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  • GBM5320GBM5320Dispositifs Mdicaux IntelligentsDispositifs Mdicaux Intelligents

    Sensors : IntroductionSensors : IntroductionMohamad Sawan, Professor

    Benoit Gosselin, and Louis-Francois Tanguay, Ph.D. CandidatesLaboratoire de neurotechnologies Polystim

    http://www.cours.polymtl.ca/gbm5320/[email protected]

    M5418

    9 February 2008

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    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

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    Microsensors?

    Microsensors are small devices that convert physicalor chemical signals to electrical signals. They enableobjects to interface to the real world;

    Implantable microsensors enables monitoringbiological parameters. They could allow real-timemeasurement of temperature, pressure, pH, oxygenand nitric oxide concentrations in vivo;

    They allow to help the medical research community inlearning about the progression of diseases and assessdegree of response to treatment;

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

    More functionality, better portability, and lower cost.

    Pressure sensor

    Gas sensorhttp://www.nist.gov/public_affairs/techbeat/tb2003_0910.htm

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    Definitions

    MicrosensorA microdevice that transforms a signal in measured/analyte format inan electrical signal.

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

    Indirect sensorSignal to be measured is first converted to some other variable that isthen 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.

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    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 inelectrical signal resulting from a small change in the physical signal tobe measured.

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

    Linearity: The maximum deviation from a linear transfer function overthe specified dynamic range.

    Accuracy: Generally defined as the largest expected error betweenactual and ideal output signals.

    Resolution: The resolution of a sensor is defined as the minimumdetectable signal fluctuation.

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    Sensor Performance Characteristics

    Hysteresis: Some sensors do not return to the same output valuewhen the input stimulus is cycled up or down. The width of theexpected error in terms of the measured quantity is defined as thehysteresis.

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

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

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    Microsensors: General architecture

    A generalized architecture of a microsensor system:

    Sensor/ActuatorArray

    Signal Conditioners(Analog + Digital)

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

    Drivers Comm.Interface

    Inputs

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    Strain sensors - ResistiveResistance is related to length and area of cross-section of theresistor and resistivity of the material as

    By differentiating both sides, the equation becomes

    DimensionalPiezoresistance

    Strain gage component can be related by poissons ratio (v) as

    LengthTransfer 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 orchest to measure force of musclecontraction or respiration, respectively

    Used in prosthesis or neonatal apneadetection, respectively.

    = dL/L

    Webster, Medical Instrumentation www.microstrain.com/

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    Piezoelectric Sensors

    What is piezoelectricity ?

    Strain causes a redistri-bution of charges andresults in a net electricdipole

    where q = charge, f = force

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

    Different transducerapplications:- Accelerometer,- Microphone.

    q = k f & V = q / C

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

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    Displacement Sensor - LVDT

    LVDT

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

    An LVDT (Linear Variable Differential Transformer) is used as asensitive displacement sensor: for example, in a cardiac assist deviceor a basic research project to study displacement produced by acontracting muscle.

    Signal ConditioningElectronics Muscle

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

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    Capacitance-based Sensors

    DifferentialMode

    Variable Dielectric ModeVariable Area Mode

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    Acceleration sensor

    Accelerometer fordisplacement monitoring- Surface micromachined,

    capacitive sensor- Sensor + Electronics on same

    substrate= smart

    Analog Devices ADXL-50

    C1 C2

    g

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    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 outsideof the animal at a frequency dependent upon the pressure in the eye.

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    15

    The value of capacitorchange with pressuredue to the deflectablediaphragm. Thisvariation change theresonant frequency ofthe LC circuit and ismeasured wirelessly.

    Pressure sensors

    Allen, GA Tech, 1999-2002.

    PTFE = PolytetrafluoroethyleneFEP = Fluorinated Ethylene Propylene

    Ceramic chamber

    Flexible Wireless Passive PressureSensors for Biomedical Applications.

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

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    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.htmlwww.memstouch.net/

    High sensitivity capacitivestrain sensor.

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    Temperature sensors

    Temperature sensors have become common elements in wide range ofmodern 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/

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    Thermistors

    Thermistors are made fromsemiconductor material

    Generally, they have a negativetemperature coefficient (NTC), that isNTC thermistors are most commonlyused

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

    Webster, Medical instrumentation

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    Thermocouples

    A conductor generates a voltage when subjected to a temperature gradient. Tomeasure this voltage, one must use a second conductor material whichgenerates a different voltage under the same temperature gradient. So,Thermocouples measure temperature differences and need a known referencetemperature to yield the absolute readings.

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

    Webster, Medical Instrumentationwww.efunda.com/.../images/thermocouple_A.gif

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    CMOS temperature sensor

    VBE 2 !VBE1 = "VBE (T)

    =kT

    qln

    pIE

    IS2

    #

    $ %

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    ' ( !

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    The voltage difference between the two diodes, operated at a differentcurrent density, is used to generate a Proportional To AbsoluteTemperature (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 theoutput is PTAT:

    VX!V

    Y

    VR1 =VY !VZ "VX !VZ

    VR1 =VEB1 !VEB 2 =kT

    qln

    A1

    A2

    #

    $ %

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    = I2

    =VR

    1

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    # $

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    pH Electrodes

    Glass electrodes develop a gel layerwith mobile hydrogen ions when dippedinto an aqueous solution;

    pH changes cause ion diffusionprocesses generating an electrodepotential. Lithium-rich glasses are wellsuited for this purpose;

    The potential is measured in comparisonto a reference electrode which is usuallyan Ag/AgCl system;

    The electric circuit is closed via adiaphragm separating the referenceelectrolyte from the solution.

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

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    Oxygen Partial Pressure (pO2) electrode

    A membrane through which oxygenmust diffuse separates the measuringsolution from the electrolyte

    Oxygen is reduced by electronscoming from the central platinumcathode which is surrounded by aglass insulator.

    This design, a so-called polaro-graphicelectrode, needs an external powersupply.

    For oxygen, the polarization voltage isin the order of 700 mV and the typicalcurrent for atmospheric pO2 is in theorder of 107 A.

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

    Clark-type oxygenpartial pressure (pO2)

    electrode

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    Carbon Dioxide Partial Pressure (pCO2) electrode

    CO2 diffuses through the membrane into or out of the electrolyte whereit equilibrates with HCO3 thus generating or consuming protons.

    The respective pH change of the electrolyte is sensed with a pHelectrode and is logarithmically proportional to the pCO2 in themeasuring solution.

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

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

    The construction of an ISFET differs from the conventional MOSFETdevices, in that the gate metal is omitted and replaced by amembrane sensitive to the ions of interest.

    ISFET/CHEMFET sensors

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

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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 PowerBiochemical Sensing , Sensors and Actuators B (Chemical), v107, 2005.

    pH-ISFET Macromodel

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    Classification of biosensors

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

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    Biosensors

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

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

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

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    Example : Glucose Sensors

    Enzymatic Approach

    Glu e O GluconicAcid H OGlu eOxidase

    coscos

    + ! "!!!!!! +2 2 2

    Makes use of catalytic (enzymatic)oxidation of glucose

    The setup contains an enzymeelectrode and an oxygen electrode andthe difference in the readings indicatesthe glucose level.

    The enzyme electrode has glucoseoxidase immobilized on a membrane ora gel matrix*.

    Platinumelectrode

    Plasticmembrane

    Glucose

    O2

    Gluconicacid

    Silveranode

    O2

    H2O2O2

    *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 SensorsAffinity Approach (Optical)

    This approach is based onthe immobilized competitivebinding of a particularmetabolite (glucose) and itsassociated fluorescent labelwith receptor sites specific tothe metabolite and thelabeled ligand. This changein light intensity is thenpicked up. 3 mm

    0.3 mm

    Hollow dialysis fiber

    Excitation

    Emission

    OpticalFiber

    Glucose

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

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