2.2.

2 Biomedical Sensors and Biosensorss

Many predict that the biomedical
tems after
the automotive
industry will be the next major user of microsyS
ne
industry. The term BioMEMS has been used extensively by
MEMS
industry and academe in recent years. It
encompasses (1) biosenSOrs,
Dioinstruments and surgery tools, and (3) systems for biotesting and analysis for
quick, accurate, and
low-cost testing of biological substances. BioMEMS
great challenge to presenta
engineers, as the design and manufacture of this type of sensor and
nstrument require the
knowledge and experience in molecular biology as well as
physical chemistry, in addition to
engineering.
Major technical issues involved in the application of MEMS in biomedicine are:
1.
Functionality for biomedical operations
2.
Adaptivity to existing instruments and
3.
Compatibility with biological systems ofequipment
patients
4.
Controllability, mobility, and easy navigation for operations such as those
required in a laparoscopy surgery
5. Fabrication of MEMS structures with a high aspect ratio, defined as the
ratio of the dimensions in the depth of the structure to the dimensions
the surface. of
Microsensors constitute the most fundamental element in any bioMEMS
uct. There are
generally two types of sensors used prod-
in biomedicine: (1) biomedical
sensors and (2) biosensors. Biomedical sensors are used to detect
stances, whereas biosensors may be biological sub-
contain a biological element broadly defined as any measuring devices that
[Buerk 1993]. These sensors usually involve
molecules such as antibodies or
enzymes, which interact with biological
detected. analytes that are to be

Biomedical Sensors Biomedical sensors can be classified as

struments that are used to measure biomediçal in-
nosis purposes. These sensors can
biological substances as well as for
medical diag-
analyze biological samples in quick and accurate
ways. These miniaturized biomedical sensors have
tional instruments. They require many advantages over the tradi-
form
typically minute amount of samples and can
a
analyses much faster with virtually no dead volume.
There are many
per-
types of biomedical sensors in the marketplace. different
Electrochemical sensors work on the principle that certain
such as glucose in human blood, can release certain elements biological substances,
These elements can alter the by chemical reaction.
electricity flow pattern in the sensor, which can be
read-
ily detected. An example of such a sensor is illustrated as
follows [Kovacs
In Figure 2.1, a small
sample of blood is introduced to a sensor with a 1998].
alcohol solution. Two electrodes are in the sensor: a platinum film
polyvinyl
and a thin Ag/AgCI film (the reference present electrode
electrode). The following chemical reaction
 and the oxygeni
t blood sample the
takes place
between the glucosein
inthe
polyvinyl
alcohol solution:

Glucose+Ogluconolactone + H,0,

electrolyzed by applvin
chemical
reaction 1s
a potential
The H.O,produced bythis production of positiv hydrogen ions
tive hydrogen ions, which wi
platinum
electrode, with
concentration in the b
low
to the The amount of glucose can
sard this electrode.
currentfflow between the electrodes.
measured by
measuring the
thus be
biomedical sensOr tor measuring glucose concentration
on.
Figure 2.1 TA

PRelectrode

Blood sampe
Polyvinyl alcohol solution

Ag/AgCl reference electrode

Biosensors Biosensors work on the principle of the interaction of the analytes that
need to be detected with biologically derived biomolecules, such as enzymes
tain forns, antibodies, and other forms of protein. These biomolecules, when attached
to the sensing elements, can alter the output signals of the sensors when they interact
with the analyte. Figure 2.2 illustrates how these sensors are made to function. Proper
selection of biomolecules for sensing elements (chemical, optical, etc., as indicated in
the right box in the figure) can be used for the detection of specific analyte. In-depth
description of biosensors is available in a specialized book by Buerk [1993]

Figure 2.21 Schematic of biosensors.

Analyte

Biomolecule (B
supply
Biomolecule layer
Chemical
Optical
Output
signal Sensor Thermal
Resonant
Electrochemical
ISFET (lon-sensitive
field-effect transducer)

Biotesting and
Analytical Systems These systems separate variou cies
n biological samples. Analytes include various biological substances and human
 MEMS and
Microsystems: Design and Manufacture

genomes. Operation of these

order of systems involves the passage of minute
nanoliters in capillary tubes or samples in the
namic means such as microchannels driven by
electro-OSmosis
volves the driving of an and
electrophoresis. electrohydrody
of fluid flow will be
ionized fluid by the
application
Electrohydrodynamics in-
of electric fields. This form
described in
capillary tubes or microchannels Chapter 3. Isolation and
are achieved separation of species in the
osmotic mobility of these by the inherent difference of electro-
after the species. Optical means are used
separation. Often, these minute to identify these species
microelectronic circuits for signal electrohydrodynamic systems are built with
transduction,
these capillary tubes can conditioning,
dreds and thousands of and processing. Hun-
be constructed on a
parallel testing. Microbioanalytical single chip for
systems typically
sample, yet they offer accurate and nearly instant results.require minute amounts of
A simple
analyte system used in biotesting and
trophoresis (CE) network, as illustrated in Figure 2.3.analysis uses a
capillary elec-
The system consists of two
capillary tubes of diameters in the order of 30 or
The shorter channel is connected um microchannels of similar sizes.
to the sample injection reservoir A and the analyte
waste reservoir
A whereas the
,
longer channel is connected to the buffer soivent
reservoirs B and B'. A
distinct electro-osmotic
biological sample consisting of species S1, S2, Sz, with .,
mobilities, is injected into reservoir A. Application of an
electric field between the terminals at
reservoir A and A' prompts the flow of the in-
jected samples fromA to A'. A congregation of the
of the two channels because of sample forms at the intersection
higher resistance to the flow at that location. A high-
voltage electric field is then switched to the terminals B and B.
This electric field can
drive the congregated sample in the buffer solvent to flow from reservoir B to B'. The
species in the sample can separate in this portion of the flow because of their inher-
ent differences in electro-osmotic
mobility.
Figure 2.3 1 Schematic diagram of a capillary electrophoresis system.
Analyte injection
reservoir, A
Sample with species:
S1, S2, Sg
Species: S1 Species: S3
Buffer solvent Buffer solvent
injection reservoir, B waste reservoir, B

Species: S2

Analyte waste
reservoir, A'

The above description is used to illustrate the working principle of capillary

electrophoresis analytical systems. There are obviously other forms of CE systems,
as well as other means of biotesting and analytic devices, as described in [Kovacs
1998).