High Sensitivity Handheld Analog Readout Circuit for Microfluidic Based Electrical Impedance Sensing

High Sensitivity Handheld Analog Readout Circuit for Microfluidic Based Electrical Impedance Sensing

Presented by: Niloy TalukderRutgers, the State University of New JerseyAuthors:Niloy Talukder, Tuan Le, Pengfei Xie, Steve Orbine, Xinnan Cao, and Mehdi JavanmardIEEE Signal Processing in Medicine and Biology Symposium 2015112/10/2015

Flow CytometryUsed for cell characterizationCan be based on optical (gold standard), electrical detection etc.

2IEEE Signal Processing in Medicine and Biology Symposium 2015Optical DetectionElectrical Detectionexpensive fluorescent labeling of biological cellsbulky and costly optical instrumentationNo labeling neededCheaperLightweight portability

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IS involves measuring impedance of biological cells over a wide range of frequencies.Single cell detection capability suitable for disease diagnosis.Cytometer is scalable and can be integrated in PCB with CMOS compatible readout circuit.Ideal candidate for portable medical devices.

Challenge: detecting low SNR output signals from electrochemical sensors which is orders of magnitude smaller than noise level.3Impedance Spectroscopy Microfluidic CytometerIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

LIA: synchronous phase sensitive detectionnarrow BW around modulation frequency is selected and rest is filtered out.ref. freq shorts Cap coupling linear amplification Desired reference frequency (500 kHz 1 MHz)4Lock-In-Amplification (LIA) TechniqueIEEE Signal Processing in Medicine and Biology Symposium 2015Digital LIAAnalog LIAMulti freq operationHigh resolution DACComplex architecture costly and bulkyScalable low costNo high resolution DAC

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Fully analog architecture best solution for portable medical devicesRecent trend in the analog readout chip development:Double to single supply Voltage supply reduction (1.8V MayaHernandez et al.)Reducing chip area (0.013 mm2 MayaHernandez et al.)Reducing power consumption (207.7 W Jinlong Gu et al.)exploiting new architectures to improve performance (for example current mode multi freq LIA Jinlong Gu et al.)

5Previous Work on Designing Readout Circuit for IS CytometryIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

Novel LIA designObjective: micron size bead detection as single peak extend it to single cell detectionRestrictions in LIA design:DC offset at output hinders large amplificationAccurate phase matching between ref & data signal

In our design:DC blocking capacitor to remove dc offset since we are only interested in AC signal peakOutput only depends on input signal phaseAdjustable high gain stage (1.1Meg) amplifies peak amplitude to order of volts. Unique upward and downward peak signature.

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7Novel LIA Architecture

Figure 1: Modified LIA architecture for our applicationIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

8Analytical Noise Model

IEEE Signal Processing in Medicine and Biology Symposium 2015Figure 2: Analytical noise model12/10/2015

9Noise Simulation in LTSpice IV

Figure 3: Noise simulation resultIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

10Noise Measurement from Implemented Circuit Board

Figure 4: Noise measurement from circuitIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

Analytical and simulation result closely matches.

The discrepancy is attributed to:No flicker noise model in simulationRegulator and reference frequency generator circuit is not considered in simulationInterference noise (60 Hz) from environment

11Noise ComparisonSimulation ResultNoise measurement26.127 mV RMS73.47 mV RMS

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Device fabricated using standard photolithographyMicrofluidic channel is 300 m wide, 8 m high, and 1 cm longgold electrodes on a glass wafer are 10 m wide and 15 m apart from each other.PDMS exposed to oxygen plasma thin layer silanol (SiOH) termination bonding with glass wafer.Oxygen plasma treatment on PDMS changes surface properties from hydrophobic to hydrophilic bead flow12Biosensor Fabrication

Figure 5: Schematic of sensorIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015

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Printed Circuit board with SensorFigure 6: PCB with sensorIEEE Signal Processing in Medicine and Biology Symposium 201512/10/2015 Area:100 mm x 80 mm

Flow rate 0.08 l/min.Current coming out of sensor in order of 20 nATransit time between 0.13 to 0.15sec & peak freq 6 to 8 Hz.

14Result

IEEE Signal Processing in Medicine and Biology Symposium 2015Figure 7: Recorded output signal from the readout circuit12/10/2015

8 micron bead flow video12/10/2015IEEE Signal Processing in Medicine and Biology Symposium 201515

12/10/201516Result

IEEE Signal Processing in Medicine and Biology Symposium 2015

DC blocking cap removes baseline drift but adds small -ve overshoot two high gain stages amplify ve overshoot significantly

17ResultIEEE Signal Processing in Medicine and Biology Symposium 2015

Figure 8: Simulation result to justify nature of peak12/10/2015

BeadSignal to Noise Ratio (SNR)Percentage of Bead Volume with Respect to Active Sensing Channel VolumeRawProcessed8 micron401840.55%

18SummaryIEEE Signal Processing in Medicine and Biology Symposium 2015Future work:fully integrated CMOS solution improving the detection limit reducing the overall size and power consumption providing wireless connectivity12/10/2015

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I will be glad to answer any of your questions.

Please email me @niloy.talukder@rutgers.edu for further inquiries.