BME804/BE8102 – Winter 2021

Design of BioMEMS

Dr. Virgilio (Vivo) Valente

ENG450 – [email protected]
BME804/BE8102 W2021
Lecture 7
Microsensors

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Contents
• Sensor definitions
• Sensor classification
• Sensor types
• Mechanical sensors
• Thermal sensors
• Electrochemical sensors
• Optical sensors
• CMOS sensors

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Sensor - Definitions
• A sensor is a transducer that converts a
measurand into a signal
• The measurand is a quantity, property,
effect, parameter, behavior.. Transducer Readout

• Signals carry information about the

properties of the measurand
• Different stimuli: acoustic, biological,
chemical, electrical, magnetic, optical,
mechanical, radiation, thermal

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Sensor System

Webster CRC Press

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Ideal Biomedical Sensor – Brainstorming

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Sensor Classification
Information from the environment is ‘translated’ to an electrical signal
Classification by:
 Measurand: Temperature, pressure, flow, displacement, chemical,
force, etc..
 Transduction mechanism: electrical, electrochemical, chemical,
physical
 Material: resistive, piezoelectric, magnetic, metamaterial etc
 Technology: MEMS, BioMEMS, CMOS,
 Application: Medical, industrial, scientific, consumer electronics,
automotive, aerospace etc
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Sensor Specifications
 Static  Impedance
 Transfer characteristic  Offset
 Linearity  Hysteresis
 Dynamic range  Noise (limit of detection)
 Efficiency
 Dynamic
 Response time
 Frequency response, bandwidth
 Drift

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Sensor Response – Transfer Characteristic

𝑺𝑺 = 𝒂𝒂 + 𝒃𝒃𝒃𝒃

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Sensor Specifications - Static

 Linearity: Deviation of the sensor curve from a straight line
 Resolution: Smallest change in the input that results in a change in
the output
 Sensitivity: Slope of the transfer curve (dy/dx)
 Selectivity: sensor response to target/sensor response to non-target
 Dynamic range: span of input that is measureable
 Noise (thermal): Smallest measurable input (limits of detection)
 Offset: Sensor output with no input

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Sensor Response - Dynamic

 Response delay, δ
 Time constant, τ
 Settling time (90%)
 Tolerance, ε
 Noise
 Drift (low-frequency
changes)

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SENSOR TYPE SENSING METHOD TYPICAL APPLICATIONS
 Thermomechanical  Thermometry
 Thermoresistive  Metabolism
Thermal
 Thermocouple  Biochemical reactions (thermal)
 Flow
 Conductometric  Biopotential monitoring
Electrical  Resistive  Temperature
 Potentiometric  Biosensing/Bacterial detection
 Amperometric  pH, O2
Electrochemical  Impedimetric (resistive/capacitive)  Tissue properties
 Ion-sensitive FETs  Dielectrics
 Absorption  Biosensing
Optical  Fluorescence  Imaging
 Chemiluminescence  Microscopy
 Piezoresistive  Biomarkers
 Piezoelectric  Biosensing/Bacterial detection
Mechanical  Capacitive (displacement)  Humidity
 Resonant  Pressure/force
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Thermal Sensors

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Thermal Sensor Types

Webster CRC Press

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Thermocouples, Thermopiles

isothermal

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Thermodiode and Thermotransistors

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MEMS-CMOS Thermal Flow Sensor

 Silicon resistors heat the fluid
 Diodes measure cooling effect of the fluid

De Luca TRANSDUCERS 2017

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Electrochemical Sensors

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Impedance Measurement
 Low complexity and low cost
 Compatible with standard instrumentation
 Label-free
 Measure electrical properties of the interface and medium (e.g. cells,
particles)
 Applications
 Capacitive sensing (cell fingerprinting)
 Impedance flow cytometry
 Cell growth

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Electrical Impedance Spectroscopy (EIS)

 Impedance at interface between metallic electrodes and electrolyte
 A small AC excitation voltage induces a frequency-dependent current
𝑉𝑉(𝜔𝜔)  Rs: Solution resistance
𝑍𝑍 𝜔𝜔 = = 𝑍𝑍𝑅𝑅𝑅𝑅 𝜔𝜔 + 𝑗𝑗𝑍𝑍𝐼𝐼𝐼𝐼 (𝜔𝜔)
𝐼𝐼(𝜔𝜔)  CDL: double-layer capacitance
 RCT: Charge-transfer resistance
Randles model Nyquist plot  ZW: Warburg impedance (diffusion)

 CDL not a real capacitor but

modeled as a constant-phase
element (CPE) with:
1
𝑍𝑍𝐶𝐶𝐶𝐶𝐶𝐶 = 𝑛𝑛
, 0 < 𝑛𝑛 < 1
𝐶𝐶 𝑗𝑗𝜔𝜔
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EIS Applications
 Cell culture studies
 Cell proliferation, morphology, migration,
differentiation, adhesion, size, type, activity, cytometry 𝑣𝑣𝑠𝑠

 Individual cell parameters can be

extracted at different frequencies
 Double-layer capacitance dominant
at low frequencies
 Monitor both attached cells and cells
in suspension

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Impedance Microsensors Valente ‘17

Interdigitated electrodes (IDE): Strong E at the surface
Substrate: Si, glass, ceramic, plastic, paper
Electrodes: Au, Pt, C
Protective layer: SU-8, PDMS, PMMA

Dropsens
Schormans and Valente ‘17

Jin Appl Sci 2020

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Impedance Measurement of Cells

 Cardiomyocyte contractility
 Drug discovery/dosage

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Impedance Measurement of Cells

 Microfluidic single-cell impedance flow cytometer

Chow JMS 2009

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Impedance Flow Cytometry

 Distinguish cells based on their ‘impedance profiles’ in a microfluidic channel
 Cell sorting
 Real-time analysis

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Implantable Impedance Sensor

 Gastroesophageal reflux disease (GERD)
 Wireless – no catheter

IDE

Ativanichayaphong MTT-S 2010

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Potentiostatic Sensors Oxidation Reduction

 Three-terminal electrochemical cells
 VWE-RE fixed by ctrl amp
 Ox/redox current between CE & WE
 Amplitude of current  Concentration analyte

Control
Amplifier
𝐈𝐈𝐒𝐒𝐒𝐒 = 𝐧𝐧 � 𝐅𝐅 � 𝐀𝐀 𝐞𝐞𝐞𝐞 � 𝐃𝐃 � 𝐂𝐂𝐢𝐢 /𝐝𝐝𝐝𝐝𝐝𝐝

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BioMEMS Potentiostat
 Cortisol detection for PoC diagnostics
 Cr/Au (20nm/150nm) electrodes on Si substrate

potentiostat PCB

Cruz BB 2014

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Optical Sensors

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Optical Sensors – Absorption Spectroscopy

• UV or visible light used in absorption spectroscopy
• Absorption spectra related to the concentration and structure of the analytes
• Biological samples absorb EM radiation at specific wavelengths
• Absorbance, A, depends linearly on concentration, C0.

Beer-Lambert law
• I0: Intensity of excitation source
𝐴𝐴 = − log10 (𝐼𝐼 ⁄𝐼𝐼0 ) • I: Measure light intensity
𝐴𝐴 = 𝜀𝜀𝐶𝐶0 𝑙𝑙 • 𝜀𝜀: molar absorption coefficient
• C0 : analyte concentration
• l: light pathlength

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Example in BioMEMS
 Pulse oximetry – Absorption
 O2Hb has higher absorption of IR light Red/IR modulation ratio
 HHb has higher absorption of red light

Chan RM 2013
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Optical Sensors - Chemiluminescence

 Chemiluminescence – generation of light (visible, UV, IR) by the
release of energy from a chemical reaction
 No excitation source
 Optical detection, e.g. CMOS image sensors, photomultiplier, CCD
camera

Ramon SPIE 2017

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Optical Sensors - Fluorescence

• Fluorophore is a chemical compound that emits light after light excitation
• Fluorophores used as markers (‘labels’) that bond to a molecule
• Excitation and emission cycle of fluorophores
• High sensitivity and high selectivity
• Specific excitation and emission spectra

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Additional Optical Sensors

Surface plasmon resonance sensors
 Incident light induces resonant waves at the
metal/dielectric interface (plasmons)
 Plasmons travel along the chip surface
 Frequency depends on the characteristics of
the interface

Waveguide-based sensors
 Confine the light within a
microfluidic channel
 Ease of implementation in lab-on-
chip/microfluidic devices
 E.g. fiber optics
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Implantable Oxygen Sensor

 Phosphorescence lifetime decay and is directly correlated with oxygen level
surrounding the sensor
Lumee by Profusa https://profusa.com

https://youtu.be/5P6SzzeUes8

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Mechanical Sensors

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Piezoresistive
 Strain is piezoelectric material causes change in resistance
 Piezoresistance depends on device geometry and material resistivity
 Temperature dependance

𝜌𝜌𝜌𝜌 ∆𝑅𝑅 ∆𝐿𝐿

𝑅𝑅 = = 𝐺𝐺𝐹𝐹 �
𝐴𝐴 𝑅𝑅 𝐿𝐿
 𝜌𝜌: Material resistivity
 A: Cross-sectional area
 L: length
 GF: Gauge factor
Algamili N Res Lett 2021
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Wheatstone Bridge

 ‘Bridge balance’ : V=0 when all

resistors have the same value
 Insensitive to temperature changes
 R1=R3
 R2 variable resistor used for balancing
 Strain changes RG which produces a
change in V RG

Algamili N Res Lett 2021

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Piezoelectric Pressure Sensor

scme-nm.org

https://youtu.be/juf4d3sgOJw
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Piezoelectric
• Strain is piezoelectric material causes change in voltage
• Transduction from mechanical to electrical signals and vice versa
• Charge vs Strain – Deformation proportional to electric field
• Can be used both as sensor or actuator

Direct effect Converse effect

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Piezoelectric Material
 Crystals
 Quartz
 Lithium niobate and tantalate
 Langasite
 Ceramics
 Lead zirconate titanate – PZT
 Others
 Zinc oxide (ZnO)
 Aluminum nitride (AlN)

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Micro Cantilevers
• Used in combination with both piezoresistive and piezoelectric sensors
• Particles sitting on the surface induce change in sensor resonant frequency
(dynamic) or deformation (static) - ‘Microscales’

Pujol-Vila FME 2020

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Micro Cantilevers - Resonant

• Cantilever driven at a resonance (vibration) by noise
or external excitation
• With particles on the surface, the resonant frequency
shifts
• High sensitivity – single cell
• Cell growth monitoring
• Quality factor highly dependent of surrounding
medium (e.g. viscosity)
• f : oscillation frequency ∝ size
1 𝑘𝑘 • k : cantilever spring constant
𝑓𝑓 − Δ𝑓𝑓 =
2𝜋𝜋 𝑚𝑚 + Δ𝑚𝑚 • m : effective mass
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Micro Cantilevers - Static

• Change in surface stress, ∆σ causes deflection, ∆z
• Sensitivity depends on material and size
• Stoney’s equation

 E : Young’s modulus
 t : Thickness
 L: Length
 υ: Poisson’s ratio
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Piezoelectric Sensor Micromachining

a) Si waver
b) Thermal oxidation
c) Pt deposition
d) PZT deposition
e) Au deposition
f) Stack etching
g) Front Si etching
h) Bulk Si etching
Tadigadapa Meas Sci Tech 2009
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CMOS Sensors

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CMOS Sensors – BioCMOS/Lab-on-CMOS

 Very high resolution
 Scalability (>100 sensors/electrodes)
 Integration with CMOS electronics
 Complex design and fabrication
 Expensive cleanroom facilities (>>$10M)
 Applications
 Cell culture studies
 Point-of-care
 Implantable devices
 Smart pills
 Smart catheters
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CMOS Sensors – Postprocessing (PP)

 CMOS chips postprocessed at
die or wafer level
 PP using ‘carrier’ wafers
 Usual PP for electrode/sensor
material and microchannel

Manickam Sensors 2021

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Capacitive Sensing
Reconstructed images dielectric
 Real-time cell imaging Electrode
256 x 256

Electrode

conductive

Laborde Nnano 2015

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CMOS Bioimaging
 EWoD digital microfluidic
 qPCR on CMOS
 Fluorescence detection

Norian LoC 2014

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CMOS Bioimaging Pixel

 16 mm2 chip
 7 x 8 array of EWoD electrodes
 Integrated temperature sensor, light sensor and heaters
 Parylene C as dielectric
 Teflon AF for hydrophobicity
 ITO cover

Norian LoC 2014 Post-processing

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Additional BioMEMS Sensor Families

• Microelectrodes & microelectrode arrays (MEAs)
• Nanopores
• Pressure sensors
• Flow sensors
• Ion-sensitive FETs (ISFETs)
• Biodegradable
• MEMS accelerometers, gyroscopes

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 Group Discussion
 If you were to incorporate sensors in your BioMEMS device,
what type would be most suitable for your application?
 If your design already incorporates sensors, can you think of
additional complementary sensors useful in your application?
 In either cases above, what would be a simple method to fabricate
these sensors within your device?
 What about the external equipment that would ne required to
operate the sensors?
Suggestion: you can include some of these discussion points in your group’s
report discussion/conclusion section

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