely related to,
and overlaps with, microfluidics which describes primarily the physics, the manipulation and
study of minute amounts of fluids. However, strictly regarded "Lab-on-a- Chip" indicates
generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS"
is dedicated to the integration of the total sequence of lab processes to perform chemical
analysis.
The first real lab-on-a-chip was created in 1979 at Stanford University for gas chromatography.
However, major lab-on-a-chip research only began in the late 80s with the development of
microfluidics and the adaptation of microfabrication processes for the production of polymer
chips. The ability to easily fabricate polymer microchips enabled many research laboratories to
start their own investigations into lab-on-a-chip technologies. Today, it is even possible to
fabricate fully customized lab-on-a-chip devices in any lab without the need of a clean room
3.4Applications
3.4.1Lab-On-A-Chip And Cell Biology
Lab-on-a-chip demonstrates the ability to control cells at the single-cell level while dealing
with a large amount of cells in seconds. At the microscale level flow switch can be very fast
and goes down to just tens of milliseconds. Using fast optical detectors (such as the Opto
Reader, for example) one can detect and isolate a given cell (such as cancerous cell made
fluorescent using antibodies) with high throughput. There are several other applications for
lab-on-a-chip in cell biology, including micro patch clamp, control of stem cell differentiation,
high-speed flow cytometry and cell sorting.
3.4.2Lab-On-A-Chip and Chemistry
The ability to perform fast heating and cooling at the microscale enables higher efficiency in
some chemical reactions. Therefore, much research has been conducted on using labs-on-a-
chip as microsized and highly parallelized micro chemical reactors. Lab-on-a-chip devices can
also be of interest when dealing with dangerous and explosive compounds in that they contain
risk by dealing with smaller volumes at a time.
3.4.3Fabrication Technologies
Lab-on-a-chip uses the most common microfluidic device fabrication technologies, and
depending on their applications, various polymers.
PDMS lab-on-a-chip: PDMS (polydimethylsiloxane) is a transparent and flexible elastomer.
PDMS is widely used because it is very easy and cheap to fabricate PDMS labs-on-a-chip by
casting .Moreover, labs-on-a-chip made of PDMS take advantage of the easy integration of
quake microvalves for fast flow switch and permeability of air for cell culture and studies.
Widely used for lab-on-a-chip prototyping, PDMS shows severe limitations for industrial
8
production. Because the material is subject to ageing, and because PDMS absorbs hydrophobic
molecules, it is hard to integrate electrodes into a PDMS
Thermopolymers (PMMA PS…) lab-on-a-chip: Thermoplastics are good candidates for the
fabrication of labs-on-a-chip since they are transparent, compatible with micrometer-sized
lithography and more chemically inert than PDMS.
Glass lab-on-a-chip: Transparent, compatible with micrometer sized machining, chemically
inert, with a wide range of well-known chemical surface treatments and reproducible electrode
integration, glass is a very good candidate for the industrialization of labs-on-a- chip. From a
research point of view, the fabrication of glass labs-on-a-chip require clean rooms and
researchers with a strong knowledge of microfabrication..
Silicon lab-on-a-chip: The first lab-on-a-chip was done in silicon, and it seems like quite a
normal choice since microtechnologies are based on the micromachining of silicon. Silicon is
expensive, it is not optically transparent (except for IR) and it requires a clean room as well as
a strong knowledge of microfabrication. Moreover, the electrical conductivity of silicon makes
it impossible to use for lab-on-a-chip operations requiring high voltage (like electrophoresis).
Still, even if nowadays silicon seems like an obsolete candidate for the industrialization of
lab-on-a-chip, it is not commonly used unless very necessary.
3.4.4Advantages
Low cost, High parallelization,Ease of use and compactness, Reduction of human error, Faster
response time and diagnosis, Low volume samples, Real time process control and monitoring
increase sensitivity, Expendable.
3.4.5Limitations
Industrialization, Signal/noise ratio, Ethics and human behaviour, Lab-on-a-chip needs an
external system to work.
3.5 Silicon And Glass Micromachining For Micro Total Analysis Systems (µ TAS)
Micro total analysis system is a sub set of devices comprising the lab on the chip. It uses both
hard and soft microfabrication techniques. It can be a hybrid of several chips. It is an integrated
and miniaturised chemical analysis system.

Fig. 3.1 Elements of a µ TAS

In general, four types of subsystems are thought to comprise amTAS: a sampling unit, a
microfluidic unit, a detector system and an electronic controller. .An important aspect is the
very small size required for the sensing element operating in a microchannel of a few hundreds
9
of microns width.
A single chip includes sample preparation, separation and detection system.

Fig.3.2 MICROTOTAL ANALYSIS SYSTEM

3.5.1Fabrication
μTAS fabrication has matured, affording microstructure generation from a wide range of
materials (e.g. glass, silicon, elastomers, plastics, thermosets, paper) and using an equally
broad set of microfabrication methods (e.g. photolithography, soft lithography, injection
molding, hot embossing, laser micromachining).
Recent innovations in fabrication explored unconventional materials and fabrication strategies.
Corn protein (zein) was processed by soft lithography and bonded to both a glass slide and
another zein film by ethanol vapor deposition to form green microfluidic devices.
An origami (paper folding) method was developed to fabricate three-dimensional (3D) paper
devices from single sheets of flat paper in a single photolithographic step.
Curved microfluidic networks were built from the self-assembly of differentially photo-
crosslinked SU-8 films, which spontaneously and reversibly curled on film de-solvation and
re-solvation .
Advantages

 Limited mixing of fluids

 Portability
 Automation
 Reduction of sample
 Low cost
 Fast
Disadvantages
 Blockages due to gas bubbles
 Contamination
10
11
3.5.2Silicon micromachining
Bulk Etching- Anisotropic wet chemical etching.
Surface micromachinig- Build structures on top of the substrate surface. Wafer bonding –
Direct bonding, Anodic bonding
3.5.3Glass Micromachining
Glass is often considered a more desirable material for particular MEMS device applications
due to its unique properties, such as optical transparency and biological compatibility.
MEMS applications where micro-machined glass is used include:
* sensors, such as those incorporating pressure, accelerometer, gyroscope transducers
* bioMEMS devices enabled by lab-on-chip and microfluidics technologies
* membranes
* spacers for cell phone cameras
Different glass micromachinig methods are powder blasting, laser, wet etching, ultrasonic and
DRIE.
3.5.4Powder Blasting
Powder blasting is also referred to as sandblasting, impact abrasive machining or abrasive jet
machining (AJM). In this process, fine abrasive particles are propelled by compressed air at the
workpiece and these particles mechanically remove material by small chipping.
Powder blasting can be used to create membranes in glass for MEMS applications. The process
can be controlled to leave as thin as 75-100 um of glass material with a depth uniformity within
15 microns.
Advantages
 It can quickly create through-holes in brittle materials without creating burrs on the
surface.
 Process is anisotropic
 All surfaces are fully protected throughout the manufacturing process
Disadvantages
 The machined surface finish is slightly rough unless is it is wet etched after powder
blasting.
3.5.5Laser Machining
With the laser machining process, glass material removal is from thermal shock or ablation by
directed optical energy. There are several sources of lasers for machining glass and their
selection is based on the type of application. The laser systems that are available for glass
include CO2, Nd:YAG and excimer. The wavelength of the laser needs to be such that it
12
doesnot pass through the glass without etching it. Computer-controlled equipment (most
commonly an X-Y table) directs the beam to the desired location.
Advantages

 Easy to create a pattern from a CAD drawing and there is no mask, tooling or tool
wear.

 The process can be easily automated.

 This process has a low taper angle and can be used on large pieces.
Disadvantages
 Laser machining creates subsurface micro-cracks and also creates a HAZ (Heat
Affected Zone) which results in a kerf or damaged area at the top surface of the hole.
 Laser machining can crack or break thin glass pieces.
3.5.6 Ultrasonic Machining
This is a non-impact process in which a mechanical tool oscillates above the workpiece at a
high frequency, roughly 20,000 cycles per second. The tool end (horn) is formed in the shape of
the desired feature. The tool end (horn) and workpiece are submerged in abrasive slurry. The
majority of the machining occurs by the tool end and abrasive particles hitting the workpiece.
Advantages
 Ability to drill straight sidewalls and produce very fine features.
 High aspect ratios that can be achieved.
 It is also easily repeatable until tool wear.
 Also, multiple depths and contoured surfaces (2-1/2 D) can be achieved.
Disadvantages

 A slow process with a large capital investment.

 The tooling needs to be redressed for every 25-50 pieces to avoid feature degradation.
 It is more difficult to engrave contoured and interior surfaces.
3.5.7Wet Etch
Wet etching involves the creation of a pattern in glass by immersing the wafer in an acid, most
commonly hydrofluoric. An acid-resistant mask material can be used for selective material
removal and the part can be etched to multiple levels. Common mask materials are Cr-Au
and/or an acid resistant photoresist.
Advantages

 Wet etching can create very high detailed features and works well for removing thin
films
13
  The shape and size of the part is not usually limited.
 Produced features have a low surface roughness and therefore this process can be used
with applications where near optical clarity is desired.
Disadvantages
 The wet etch process is isotropic and there is undercutting of the photoresist that is
equal in distance to the etch depth. This gives the process a low aspect ratio.
 The acid material is extremely hazardous to humans and the environment.
3.5.8 Deep Reactive Ion Etching (DRIE)
A dry etch micro-machining method is Deep Reactive Ion Etching, or DRIE. The process uses
directional plasma ions to hit the glass causing erosion. A metal mask can be used to direct the
ions and create the desired features. The process can be used on glass, but the gas chemistry is
geared more toward silicon etching.
Advantages

 The process can be extremely accurate with feature creation and can achieve very
small features.

 There is a low amount of surface roughness and it is a highly anisotropic process.

Disadvantages
 Depending on the number and type of features, the DRIE process can be very slow and
because of this, it is not good for removing material across a wide area.
 Ion etching works well for etching silicon, but the process is extremely slow for
etching glass. In fact, since it etches so slowly, glass is often used as a mask for etching
silicon.
3.6.Surface Chemistry in Polymer Micro Fluidic System
Polymers exhibit comparatively low material cost and feature a wide range of (customizable)
material characteristics. Furthermore, their thermally induced castability makes polymers
amenable to commercially very well-established, high-fidelity replication schemes such as hot
embossing and injection molding, thus covering the full scope for upscale from small- series to
mass production.
3.6.1Materials
The most frequently used polymers include poly(methyl methacrylate) (PMMA),
polycarbonate (PC), cyclic olefin materials, SU-8 and poly(dimethylsiloxane) (PDMS) which
is commonly processed by the so-called ‘soft lithography’ fabrication scheme.
PMMA has been one of the most widely used polymers formicrofluidics. It is particularly
useful for microfluidic chips due to its comparatively low cost, high optical transparency, and
well definable electric and mechanical properties.PMMA is the least hydrophobic polymer,
and can directly generate stable EOF in the microchannels . Owing to its unique absorption
14
characteristics in the infrared regime, PMMA is also amenable to direct-write
microstructuringby common CO2 laser ablation systems. These favorable physicochemical
properties frequently make PMMA the material of choice for the fabrication of microfluidic
devices.
PC is a widely used thermoplastic polymer which is,for instance, used for the fabrication of
optical data storage media such as compact disks. Its high durability, strength, temperature
resistance, lowdensity and good optical properties have also made PC a popular material for the
fabrication of microfluidic devices.
Cyclic olefin polymer (COP) and cyclic olefin copolymer (COC) high optical clarity, even into
the deep-UV range, low water absorption and, compared to other polymers, an exceptionally
high resistance to organic solvents.
SU-8 is a UV-sensitive epoxy-based negative photoresist known from surface micromachining
which can be obtained with range of viscosities for forming high thickness films (∼100 μm) by
spin coating. It has also been shown that the SU-8 native resin itself or through suitable
functionalization procedures is compatible with a range of chemical and biological assays
PDMS, an elastomeric material, has been widely used for the fabrication of microfluidic
devices by ‘soft lithography. Features on the micron scale can be replicated with high fidelity
in PDMS using replica molding from a microstructured, e.g. SU-8,master. The replica can be
sealed reversibly or irreversibly without disfeaturing of the microchannels. PDMS substrates
have been utilized with biological samples because of their low toxicity and their rather high
optical transparency down to 280 nm, making PDMS compatible to a number of detection
methods.
3.6.2Processing
There is a variety of machining techniques used for the fabrication of polymeric microfluidic
devices, which can be coarsely categorized into direct/serial writing and replication schemes
Often used direct structuring methods comprise (ultra-)precision milling, laser ablation
photolithography, hot embossing, and injection molding,
3.6.3Surface Modification
Several coating techniques are available.
Common techniques include vapor-, plasma- and liquid-phase techniques. These techniques
result in different levels of process control, layer thickness uniformities, and bring about
certain restrains about the topology of surfaces to be coated. Surface treatments can lead to
deposition of new and/or conversion of native surface layers.
Techniques include- Chemical vapour deposition, plasma activation, UV irradiation, sol gel
chemistry, dynamic coatings, serial writing, mask based techniques
TEXT / REFERENCE BOOKS
1. Tai-Ran Hsu, MEMS & Microsystem, Design and manufacture, Mc. Graw Hill 2002.
2. Malsch, NeelinaH., ed., Biomedical Nanotechnology, Washington, DC: CRC Press, 2005
3. 3. Marc J. Madou, Fundamentals of Microfabrication and Nanotechnology, 3rd Edition,
Three-Volume Set,CRC Press 2011.
4. Mohamed Gad-el-Hak, The MEMS Handbook, CRC Press, 2005
15
16
 SCHOOL OF BIO & CHEMICAL ENGINEERING

DEPARTMENT OF BIOMEDICAL ENGINEERING

UNIT – IV – TRENDS IN MEMS FOR HEALTH CARE – SBM1606

1
 UNIT – 4: TRENDS IN MEMS FOR HEALTH CARE

4. There are many applications of MEMS in human body which are being implanted in
the human.
4.1 Pacemaker
- It is also known as artificial pacemaker of heart.
- It is small device implanted onto the heart which uses the battery.
- It sends electrical impulses which helps in heart beat rhythm.
- It is used when the heart natural pacemaker is defective and makes the heart to beat in
regular rhythm.
4.2 Capsule Endoscopy
- It is used for imaging the digestive tract.
- It poses video, light source and transmitter.
- 50,000 images can be transferred during 8 hours of exposure
- It does not require skill technician
- It follows natural peristaltic movements of digestive tract.
4.3 Cochlear Implant
- It is a prosthetic device which is used as a hearing aid.
- It consists of microphone, signal processor RF transmitter, implant KF receiver,
converter and electrode array.
- It can stimulate cochlear nerve and produces high quality device.
4.4 Artificial Retina
- It is a electronic device implanted in eye which restores the vision.
- This device captures visual signal and send to brain in form of electrical impulses.
- Video camera mounted on glass which captures images and are converted to a signal on
a implanted material and they relay to the optic nerve.
4.5 Heart Tissue Production
- Heart cells are grown and subjected to electrical current, so they react like heart
muscles.
- They can be grafted upon where heart muscles are weak end.
- It will produce heart rhythm in a regular waveform.

2
4.2 DRUG DELIVERY SYSTEM
- Drug delivered systems are engineered technology for the targeted delivery or
controlled release of therapeutic agent.
- Drugs have long been used to improve health and extent life.
- The practice of drug delivery has changed dramatically in last few decades and
even greater changes or anticipated in a near future.
- Biomedical engineers are contributed to the development of number of new
models of drug delivery that have entered clinical practice.
- Side effect have been limited by this drug delivery method for many diseases such
as cancers, neutrodegenerative disease and infectious diseases.
- Drug delivery system controls the rate at which a drug is released and location in
the body where it is released.
Different modes of drug delivery system.
- Conventional route
- Sustained drug delivery system
- Controlled drug delivery system
- Implantable drug delivery system
- Transdermal drug delivery system

4.2.1Conventional route
- Conventional dosage form compromises solution, suspension and emulsion (liquid
dosage form).
- Capsule, tablet etc. (solid dosage form)
4.2.2..1Mode of action
- When rapid efficient absorption of drug is desired for GI tract it represents the oral
dosage form of choice.
- Drugs in suspension are also readily disorders the large available surface area of the
dispersed solid facilitates rapid dissolution and absorption.
4.2.2 Sustained drug delivery system
- Sustained release dosage form are designed to release a drug at a pre-determined
rate by maintaining a constant drug level for a specific period of time with minimal
side effect.

3
 - This can be achieved through a variety of formulation including liposome and drug
polymer conjugates.
- Liposome have been used via a variety of administration route including
intravenous, intramuscular, intraperitoneal and oral
- The half life of liposome ranges from few minutes to few hours depending upon the
size and lipid composition.
4.2.2.1Mode of action
- Active agents are coated with the carrier molecule such as liposome which
resulted in the complex called hapten carrier molecule. This complex by
macrophage results in phagocog** carrier molecule forms a phagolysosome
complex by fusing with lysosome. This phagolysosome fuses with the phagocytic
cell and releases the drug towards the target site of a predetermined level.
4.3 Controlled drug delivery system
- Controlled release system have become very useful tool in medical practice.
- Controlled release system maintains constant therapeutic concentration of the
drug within a therapeutic range of drug over prolonged period.
- Controlled delivery system offers an alternative approach to regulate both
duration and localization of therapeutic agents in control delivery the active
agents combined with a synthetic components to produce a delivery system.
- It frequently involves combination of active agents with inert polymeric material
for the release of the drug. eg: chemically controlled system.
- Drug molecule is chemically linked to the backbone of the polymer
- In the body, in the presence of enzymes and biological fluid, chemical hydrolysis
or enzymatic cleavage occurs with concomitant release of the drug at a control
rate.
4.4 Implantable drug delivery system: eg. Program controlled insulin dosing
- It is also known as artificial pancreas
- This insulin pump delivers insulin through a catheter inserted in the body
- This device can deliver insulin in two ways: i) The fixed program unit with the
pre-set 24 hour rate per time profile ii) The demand program unit which is basal rate
preselected and a supplementary dose is trigger at mean time.
- Treatment drug delivery patch in contact to the skin for iontophoretic delivery.
- An electrode of the same polarity at a charge of the drug is placed in the reservoir.
- The electrical circuit is completed by the application of second electrode of the
opposite polarity at different skin site.

4
4.5 Bio-Chip
- Bio-Chip is the collection of microarray arranged on a solid substrate
- It can perform millions of mathematical operations.
- A micro-chip can also perform thousands of biological operations.
- It increases the speed of identification of genes.
4.5.1Components of Bio-Chip
- There are 2 components of bio-chip i) Transponder ii) Reader / scanner.
4.5.2 Transponder
- It is a device for receiving a radiosignal and automatically transmit it to a different
signal.
4.5.3 Reader / Scanner
- It consist of an exciter coil which creates electromagnetic signals.
- It provides energy to activate the implanted chip
- It also carrier a receiver coil to receive ID number.
- It contains the software and components to decodes and all this is done in milliseconds.
4.5.4Working
Reader transmits a low power radio signal and activate the implanted bio-chip


ID numbers are transmitted by transponder and received by reader


Reader displays the ID number on the readers LCD display

4.5.5 Bio-Chip Implant

- It is injected by the hypodermic syringe beneath the skin
- Injection is safe and simple
- Anesthesia is not required
- Route of injection depends upon the type of implanted material and their application.
4.5.6Application
- In the bio-chip, tracing of any person in the world is very easy.

5
- It stores all the data information and has the potential to replace passport, medical
records etc.
- Medicinal implementation of bio-chip are glucose detector, oxygen sensor, blood
pressure sensor etc (explain all the sensor briefly).

6
4.5.7Advantages
- It is smaller in size
- It performs of biological reaction in few seconds
- It increases the speed of diagnosis
- It is very faster and powerful technique
4.6Needle Electrode (Micro needle)
- It is used to record peripheral nerves action potential
- It is used to reduce movement artifacts and interface impedance.
- These electrodes merely penetrate skin and are placed parallel to the skin surface.
- Basic needle consists of a solid needle made up of stainless steel (SS) with sharp
point.
- Needle insulated with varnish and tip is left exposed.
- Lead wire attached to the other end of needle and encapsulated in a plastic hub to
protect it.
- It is mainly used in EMG.
2nd type
- Used to monitor ECG continuously during surgery
- Has SS hypodermic needle placed subcutaneously an each limb
- Lead wires with connectors connects the electrode to the monitor
- Epoxy resin fills the human and once it is set, needle is inserted card serves as
active electrode.
3rd type
- Bipolar coaxial electrode
4th type
- It has a fine wire made of SS with diameter 25 – 125 µm insulated with varnish
- Lip is introduced into lumen for needle
- It is inserted through skin into muscle.
- Coiled wire also used.
- If one monopolar needle electrode  one wire is used for measuring electrode
and other a separate reference electrode.

7
 - The bipolar needle electrode  2 wires are used, one as reference and other as
measuring electrode.
4.7 Neuroprothetics
- Neuroprosthetics is a discipline related to neuroscience and biomedical
engineering concerned with developing neural prosthesis.
- There are sometimes contrasted with a brain computer interface which connects
the brain to a computer rather than a device meant replace missing biological
functionality
- Neural prosthetics are a series of device that can substitute a motor, sensory or
cognitive mortality that might have been damaged as a result of an injury or a
disease.
4.7.1Visual prosthetics
- The visual prosthetics can create a sense of image by electrically stimulating
neurons in the visual system.
- A camera would wirelessly transmit to an implants the implant would map the
image across an array of electrode.
- The array o electrodes has effectively stimulate 600 – 1000 locations, stimulating
optic neuron in the retina thin creating an image.
- A visual prostheses system consists of an external or implantable imaging system
which acquires and process the video.
- Power and data will be transmitted to the implant wirelessly by the external unit.
- The implant uses the received power / data which converts the digital data into
analog output which will be delivered to the nerve via microelectrode.
- Photoreceptors are the specialized neurons that convert photons into electrical
signal.
4.7.2Auditory prosthetics: eg. Cochlear implant these devices substitute the function
performed by the ear drum.
- A microphone on external unit gathers the sound and process it, the processed
signal is then transferred to an implanted unit that stimulated the auditory nerve
via a microelectrode array.
- Three main categories for auditory prosthetics cochlear implant cochlear
electrode arrays are implanted.
- Auditory brain stem implant – ABI electrode array stimulates the cochlear nuclear
complex.
- Auditory mid brain implant – AMI stimulates auditory neurons in the inferior
colliculus.

8
4.7.3Motor Prosthetics
- Devices which supports the function of autonomous nervous system includes the
implant for bladder control.
- In the attempts to gain conscious control of the movement which includes
electrical stimulation.
4.7.4Bladder control implant.
- When the spinal cord injury leads to paraplegia, patients have difficult in empting
their bladder and this can cause infection.
- This device is implanted over sacral anterior route ganglia of the spinal cord
controlled by an external transmitter.
- It delivers intermitter stimulation which improved bladder implying.
4.7.5Cognitive prosthetics
- Cognitive prosthetics can store the function to individuals with brain tissue loss
due to injury, disease etc.
- The function of the damaged tissue can be rectified with integrated tissue.
- Brain plasticity suggest that the brain is capable of rewiring itself so that an area
of the brain associated with a particular function can even perform function
associated with another portion of brain. Eg: Auditory cortex can perform
function simultaneous improves the auditory process cortex visual information.
- Implants could take advantage of brain plasticity to restore cognitive function
even if the native tissue has been destroyed.
4.7.6Spinal cord injury
- It consists of an implanted receiver stimulator, an external shoulder position
sensor and a terminal electrode.
- The terminal electrode is placed on the motor point of a muscle. This enables a
low electrical threshold to the utilized.
- The external sensor measures voluntary movement that occur in the countralteral
shoulder and basis motor output command on this information.
- A radio frequency signal is then transmitted to the implanted receiver stimulator
which converts to an electrical stimuli that depolarizes the peripheral nerve.
4.8Shape Memory Implant
- Shape memory is a terms which dendex a material ability to return from a
program frozen temporary shape the original permanent shape as a result of
external physical stimulate (temp, tight, radiation etc) or chemical factor (pH
change, ionic strength and solvents).

9
 - The first materials in which the shape memory effect has been where metal
alloys are in particular on alloy of nickel and titanium which has been applied in
medical practice.
- Implant made up on an alloy have been applied in the bone surgery as a self
blocking material for bond bones coral, maxillofacial surgery spine surgery.
4.8.1Drawback
- Inflammation, corrosion, difficult removal after complete bone adhesion.
- SMA can be replaced by polymers due to the lower production cost, shape
stability, widal range of shape change and production of complicated shape.
4.8.2Shape Memory Effect
- Shape memory effect which conilines the right morphology of a polymer and the
technology process is associated with its finer molecular structure
- For a polymer to have specific property it has to have atleast two molecular
elements in its structure net points and switching segments.
- Two categories of shape memory polymers are distinguish in terms of the nature
of bond which fix the original and temporary shapes.
4.8.3Net points
- It determine the permanent shape
- Nature of bond: chemical, covlanet bond, physical – intermolecular intraction.
4.8.4Switching segments
- It is responsible for fixing the temporary shape
- It possess the nature of reversible bond.
- Chemical  covalent bond physical  intermolecular interaction.
4.8.5 Biodegradable shape memory polymer
- Degradable shape memory materials have been found to be especially useful in
low invasive tissue surgery.
- A shape memory implant of a temporary shape could be placed inside the body by
requiring only a minimum surgery.
- After a pre-determined period or responding to an external stimulus it would
assume permanent shape meeting the therapeutic requirements.
- After a period to heal the lesion the material would be reabsorbed which would
prevent long term cellular response and other delayed undesired interaction
between the body and the implant.

10
 - Biocompatible shape memory polymer successfully replaced previously used
implant made of metal alloys.
- They can be used to make surgical devices such as self locking staples and
surgical pins.
4.8.6Biocompatibility of polymers (in vivo)
- Synthetic materials which are foreign substances in a human body can be applied
in vivo if they need fundamental criterion of the biocompatibility.
- This means that they have to remain non-toxic throughout the period of contact
with tissues that they cannot induce inflammation, allergy, carcinogensis or
mutagenic.
- Biocompatable shape memory implants or materials it is extremely difficult to get
rid of certain compounds which are found in a finished product.
- Traces of such low molecule compound are released from implant polymer to the
human body and have toxic effect on it as well as induce inflammation at te
implant site.
- Toxic components should be avoided when designing the synthesis method and
the composition of such material.
- Biocompatability is not only a result of the composition but also of the dimension
and the shape of the material which induces cellular response (in vivo) for eg:
large fragments of materials they induces a inflammatory condition if the
dimension enable endocytosis by macrophages.
- It is also extremely important to make the right choice of the type of material from
which the implant is to be made and to select the right shape so that its mechanical
properties are appropriate for its role at the implant site.
- Synthesis involves introducing functional group into the skeleton of the degraded
polyester chain which can cross link the materials when treated with the UV
radiation.
TEXT / REFERENCE BOOKS
1. Tai-Ran Hsu, MEMS & Microsystem, Design and manufacture, Mc. Graw Hill 2002.
2. Malsch, NeelinaH., ed., Biomedical Nanotechnology, Washington, DC: CRC Press, 2005
3. Marc J. Madou, Fundamentals of Microfabrication and Nanotechnology, 3rd Edition,
Three-Volume Set,CRC Press 2011.
4. Mohamed Gad-el-Hak, The MEMS Handbook, CRC Press, 2005
5. HocineYahia, Shape Memory Implants Springer Verlag 2000.
-

11
 SCHOOL OF BIO & CHEMICAL ENGINEERING

DEPARTMENT OF BIOMEDICAL ENGINEERING

UNIT – V – MEDICAL APPLICATIONS IN NANOTECHNOLOGY – SBM1606

1
 UNIT – 5 - MEDICAL APPLICATIONS IN NANOTECHNOLGOY

5.1 Introduction
- In the day today life various disease like diabetes, cancer, sparkinsen diseases,
Alzheimer disease, cardiovascular disease and multiple sclerosis.
- As well as different kinds of serious inflammatory or infectious disease.
- Nanomedicine is an application of nanotechnology which works in the field of health
and medicine
- Nanomedicine makes use of nanomaterials and nanoelectronic biosensor.
- Nanomedicine helps in earlier detection, prevention, ** and effective therapeutic
regime.
5.1.1Drug delivery
- Nanoparticles are used for site specific drug delivery.
- In this technique the required drug dose is used and side effects are lowered
significantly as the active agents is deposited in the morbid region only.
- This highly selective approach can reduce cost and pain to the patients.
- There are variety of nanoparticles such as dendrimers, nanoporous material, are
used for drug encapsulation.
- They transport small drug molecules to the desired location for the active release of
the drug.
- In or gold nanoparticles are finding important application in the cancer treatment.
- The targeted medicine reduces the drug consumption and treatment expensive
making a treatment of patient cost effective.
5.1.2 Protein / Peptide Delivey
- Nanoparticles were found useful in delivery the myclin antigen which induce
immune tolerance in a mouse model with relapsing multiple sclerosis.
- In this technique biodegradable polyesterinemicroparticles coating with the myclin
sheath peptide will reset the mouse immune system and this prevents the
reoccurrence of disease and reduces the symptom.
- Protective myclin sheath forms protein on the nerve flues of the central nervous
system.
- This method of treatment can potentially be used in the treatment of various other
autoimmune disorder.

2
5.1.3 Oncology
- Due to the small size of nanoparticles, it can be great use in particularly in imaging
- Nanoparticles such as quantum dots with quantum confinement properties such as
light emission can be used in conjunction with MRI to produce exceptional images
tumor size.
- They also used in cancer therapy.
- Ex: 1. Carbon nanotubes: 0.5 – 3 nm in diameter
20 – 1000 nm in length
Used for detecting DNA mutastion.
Detection of disease protein biomaker
2. Dendrimers Less than 10 nm in size
Useful for release drug delivery
Image contrast agent
3. Nano crystals 2 – 9.5 nm in size
It improves formulation for poorly soluble drugs.
Labelling of breast cancer marker
4. Nano particles 10 – 100 nm in size
It is used in MRI
Ultrasound images as a image contrast agents.
Targetted drug delivery
Reporters of apoptosis and angiogenesis.
5. Nanoshells Application in tumour specific imaging
Deep tissue thermal ablation.
6. Nanowires Useful for disease protein biomarker detection
DNA mutation detection
Gene expression detection
7. Quantum dots 2 – 9.5 nm in size
Cell assays
5.1.4Modified Medicated Textiles :
- Using nanotechnology newer antibacterial cotton has been developed and used
for antibacterial textiles.
3
 - Developmental works during nanotechnology new modified antibacterial textiles
have been developed to inhibit the growth bacteria, fungi etc.
5.1.5Nanopharmaceuticals
- Nanopharmaceuticals can be used to detect disease at much earlier stages and the
diagnostic application could build upon convenient procedure using
nanoparticles.
- Nanopharmaceuticals are an emerging field where the size of the drug particle or a
therapeutic delivery system work at the nano scale.
- Delivering the appropriate dose of a particular active agent to specific disease still
remains difficult in the pharmaceutical industry.
5.1.6 Antibiotic resistance
- Antibiotic resistance can be decreased by use of nanoparticle in combination
therapy.
- Zinc oxide nanoparticle can decrease the antibiotic resistance and enhance the
antibacterial activity of ciprofloxacin against microorganism by interfering with
various protein that are interacting with antibiotic resistance.
5.1.7 Tissue engineering
- In tissue engineering, nanotechnology can be applied to reproduce or repair
damaged tissue.
- By using suitable nanomaterial paste scaffolds and growth factor which artificially
stimulant cell proliferation in organ transplant or artificial implant therapy.
- Nanotechnology can be useful which can lead to life extension
5.2.Synthesis of Nanomaterials
5.2.1 Introduction
There are a large number of techniques available to synthesize different types of nanomaterials
in the form of colloids, clusters, powders, tubes, rods, wires, thin films etc. There are various
physical, chemical, biological and hybrid techniques available to synthesize nanomaterials.
The technique to be used depends upon the material of interest, type of nanostructure viz., zero
dimensional, one dimensional, or two dimensional material size, quantity etc.
5.2.2Physical methods:(a) mechanical: ball milling, melt mixing
(b)Vapor: physical vapor deposition, laser ablation, sputter deposition, electric arc
deposition, ion implantation
5.2.3Chemical methods: colloids, sol-gel, L-B films, inverse micelles.
5.2.4Biological methods:biomembranes, DNA, enzymes, microorganisms.

4
5
5.3 Physical methods
5.3.1 Ball milling: It is used in making of nanoparticles of some metals and alloys in the form
of powder. Usually the mill contains one or more containers are used at a time to make fine
particles. Size of container depends upon the quantity of interest. Hardened steel or tungsten
carbide balls are put in containers along with powder or flakes (<50 um) of a material of
interest. Initial material can be of arbitrary size and shape. Container is closed with tight lids.
The containers are rotated at high speed (a few hundreds of rpm) around their own axis.
Additionally they may rotate around some central axis and are therefore called as ‘planetary
ball mill’. When the containers are rotating around the central axis, the material is forced to the
walls and is pressed against the walls. But due to the motion of the containers around their own
axis, the material is forced to other region of the container. By controlling the speed of rotation
of the central axis and container as well as duration of milling, it is possible to ground the
material to fine powder whose size can be quite uniform. Some of the materials like Co, Cr, W,
Ni-Ti, Al-Fe, Ag-Fe etc. are made nanocrystalline using ball mill.
Large balls, used for milling, produce smaller grain size and larger defects in the particles. The
process may add some impurities from balls. The container may be filled with air or inert gas.
However, this can be an additional source of impurity. A temperature rise in the range of 100 to
1100 C is expected to take place during the collisions. Cryo-cooling is used to dissipate the
generated heat.
5.3.2 Melt Mixing: It is possible to form or arrest the nanoparticles in glass. Structurally, glass
is an amorphous solid, lacking long range periodic arrangement as well as symmetry
arrangement of atoms/molecules. When a liquid is cooled below certain temperature, it forms
either a crystalline or amorphous solid (glass). Nuclei are formed spontaneously with
homogenous (in the melt) or inhomogeneous (on the surface of other materials) nucleation,
which can grow to form ordered, crystalline solid. Usually, metals form crystalline solids but,
if cooled at very high cooling rate, they can form amorphous solids. Such solids are known as
metallic glasses. Even in such cases the atoms try to reorganize themselves into crystalline
solids. Addition of elements like B, P, Si etc. helps to keep the metallic glasses in amorphous
state. It is possible to form nanocrystals within metallic glasses. It is also possible to form
some nanoparticles by mixing the molten streams of metals at high velocity with turbulence.
On mixing thoroughly, nanoparticles are formed.
5.3.3 Physical Vapor Deposition: It involves material for evaporation, an inert gas or reactive
gas for collosion of material vapor, a cold finger on which clusters or nanoparticles can
condense, a scraper to scrape the nanoparticles and piston- anvil (an arrangement in which
nanoparticle powder can be compacted). All the processes are carried out in a vacuum chamber
so that the desired purity of the end product can be obtained.
Metals or high vapor pressure metal oxides are evaporated or sublimated from filaments or
boats of refractory metals like W, Ta, Mo in which materials to be evaporated are held. Size,
shape and even the phase of evaporated material can depend upon the gas pressure in
deposition chamber. Clusters or nanoparticles condensed on the cold finger (water or liquid
nitrogen cooled) can be scraped off inside the vacuum system. The process of evaporation and
condensation can be repeated several times until enough quantity of material falls through a
funnel in which a piston-anvil arrangement has been provided.
6
5.3.4 Ionized Cluster Beam Deposition: It is useful to obtain adherent and high quality single
crystalline thin films. The set up consists of a source of evaporation, a nozzle through which
material can expand into the chamber, an electron beam to ionize the clusters, an arrangement
to accelerate the clusters and a substrate on which nanoparticle film can be deposited, all
housed in a suitable vacuum chamber. Small clusters from molten material are expanded
through the fine nozzle. The vapor pressure, ~10 torr to 10-2 torr needs to be created in the
source and the nozzle needs to have a diameter larger than the mean free path of atoms or
molecules in vapor form in the source to form the clusters. On collision with electron beam
clusters get ionized. Due to applied accelerating voltage, the clusters are directed towards the
substrate. By controlling the accelerating voltage, it is possible to control the energy with
which the clusters hit the substrate. Thus it is possible to obtain the films of nanocrystalline
material using ionized cluster beam.
5.3.5 Laser Vaporization: In this method, vaporization of the material is effected using pulses
of laser beam of high power. The set up is aultra high vacuum or high vacuum system equipped
with inert or reactive gas introduction facility, laser beam, solid target and cooled substrate.
Clusters of any material of which solid target can be made are possible to synthesize. Usually
laser giving UV wavelength such as excimer laser is necessary because other wavelengths like
IR or visible are often reflected by some of the metal surface. A powerful beam of laser
evaporates the atoms from a solid source, atoms collide with inert gas atoms (or reactive gases)
and cool on them forming clusters. They condense on the cooled substrate. The method is often
known as laser ablation. Gas pressure is very critical in determining the particle size and
distribution. Simultaneous evaporation of another material and mixing the two evaporated
materials in inert gas leads to the formation of alloys or compounds.
5.3.6 Laser Pyrolysis or Laser Assisted Depositon: Here a mixture of reactant gases is
decomposed using a powerful laser beam in presence of some inert gas like helium or argon.
Atoms or molecules of decomposed reactant gases collide with inert gas atoms and interact
with each other, grow and are then get deposited on cooled substrate. Many materials like
Al2O3, WC, Si3Ni4 etc. are synthesized in nanocrystalline form by this method. Here too, gas
pressure plays an important role in deciding the particle size and their distribution.
5.3.7 Sputter Deposition: In sputter deposition, some inert gas ions like Ar are incident on a
target at a high energy. The ions become neutral at the surface but due to their energy, incident
ions may get implanted, get bounded back, create collision cascades in target atoms, displace
some of the atoms in the target creating vacancies, interstitials and other defects, desorb some
adsorbents, create photons while loosing energy to target atoms or even sputter out some target
atoms/molecules, clusters, ions and secondary electrons. Sputter deposition is a widely used
thin film deposition technique, specially to obtain stoichiometric thin films from target
material. Target material may be some alloy, ceramic or compound. It is a very good technique
to deposit multilayer films for mirrors or magnetic films for spintronic applications. Sputter
deposition can be carried out using Direct Current (DC) sputtering, Radio Frequency (RF)
sputtering or magnetron sputtering. In all these methods, one uses discharge or plasma of some
inert gas atoms or reactive gases. The deposition is carried out in a required gas pressurized
high vacuum or ultra high vacuum system equipped with electrodes, one of which is a sputter
target and the other is a substrate, gas introduction facility etc.

7
In DC sputtering, the target is held at high negative voltage and substrate may be at positive,
ground or floating potential. Substrates may be simultaneously heated or cooled depending
upon the requirement. Once the required base pressure is attained in the vacuum system,
usually argon gas introduced at a low pressure. A visible glow is observed and current flows
between anode and cathode indicating the deposition onset. When sufficiently high voltage is
applied between anode and cathode with a gas in it, a glow discharge is set up with different
regions as cathode glow, Crooke’s dark space, negative glow, Faraday dark space, positive
column, anode dark space and anode glow. These regions are the result of plasma. Plasma is a
mixture of free electrons, ions and photons. Plasma is overall neutral but there can be regions,
which are predominantly of positive or negative charge. The density of various particles and
the length over which they are spread and distributed depends upon the gas pressure.
In RF sputtering 5-30 MHz frequency is used and the electrodes can be insulating. However,
13.56 MHz is a commonly used frequency for deposition. Target itself biases to negative
potential becoming cathode.
RF and DC sputtering efficiency can be further increased using magnetic field. When both
electric and magnetic fields act simultaneously on a charged particle, force is acted upon it.
Electrons moves in a helical path and is able to ionize more atoms in the gas. In practice, both
parallel and magnetic fields to the direction of electric field are used to further increase the
ionization of the gas, increasing the efficiency of sputtering. By introducing gases like O2, N2,
NH3, CH4, H2S etc. while metal targets are sputtered, one can obtain metal oxides like Al2O3,
nitrides, carbides etc., This is known as reactive sputtering.
The plasma density can be further enhanced using microwave frequency and coupling the
resonance frequency of electrons in magnetic field. Ionization density using Electron
Cyclotron Resonance plasma is about 2-3 orders of magnitude larger. Thin films and
nanoparticles of Si2O3, SiN, GaN etc. have been obtained using this technique.
5.3.8 Chemical Vapour Deposition (CVD): It is a hybrid method using chemicals in vapour
phase. Basic CVD process can be considered as a transport of reactant vapour or reactant gas
towards the substrate kept at some high temperature where the reactant cracks into different
products which diffuse on the surface, undergo some chemical reaction at appropriate site,
nucleate and grow to form the desired material film. The by-products created on the substrate
have to be transported back to the gaseous phase removing them from the substrate. Vapours of
desired material may be often pumped into reaction chamber using some carrier gas. In some
cases the reactions may occur through aerosol formation in gas phase. There are various
processes such as reduction of gas, chemical reaction between different source gases, oxidation
or some disproportionate reaction by which CVD can proceed. However, it is preferable that
the reaction occurs at the substrate rather than in the gas phase. Usually temperature ~ 300 to
1200 C is used at the substrate. There are two ways viz., hot wall and cold wall by which
substrates are heated. In hot wall set up the deposition can take place even on reactor walls.
This is avoided in cold wall design. Besides this, the reaction can take place in gas phase with
hot wall design,which is suppressed in cold wall set up. Further, coupling of plasma with
chemical reaction in cold wall set up is feasible. Usually gas pressures in the range of 0.1 torr to
1.0 torr are used. Growth rate and film quality depend upon the gas pressure and the substrate

8
temperature. When the growth takes place at low temperature, it is limited by the kinetics of
surface tension.
CVD is widely used in industry because of relatively simple instrumentation, ease of
processing, possibility of depositing different types of materials and economic viability. Under
certain deposition conditions nanocrystalline films or single crystalline films are possible.
There are many variants of CVD like metallo organic CVD (MOCVD), atomic layer epitaxy
(ALE), vapor phase epitaxy (VPE), plasma enhanced CVD (PECVD) etc. They differ in source
gas pressure, geometrical layout, temperature used etc.
5.3.9 Electric Arc Deposition: This is one of the simplest and useful methods, which leads to
mass scale production of fullerenes and carbon nanotubes. It requires water cooled vacuum
chamber and electrodes to strike an arc between them. The positive electrode itself acts as the
source of material. If some catalyst are to be used, there can be some additional thermal source
of evaporation. Inert gas or reactive gas introduction is necessary. Usually the gap between the
electrodes is ~1mm and high current ~50 to 100 amperes is passed from a low voltage power
supply (~12-15 volts). Inert gas pressure is maintained in the vacuum system. When an arc is
set up, anode material evaporates. This is possible as along as the discharge can be maintained.
By striking the arc between the two graphite electrodes, it is possible to get fullerenes in large
quantity. In case of fullerenes, the formation occurs at low helium pressure as compared to that
used for nanotube formation. Also, fullerenes are obtained by purification of soot collected
from inner walls of vacuum chamber, whereas nanotubes are found to be formed only at high
He gas pressure and in the central portion of the cathode. No carbon nanotubes are found on the
chamber walls
5.3.10 Ion Implantation: In this method high energy (few keV to hundereds of keV) or low
energy (<200 eV) ions are used to obtain nanoparticles. Ions of interest are usually formed
using an ion gun specially designed to produce metal ions, which are accelerated to high or low
energy towards the substrate heated to few hundered of C. Depending upon the energy f the
incident ions, various other processes like sputtering and generation of electromagnetic
radiation may take place. It is possible to obtain single element nanoparticles or compounds
and alloys of more than one element. In some experiments it has been possible to even obtain
doped nanoparticles using ion implantation. There is possibility of making nanoparticles
using swift heavy ions (few MeV energy) employing ion accelerators like a pelletron.
5.3.11 Molecular beam epitaxy (MBE): This technique of deposition can be used to deposit
elemental or compound quantum dots, quantum wells, quantum wires in a very controlled
manner. High degree of purity in materials is achievable using ultra high vacuum (better than
torr ). Special sources of deposition known as Kundsen cell (K-cell) or effusion cell are
employed to obtain molecular beams of the constituent elements. The rate of deposition is kept
very low and substrate temperature is rather high in order to achieve sufficient mobility of the
elements on the substrate and layer by layer growth to obtain nanostructures.
5.3.12Thermolysis: Nanoparticles can be made by decomposing solids at high temperature
having metal cations, and molecular anions or metal organic compounds. The process is called
thermolysis. For example, small lithium particles can be made by decomposing lithium azide,
LiN3. The material is placed in an evacuated quartz tube and heated to 400 C. At but 370 C
LiN3 decomposes, releasing N2 gas, which is observed by an increase in the pressure on the
9
vacuum gauge. In a few minutes the pressure drops back to its original low value, indicating
that all the N2 has been removed. The remaining lithium atoms coalesce to form small colloidal
metal particles. Particles less than 5nm can be made by this method. Passivation can be
achieved by introducing an appropriate gas.
5.3.13Pulsed laser method: Pulsed lasers have been used in the synthesis of nanoparticles of
silver. Silver nitrate solution and a reducing agent are flowed through a blenderlike device. In
the blender there is a solid disk, which rotates in the solution. The solid disk is subjected to
pulses from a laser beam creating hot spots on the surface of the disk. Silver nitrate and the
reducing agent react at these hot spots, resulting in the formation of small silver particles,
which can be separated from the solution using a centrifuge. The size of particles is controlled
by the energy of the laser and rotation speed of the disk. This method is capable of a high rate of
production.
5.4Chemical Methods (Wet Chemical route)
There are numerous advantages of using chemical methods, which are –
 Inexpensive, less instrumentation compared to many physical methods
 Low temperature (< 350 C) synthesis
 Doping of foreign atoms (ions) possible during synthesis
 Variety of size and shapes are possible
 Self assembly or patterning is possible
5.4.1Colloids and Colloids in solutions: A class of materials in which two or more phases
(solid, liquid, gas) of same or different materials co-exist with at least one dimension less than
a micrometer is known as colloids. Colloids may be particles, plates, or fibers. Nanomaterials
are a sub-class of colloids, in which one of the dimensions of colloids is in about 1 to 100 nm
range. Colloids are the particles suspended in some host matrix.
5.4.2Interactions: Colloids are particles with large surface to volume ratio. Therefore atoms on
the surface are in a highly reactive state, which easily interact to form bigger particles or tend to
coagulate. It is thus necessary to understand the stability of colloids i.e., how the colloids
dispersed in a medium can remain suspended particles. In general there are a number of
interactions involved. There are two types of interactions: attractive and repulsive. Repulsive
interaction involves short distance of Born repulsive interaction and long range attractive
interaction van der Waals attraction. Repulsive part arises due to repulsion between electron
clouds in each atom and attractive part is due to interaction between fluctuating or permanent
dipoles of atoms/molecules. The attractive forces between colloidal particles reduced in
colloids in a liquid medium. Colloids in liquid may be positively charged, negatively charged
or even neutral. But in most cases they are charged. As there are some charges on particles,
ions of opposite charges accumulate around them. Oppositely charged ions are known as
counter ions. This accumulation of counter ions leads to formation of an electric double layer.
Stability of colloids can be increased by stearic hinderance or repulsion. By adsorbing some
layers of a different material on colloidal particles eg.polymer it is possible to reduce the
attractive forces between them..
10
5.4.3Synthesis: Chemical reactions in which colloidal particles are obtained are carried out in
glass reactor of suitable size. Glass reactor usually has a provision to introduce some
precursors, gases as well as measure temperature, pH etc. during the reaction. It is usually
possible to remove the products at suitable time intervals. Reaction is usually carried out under
inert atmosphere like argon or nitrogen gas so as to avoid any uncontrolled oxidation of the
products. There is also provision made to stir the reactants during the reaction by using Teflon
coated magnetic needle.
Although chemical synthesis of nanoparticles is a complex process, by understanding how
nucleation and growth of particles takes place, it is possible to control the various steps and try
to achieve monodispersed nanoparticles. This can be done with the help of LaMer diagram. As
we keep on increasing the concentration of the reactants in the solution, at certain
concentration, say CO, the formation of nuclei begins. There is no precipitate at this
concentration. Further increase in concentration increases nuclei formation up to a
concentration CN, above which there is ‘super saturation’ between CN and CS. Concentration
CN denotes the maximum rate of nuclei formation. When nuclei formation reduces, again C O
the minimum concentration for nucleation is reached. No new nuclei can be formed and crystal
growth reduces the concentration. At this concentration CS, an equilibrium is obtained. If new
nuclei are formed during the growth of particles, particle with large size distribution are
obtained. Therefore it is very important that concentration of solute and its diffusion to dissolve
species be adjusted properly in order that no fresh nuclei are formed once the concentration of
solute and its diffusion to dissolve species be adjusted properly in order that no fresh nuclei are
formed once the concentration has reached CN. Particles can grow even at the expense of
smaller particles. Larger particles are more stable and grow at the expense of smaller particles.
This growth mode is known as Ostwald ripening. The driving force for large particles is the
reduction in surface free energy.
5.4.4Colloidal metal nanoparticles are often synthesized by reduction of some metal salt or
acid. For example highly stable gold particles can be obtained by reducing choloroauric acid
(HAuCl4) with tri sodium citrate (Na3C6H5O7). The reaction takes place as follows –
HAuCl4 + Na3C6H5O7 Au+ +C6H5O- + HCl + 3NaCl.
Au atoms are formed by nucleation and condensation. They grow bigger in size by reduction
of more Au+ ions on the surface. These atoms are stabilized by oppositely charged citrate ions.
Metal gold nanoparticles exhibit intense red, magenta etc., colours, depending upon the particle
size. Gold nanoparticles are stabilized by repulsive Coulomb interaction. It is also possible to
stabilize gold nanoparticles using thiol or some other capping molecules. In a similar manner,
silver, palladium, copper and other metal nanoparticles can be synthesized using appropriate
precursors, temperature, pH, duration of synthesis etc., Particle size, size distribution and shape
strongly depend on the reaction parameters and can be controlled to achieve desired results. It
is also possible to synthesize alloy nanoparticles using appropriate precursors.
5.4.5Compound semiconductor nanoparticles can be synthesized by wet chemical route using
appropriate salts. Sulphide semiconductors like CdS and ZnS can be synthesized easily by
what is known as co-precipitation. For example to obtain ZnS nanoparticles any zinc salt like
Zinc sulphate (ZnSO4), zinc chloride (ZnCl2) can be dissolved in aqeous (or nonaqeous) liquid
and Na2S is added to the solution. Following simple reaction results to give particles of ZnS.
11
ZnCl2 + Na2S ZnS + 2NaCl
To obtain zinc oxide particles one can use following reactions:
ZnCl2 + 2NaOH Zn(OH)2 + 2NaCl
Zn(OH)2ZnO + H2O
Selenide particles can be obtained using appropriate selenium giving salt. However, all these
nanoparticles need to be surface passivated as colloids formed in liquids have a tendency to
coagulate or ripen due to attractive forces existing between them. The electrostatic and other
repulsive forces may not be sufficient to keep them apart. However, stearic hindrance can be
created by appropriately coating the particles to keep them apart. This is often known as
‘chemical capping’ and has become a widely used method in the synthesis of nanoparticles.
Advantage with this chemical route is that, one can get stable particles of variety of aterials not
only in the solution, but even after drying off the liquid. Coatings may be part of post-treatment
or a part of the synthesis reactions to obtain nanoparticles. If it is a part of the synthesis
reaction, the concentration of capping molecules can be used in two ways, to control the size as
well as to protect the particles from coagulation. Chemical capping can be carried out at high or
low temperature depending on the reactants. In high temperature reactions, cold
organometallic reactants are injected in some solvent like triocylphosphineoxide held at
temperature >300 C.
5.4.6 Langmuir-Blodgett (L-B) method: This technique to transfer organic layers at
air-liquid interface onto solid substrates is known for nearly 70 years. The technique was
developed by the two scientists Langmuir and Blodgett. In this technique one uses
amphiphilic long chain molecules like that in fatty acids. An amphiphilic molecule has a
hydrophilic group (water loving) at one end and a hydrophobic group (water hating) at the
other end. As an example consider the molecule of arachidic acid, which ahs a chemical
formula [CH3(CH2)16 COOH]. There are many such long chain organic chains with general
chemical formula [CH3(CH2)nCOOH], where n is a positive integer. In this case, -CH3 is
hydrophobic and –COOH is hydrophilic in nature.
Usually molecules with n>14 are candidates to form L-B films. This is necessary in order to
keep hydrophobic and hydrophilic ends well separated from each other. When such molecules
are put in water, the molecules spread themselves on surface of water in such a way that their
hydrophilic ends, often called as heads, are immersed in water, whereas the hydrophobic ends
called as tails remain in air. They are also surface active agents or surfactants. Surfactants are
amphiphilic molecules i.e. an organic chain molecule in which at one end there is polar,
hydrophilic (water loving) and at the other a nonpolar, hydrophobic (water hating) group of
atoms. Using a movable barrier, it is possible to compress these molecules to come close
together to form a monolayer and align the tails. It is however necessary that hydrophilic and
hydrophobic ends are well separated. Such a monolayer is two dimensionally ordered and can
be transferred on some suitable solid substrates like glass, silicon etc. This is done by dipping
the solid substrate in the liquid, in which ordered organic molecular monolayer is already
formed.
Deposition of L-B films is done by following steps: (1) A monolayer of amphiphilic molecules
is formed (2) A substrate is dipped in the liquid (3) The substrate is pulled out, during which
12
ordered molecules get attached to the substrate (4) When the substrate is again dipped,
molecules again get deposited as the substrate forming a second layer on the substrate (5) As
the substrate is again pulled out a thin layer gets deposited. By repeating the procedure large
number of ordered layers can be transformed on a substrate.
In general there are three types of L-B films with different multilayer sequence. These are
known as X, Y, and Z type. (1) X-type: Deposition only during insertion of substrate
(2)Y-type: Deposition both the times except no deposition during first immersion (3) Z-type:
Deposition only during removal of substrate. Y type of films are most common. Although the
layers are ordered, there is only the van der Waals interaction between different layers. Thus
L-B films are good examples of nanostructured materials.
It is possible to obtain nanoparticles using L-B technique. A metal salt like CdCl2 or ZnCl2 is
dissolved in water on surface of which a compressed uniform monolayer of surfactant is
spread. When H2S gas is passed in the solution, CdS or ZnS nanoparticles of few tens of
nanometers can be formed. Particles are uniform in size. If surfactants are not present, uniform
nanoparticles are not formed.
5.4.7 Sol-Gel Method: As the name implies sol-gel involves two types of materials or
components ‘sol’ and ‘gel’. There are several advantages of sol-gel: All sol-gel formation
process is usually a low temperature process. This means less energy consumption and less
pollution too. Some of the benefits like getting unique materials such as aerogels, zeolites,
ordered porous solids by organic-inorganic hybridization are unique to sol-gel process. It is
also possible to synthesize nanoparticles, nanorods, nanotubes etc., using sol-gel technique.
Sols are solid particles in a liquid. They are thus a subclass of colloids. Gels are nothing but a
continuous network of particles with pores filled with liquid (or polymers containing liquid). A
sol-gel process involves formation of ‘sols’in a liquid and then connecting the sol particles (or
some subunit capable of forming a porous network) to form a network. By drying the liquid, it
is possible to obtain powders, thin films or even monolithic solid.
Synthesis of sol-gel in general involves hydrolysis of precursors, condensation followed by
polycondensation to form particles, gelation and drying process by various routes. Precursors
(starting chemicals) are to be chosen so that they have a tendency to form gels. Both alkoxides
or metal salts can be used. Alkoxides have a general formula M(ROH)n, where M is a cation, R
an alcohol group, and n is the number of (ROH) groups with each cation. Salts are denoted as
MX, in which M is a cation and X is an anion. Although it is not mandatory that only oxides be
formed by a sol-gel process, often oxide ceramics are best synthesized by a sol-gel route. For
example in silica, SiO4 group with Si at the centre and four oxygen atoms at the apexes of
tetrahedron are very ideal for forming sols with interconnectivity through the corners of
tetrahedrons, creating some cavities or pores. By polycodensation process (i.e., many
hydrolyzed units coming together by removal of some atoms from small molecules like OH)
sols are nucleated and ultimately solgel is formed. Sol-gel method is particularly useful to
synthesize ceramics or metal oxides although sulphides, borides and nitrides also are possible.
5.4.8 Microemulsion: Synthesis of nanoparticles in the cavities produced in microemulsion is
a widely used method. Advantage of this method is the biocompatibility and biodegradability
of synthesized materials. Biocompatability is useful in drug delivery of nanomaterials and
13
biodegradability is environmentally useful. Whenever two immiscible liquids are mechanically
agitated or stirred together, they are known to form what is called ‘emulsion’. The tendency of
the liquids is such that the liquid is smaller quantity tries to form small droplets, coagulated
droplets or layers so that they are all separated from the rest of the liquid (for example droplets
of fat in milk). The droplet sizes in emulsion are usually larger than 100 nm upto even few
millimeters. Emulsions are usually turbid in appearance. On the other hand, there is another
class of immiscible liquids, known as microemulsions which are transparent and the droplets
are in the range of ~1 to 100 nm. This is size needed for the synthesis of nanomaterials.
Microemulsions are stabilized using surfactants (surface stabilized active agents). When an
organic liquid or oil (O), water (W) and surfactant (T) are mixed together, under some critical
concentration, ‘micelles’ or inverse micelles are formed, depending upon the concentration of
water and organic liquid. Micelles are formed with excess water and inverse micelles are
formed in excess of organic liquid or oil. The ratio of water, oil and surfactant is important to
decide which type of micelle will be formed and can be represented in a ternary phase diagram,
using a triangle. Composition can be determined by drawing lines parallel to all three sides of
the triangle. A modified phase diagram known as ‘Winsor Diagram’ also can be constructed for
finer details. The critical micelle concentration (CMC) depends upon all W, O and T
concentrations. Effect of T is to reduce the surface tension of water dramatically below CMC
and remain constant above it, as the organic solvent concentration is kept on increasing. There
are four types of surfactants in general:
Cationic: eg. CTAB
Anionic: eg. R-SO3-Na+
Nonionic: R-(CH2-CH2-O)20-H
Amphoeric: eg. betaines.
A large number of nanoparticles of (metals, semiconductors and insulators) cobalt, copper,
CaCO3, BaSO4, CdS, ZnSetc, have been synthesized using microemulsions or inverse
micelles. Eg.synthesis of cobalt nanoparticles – A reverse miceller solution of water and oil can
be stabilized using a monlayer of surfactant like sodium bis (2-ethylhexyl) sulfosuccinate or
Na(AOT). The droplet diameter is controlled simply by controlling the amount of water. Two
micellar solutions having same diameter of droplets can be formed. Thus one solution shuld
have Co(AOT)2 i.e., cobalt bis (2-ethylhexyl) sulfosuccinate and the other should have sodium
tetrahydroborate (NaBH4). When two solutions are mixed together the solution appears clear
but the color changes from pink to black. One can find by electron microscopy analysis that
cobalt nanoparticles are formed.
5.4.9 Other Chemical Methods: Several types of reducing agents can be used to produce
nanoparticles such as NaBEt3H, LiBEt3H, and NaBH4 where Et denotes ethyl (-C2H5)
radical. For example, nanoparticles of molybdenum (Mo) can be reduced in toluene solution
with NaBEt3H at room temperature, providing a high yield of Mo nanoparticles having
dimensions of 1-5 nm.
Nanoparticles of aluminum have been made by decomposing Me2EtNAlH3 in toluene and
heating the solution to 105 C for 2 h (Me is methyl, -CH3). Titanium isopropoxide is added to
the solution. The titanium acts as a catalyst for the reaction. The choice of catalyst determines
14
the size of the particles produced. For instance, 80 nm particles have been made using titanium.
A surfactant such as oleic acid can be added to the solution to coat the particles and prevent
aggregation.
5.5Biological Methods
Synthesis of nanomaterials using biological ingredients can be roughly divided into following
three types:
 use of microorganisms
 use of enzymes or plant extracts
 use of templates like DNA, membranes, viruses
5.5.1Synthesis using microorganisms: Microorganisms are capable of interacting with
metals coming in contact with them through their cells and form nanoparticles. Different
processes of metal-microorganism interactions are: (i) Some microorganisms produce
hydrogen sulfide (H2S). It can oxidize organic matter forming sulphate, which in turn acts like
an electron acceptor for metabolism. This H2S can, in presence of metal salt, convert metal
ions into metal sulphide, which deposits extracellulary. (ii) In some cases, metal ions from a
metal salt enter the cell. The metal ions are then converted into a nontoxic form and covered
with proteins in order to protect the remainder of cell from toxic environment. (iii) certain
microorganisms are capable of secreting some polymeric materials like polysaccharides. They
have some phosphate, hydroxyl and carboxyl anionic groups which complex with metal ions
and bind extracellularly (iv) cells are also capable of reacting with metals or ions by processes
like oxidation, reduction, methylation, demethylation etc.
Examples:
 Pseudomonas stutzeri Ag259 bateria are found in silver mines and are capable of
accumulating silver inside or outside of their cells walls. Using this fact these bacterial
strains can be challenged with high concentration of silver salt like AgNO3. Numerous
silver nanoparticles of different shapes can be produced having size <200 nm
intracellularly.

 Low concentrations of metal ions (Au+, Ag+ etc.) can be converted to metal
nanoparticles by Lactobacillus strain present in butter milk. By exposing the mixture of
two different metal salts to bacteria, it is indeed possible to obtain alloys under certain
conditions.

 Fusariumoxysporum challenged with gold or silver salt for approximately three days
produces gold or silver particles
extracellularly..ExtremophilicactinomyceteThermomonospora sp. produces gold
nanoparticles extracellularly.

 When silver metal salt is treated with fungus Verticillium sp. the nanoparticles can be
produced intracellularly. Changes in biomass colour from initial yellow to final
brown, after exposure to silver salt, is a visual indication of silver nanoparticles
formation. Particles can be recovered by washing with some suitable detergent or
15
 ultrasonication. In a similar way, gold nanoparticles can be produced using Verticillium
sp. However, the colour of biomass is from pink to blue depending upon the particle
size.
 Semiconductor nanoparticles like CdS, ZnS, PbS etc. can be produced using different
microbial routes. Desulfobacteriaceae can form 2-5 nm ZnS nanoparticles. Bacteria
Klebsillapneumoniae can be used to synthesize CdS nanoparticles. When Cd(NO3)2 is
mixed in a solution containing bacteria and solution is shaked for about one day at ~38
C, then the CdS nanoparticles in the size range ~5-200 nm can be formed. CdS
nanoparticles with narrow size distribution can be synthesized using the yeasts like
Candida glabrata and Schizosaccharomycespombe. Similarly it is possible to
synthesize PbS by challenging Torulopsis sp. with lead salt like PbNO3.
5.5.2 Synthesis using plant extracts: It has been reported that live alfalfa plants are found to
produce gold nanoparticles from solids. Leaves from geranium plant (pelargonium graveolens)
have also been used to synthesize nanoparticles of gold. Nanoparticles obtained using
Collectotrichum sp. Fungus related to geranium plant has a wide distribution of sizes and
particles are mostly spherical. On the other hand, geranium leaves produce rod and disk shaped
nanoparticles. Synthesis procedure to obtain gold nanoparticles form geranium plant extract is
as follows: Finely crushed leaves are put in Erlenmeyer flask and boiled in water just for a
minute. Leaves get ruptured and cells release intracellular material. Solution is cooled and
decanted. This solution is added to HAuCl4 aqueous solution and nanoparticles of gold start
forming within a minute.
5.5.3 Use of templates: DNA, S-layers or some membranes have long range periodic order in
terms of some molecular groups of their constituents. Therefore on some periodic active sites
preformed nanoparticles can be anchored. Alternatively, using certain protocols nanoparticles
can be synthesized using DNA, membranes etc., as templates. Such ordered arrays are formed
as a result of various interactions that take place between the templates and the particles.
Ferritin is a colloidal protein of nanosize. It stores iron in metabolic process and is abundant in
animals. It is also capable of forming uniform three dimensional hierarchical architechture.
There are 24 protein (peptides) subunits in a ferritin, which are arranged in such a way that they
create a central cavity of ~6nm. Diameter of polypeptide shell is 12 nm. Ferritin can
accommodate 4500 Fe atoms. They are in Fe3+ state as hydrated iron oxide mineral,
ferrihydrite. The protein subunits are composed of light as well as heavy chains having
dinuclearferroxidecentres. These centres are catalysts for in vitro oxidation of Fe2+ ions. The
ferritin without inorganic matter in its cavity is known as apoferritin and can be used to entrap
desired nanomaterial inside the protein cage. Therefore, first step is to remove iron from
ferritin to form apoferritin and then introduce metal ions to form metal nanoparticles inside the
cavity or carry out some controlled reaction with metal ions to make a compound inside the
cavity. In any case, ions can be removed or introduced inside the ferritin, through some
available channels.
Horse spleen ferritin, diluted with sodium acetate buffer, should be placed in dialysis bag. A
solution of sodium acetate and thioglycolic acid is made in which dialysis bag is kept under
nitrogen gas flow for 2-3hours. Solution needs to be replaced from time to time for total 4-5
hours. Further dialysis of apoferritin solution should be done against saline for one hour and in
16
refreshed saline for ~15-20 hours. Apoferriting should then be mixed with solution having
sodium chloride (NaCl) and N-tris (hydroxymethyl) methyl-2-aminoethanosuphonic acid
(TES). Aqueous cadmium acetate is added to this solution and stirred continuously with
constant N2 gas purging. Process of CdS formation is stepwise with Cd loading of 55 atoms
per apoferritin colloid taking place in each step. Higher loading like 110, 165, 220 are possible.
Due to remarkably constant size of ferritin colloids and apoferritin derived from them, it is
possible to obtain nanoparticles of very uniform size. Besides CdS there ae several other
examples like controlled iron oxide, manganese, uranyl oxide, cobalt, cobalt-platinum alloy
etc., being synthesized inside ferritin. It is possible to fabricate ordered arrays of ferritin as well
as of nanoparticles inside them.
DNA can be used for preformed charged nanoparticles can get bonded with phosphate group of
DNA and even form organized arrays of nanoparticles. CdS (or other sulfide) nanoparticles can
be synthesized using DNA. Organic molecules can cap the surfaces of nanoparticles growing
in solutions. Similarly one can use DNA to bind with surface of growing nanoparticles. For
example, double stranded Salmon sperm DNA can be sheared to an average size of 500 bp.
Cadmium acetate can be added to desired medium like water, dimethylformamide, ethanol,
propanol etc., and reaction carried out in a glass flask with facility to purge the solution and
flow with an inert gas like nitrogen. Addition of DNA should be made and then Na2S can be
added dropwise. Depending upon the concentrations of cadmium acetate, sodium chloride and
DNA nanoparticles of CdS with size less than ~10 nm can be obtained. DNA probably bonds
through its negatively charged phosphate group to positively charged (Cd+) nanoparticle
surface.
5.6NANOFABRICATION
5.6.1 Introduction
One of the widely used method for the fabrication of nanostructures is lithography, which
makes use of radiation-sensitive layer to form well-defined patterns on a surface. Current
technologies for the fabrication of nanoscale structure are limited in terms of the minimum
feature size that can be achieved. Natural macromolecules and the processes through which
their highly controlled assembly is carried out have become a source of interest to create novel
devices and materials.
5.6.2Strategies for nanoarchitecture
One approach to the preparation of nanostructure, called the bottom-up approach, is to collect,
consolidate, and fashion individual atoms and molecules into the structure. This is carried out
by a sequence of chemical reactions controlled by catalysts. It is a process that is widespread in
biology where catalysts called enzymes assemble amino acids to construct living tissue that
forms and supports the organs of the body. It is the process of self-assembly.
The opposite approach to the preparation of nanostructure is called the top-down method,
which starts with large-scale object or pattern and gradually reduces its dimension or
dimensions
. 5.6.3 Lithography

17
Conventional ‘Lithography’ is a top down approach. The word lithography has its origin in the
Greek work ‘litho’ which means stone. Lithography therefore literally means carving a stone or
writing on a stone. It is now used now to mean a process in which a sample is patterned by
removing some part of it or sometimes even organizing some material on a suitable substrate.
Lithography is extensively used in electronics industry so as to obtain integrated circuits (IC)
or very large scale integration (VLSI) on small piece of semiconductor substrate often called a
‘chip’.
Different lithography techniques like optical lithography, x-ray lithography, electron beam
lithography and some other have been developed. They depend upon using photons or particle
radiations for carving the materials. The lithography technique involve transfer of some
pre-designed geometrical pattern (called master or mask) on a semiconductor (silicon) or
directly patterning (often known as writing) using suitable radiation. Mask is usually prepared
by creating radiation opaque and transparent regions on glass or some other material.
Pre-designed patterns can be transferred on a substrate much faster as compared to direct
writing. Direct writing being a slower process is overall expensive.
Common principle in most of the lithographic technique is to expose a material sensitive to
either electromagnetic radiation or to particles at some regions. Such a radiation sensitive
material is known as resist. The selection of area is made using a mask, which is transparent is
some regions and opaque in the other regions. This causes selective exposure of the resist,
making it weaker or stronger compared to unexposed material depending upon the type of the
resist being used. By removing the exposed or unexposed material in suitable chemicals or
plasma, desired pattern is obtained.
Various steps involved in photolithography to transfer a pattern on some semiconductor
surface: A thin film coating of a metal (like chromium) is deposited on a suitable substrate (for
example glass or silicon). A positive or a negative photoresist, usually some polymer, is coated
on metal thin film. Positive photoresist material has the property that when exposed to the
appropriate radiation it degrades or some chemical bonds are broken. Negative resist on the
other hand is a material, which hardens (crosslinks) on exposure to a radiation. A mask is
placed between the resist coated substrate and the source of light. By using a suitable chemical
(developer) the weakened portion is removed (or image is developed). Remaining unexposed
part also can be removed by appropriate chemical treatment. The remaining material can be
dissolved in one step and the hardened material in another step.
Depending upon the radiation used like visible light, X-rays, electrons, ions etc., the
lithography name is tagged with it.
Nanolithography is the art and science of etching, writing, or printing at the microscopic level,
where the dimensions of characters are on the order of nanometers (units of 10-9 meter, or
millionths of a millimeter). This includes various methods of modifying semiconductor chips
at the atomic level for the purpose of fabricating integrated circuits (ICs). Instruments used in
nanolithography include the scanning probe microscope (SPM) and the atomic force
microscope (ATM). The SPM allows surface viewing in fine detail without necessarily
modifying it. Either the SPM or the ATM can be used to etch, write, or print on a surface in
single-atom dimensions.

18
5.6.4 Lithography using photons
It is possible to use visible, ultraviolet, extreme ultraviolet (EUV) or X-rays to perform
lithography. Highest resolution of the generated features ultimately depend upon the
wavelength of radiation used and interaction of radiation with matter as well as mask and
optical elements used. Smaller the wavelength used smaller can be feature size. Depth of focus
depends upon the penetration of incident radiation. In the visible range glass lenses and masks
can be used. In the UV range fused silica or calcium fluoride lenses are used.
There are three methods used to pattern a substrate viz., proximity, contact and projection. In
proximity method, mask is held close to the photoresist coated metallized substrate, whereas in
contact method the mask is in contact with photoresist. In both proximity and contact methods
a parallel beam of light falls on the mask, which transmits the radiation through some windows
but blocks through opaque parts. Although better resolution is achieved with contact method as
compared to proximity method, in contact method the mask gets damaged faster. In case of
projection method a focused beam is scanned through the mask, which allows good resolution
to be achieved along with the reduced damage of the mask. However, scanning is a slow
process and also requires scanning mechanism adding to the cost.
5.6.5 UVlight and Laser Beams: Using monochromatic light in the visible to UV range,
features as small as 1 to 1.5 um size can be routinely obtained. Often g-line (436 nm) from
mercury lamp is used. Laser beam of KrF (248 nm) or ArF (193 nm) also are employed
reaching ~150 nm as the smallest feature size.
5.6.6 X-ray lithography: Smaller features are possible to obtain by employing X-rays also.
However, it is difficult to make suitable masks for X-ray lithography. X-rays in the 0.1-5nm
range are used with appropriate metal masks in proximite geometry. Absorption of X-rays in
materials not only depends upon the thickness of the material but is also complicated by the
presence of adsorption edges. Metal masks are fabricated in such a way that through thin
portions they are transmitted and absorbed in thicker regions. Gold masks are often used.
X-ray lithography is a next generation lithography that has been developed for the
semiconductor industry. Batches of microprocessors have already been produced. The short
wavelengths of 0.8 nm X-rays overcome diffraction limits in the resolution of otherwise
competitive optical lithography. The X-rays illuminate a mask placed in proximity to a
resist-coated wafer. No lenses are used, and only rudimentary collimating mirrors. The X-rays
are broadband, typically from a compact synchrotron radiation source, allowing rapid
exposure. Deep X-ray lithography uses yet shorter wavelengths, about 0.1 nm with modified
procedures, to fabricate deeper structures, sometimes three dimensional, with reduced
resolution. The mask consists of an X-ray absorber, typically of gold or compounds of tantalum
or tungsten, on a membrane that is transparent to X-rays, typically of silicon carbide or
diamond. The pattern on the mask is written by direct write electron beam lithography onto a
resist that is developed by conventional semiconductor processes. The membrane can be
stretched for overlay accuracy.
Most X-ray lithography demonstrations have been performed by copying with image fidelity,
i.e. without magnification, 1x, on the line of fuzzy contrast as illustrated in the figure. But with
the increasing need for high resolution, X-ray lithography is now performed on the Sweet Spot,
19
using local “demagnification by bias.” Dense structures are developed by multiple exposures
with translation. Many advantages accrue from the application of 3x “demagnification": the
mask is more easily fabricated; the mask to wafer gap is increased; and the contrast is higher.
The technique is extensible to dense 15 nm prints. The resulting printing has high contrast.
X-rays generate secondary electrons as in the cases of extreme ultraviolet lithography and
electron beam lithography. While the fine pattern definition is due principally to secondaries
from Auger electrons with a short path length, the primary electrons will sensitize the resist
over a larger region than the X-ray exposure. While this does not affect the pattern pitch
resolution (determined by wavelength and gap), the image exposure contrast (max − min) /
(max + min) is reduced since the pitch is on the order of the primary photo-electron range.
Several prints at about 20 nm have been published. Another manifestation of the photoelectron
effect is exposure to X-ray generated electrons from thick gold films used for making daughter
masks. Simulations suggest that photoelectron generation from the gold substrate may affect
dissolution rates.

20
5.6.7Lithography using particle beams
Optical lithography is an important manufacturing tool in the semiconductor industry.
However, to fabricate semiconductor devices smaller than 100nm, ultraviolet light of short
wavelengths (193 nm) is required, but this will not work because the materials are not
transparent at these wavelengths. Electron beam and X-ray lithography can be used to make
nanostructures, but these processes are not amenable to the high rate of production that is
necessary for large-scale manufacturing. Electron-beam lithography uses a finely focused
beam of electrons, which is scanned in a specific pattern over the surface of a material. It can
produce a patterned structure on a surface having 10-nm resolution. Because it requires the
beam to hit the surface point by point in a serial manner, it cannot produce structures at
sufficiently high rates to be used in assembly-line manufacturing processes. X-ray lithography
can produce pattern on surfaces having 20nm resolution, but its mask technology and exposure
systems are complex and expensive for practical applications.
All the moving particles are associated with wavelength known as de Broglie wavelength. All
kinds of particles can in principle be used. But to achieve high resolution wavelength should be
as small as possible. Thus large mass and large velocity of particle makes is possible to get
adequate resolution. In fact it is possible using neutral atoms, ions or electrons to bring down
the particle associated wavelength to any desired value, even as small as 0.1 nm.
5.6.8 Electron Beam Lithography: It is very similar to a scanning electron microscope and
requires vacuum. Sometimes SEM is modified in order to use it as a lithography set up.
Electron beam lithography is a direct writing method i.e., no mask is required to generate a
pattern. Rather, pattern or masters required for other lithography processes like optical
lithography and soft lithography can be generated using electron beam lithography. Electrons
with high energy (~5KeV) are incident on the photoresist. Here also positive or negative
photoresists can be used. Common positive resists are polymethylmethacrylate (PMMA) and
polybutane-1-sulphone (PBS). Negative resist often used in electron beam lithography is
polyglycidylmethacrylatecoehylacrylate (COP). Developers used are methylisobutylkeone
(MIBK) and isopropylalcohal (IPA) in 1:1 ratio. A focused electron beam in electron beam
lithography is used in two modes viz., vector scan and raster scan. In vector scan the electron
beam writes on some specified region. After one region is completed the X-Y scanning stage
on which substrate to be patterned is mounted, moves. During its movement electron beam is
put off. Then a new region is selected and written with the beam. This is continued until whole
pattern is generated. In raster scan the beam is rastered or moved continuously over a small
area, line by line. The X-Y stage of sample moves at right angles to the beam. The beam is
turned off or turned on depending on the pattern. Although very high resolution (~50 nm) is
routinely possible using this lithography, due to scanning mode it is rather slow.
The practice of using a beam of electrons to generate patterns on a surface is known as Electron
beam lithography. The primary advantage of this technique is that it is one of the ways to beat
the diffraction limit of light and make features in the sub-micrometre regime. Beam widths
may be on the order of nanometers. This form of lithography has found wide usage in research,
but has yet to become a standard technique in industry. The main reason for this is speed. The
beam must be scanned across the surface to be patterned -- pattern generation is serial. This
makes for very slow pattern generation compared with a parallel technique like

21
photolithography (the current standard) in which the entire surface is patterned at once. As an
example, to pattern a single layer of semiconductor containing 60 devices (each device consists
of many layers) it would take an electron beam system approximately two hours; compared
with less than two minutes for an optical system.
One caveat: While electron beam lithography is used directly in industry for writing features,
the process is used mainly to generate exposure masks to be used with conventional
photolithography. However, when it is more cost-effective to avoid the use of masks, e.g., low
volume production or prototyping, electron-beam direct writing is also used.
For commercial applications, electron beam lithography is usually produced using dedicated
beam writing systems that are very expensive. For research applications, it is very common to
produce electron beam lithography using an electron microscope with a home-made or
relatively low cost lithography accessory. Such systems have produced linewidths of ~20 nm
since at least 1990, while current systems have produced linewidths on the order of 10 nm or
smaller. These smallest features have generally been isolated features, as nested features
exacerbate the proximity effect, whereby electrons from exposure of an adjacent feature spill
over into the exposure of the currently written feature, effectively enlarging its image, and
reducing its contrast, i.e., difference between maximum and minimum intensity. Hence, nested
feature resolution is harder to control. For most resists, it is difficult to go below 25 nm lines
and spaces, and a limit of 20 nm lines and spaces has been found.
With today's electron optics, electron beam widths can routinely go down to a few nm. This is
limited mainly by aberrations and space charge. However, the practical resolution limit is
determined not by the beam size but by forward scattering in the photoresist and secondary
electron travel in the photoresist. The forward scattering can be decreased by using higher
energy electrons or thinner photoresist, but the generation of secondary electrons is inevitable.
The travel distance of secondary electrons is not a fundamentally derived physical value, but a
statistical parameter often determined from many experiments or Monte Carlo simulations
down to < 1 eV. This is necessary since the energy distribution of secondary electrons peaks
well below 10 eV. Hence, the resolution limit is not usually cited as a well-fixed number as
with an optical diffraction-limited system. Repeatability and control at the practical resolution
limit often require considerations not related to image formation, e.g., photoresist development
and intermolecular forces. In addition to secondary electrons, primary electrons from the
incident beam with sufficient energy to penetrate the photoresist can be multiply scattered over
large distances from underlying films and/or the substrate. This leads to exposure of areas at a
significant distance from the desired exposure location. These electrons are called
backscattered electrons and have the same effect as long-range flare in optical projection
systems. A large enough dose of backscattered electrons can lead to complete removal of
photoresist in the desired pattern area.
5.6.9 Ion Beam Lithography: Very small features (~5-10 nm) can be written using
high-energy ion beams. Major advantage of using ion beams is that resists are more sensitive to
ions as compared to electron and have low scattering in the resist as well as from the substrate.
Commonly used ions are He+, Ga+ etc., with energy in the 100-300 KeV range.
5.6.10Neutral Beam Lithography: Neutral atoms like argon or cesium have been allowed to
impinge on substrates to be patterned through the mask. Such beams cause less damage to the
22
masks. Self assembled monolayers on gold substrate have been often patterned using neutral
beams.
5.6.11 Scanning Probe Lithography
STM and AFM microscopes using sharp tips or probes for imaging can be used for lithography
purpose. This has evolved scanning probe lithography (SPL). One major advantage is that like
optical lithography it is also carried out in air. There are different ways in which SPL can be
carried out viz., mechanical scratching or movement, optical, thermomechanical and electrical.
5.6.12Mechanical Lithography: In mechanical lithography there are different modes like
scratching, pick up and pick down or dip pen lithography.
(i) Scratching: Pits or lines can be produced using either STM tip or AFM tip on surface of bulk
material or surface of a thin film. Formation of pits or lines by scratching is like ploughing, in
which scratched material is piled up around the indented region. Variety of materials like
nickel, gold, copper, polymers, Langmuir Blogett films, high temperature superconductors are
possible to scratch. Often diamond tips can be used. Pits as small as 30 nm diameter and 10 nm
depth are possible to make.
(ii) Pick-up and Pick-down: Atoms are picked up one by one and arranged in desired pattern on
a substrate. STM/AFM tips can be used to move atoms or molecules. Systematic work by IBM
scientists made it possible for them to pile up xenon atoms on a metal substrate and write a
letter patter IBM for the first time. Some scientists moved 30 nm GaAs particles on a GaAs
substrate. Letter patterns as high as 50 nm in height were made using AFM tip. Now the
technique is used to fabricate some circuits.
(iii) Dip-pen lithography: The method bears a similarity to writing on a piece of paper with ink.
That is why the name dip pen lithography is given. An AFM tip is used as a pen and molecules
are used as ink. Appropriate molecules picked up by the tip from the source of molecules can
be transported and transferred at desired place on the substrate. Letters with line thickness as
small as 15nm have been written. Overwriting and erasing capability of dip pen lithography is
quite a unique feature.
Dip Pen Nanolithography (DPN) is a scanning probe lithography technique where an atomic
force microscope tip is used to transfer molecules to a surface via a solvent meniscus. This
technique allows surface patterning on scales of under 100 nanometres. DPN is the
nanotechnology analog of the dip pen (also called the quill pen), where the tip of an atomic
force microscope cantilever acts as a "pen," which is coated with a chemical compound or
mixture acting as an "ink," and put in contact with a substrate, the "paper." DPN enables direct
deposition of nanoscale materials onto a substrate in a flexible manner. The vehicle for
deposition can include pyramidal scanning probe microscope tips, hollow tips, and even tips on
thermally actuated cantilevers. Applications of this technology currently range through
chemistry, materials science, and the life sciences, and include such work as ultra high density
biological nanoarrays, additive photomask repair, and brand protection for pharmaceuticals.
The technique was discovered in 1999 by a research group at Northwestern University led by
Chad Mirkin. The company NanoInk, Inc. holds a patent on Dip Pen Nanolithography, and
"DPN" and "Dip Pen Nanolithography" are trademarks or registered trademarks of NanoInk.

23
 Fig.5.1 ATOMIC FORCE MICROSCOPE
5.6.13Optical scanning probe lithography: Very high resolution ~20-50 nm is possible,
overcoming the diffraction limit, with visible light using Scanning Near-Field Optical
Microscope (SNOM). This is attributed to near-field component of electromagnetic radiation.
In SNOM, a fine spot of light emerging through an aperture, scans on the surface within a
distance of less than wavelength of light used for scanning. By placing the aperture close to the
photoresist coated substrate, it is possible to obtain as small as ~50nm size features routinely.
5.6.14 Thermo-mechanical lithography: It is also possible to use an AFM tip along with a
laser beam and carry out nanolithography. While the AFM tip is in contact with a coating like
polymethylmethaacrylate (PMMA), laser beam strikes the same point of the coating. This heats
the film locally enabling the tip to penetrate in the material and make a pit. This
thermo-mechanical method is capable of producing resolution as high as ~30nm.
5.6.15Electrical Scanning Probe Lithography: In this method, a voltage is applied between
the SPM tip and the sample. Above some critical voltage if large current flows between the tip
and the sample, an irreversible change can occur in sample surface. Variety of bulk solid and
think films surfaces has been patterned using this method. In silicon or modified silicon surface
~30 -60 nm wide and ~5-10 nm deep lines have been engraved.
5.6.16 Soft Lithography
The name soft lithography is used to mean the techniques using materials like polymers,
organic materials or self assembled films. It is a useful alternative to obtain resolution better
than ~100nm at low cost. Moreover, the method is applicable from few nm to few um size
features. In general, soft-lithography technique involves fabrication of a patterned master,
molding of master and making replicas. A master is usually made using X-ray or electron beam
lithography. It is supposed to be quite rigid. A mold is usually made using a polymer like
polydimethylsiloxane (PDMS), epoxide, polyeurethane etc., PDMS is most common amongst
the polymers used for molding due to its attractive properties like thermal stability (~150 C),
optical transparency, flexibility (~160% elongation), capability of cross-linking using IR or
UV radiation etc. However, during molding, some distortions can take place and adequate
control has to be practiced to achieve reproducible and required results.

24
"Inking" a stamp. PDMS stamp with pattern is placed in Ethanol and ODT solution

ODT from the solution settles down onto the PDMS stamp. Stamp now has ODT attached to it
which acts as the ink.

The PDMS stamp with the ODT is placed on the gold substrate. When the stamp is removed,
the ODT in contact with the gold stays stuck to the gold. Thus the pattern from the stamp is
transferred to the gold via the ODT "ink."
In technology, soft lithography refers to a set of methods for fabricating or replicating
structures using "elastomeric stamps, molds, and conformable photomasks. It is called "soft"
because it uses elastomeric materials. Soft lithography is generally used to construct features
measured on the nanometer scale. Soft lithography includes the technologies of Micro
Contact Printing (µCP), replica molding (REM), microtransfer molding (µTM), micromolding
in capillaries (MIMIC) and solvent-assisted micromolding (SAMIM). One of the soft
lithography procedures is as follows:
1. The steps of any of your favorite micro- or nano- scale lithography procedures
(photolithography, EBL, etc.) are followed to etch a desired pattern onto a substrate
(usually silicon)
2. Next, the stamp is created by pouring a degassed resin overtop of the etched wafer.
Common resins include PDMS and Fluorosilicone.
3. Removing the cured resin from the substrate, a stamp contoured to your pattern is
acquired.
4. The stamp is then "inked" by placing it, pattern-up, in a bath of inking solution (for
example, ODT in ethanol) for a short period of time. The ink molecules will fall and

25
 adhere to the surface of the stamp creating a single-molecule layer of the ink on the
stamp.
5. The inked stamp is then pressed on the substrate and removed, leaving the desired
single-molecule thick pattern on the substrate
6. Steps 4 and 5 are repeated for each substrate on which the pattern is desired
Advantages: Soft lithography has some unique advantages over other forms of lithography
(such as photolithography and electron beam lithography). They include the following:
 Lower cost than traditional photolithography in mass production
 Well-suited for applications in biotechnology
 Well-suited for applications in plastic electronics
 Well-suited for applications involving large or nonplanar (nonflat) surfaces
 More pattern-transferring methods than traditional lithography techniques (more "ink"
options)
 Does not need a photo-reactive surface to create a nanostructure
 Smaller details than photolithography in laboratory settings (~30nm vs ~100nm)
5.6.17 Nanoimprint lithography: It has been developed that may provide a low-cost,
high-production rate manufacturing technology. Nanoimprint lithography patterns a resist by
physically deforming the resist shape with a mold having a nanostructure pattern on it, rather
than by modifying the resist surface by radiation, as in conventional lithography. A resist is a
coating material that is sufficiently soft that an impression can be made on it by a harder
material. A mold having a nanoscale structured pattern on it is pressed into a thin resist coating
on a substrate, creating a contrast pattern in the resist. After the mold is lifted off, an etching
process is used to remove the remaining resist material in the compressed regions. The resist is
a thermoplastic polymer, which is a material that softens on heating. It is heated during the
molding process to soften the polymer relative to the mold. The polymer is generally heated
above its glass transition temperature, thereby allowing it to flow and conform to the mold
pattern. The mold can be a metal, insulator or semiconductor fabricated by conventional
lithography methods. Nanoimprint lithography can produce patterns on a surface having 10 nm
resolution at low cost and high rates because it does not require the use of sophisticated
radiation beam generating pattern for the production of each structure.
5.6.18Microcontact Printing (uCP): A PDMS stamp is dipped in an alanethiol solution and
pressed against the metallized (Au, Ag, Cu) substrate. Those parts of substrate, which come in
contact with the PDMS receive layers of alkanethiol. The monolayers do not spread on the
substrate. Further, these self assembled monolayers can be used as resists for selective etching
or deposition. The printing being simulateous, it is a fast method.

26
Fig.10 Schematic procedures for ¹uCP of hexadecanethiol (HDT) on the surface of gold: (a)
printing on a planar surface with a planar stamp (b) printing on a planar surface over large
areas with a rolling stamp, and (c) printing on a nonplanar surface with a planar stamp.
5.6.19 Relica Molding: In this method, a PDMS master or stamp is used to replicate a number
o copies. For example a solution of polyurathene is poured in PDMS and cured using UV light
or thermal treatment so that polyurathene becomes solid. PDMS can be easily removed so that
a pattern opposite to that is produced in polyurathene. By applying small pressure on PDMS, it
is possible to further reduce the size o the features smaller than in the original pattern.
Nanostructure ~30 nm have been achieved using this method.
5.6.20Micro Transfer Molding (uTM): A preformed polymer is poured in PDMS stamp.
Excess polymer is removed and the stamp is pressed against a substrate. Using thermal
treatment polymer is imprinted on the substrate and mould is removed.
5.6.21Micromolding in Capilleries (MIMIC): In this technique, a PDMS stamp is placed on
a substrate to be patterned. A low viscocity polymer is then placed in contact with PDMS. The
liquid flows into channels of PDMS by capillary action. After thermal treatment of curing with
UV radiation the polymer gets solidified. PDMS stamp is then removed to obtain the patterned
substrate.
5.6.20 Solvent-Assisted Micromolding (SAMIM): A PDMS stamp coated with a solvent is
pressed against the substrate coated with a polymer film. Solvent softens the polymer surface in
contact. PDMS can be removed after the solvent has evaporated. PDMS stamp itself is not
affected by the solvent. Volatile and substrate dissolving solvents, but not PDMS stamp
dissolving, need to be used. Polymethylmethacrylate (PMMA), cellulose acetate, polyvinyl
chloride etc., are used as polymers.

27
Fig.5.2Schematic illustration of procedures for (a) replica molding (REM), (b) microtransfer
molding (uTM), (c) micromolding in capillaries (MIMIC), and (d) solvent-assisted
micromolding (SAMIM).
5.7 Self Assembly
The ‘bottom up’ approach of nanofabrication proposes to overcome the limitations of
traditional ‘top down’ lithographic techniques by relying on the self-organization of molecular
building blocks into higher order assemblies having a desired configuration. A variety of
molecular building blocks with programmed non-covalent recognition sites have been
designed and produced by organic synthesis. Nature has been working on nanoscale
self-assembly. Consequently, today biological materials are used as building blocks for
self-assembly applications. These biological materials include DNA nanostructures, small
peptides, S-layer glycoproteins, viral proteins and even whole bacteriophages.
5.7.1Process of self-assembly: The spontaneous organization of small molecules into larger
well-defined, stable, ordered molecular complexes or aggregates is known as self assembly.
Self assembly takes place spontaneously by adsorption of atoms or molecules onto a substrate
in a systematic, ordered manner. This process involves the use of weak, reversible interactions
between parts of molecules without any central control, and the result is a configuration that is
in equilibrium. The procedure is automatically error-checking, so faulty or improperly attached
subunits can be replaced during the growth.
The traditional organic synthesis of very large molecules called macromolecules comprises a
number of time-consuming steps that involve breaking and remaking strong covalent bonds,
28
and these steps are carried out under kinetic control. They yields are small, and errors are not
readily recognized or corrected. In contrast to this, self-assembly variety of synthesis makes
use of weak, noncovalent bonding interactions such as those involving hydrogen bonds and
van der Waals forces, which permit the reactions to proceed under thermodynamic control,
with continual correction of errors. The initial individual molecules or subunits are usually
small in size and number and easy to synthesize, and the final product is produced in a
thermodynamically equilibrium state.
On one hand, fabrication methods in micro- and nanoscience allow for batch processing. That
is, we have the ability to make many copies of the same device simultaneously. How do we
design these devices so that they spontaneously assemble themselves into a useful working
structure? On the other hand, traditional fabrication methods are limited in resolution. To make
smaller structures, i.e., true nanoscale structures, requires the development of new methods.
Taking their cue from nature, coaxing nanostructures into self assembling is an avenue many
scientists are exploring. Ultimately, a deeper understanding of self assembly may shed light on
the nature of life itself.
Assembly by capillary forces: G.M. White sides and his group at Harvard University have
designed and studied various self assembling systems. Many of these are based on the so-called
"capillary bond." This "bond" exploits two properties of objects in water. First, small objects
resting on the surface of water attract one another. In this way, interacting particles feel a force
of attraction. Second, when two hydrophobic surfaces come into contact they remain in
contact. In other words, they bond. In their experiments Whitesideset. al. have used the
polymer polydimethylsiloxane (PDMS) to fabricate their self assembling shapes. PDMS is
naturally hydrophobic and its surface properties can be easily changed from hydrophobic to
hydrophilic by treating with an oxygen plasma. In this way interacting particles with varying
surface properties can be fabricated. Whitesideset. al. have designed planar systems that self
assemble to tile the plane, tile the plane with gaps, and form chain-like structures.
Assembly by electrostatic forces: Assembly by capillary forces relies upon particle-particle
interaction and interaction between particles and their enviornment. The particles have surface
properties (hydrophobic or hydrophillic) and the enviornment is water.
Assembly by magnetic forces: simple to construct self assembling system involves magnets. In
its simplest incarnation, the system is no more than a collection of disk shaped magnets
randomly strewn about a inside a container. Here, simple shaking is enough to cause formation
of a more highly ordered state
5.7.2Interactions governing self-assembly: Self organization and self-assembly are
ubiquitous in nature, ranging from the simplest chemical reactions to the formation of living
organisms. Self-assembly is synonymous for the spontaneous occurrence of order in a given
open system. Any spontaneous process is irreversible and is accompanied by an increase in the
combined entropy for both the system and its environment. The basic thermodynamic quantity,
which dictates these processes at constant pressure, is system’s Gibbs free energy change.
∆G=∆H-∆TS, where ∆H and ∆S are the changes of enthalpy and entropy, respectively, after the
reaction or self-assembly processes. For spontaneous process, ∆G must to be <0. One major
contribution to ∆H comes from the potential attractive interactions. The forces that determine
29
∆H include: van der Waals, hydrogen bonding, electrostatic, hydrophobic, and other
non-bonding interactions. Entropy is related to quality of energy and order in any given system
and is measured by the statistical probability. In the process of self-organization and
self-assembly of the inorganic materials, major contributions to ∆G come from the system’s
enthalpy change, because entropy change is generally of less importance due to the limited
freedom of inorganic compounds in condensed phase.
Self assembly is the organization of molecules or materials into order from disorder. Quantum
mechanics determines the forces that organize the system on the nanometer scale. There are
only four forces known in nature, these are the strong and weak forces existing in the nuclei,
gravitational forces, and electromagnetic forces. Of these only the electromagnetic force will
be relevant for the self-assembly. The chemical bonding interaction is one the strongest among
all electromagnetic forces. Since self-assembly does not involve the breaking or the formation
of chemical bonds, only non-bonding interactions are important. The non-bonding
electromagnetic force is expressed in various forms e.g van der Waals forces, hydrogen
bonding, electrostatic forces, magnetic interactions and others such as cation- and metal
complexation interactions. In some cases, one type of interaction dominates, in others, several
interactions may be of equal importance and these interactions may be cooperative instead of
additive.
Van der Waals interaction is a weak short-range attractive force due to the temporary
dipole-dipole moment interaction that results from electron movement surrounding the nuclei.
It is non-discriminate and contributes to less than 2kcal/mol for each pair of interacting dipole
moments. It is a high order interaction. Electrostatic interaction is Columbic in nature. Its
interacting energy is inversely proportional to the distance between the charged particles.
Electrostatic interaction is strong and constitutes one of the major forces. Temperature does not
have a strong effect on electrostatic interactions. The hydrogen bonding interaction very
unique interaction between hydrogen bond donors (e.g N-H, O-H ) and acceptors (eg. N, O).
Hydrogen bonding plays an important role in hydrophobic interactions and in molecular
recognition of proteins because of its directionality. It was originally thought that hydrogen
bonding interaction is mostly electrostatic in nature, but it is now generally accepted that the
hydrogen bond consists of many different interactions, including Coulombic attraction,
exchange repulsion, polarization and charge transfer and dispersion. The hydrogen bonding
interaction contributes to about 2-20 kcal/mol to the total energy. If one or both of the donor
and acceptor are charged, the interaction becomes much stronger. Hydrophobic interactions
between the non-polar solutes in aqueous solution arises from the stronger attraction between
the water-water molecules than between the solute-water molecules. Metal complexation is
due mostly to a combination of electronic, electrostatic, charge transfer, van der Waals
interactions and the polarization effect. In the case of complexation between transition metal
ions and ligands, four or six coordinates is generally found.
5.7.3Examples of self-assembly: (i) Semicondutor islands: One type of self-assembly
involves the preparation of semiconductor islands. It can be carried out by a technique called
heteroepitaxy, which involves the placement or deposition of the material that forms the
islands on a supporting substrate called a substrate made of a different material with a closely
matched interface between them. It involves bringing atoms or molecules to the surface of the
substrate where they do one of three things. They either are adsorbed and diffuse about on the
30
surface until they join or nucleate with another adatom to form an island, attach themselves to
or aggregate into an existing island, or desorb and thereby leave the surface. Small islands can
continue to grow, migrate to other positions, or evaporate. There is critical size at which they
become stable, and no longer experience much evaporation. Thus there is an initial nucleation
stage when the number of islands increases with the coverage. This is followed by an
aggregation stage when the number of islands levels off and the existing ones grow in size.
Finally there is the coalescence stage when the main events that take place involve the merge of
exisiting islands with each other to form larger clusters.
It is possible to spontaneously create quantum dots of Ge on Si, InAs on GaAs etc. The origin
of self assembly is strain induced. For example germanium and silicon have only 4% lattice
mismatch. Therefore Ge can be deposited epitaxially on Si single crystal upto 3-4 monolayers.
This results into spontaneous formation of nanosized islands or quantum dots. However,
temperature of substrate has to be >350 C during deposition or post deposition annealing is
required. Size of the islands depends upon growth temperature as well as substrate plane on
which it grows.
5.7.4 Monolayers: A model system that well illustrates the principles and advantages of the
self-assembly process is a self-assembled monolayer. The Langmuir-Blodgett technique, had
been widely used for the preparation and study of optical coatings, biosensors,
ligand-stabilized Au clusters, antibodies and enzymes. It involves starting with clusters,
forming them into monolayer at an air-water interface, and then transferring the monolayer to a
substrate in the form of what is called a Langmuir-Blodgett film. Self assembled monolayers,
are stronger, are easier to make, and make use of a wide variety of available starting materials.
Self-assembled monolayers and multilayers have been prepared on various metallic and
inorganic substrates such as Ag, Au, Cu, Ge, Pt, Si, GaAs, SiO2, and other materials. This has
been done with aid of bonding molecules or ligands such as alkanethiols RSH, sulfides RSR’,
disulfides RSSR’, acids RCOOH, and siloxanes RSiOR3, where the symbols R and R’
designate organic molecule groups that bond to a thiol radical –SH or an acid radical –COOH.
The binding to the surface for the thiols, sulfides, and disulfides is via the sulfur atom; that is,
the entity RS-Au is formed on a gold substrate, and the binding for the acid is RCO2-(MO)n
where MO denotes a metal oxide substrate ion, and the hydrogen atom H of the acid is released
at the formation of the bond. The alkanethiols RSH are the most widely used ligands because of
their greater solubility, their compatibility with many organic functional groups, and their
speed of reaction. They spontaneously adsorb on the surface; hence the term self-assemble is
applicable.
For self-assembled monolayers to be useful in commercial microstructures, they can be
arranged in structured regions or pattern on the surface. An alkaenthio ‘ink’ can systematically
form or write pattern on a gold surface with alkanethiolate. The monolayer-forming ‘ink’ can
be applied to the surface by a process called microcontact printing, which utilizes an elastomer,
which is a material with rubber like properties, as a ‘stamp’ to transfer the pattern. The process
can be employed to produce think radiation-sensitive layers called resists for nanoscale
lithography. The monolayers themselves can serve for a process called passivation by
protecting the underlying surface from corrosion.

31
Self-assembled monolayer: Self assembled monolayers (SAMs) are surfaces consisting of a
single layer of molecules on a substrate. Rather than having to use a technique such as chemical
vapor deposition or molecular beam epitaxy to add molecules to a surface (often with poor
control over the thickness of the molecular layer), self assembled monolayers can be prepared
simply by adding a solution of the desired molecule onto the substrate surface and washing off
the excess.
A common example is an alkane thiol on gold. Sulfur has particular affinity for gold, with a
binding energy in the range of 20–35 kcal/mol (85–145 kJ/mol). An alkane with a thiol head
group will stick to the gold surface and form an ordered assembly with the alkyl chains packing
together due to van der Waals forces. For alkyl thiols on gold, the extended alkyl chains
typically orient with an angle of ~30 degrees from the perpendicular of the substrate, and are
assumed to be in a fully extended linear arrangement. There has been a great deal of work done
determining the process by which alkyl thiol on gold assemblies are produced. It is generally
thought that alkyl thiol molecules first bind to the gold surface in a 'lying down' position, where
the alkyl chain tails of the molecules lie flat on the gold surface. The thiol interaction provides
about 20–30 kcal/mol (85–130 kJ/mol) of driving force for the initial binding, which is
modeled as a Langmuir binding isotherm. These binding events continue until the lying down
molecules are dense enough on the surface to interact with each other. At some point the alkyl
chains lift off the substrate and point outwards, tethered by the thiol anchor to the surface.
There is a shift to a mixture of lying down molecules and island domains of upright alkyl
chains, tilted at 30 degrees to the normal. At this stage binding kinetics become more complex
and can no longer be modeled with a simple Langmuir binding isotherm. Over time the island
domains merge and cover the bulk of the substrate, and the process can be compared to a 2-D
crystallization process on a surface. Alkyl thiol SAMs exhibit grain boundaries and defects
even after long periods of assembly. The initial stage of SAM formation usually takes minutes
or less under the normal conditions of 0.1-10 mmol/L thiol concentration in a solvent. More
ordering of the assembly can take place over days or months, depending on the molecules
involved.
A variety of other self-assembled monolayers can be formed, although there is always debate
about the degree to which systems self-assemble. Alkyl thiols are known to assemble on many
metals, including silver, copper, palladium, and platinum. Alkyl silane molecules (e.g.
octadecyltrichlorosilane) are another well-known example of self-assembly on silicon oxide
surfaces and potentially be of greater technical relevance than alkyl thiol assembly on metals.
Alkyl carboxylates are known to assemble on a variety of surfaces, such as aluminium and
mica. Silicon has been used through the reaction of silicon hydride surface and a radical
generator, such as heat, UV or radical initiator molecule, or with reagents such as Grignard and
chlorosilanes. Once assembly has been accomplished, chemistry can be performed on the
layer, especially if self-assembly places a reactive functional group on the outside of the
monolayer.
SAMs have several applications in scientific research; they tend to have quite different
chemical kinetics than the same molecules in another form, because of their exposed,
2-dimensional distribution, and as such are useful for some chemical and biochemical
experiments. They can also be used for simulation of biological membranes and as substrates
for cell culture. As technology develops to control the functional groups present in SAMS,
32
either by direct deposition of molecules with those groups or by chemical modification of the
layer, many other applications are also developing, for example in nanoscale fabrication of
electronics.
5.7.5 Protein folding and aggregation: Protein folding is a typical example of self-assembly
regulated by many subtle interacting forces. Protein folding is the process by which the
polypeptide is folded into a functional three-dimensional protein structure based on the
amino-acid sequence. When polypeptides are newly produced under physiological conditions,
their folding is based on the interacting forces and the laws of thermodynamics. However, in
some cases, molecular chaperones have to be employed to assist protein folding to prevent
incorrect interactions within and between non-native polypeptides.
Molecular recognition means that there is specific interaction between protein and ligand, or
between antibody and antigen. As was observed experimentally, topography (conformational
match seems to play an essential role in protein-ligand recognition. Because hydrophobic and
van der Waals interactions are not specific; they cannot alone be responsible for molecular
recognition. Directional hydrogen bonding and electrostatic interactions play an important
role.

Fig.5.3 PROTEIN FOLDING AGGREGATION

Hydrophobic and hydrophilic interactions are important because many molecules in biology
such as proteins and the molecules that make up the cell membrane have hydrophilic and
hydrophobic regions on the same molecule. When put in water these molecules automatically
organize themselves into more complex and biologically useful structures. This process is
termed self assembly. It is illustrated in the diagram for a molecule with a polar head and a
non polar tail.
5.7.6Applications: (i) Self assembly using biological templates: There are many examples
of self assembly at biological templates like S-layers, proteins, DNA, lipids etc. When
organized arrays of inorganic crystals are embedded in biological systems they are often
referred to as biomineralized systems.
Mangetotactic bacteria are small bacteria, ~35 to 120 nm sized permanent magnets are present
inside them. The magnets are of either iron sulphide (Fe3S4-gregite) or iron oxide (Fe3O4 –
magnetite). Such magnetic particles make a chain of nanomagnets. It is useful for navigation of
33
bacteria. Earth’s magnetic field has a dip in the north and south hemisphere which helps
bacteria to seek direction.
Another example of self-assembly in biological systems is S-layers. They are part of cell
envelope of prokaryotic organisms. They are two dimension, crystalline single proteins or
glycoprotein monomers organized in hexagonal, oblique or square lattices. These lattices have
ordered pores. The periodicity of pores can vary, depending upon the protein, from 3-35 nm.
Such S-layers after extraction from bacterial cells have been transferred on some metallic
substrates (or grids). When treated with cadmium salt and subsequently with Na2S, ordered
arrays of CdS nanoparticles could be formed. S-layers have been used to assemble Au, Pt, Fe,
Ni etc., metal nanoparticles. In general, S-layers extracted from the biological cells can be
directly used to deposit nanoparticles from liquid phase.
Ferritins are protein colloids of 12 nm size found in all animals. Ferritins have a cavities ~6-8
nm in size filled with iron oxide. It is possible to remove iron oxide and replace it with metal or
other nanoparticle. Further it is possible to make a two dimensional array of ferritins in
solution. For example, ferritin solution in NaCl and phosphate at ~5.8 pH can be filled in a
trough. Chloroform containing dichloroacetic acid can be used to dissolve
poly-1-benzal-L-histidine (PBLH) and spread over ferritin solution in trough. After about two
hours the solution can be heated at 38 C for one hour and cooled back to room temperature.
This produces ordered layer of ferritin at liquid-air interface. The layer can be transferred on
silicon substrate by dipping in the solution.
DNA is a long helical molecule. It has large aspect ratio and acts like a long one dimensional
template in its simplest form. Its four nucleotide bases viz., guanine, cytosine, adenine, and
thymine can form a rich variety of sequences and structures. Thus, cirucular, square, branched
etc. long or short DNA templates are possible. Besides planar geometry, they can adopt even
three dimensional structures. As DNA has alternate sugar and phosphate groups on its strands,
it is possible to anchor metal, semiconductor or oxide particles by different bonding on DNA to
have assembly of particles.
5.7.7 Self assembly using organic molecules: Preformed inorganic nanoparticles can be
assembled on solid substrates through some organic molecules adsorbed on their surfaces. CdS
nanoparticles functionalized with carboxylic group can be transferred to aluminium thin films.
Dithiols adsorbed on metals surface also could adsorb CdS nanoparticles to form layers of
them. Silver particles have been adsorbed on oxidized aluminium layers using bifunctional
molecule such as 4-carboxythiophenol. These molecules bind to aluminium oxide layer by
carboxylic group and thiol attaches to silver particles.
Using a two phase reaction alkanethiol or alkylamine capped gold, silver and palladium
nanoparticles have been self assembled. Here chemical reaction takes place in an aqueous
medium. The particles are then transferred into an organic solvent. Solvent is allowed to
evaporate which leaves self-assembled layer.
Using Langmuir Blodgett technique it is possible to transfer organic layers along with the
attached nanoparticles in liquid subphase to form ordered monolayer or multiple layers on solid
substrate. It is possible to order different bilayers of nanoparticles by simply dipping the same
substrate alternately in different baths.
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5.7.8 Others
(a) Sputtering (a bottom-up approach): One method used to make thin layers of material that
are only a few atoms thick is called "sputtering." Sputtering involves transferring atoms from a
block of source metal over to a surface waiting to be coated. The atoms are knocked loose from
the source metal by bombarding them with other high-energy particles. The common
aproachtaken when explaining sputtering is to imagine billiard balls being struck by the cue
ball. The cue ball is rather like the hihg-energy incident particle. As it strikes a bunch of billiard
balls (atoms in a block of source metal) they scatter from one another. This is where the
analogy breaks down, though, as there is no second surface that the billiard balls attach to
besides the pool table. In sputtering, however, the loose atoms are free to deposit on some
material that needs to be coated.

Fig.5.4 SPUTTERING-BOTTOM TO TOP APPROACH

5.7.9Nanoscale Crystal Growth (a bottom-up approach): Just like it sounds, this method
involves rather tricky selection of seed crystals and growing conditions with the hopes of
creating crystals that have unusual shapes. Nanowires, which happen to exhibit tremendous
conductivity, are typically created in this way.
5.7.10Focused ion beam: Focused ion beam, also known as FIB, is a scientific instrument that
resembles a scanning electron microscope. However, whereas the SEM uses a focused beam of
electrons to image the sample in the chamber, a FIB instead uses a focused beam of gallium
ions. Gallium is chosen because it is easy to build a gallium liquid metal ion source (LMIS). In
a Gallium LMIS, gallium metal is placed in contact with a tungsten needle and heated. Gallium
wets the tungsten, and a huge electric field (greater than 10 8 volts per centimeter) causes
ionization and field emission of the gallium atoms. These ions are then accelerated to an energy
of 5-50 keV (kiloelectronvolts), and then focused onto the sample by electrostatic lenses. A
modern FIB can deliver tens of nanoamps of current to a sample, or can image the sample with
a spot size on the order of a few nanometers.
Unlike an electron microscope, the FIB is inherently destructive to the specimen. When the
high-energy gallium ions strike the sample, they will sputter atoms from the surface. Gallium
atoms will also be implanted into the top few nanometers of the surface, and the surface will be
made amorphous. Because of the sputtering capability, the FIB is used as a micro-machining
tool, to modify or machine materials at the micro- and nanoscale. A FIB can also be used to
deposit material via ion beam induced deposition. FIB-assisted chemical vapor deposition
occurs when a gas, such as tungsten carbonyl (W(CO) 6) is introduced to the vacuum chamber

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and allowed to chemisorb onto the sample. By scanning an area with the beam, the precursor
gas will be decomposed into volatile and non-volatile components; the non-volatile
component, such as tungsten, remains on the surface as a deposition. This is useful, as the
deposited metal can be used as a sacrificial layer, to protect the underlying sample from the
destructive sputtering of the beam. Other materials such as platinum can also be deposited.
FIB is often used in the semiconductor industry to patch or modify an existing semiconductor
device. For example, in an integrated circuit, the gallium beam could be used to cut unwanted
electrical connections, or to deposit conductive material in order to make a connection. The
FIB is also commonly used to prepare samples for the transmission electron microscope. The
TEM requires very thin samples, typically ~100 nanometers. Other techniques, such as ion
milling or electropolishing can be used to prepare such thin samples. However, the
nanometer-scale resolution of the FIB allows the exact thin region to be chosen. This is vital,
for example, in integrated circuit failure analysis. If a particular transistor out of several million
on a chip is bad, the only tool capable of preparing an electron microscope sample of that single
transistor is the FIB. The drawback to FIB sample preparation is the above-mentioned surface
damage and implantation. However, this is usually only noticeable in high-resolution "lattice
imaging" TEM. By lightly ion-milling the sample after completing the FIB preparation, much
of this damage can be removed. In short, the FIB is a useful and versatile tool in the materials
sciences and semiconductor fields.
5.8 NANOMATERIALS IN HUMANS: Exposure of environment and humans
Exposure of nanomaterials to workers, consumers, and the environment seems inevitable
with the increasing production volumes and the increasing number of commercially available
products containing nanomaterials or based on nanotechnology exposure is a key element in
risk assessment of nanomaterials since it is a precondition for the potential toxicological and
ecotoxicological effects to take place. If there is no exposure – there is no risk. Nanoparticles
are already being used in various products and the exposure can happen through multiple
routes.
Human routes of exposure are:
- Dermal (for instance through the use of cosmetics containing nanoparticles);
- Inhalation (of nanoparticles for instance in the workpiece);
- Ingestion (for instance food products containing nanoparticles);
- And injection (for instance medicine based on nanotechnology).
5.8.1Hazard Identification
In order to complete a hazard identification of nanomaterials, the following is ideally required.
- ecotoxicological studies
- Data about toxic effects
- Information on physical – chemical properties
- Solubility
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 - Sorption
- Biodegrability
- Accumulation
And all likely depending on the specific size and detailed composition of the nanoparticles.
In addition to the physical – chemical properties normally considered in relation to chemical
substances, the physical chemical properties of nanomateials is dependent on a number of
additional factors such as size structure, shape, and surface area. Opinions on, which of these
factors are important differ among scientists, and the identification of key properties is a key
gap of our current knowledge.
There is little doubt that the physical – chemical properties normally required when doing a
hazard identification of chemical substances are not representative for nanomaterials, however
there is at current no alternative methods. In the following key issues in regards to determining
the destiny and distribution of nanoparticles in the environment will be discussed, however the
focus will primarily be on fullerenes such as C60.
5.8.2Interaction in the environment
Nanoparticles can be used to enhance the bioavailability of other chemical substances so that
they are easily degradable or harmful substances can be transported to vulnerable ecosystems.
Besides the toxicity of the nanoparticeles itself, it is furthermore unclear whether nanoparticles
increases the bioavailability or toxicity of other xenobiotics in the environment or other
substances in the human body. Nanoparticles such as C60 have many potential uses in for
instance in medicine because of their ability to transport drugs to parts of the body which are
normally hard to reach. However, this property is exactly what also may be the source to
adverse toxic effects. Furthermore research is being done into the application of nanoparticles
or spreading of contaminants already in the environment. This is being pursued in order to
increase the bioavailability for degradation of microorganism, however it may also lead to
increase uptake and increased toxicity of contaminants in plants and animals, but to the best of
our knowledge, no scientific information is available that supports this.
5.8.3Conclusion
It is still too early to determine whether nanomaterials or nanoparticles are harmful or not
however the effects observed lately have made many public and governmental institutions
aware of the lack of knowledge concerning the properties of nanoparticles the urgent need for a
systematic evaluation of the potential adverse effect of Nanotechnology. Furthermore, some
guidance is needed as to which precautionary measures are warranted in order to encourage the
development of “green nanotechnologies” and other future innovative technologies, while at
the same time minimizing the potential for negative surprises in the form of adverse effects on
human health and/or the environment, it is important to understand that there are many
different nanomaterials and that the risk they pose will differ substantially depending on their
properties. At the moment it is not possible to identify which properties or combination of
properties make some nanomaterials harmful and which make them harmless, and property it
will depend on the nanomaterial is question. This makes it is extremely difficult to do risk
37
assessments and life-cycle assessment of nanomaterials because, in theory, you would have to
do a risk assessment for each of the specific variation of nanomaterials – a daunting task!
5.9Nanotoxicology
Nanotoxicology is the study of the toxicity of nanomaterials. Because of quanum size
effects and large surface area to volume ratio, nanomaterials have unique properties compared
with their larger counterparts.
Nanotoxicology is a branch of bionanoscience which deals with the study and application
of toxicity of nanomaterials.
Nanomaterials, even when made of inert elements like gold, become highly active at
nanometer dimensions.
Nanotoxicological studies are intended to determine whether and to what extent these
properties may pose a threat to the environment and to human beings. For instance, diesel
nanoparticles have been found to damage the cardiovascular system in a mouse model.
Nanotoxicology is a sub-speciality of particle toxicology. It addresses the toxicology of
nanoparticles (particles <100 nm diameter) which appear to have toxicity effects that are
unusual and not seen with larger particles. Nanoparticles can be divided into
combustion-derived nanoparticles (like diesel soot), manufactured nanoparticles like carbon
nanotubes and naturally occurring nanoparticles from volcanic eruptions, atmospheric
chemistry etc.
Typical nanoparticles that have been studied are titanium dioxide, alumina, zinc oxide,
carbon black, and carbon nanotubes, and “nano-nC60”. Nanoparticles have much larger
surface area to unit mass ratios which in some cases may lead to greater pro-inflammatory
effects (in, for example lung tissue). In addition, some nanoparticles seem to be able to
translocate from their site of deposition to distant sites such as the blood and the brain. This has
resulted in a sea-change in how particle toxicology is viewed – instead of being confined to the
lungs, nanoparticle toxicologists study the brain, blood, liver, skin and gut.
5.9.1Toxicity of QDs
There are different opinions about the toxicity of QDs; therefore, we investigated their
toxicity in amoeba as primary eukaryotes, in plant, and in animal.
5.9.2 In amoeba
It has been determined that QD labeling had no detectable effect on cell growth and had no
deleterious effects on cellular signaling and motility during development of the
Dictyosteliumdiscoideum cells.
5.9.3in plant
The ratio of reduced glutathione levels (GSH) relative to the oxidized glutathione (GSSG)
in plants suggests that QDs caused oxidative stress on the plant at this condition.
5.9.4 In animal

38
 Yan et al. investigated the potential vascular endothelial toxicity of mercaptosuccinic acid
(2-sulfanylbutanedioic acid) – capped QDs in vitro.
Their results suggested that QDs could not only impair mitochondria but also exert
endothelial toxicity through activation of mitochondrial death pathway and induction of
endothelial apoptosis.
More recently, Chen et al. have studied the cytotoxicity of CdTe/CDs (core-shell)
structured and also CdTe/CDs/ZnS (core-shell-shell) structured aqueous synthesized QDs, and
their results suggest that the cytotoxicity of CdTe QDs not only comes from the release of Cd 2+
ions but also intracellular distribution of QDs in cells and the associated nanoscale effects.
5.9.5Metal nano particles
Nanomaterials are consistently being released into the environmental via spillages, wear
washing and disposal at a rate proportional to their level of use. We don’t know where the go or
what happens to them after they are released: they may accumulate on land or water and enter
the food chain via plants and aquatic life, where they could exist harmlessly or react. They
might enter the human body: routes include inhalation, ingestion or even possibly through our
skin.
It has been suggested that once inside the body, the smallness of nanomaterials allows them
to easily could allow them to penetrate living cells, where they can amass, disrupt cell activity
or corrupt genes. They can also bypass the visual transportation channels, cross the blood-brain
barrier.
5.9.6Lungs
There has been much interest in the health effects of airborne particles, specifically PM10
(thoracic fraction).
PM2.5 (respirable fraction), PM1, and ultrafine particles (PM0.1), which are = 10, 2.5, 1,
and 0.1 µm (100 nm), respectively. One to 5 nm air suspended ENMs that enter the lungs are
not predicted to reach the alveoli; instead a high percentage is likely to deposit in the mucus –
lined upper airways (tracheobronchial region) due to their strong diffusion properties. On the
other hand -45% of 10 nm, - 50% of 20 nm, and – 25% of 100 nm ENMs deposit in the alveoli.
Deposition is greater during exercises. Chronic obstructive pulmonary and decreases alveolar
particle deposition.
5.9.7 Nasal cavity
Uptake from the nasal cavity into the olfactory nerve, followed by retrograde axonal
transport to the olfactory bulb and beyond, was shown in studies of the polio virus (30 nm) and
colloidal silver coated gold (50 nm). Uptake of -35 nm 13C particles along the olfactory
pathway to the olfactory bulb, and to a lesser extent into the cerebrum and cerebellum, was
shown 1 to 7 days later. Exposure to ~30 nm agglomerates of Mn by inhalation resulted in upto
a 3.5 fold increase of Mn in the olfactory bulb, and lower (but significant) increases in 4 rat
brain regions. The increase of Mn in brain regions other than the olfactory bulb may have
resulted from translocation to the brain by route(s) other than via the olfactory nerve, such as
through cerebrospinal fluid or across the blood-brain barrier. The nasal cavity is the only site
39
where the nervous system is exposed directly to the environment. This is an often overlooked
potential route of small amounts of ENMs into the brain.
5.9.8 Dermal exposure
Skin is composed of 4 primary layers, the outermost epidermis (which contains the stratum
corneum, stratum granulosum and stratum spinosum), dermis, and hypodermis. The hair
follicle is an invagination of the stratum comeum, lined by a horny layer (acroinfundibulum).
Dermal uptake routes are intercellular, intracellular, and follicular penetration. Uptake is
primarily by diffusion. Materials that diffuse through the lipid-rich intercellular space of the
stratum comeum typically have a low molecular weight (< 500 Da) and are lipophilic.
Materials that penetrate to the stratum corneum into the stratum granulosum can induce the
resident keratinocytes to release proinflammatory cytokines. Materials that penetrate to the
stratum spinosum, which contains langerhands cells (dendritic cells of the immune system),
can initiate an immunological response.
This is mediated by the Langerhans cells, which can become antigen-presenting cells and
can interact with T-cells. Once materials reach the stratum granulosum or stratum spinosum
there is little barrier to absorption into the circulatory and lymphatic systems. Whereas dry
powder ENMs pose a greater risk for inhalation exposure than those in liquids, liquid dispersed
ENMs present a greater risk for dermal exposure.
Consumer materials most relevant to dermal exposure include quntum dots, titania, and
zinc oxide in sunscreens, and silver as an anti-microbial agent in clothing and other products.
Prolonged dermal application of microfinetitania sunscreen suggested penetration into the
epidermis and dermis. However, subsequent studies did not verify penetration of titania from
sunscreens into epidermis or dermis of human, porcine or psoriatic skin or find evidence of
skin penetration of zinc oxide from sunscreen or positively or negatively – changed iron
containing ENMs. Nanoparticles with dye penetrated deeper into hair follicles of massaged
porcine skin in vitro and persisted thirty nm carbodylated quantum dots applied to the skin of
mice were localized in the folds and defects in the stratum corneum and hair follicles. A small
amount penetrated as deep as the dermis. Ultraviolet radiation increased penetration, raising
concern that these results might generalize and enter the central nervous system. The high
surface area and surface activity of nanomaterials means they may have amplified effects tests
on human cells grown in laboratories have shown immune reactions and inflammations in lung
tissue. However, it is important to remember that many of these dangers are still speculative,
man made nanoparticles are relatively simple, and existing materials are not considered to have
the complexity of systems like viruses that themselves struggle to enter and corrupt cells, and
are of a similar size to nanomaterials. There is only one way to find out whether these risks are
realistic or speculative at normal nanomaterial concentrations – testing. But this is rather
difficult.
5.9.9Problems with Testing
Toxicity is not only idiosyncratic to the chemical composition and structure of each
nanomaterial, but is also dependent upon other factors in particular, shape and solubility. Shape
may affect interactions with binding sites on enzymes, and sphercity or regularity may affect
surface reactivity and mobility.
40
 Surface charge fundamentally changes reactivity negatively charged membranes interact
with positively charged particles, but not negative ones. Even size matters. After all, a 100 nm
diameter particles is one million times bigger (in volume) than a 1 nm diameter particles – and
even across the nanosclae, transitions may occur between fundamental properties.
Whether the tests are carried out n plants, cells, or organisms can also affect the conclusions
of testing, as can the materials used during nanomaterial synthesis to direct the nano size and
shape since most of these are toxic themselves and might contaminate products. These factors
all depend on the experimental conditions under which the nanomaterial was synthesized and
tested, making comparison between research groups almost impossible.
For the toxicity of nanomaterials to be meaningful, they need to be compared with the
toxicity of the bulk material, but not all materials can exist when the same chemical structure
for nano and bulk types. Even if they do, we can’t be sure nanomaterials retain their dimensions
under testing they might form chains, aggregate lumps, or break down into smaller
nanoparticles. Without accounting for these variations, we can’t be sure how the “nano” factor
affects toxicity, and whether nanomaterials pose us any risk. This is wahy no regulatory
guidelines exist, and why nanomaterials are so freely used. But precisely because they are
being freely used, we really need to know the answers.
5.9.10Metal oxide nanomaterials
The knowledge on potential harmful effects of metallic nanomaterials lags behind their
increased use in consumer products and therefore, the safety data on various nanomaterials
applicable for risk assessment are urgently needed. In this study, 11 metal oxide nanoparticles
(MeOx NPs) prepared using flame pyrolysis method were analysed for their toxicity nanoscale
sunscreens. PEG-coated ~37 nm quantum dots accumulated in the lymphatic duct system after
intra-dermal injection in mice. Cadmium, determined by ICP-MS, from cadmium-containing
quantum dots was seen in liver, spleen, and heart, however, it is uncertain if this was from
cadmium or translocation of the quantum dots because methods were not used to show the
presence of quantum dots. The above results suggest topically applied ENMs that penetrate to
the dermis might enter the lymphatic system, and the ENMs or dissolved components
distribute systematically. To address these concerns ENMs intended for dermal application
such as titania, are often surface coated, eg. With silica, alumina, or manganese. One goal of
the surface treatment is to minimize toxicity by trapping the free radicals of reactive oxygen
species (ROS).
An in vitro study showed that mechanical stretching of human skin increased penetration of
500 and 100 nm fluorescent dextran particles through the stratum corneum, with some
distribution into the epidermis and dermis. Similarly, mechanical flexing increased penetration
of a 3-5 nm phenylalanine based C60 amino acid ENM through porcine skin in vitro. The
contribution of skin flexing and immune system response was further addressed wit three
titania formulations applied to minipigs. There was some ENM penetration into epidermis and
abdominal and neck dermis, but no elevation of titanium in lymph nodes or liver. Topical
exposure of mice to SWCNTs resulted in oxidative stress in the skin and skin thickening,
demonstrating the potential for toxicity not revealed by in vitro studies of ENM skin
penetration. There are no reports of long-term studies with topical ENM exposure.

41
 In the absence of organic solvents, the above suggests that topically applied ENMs do not
penetrate normal skin. Not surprisingly, organic solvents (chloroform >coclohexane> toluene)
increased penetration of fullerene into skin that had the stratum corneum removed by tape
stripping. As the fullernes were not detected in systemic circulation, there was no evidence of
systemic absorption.
5.9.11 Oral exposure
Little is known about the bioavailability of ENMs from the buccal cavity or the sub-lingual
site, or possible adverse effects from oral ingestion.
Particle absorption from the intestine results from diffusion though the mucus layer, initial
contact with enterocytes or M (microfold or membranous specialized phatocytic enterocyte)
cells, cellular trafficking, and post-translocation events . Colloidal bismuth subcitrate particles
(4.5 nm at neutral pH) rapidly penetrated the mucosa of dyspeptic humans, resulting in bismuth
in the blood. Particles appeared to penetrate only in regions of gastric epithelial disruption.
Greater uptake of 50 to 60 nm polysterene particles was seen through Peyer’s patches and
enterocytes in the villous region of the GI tract than in non-lymphoid tissue, although the latter
has a much larger intestinal surface area. Peyer’s patches are one element of gut-associated
lymphoid tissue, which consist of M cells and epithelial cells with a reduced number of goblet
cells, resulting in lower mucin production. It was estimated that ~7% of 50 nm and 4% of 100 –
nm polysterene ENMs were absorbed.
Fifty nm polystyrene ENMs fed to rats for 10 days by gavage showed 34% absorption, of
which about 75% was in the liver, spleen, blood and bone marrow, no ENMs were seen in heart
or lung. After oral administration of 50 nm fluorescence – labeled polystyrene ENMs, 18% of
the dose appeared in the bile within 24 h and 9% was seen in the blood at 24h, none was
observed in urine. The mechanism of GI uptake of 4, 10, 28 or 58 nm colloidal (maltodextran)
gold ENMs from the drinking water of mice was shown to be penetration through gaps created
by enterocytes that had died and were being extruded from the villus. Gold abundance in
peripheral organs inversely correlated with particle size.
In summary, there appears to be significant absorption of some ENMs from the GI tract,
with absorption inversely related to ENM size. The absorption site seems to be regions of
compromised gastric epithelial integrity and low mucin content.
5.9.12Ocular and mucous membrane exposure
Ocular exposure might occur from ENMs that are airborne, intentionality placed near the
eye (e.g. cosmetics), accidently splashed onto the eye, or by transfer from the hands during
rubbing of the eyes, which was shown to occur in 37% of 124 adults every hour. This route of
exposure could result in ENM uptake through the cornea into the eye or drainage from the eye
socket into the nasal cavity through the nasolacrimal duct. Other than a study that found uptake
of a polymer ENM into conjuctival and corneal cells, this route has been largely ignored in
research studies of ENM exposure.
TEXT / REFERENCE BOOKS
1. Tai-Ran Hsu, MEMS & Microsystem, Design and manufacture, Mc. Graw Hill 2002.
2. Malsch, NeelinaH., ed., Biomedical Nanotechnology, Washington, DC: CRC Press, 2005
3. 3. Marc J. Madou, Fundamentals of Microfabrication and Nanotechnology, 3rd Edition,
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 Three-Volume Set,CRC Press 2011.
4. Mohamed Gad-el-Hak, The MEMS Handbook, CRC Press, 2005
5. HocineYahia, Shape Memory Implants Springer Verlag 2000.

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