Ch4 Capteurs - Polytechnique Montréal · 2/24/11 3 GBM8320 – Dispositifsmédicauxintelligents 7...

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February 2011

GBM8320 – Dispositifs médicaux intelligents 2

Biomedical microsensors : Course outline

•  Microsensors -  Overview -  Definitions

•  Microsensors types: -  Strain -  Pressure -  Displacement -  Temperature -  Gas (Electrode-based) -  Chemical sensors (ISFET, CHEMFET)

•  Biosensors •  Lab-on-chip technology


Microsensors?

•  Microsensors are small devices that convert physical or chemical signals to electrical signals. They enable objects to interface to the real world;

•  Implantable microsensors enables monitoring biological parameters. They could allow real-time measurement of temperature, pressure, pH, oxygen and nitric oxide concentrations in vivo;

•  They allow to help the medical research community in learning about the progression of diseases and assess degree of response to treatment;

•  More & better access to measurement sites - Do not perturb the system under test - Accurate measurements and less invasive - Less psychological trauma & feedback

•  More functionality, better portability, and lower cost.

Pressure sensor

Gas sensor http://www.nist.gov/public_affairs/techbeat/tb2003_0910.htm

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Sensors / microsensors: Definitions

• Microsensor A microdevice that transforms a signal in measured/analyte format in an electrical signal.

• Direct sensor Signal to be measured is directly transformed to electrical signal. Example: photo-conductor converts light to change of resistance.

•  Indirect sensor Signal to be measured is first converted to some other variable that is then converted to an electrical signal – Example: acceleration sensor converts acceleration to strain which is

then sensed. • Biosensor A microsensor dedicated for medical implantable and cellular devices.


Sensor Performance Characteristics

•  Transfer Function: The functional relationship between physical input signal and electrical output signal.

•  Sensitivity: The sensitivity is the ratio between a small change in electrical signal resulting from a small change in the physical signal to be measured.

• Dynamic Range: The range of input physical signals which may be converted to electrical signals by the sensor. Signals outside of this range are expected to cause unacceptably large inaccuracy.

•  Linearity: The maximum deviation from a linear transfer function over the specified dynamic range.

• Accuracy: Generally defined as the largest expected error between actual and ideal output signals.

• Resolution: The minimum detectable signal fluctuation.


Sensor Performance Characteristics

•  Hysteresis: Some sensors do not return to the same output value when the input stimulus is cycled up or down. The width of the expected error in terms of the measured quantity is defined as the hysteresis.

•  Noise: All sensors produce some output noise in addition to the output signal. The noise of the sensor limits the performance of the system based on the sensor. Noise is generally distributed across the frequency spectrum.

•  Bandwidth: All sensors have finite response times to an instantaneous change in physical signal. In addition, many sensors have decay times, which would represent the time after a step change in physical signal for the sensor output to decay to its original value. The reciprocal of these times correspond to the upper and lower cutoff frequencies, respectively. The bandwidth of a sensor is the frequency range between these two frequencies.

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Microsensors: General architecture

•  A generalized architecture of a microsensor system:

Sensor/Actuator Array

Signal Conditioners (Analog + Digital)‏

Embedded Controller (Calibrate-measure, process & compress, store & forward)

Drivers Comm. Interface

Inputs


Microsensors

•  Microsensors are often complete microsystems that include microelectronic circuits for A/D and D/A conversion, storage, communciation, etc.

Hierlemann et al., “Microfabrication techniques for..,” Proc. of the IEEE, V 91, 2003.

Example: Complete device




•  Microsensors types: -  Strain -  Piezoelectric -  Displacement (LVDT) -  Acceleration (capacitive) -  Pressure -  Temperature -  Gas (pH, O2, CO2, etc..) -  Chemical sensors (ISFET, CHEMFET)


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GBM8320 - Dispositifs Médicaux Intelligents 10

•  Blood flow/pressure

•  Impact, acceleration

•  Surgical forceps to measure force applied

• Airbag

•  Body temperature

Physical Quantity Sensor Variable

Fluidic Pressure Transducer Flow meter

Pressure Flow

Force Torque

Load cell Applied force Applied torque

Geometric Strain Gauge L. Variable Diff. Transformer (LVDT) Ultrasonic transit time

Strain Displacement Displacement

Kinematic Velocimeter Accelerometer

Velocity Acceleration

Thermal Thermometer Thermal flux sensor

Temperature Heat flux

Physical Variables and Sensors

GBM8320 - Dispositifs Médicaux Intelligents 11

Sensor Application Signal Range Liquid metal strain Guage Breathing movement 0-0.05

Magnetic displacement sensor Breathing movement 0-10 mm

LVDT Muscle contraction Uterine contraction sensor

0-20 mm 0-5 mm

Load cell Electronic scale 0-200 kg

Accelerometer Subject activity 0-20 m/s2

Miniature silicon pressure sensor Intra-arterial blood pressure Urinary bladder pressure Intrauterine pressure

0-350 mm Hg 0-70 mm Hg 0-100 mm Hg

Electromagnetic flow sensor Cardiac o/p (with integrator) Organ blood flow

0-500 ml/min 0-100 ml/min


Strain sensors - Resistive Resistance is related to length and area of cross-section of the resistor and resistivity of the material as

By differentiating both sides, the equation becomes

Dimensional Piezoresistance

Strain gage component can be related by Poisson’s ratio (v) as

Length Transfer Function : Input is strain, output is dR.

Webster, “Medical Instrumentation”

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Strain sensors - Resistive

Gage Factor of a strain gage

G is a measure of sensitivity

•  Put mercury strain gage around an arm or chest to measure force of muscle contraction or respiration, respectively

•  Used in prosthesis or neonatal apnea detection, respectively.

ε = dL/L

Webster, “Medical Instrumentation” www.microstrain.com/


Strain sensors - Resistive

•  Strain gages are generally mounted on cantilevers and diaphragms and measure the deflection of these.

•  More than one strain gage is generally used and the readout generally employs a bridge circuit.


Piezoelectric Sensors

What is piezoelectricity ?

•  Strain causes a redistri-bution of charges and results in a net electric dipole

where q = charge, f = force

k = 2.3 pC/N for quartz = 140 pC/N for Barium

•  Different transducer applications: - Accelerometer, - Microphone.

q = k f & V = q / C

www.ipodlinux.org/ group27imaging.com/RespiratorySensor.aspx

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Piezoelectric Sensors : principle and circuits •  When force is

applied in the L,W or t directions respectively, output voltages are given by these equations. 31 & 33 denote

the crystal axis.

Charge generator

q = Kx

Charge generator

is = Kdx/dt



Displacement Sensor - LVDT

LVDT

www.pages.drexel.edu/~pyo22/mem351-2004/lecture04/pp062-073lvdt.pdf

•  An LVDT (Linear Variable Differential Transformer) is used as a sensitive displacement sensor: for example, in a cardiac assist device or a basic research project to study displacement produced by a contracting muscle.

Signal Conditioning Electronics Muscle

•  Inductive displacement sensors: - Self inductance; - Mutual inductance; - Differential transformer.


Capacitance-based Sensors

Differential Mode

Variable Dielectric Mode Variable Area Mode

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Acceleration sensor

•  Accelerometer for displacement monitoring -  Surface micromachined,

capacitive sensor -  Sensor + Electronics on same

substrate= “smart”

Analog Devices’ ADXL-50

C1 C2

g


Pressure sensors

Collins “Miniature Passive Pressure Transensor for Implanting…“, 1967.

•  Miniature Passive Pressure Transensor for Implanting in the Eye •  Measurement of intraocular and other physiological pressures. •  Displacement transducer contained in a small distensible pillbox. This passive

resonant transensor absorbs energy from an oscillating detector coil outside of the animal at a frequency dependent upon the pressure in the eye.


21 •  Wireless

micromachined ceramic pressure sensors.

•  High temperature self packaged wireless ceramic pressure sensor.

Pressure sensors

Allen, GA Tech, 1999-2002.

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22

The value of capacitor change with pressure due to the deflectable diaphragm. This variation change the resonant frequency of the LC circuit and is measured wirelessly.

Pressure sensors

Allen, GA Tech, 1999-2002.

PTFE = Polytetrafluoroethylene FEP = Fluorinated Ethylene Propylene

Ceramic chamber

•  Flexible Wireless Passive Pressure Sensors for Biomedical Applications.

•  The sensor consists of a cavity, bounded on 2 sides by capacitor plates interconnected with inductance.


Pressure sensors

Rosengren, 1992

silicone disc for implantation into the eye. •  Biocompatible encapsulation in polydimethylsiloxane. Management and

other basic research for mechanisms of glaucoma.

•  This sensor is used for Abdominal Aorta Aneurysm (AAA): •  Permanently implanted, •  RF transmission, RF powered, •  Size of a paper clip, •  Biocompatible.

•  Completely encapsulated Intraocular Pressure (IOP) sensor equipped with telemetric signal and energy transfer integrated into a

www.cardiomems.com/


Micromachined pressure sensors •  Pressure Sensor

- Resistive / capacitive based measurements - Thin Silicon Membrane deforms with

pressure - Piezoresistors change with strain induced

by bending membrane - Packaging requires sealing to maintain

pressure differential.

www.dolphin.fr/flip/mems/mems_cps.html www.memstouch.net/

High sensitivity capacitive strain sensor.

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Temperature sensors

•  Temperature sensors have become common elements in wide range of modern integrated circuits

•  The main parameters of temperature sensors are: temperature range, sensitivity, output range, linearity, accuracy

•  Types of integrated temperature sensors: -  Resistance based : Thermistors, RTDs -  Thermocouples & CMOS PTAT references.

www.singleiteration.com/


Thermistors

•  Thermistors are made from semiconductor material

•  Generally, they have a negative temperature coefficient (NTC), that is NTC thermistors are most commonly used

•  Ro is the resistance at a reference point (in the limit, absolute 0), B is material constant, and T and T0 are absolute and reference temperatures.

Webster, Medical instrumentation


Thermocouples •  A conductor generates a voltage when subjected to a temperature gradient. To

measure this voltage, one must use a second conductor material which generates a different voltage under the same temperature gradient. So, Thermocouples measure temperature differences and need a known reference temperature to yield the absolute readings.

•  When a pair of dissimilar metals are joined at one end, and there is a temperature difference between the joined ends and the open ends, thermal electromotive force (emf) is generated, which can be measured in the open ends. There are three major effects involved : the Seebeck, Peltier, and Thomson.

Webster, Medical Instrumentation www.efunda.com/.../images/thermocouple_A.gif

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Thermocouples


The Seebeck, Peltier, and Thomson effects :

• Seebeck effect describes the voltage induced by the temperature gradient along the wire. The change in material EMF with temperature is called the Seebeck coefficient or thermoelectric sensitivity. This coefficient is usually a nonlinear function of temperature.

• Peltier effect describes the temperature difference generated by EMF and is the reverse of Seebeck effect.

• Thomson effect relates the reversible thermal gradient and EMF in a homogeneous conductor.

Peletier emf Homogeneous

Intermediate metal

Intermediate temperatures


CMOS temperature sensor

�

VEB1(T) = kTqln IE

IS

⎡

⎣ ⎢

⎤

⎦ ⎥

�

VEB 2(T) = kTqln pIE

IS

⎡

⎣ ⎢

⎤

⎦ ⎥

•  A bipolar transistor can be used as a temperature sensor by using its base-emitter voltage as a measure of temperature.

•  VBE is CTAT (Complementary To Absolute Temperature) at roughly -2.2 mV/°C at room temperature.

Pertijs et al, “Precision Temperature Measurement using …,” IEEE Sensors, v4, 2004.


CMOS temperature sensor

�

VBE 2 −VBE1 = ΔVBE (T)

= kTq

ln pIEIS2

⎡

⎣ ⎢

⎤

⎦ ⎥ −

kTq

ln IEIS1 /r⎡

⎣ ⎢

⎤

⎦ ⎥ =

kTq

ln p ⋅ r[ ]

•  The voltage difference between the two diodes, operated at a different current density, is used to generate a Proportional To Absolute Temperature (PTAT) current.

•  This voltage difference is PTAT with a temperature coefficient of +0.085 mV/°C at room temperature.

Pertijs et al, “Precision Temperature Measurement using …,” IEEE Sensors, v4, 2004.

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IPTAT = I5 =W5/W4*I2

CMOS temperature sensor : Complete PTAT circuit

The current mirrored at the output is PTAT:

�

VX ≈VY

�

VR1 =VY −VZ ≈VX −VZ

VR1 =VEB1 −VEB 2 = kTqln A1A2

⎡

⎣ ⎢

⎤

⎦ ⎥

�

IR1 = I2 =VR1

R1= 1R1

⋅ kTqln A1

A2

⎡

⎣ ⎢

⎤

⎦ ⎥


pH Electrodes

•  Glass electrodes develop a gel layer with mobile hydrogen ions when dipped into an aqueous solution;

•  pH changes cause ion diffusion processes generating an electrode potential. Lithium-rich glasses are well suited for this purpose;

•  The potential is measured in comparison to a reference electrode which is usually an Ag/AgCl system;

•  The electric circuit is closed via a diaphragm separating the reference electrolyte from the solution.

Sonnleitner, Bioanalysis and Biosensors for Bioprocess Monitoring, Springer, 1999.


Oxygen Partial Pressure (pO2) Electrode

•  A membrane through which oxygen must diffuse separates the measuring solution from the electrolyte

•  Oxygen is reduced by electrons coming from the central platinum cathode which is surrounded by a glass insulator.

•  This design, a so-called polaro-graphic electrode, needs an external power supply.

•  For oxygen, the polarization voltage is in the order of 700 mV and the typical current for atmospheric pO2 is in the order of 10–7 A.


Clark-type oxygen partial pressure (pO2)

electrode

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Carbon Dioxide Partial Pressure (pCO2) Electrode

•  CO2 diffuses through the membrane into or out of the electrolyte where it equilibrates with HCO3 – thus generating or consuming protons.

•  The respective pH change of the electrolyte is sensed with a pH electrode and is logarithmically proportional to the pCO2 in the measuring solution.



•  Ion-Sensitive Field Effect Transistors (ISFETS and CHEMFETs) are basically metal oxide semiconductor field-effect devices.

•  The construction of an ISFET differs from the conventional MOSFET devices, in that the gate metal is omitted and replaced by a membrane sensitive to the ions of interest.

ISFET/CHEMFET sensors

www.sentron.nl/nieuw/index.php?id=4 Shepherd, “Weak Inversion ISFETs Sensing …,” S&A B , v107, 2005.


pH ISFET

•  The ISFET is based on a MOSFET with a remote gate (reference electrode, G) exposing a chemically-sensitive insulator (G’) to an electrolyte.

•  Voltage applied to the reference electrode is capacitively-coupled via the electrolyte to the insulator surface, where a pH dependent charge from ions on this interface modulates the channel current, causing shifts in the ISFET ID-VGS characteristic.

www.dbanks.demon.co.uk/ueng/chemsens.html unit.aist.go.jp/.../SFD-project-isfet.htm

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pH ISFET equivalent model

The drain current for the weak inversion ISFET in saturation is given by:

Shepherd & Toumazou, “Weak Inversion ISFETs for Ultra-Low Power Biochemical Sensing …,” Sensors and Actuators B (Chemical), v107, 2005.

pH-ISFET Macromodel




•  Microsensors types: -  Strain -  Pressure -  Displacement -  Temperature -  Gas (Electrode-based) -  Chemical sensors (ISFET, CHEMFET)



Biosensing: Conceptual principle

•  A biosensor can be defined as a device that consists of a biological recognition system, often called a bioreceptor, and a transducer

•  A biochip consists of an array of individual biosensors that can be individually monitored and generally are used for the analysis of multiple analytes

•  The interaction of the analyte with the bioreceptor is designed to produce an effect measured by the transducer, which converts the information into a measurable effect, such as an electrical signal.

Ferrari et al, BioMEMS and Biomedical Nanotechnology: Vol IV: Biomolecular Sensing, Processing and Analysis, Springer, 2006.

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Classification of biosensors

Ferrari et al, BioMEMS and Biomedical Nanotechnology: Vol IV: Biomolecular Sensing, Processing and Analysis, Springer, 2006.


Biosensors

•  A bioreceptor is a biological molecular species (e.g., an antibody, an enzyme, a protein, or a nucleic acid) or a living biological system (e.g., cells, tissue, or whole organisms) that utilizes a biochemical mechanism for recognition.

•  The sampling component of a biosensor contains a bio-sensitive layer. The layer can either contain bioreceptors or be made of bioreceptors covalently attached to the transducer.

•  The most common forms of bioreceptors used in biosensing are based on: -  Antibody / Antigen interactions -  Nucleic acid interactions -  Enzymatic interactions -  Cellular interactions (i.e. microorganisms, proteins) -  Interactions using biomimetic materials (i.e., synthetic bioreceptors).


Example : Glucose Sensors

Enzymatic Approach

Glu e O GluconicAcid H OGlu eOxidasecos cos+ ⎯ →⎯⎯⎯⎯⎯⎯ +2 2 2

•  Makes use of catalytic (enzymatic) oxidation of glucose

•  The setup contains an enzyme electrode and an oxygen electrode and the difference in the readings indicates the glucose level.

•  The enzyme electrode has glucose oxidase immobilized on a membrane or a gel matrix*.

Platinum electrode

Plastic membrane

Glucose

O2

Gluconic acid

Silver anode

O2

H2O2 O2

*In the enzyme electrode, when glucose is present it combines with O2, so less O2 arrives to the cathode.

Webster, Medical Instrumentation

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Example : Glucose Sensors Affinity Approach (Optical)

•  This approach is based on the immobilized competitive binding of a particular metabolite (glucose) and its associated fluorescent label with receptor sites specific to the metabolite and the labeled ligand. This change in light intensity is then picked up. 3 mm

0.3 mm

Hollow dialysis fiber

Excitation

Emission

Optical Fiber

Glucose

Schultz et al, Affinity sensor : A new technique…, Diabetes Care, 1982.

•  Measure of glucose concentration by detecting changes in fluorescent light intensity caused by competitive binding of a fluorescein-labeled indicator.


•  Several other techniques and technologies are undertaken these days •  Electronic Noses •  Lab-on-chip based sensing devices.. - Optical (CMOS based imaging) - Capacitive (CBCM)

•  Miniaturized biosensors have yet to achieve their full potential. •  They must accomodate:

•  High noise levels in chemical composition of the field environment. •  Highly variable environmental conditions (temperature, humidity).

Current limitations of biosensors

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