Laboratory-on-chip based sensors Part 2: Capacitive measurements

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1 GBM8320 Dispositifs Médicaux Intelligents Laboratory-on-chip based sensors Part 2: Capacitive measurements Mohamad Sawan et al. Laboratoire de neurotechnologies Polystim!!! M February 2012

2 Laboratory-on-Chip : Outline I. Introduction II. Biochemistry III. Microfluidic Packaging IV. Capacitive Sensors V. Cells Manipulation and Detection. GBM Dispositifs Médicaux Intelligents 2

3 Laboratory-on-Chip : Capacitive sensors GBM Dispositifs Médicaux Intelligents 3

4 Laboratory-on-Chip : Capacitor sensors Capacitive sensors for LoC applications do not require determining a single value of the sensing capacitance, but to distinguish between the device behavior in the presence rather than in the absence of analyte in microfluidic channel. 3D Accelerometer Low complexity Array of capacitive sensors Offset cancellation Sandia National Laboratories, SUMMiT TM Technologyies Capacitive sensor LOC E.coli Bacteria Ghafar-Zadeh & Sawan, IEEE-IMST3W 2008 GBM Dispositifs Médicaux Intelligents 4

LoC : Charge-Based Capacitive Measurement Interconnect or sensing capacitance can be retrieved/measured from the following equation: (I S I R ) = f V dd ΔC where Originated ΔC = Cs - C0, and C0 = CR

5 LoC : Charge-Based Capacitive Measurement Interconnect or sensing capacitance can be retrieved/measured from the following equation: (I S I R ) = f V dd ΔC where Originated ΔC = Cs - C0, and C0 = CR Year 1997 UC Berkeley ΔC IR CR M3 B M4 Vdd CBCM F1 M1 A F2 M2 Gnd Is CS External tools Main application DC Ammeter Capacitance characterization F1 F2 Resolution Sub femtofarad Frequency <15 MHz GBM Dispositifs Médicaux Intelligents 5

6 LoC : CBCM-based capacitive sensor Current mirror and integrating capacitor instead of dc Ammeter. ( Vdd VTP ) CS VS = ( Vdd VTP ) dv K ( V V ) t + C S 2 CS = K x ( Vgs VTP ) Vdd-Vs=Vgs 2 dt [( Vdd VTP ) CS ] K x AI 1 I( CS, t) 2 F1, F2 Low K ( V V ) t + C F1 F2 V d d A I S M 1 C A M 2 F1 F2 M 1 V d d M 3 M 4 Vs Cs M 2 x dd TP S [ ] x dd TP S Is I(Cs,t) Is Vout Cin Cin Ghafar-zadeh, Sawan, IEEE TBioCAS, 2007 GBM Dispositifs Médicaux Intelligents 6

V out = A I Cs C in (V dd V TP ) + V off I 0 F1 M 1 M 2 V d d A I S C F1 F2 Is/AI Vout Reset mode Charging mode Sampling Voff = f(mismatch in process,

7 LoC : CBCM-based capacitive sensor C in dv dt out = I S dv S s CS = dt A I Δ C + C V = A ( V V ) + V 0 out I dd TP Cin F2 Cancellation of C0 (C0 >> ΔC ) Accurate reference current IR is needed. V out = A I Cs C in (V dd V TP ) + V off I 0 F1 M 1 M 2 V d d A I S C F1 F2 Is/AI Vout Reset mode Charging mode Sampling Voff = f(mismatch in process, remnant in channel), Voff does not affect the accuracy, but large Voff may limit the dynamic range, then Voff should be minimized. ΔC << Cp, the effect of Cp is almost cancelled by measuring CS-CR before converting to voltage. IR Is Vout GBM Dispositifs Médicaux Intelligents 7

LoC : CBCM-based capacitive sensor Vdd M3 M5 1.5 ΔC=3fF 1.3 CBCM* F1 M1 ID1 Vout Vout (V) 1.

8 LoC : CBCM-based capacitive sensor Vdd M3 M5 1.5 ΔC=3fF 1.3 CBCM* F1 M1 ID1 Vout Vout (V) m ΔC=2fF ΔC=1fF F2 M13 Gnd CS Cint Is M10 Ck5 700m 500m ΔC=0 300m µ 200µ 300µ 400µ Time (s) Gnd GBM Dispositifs Médicaux Intelligents 8

ID1 F1 M F2 M Vb1 7 CS Gnd Vout Is M1 13 F1 M5 M3 CBCM* Dichloromethane Injection

9 LoC : CBCM-based capacitive sensor In agreement with the calculation and simulation; Higher dielectric constant of organic solvent, higher output voltage. ID1 F1 M F2 M Vb1 7 CS Gnd Vout Is M1 13 F1 M5 M3 CBCM* Dichloromethane Injection Methanol Injection Vout Is-IR IR F2 Vout Cint Gnd M10 Gnd GBM Dispositifs Médicaux Intelligents 9

10 Laboratory-on-Chip : Outline Large interdigitated electrode CBCM structure. Sensing electrodes Microchannel F1 Vdd M1 Φ2 Outlet M2 Φ1 M1 A Φ1 Inlet Vdd F2 M2 Interdigitated electrode CBCM Process Φ µm CMOS Gnd Sensing electrode µm² Vdd 1.8 Volt Frequency (f) CBCM E1 Cp1 Cs 100Hz-1MHz E2 E2 Cs/2 Cp1 Cp1 Analyte Passivation layers E1 Cp1 Cs/2 Cp1 E2 Cp2 CM-S CBCM Cp2 CM-s Cp2 Ghafar-Zadeh, E., Sawan, M., IEEE TBioCAS, 2007 GBM Dispositifs Médicaux Intelligents 10

11 LoC : CBCM-based capacitive sensor Microscopic images of chip. Interdigitated electrodes Passivation layer removal Reference and sensing electrodes. Ghafar-Zadeh et al, Sensors and Actuators A: Physical, 2008 GBM Dispositifs Médicaux Intelligents 11

LoC : CBCM-based capacitive sensor C (pf) Sensing capacitances values for different analytes; Parasitic capacitances of different chip samples; Average of recorded samples from 3 electrodes. 0.8 0.

12 LoC : CBCM-based capacitive sensor C (pf) Sensing capacitances values for different analytes; Parasitic capacitances of different chip samples; Average of recorded samples from 3 electrodes C0 (pf) Dichloromethane (D) 10.8 Acetone (A) 20.0 Methanol (M) 32.0 Deionised water (W) 80.8 Saline water (S) conductive Dielectric constant Measured chips The recorded data for a particular organic solvent shows a decoded output of a 6-bit resolution. GBM Dispositifs Médicaux Intelligents 12

500 W5 W6 W7 W8 CR M8 F2 M6 CS Cint 300 100 0% change in Wi Reset mode Vout Sampled

13 LoC : CBCM : Linearity & mismatch error Mismatch only affects an offset voltage M7 M4 M2 M % change of 1100 W1 W2 W3 W4 IR Vb1 IR M3 F1 M1 IS Vout Vb1 Vout (mv) W5 W6 W7 W8 CR M8 F2 M6 CS Cint % change in Wi Reset mode Vout Sampled voltage Cs (ff) GBM Dispositifs Médicaux Intelligents 13

14 LoC : CBCM-based capacitive sensor Cancellation of Vos Vdd Rp through Rp; A replica of sensing circuit is employed to generate reference current. M8 IR CR M10 M7 ID2 M2 M4 SR F2 Gnd Cin M1 M5 Cs M3 IS - IR ID1 M6 IS M9 FPGA F1 F2 Vo Gnd GBM Dispositifs Médicaux Intelligents 14

15 Laboratory-on-Chip : Outline Non-linearity of output voltage versus Rp1 and Rp2. Rp1 Rp2 1.2 Vdd Vo (V) 1.1 Rp2 M8 M7 M2 1.0 CR B M4 0.9 IR Rp1/2 (kohms) M10 M9 GBM Dispositifs Médicaux Intelligents 15

16 Laboratory-on-Chip : Outline Adjustable current mirror gain (D1-Dm) Three stages unity current mirror. M13 M 1 3 V d d B A I s S 1 A CBCM IR Q2 Q1 CBCM V a V b C M 10 M 9 M 8 V c M 14 I M 5 V o u t B M c m M c 1 M 15 S W 1 M 6 D m D 1 M 7 C GBM Dispositifs Médicaux Intelligents 16

17 Laboratory-on-Chip : Outline Adjustable current mirror gain (D1-Dm) 1-bit DAC Calibration circuit Vdd MDAC MCM MC1 M6 M4 M3 M5 SDAC SCM SC1 qn Dm D1 IDAC IR Vb1 M8 Vb2 M10 CR IR M2 M14 CBCM Ck1 Ck2 Gnd M1 M13 ID1 Is M7 CS Vb2 M9 Cint M11 Vb1 Vout Is-IR Ck3 M12 Gnd I R = I R0 (1 + 2 m-1 D C m-k D Ck + + D CM ). M10 GBM Dispositifs Médicaux Intelligents 17

18 Laboratory-on-Chip : Outline By adding a voltage comparator and a switch in series with a current source, a DC input sigma delta can be realized. x n I x + LPF q n Vout V R 1-bit DAC I s Xn q n = I x x Sw1 I x - + V R I(Cs, t) V o C i n Sw2 F 1 F n Q 1 Q 2 Ghafar-zadeh & Sawan, J. of IEEE Sensors, no.4, 2008 GBM Dispositifs Médicaux Intelligents 18

19 Laboratory-on-Chip : Sigma-Delta ADC Xn Post-layout simulation results Unique sequence. I x Sw1 - + V R I(Cs, t) V o C i n Sw2 Vout (output pulse) Q 1 Q C = 0.3 ff (V) C = 0.22 ff Time (msec) GBM Dispositifs Médicaux Intelligents 19

20 Laboratory-on-Chip : Outline An array of capacitive sensors. O f f - c h i p F P G A S y s t e m CS1 CS2 CS3 Adjustable reference current. Sigma-Delta DC A/D converter Offset cancellation procedure ( FPGA). Stop calibration & recording D1-m N o F 1 F 2 S1 S2 S3 U < V t h D 1 - m = D 1 - m + 1 Y e s ADC Reset UIC1 S 1 V o u t B u f f e r UIC2 S 2 I s Cin CR UIC3 S 3 I R Ajustable Current Mirror D 1-8 f s VR On-chip circuit GBM Dispositifs Médicaux Intelligents 20

21 Laboratory-on-Chip : Measurement set-up GBM Dispositifs Médicaux Intelligents 21

22 Laboratory-on-Chip : Outline ( I I ) = f V ΔC S R dd log( I I ) = log f + log( V ΔC) 2 1 dd ΔC where Cs=ΔC+C0 Extraction of sensing capacitance variation 10 Log (I2-I1) Dichloromethane Acetone Methanol DI water ( C0: Parasitic capacitance) D C B A 1E1 1E2 1E3 f(hz) 1E4 1E5 1E6 GBM Dispositifs Médicaux Intelligents 22

23 Laboratory-on-Chip : Outline Microscopic image of fabricated chip (a) Die including the electrodes and sigma delta sensor, (b) Interdigitated electrode. Ghafar-Zadeh et al, Sensors and Actuators A: Physical, 2008 GBM Dispositifs Médicaux Intelligents 23

24 Laboratory-on-Chip : Bacteria growth monitoring GBM Dispositifs Médicaux Intelligents 24

25 Laboratory-on-Chip : Outline Illustration of the proposed system for Bacteria-on- Chip monitoring: LB : medium for bacteria Bacteria settles on the surface of chip which results in a capacitive element. GBM Dispositifs Médicaux Intelligents 25

26 Laboratory-on-Chip : Bacteria growth monitoring Output of sensor versus parameters V C = 1 T = 2t t T RBC1 RL CB (C Vdd VTP e e AI ( C 0 in RB RL (C / 2 1 / 2) )dt /2) T >> 0 1 B 1 (V dd VTP ) AI + Cin C C + V Instead of Impedance measurement with R, we measure here only Cs. V OS OS GBM Dispositifs Médicaux Intelligents 26

27 Laboratory-on-Chip : Bacteria growth monitoring GBM Dispositifs Médicaux Intelligents 27

28 Laboratory-on-Chip : Magnetic manipulation Carbon array of electrodes used to push the bacteria toward the sensing electrode for measurement. GBM Dispositifs Médicaux Intelligents 28

29 Laboratory-on-Chip : Cells Detection/manipulation LoC Intracortical neural Control Data acquisition Implantable devices Neurotransmitter detection & separation High sensitivity / selectivity Target diseases: Epilepsy Alzheimer Parkinson GBM Dispositifs Médicaux Intelligents 29

Laboratory-on-Chip : Cells Detection/manipulation Actuation

capacitive sensor * DEP force CMOS chip ** (0.

Actuation module: Frequency / Magnitude control CMOS chip

18µm) Acquisition module: CBCM technique * Technology:

30 Laboratory-on-Chip : Cells Detection/manipulation Actuation electrode matrix Quadrature signals Sensing electrodes: capacitive sensor * DEP force CMOS chip ** (0.18µm) Output signal referring to liquid concentration Actuation module: Frequency / Magnitude control CMOS chip ** (0.18µm) Acquisition module: CBCM technique * Technology: Mixed CMOS-Microfluidic ** The same CMOS chip include both the acquisition and actuation module. GBM Dispositifs Médicaux Intelligents 30

31 Laboratory-on-Chip : References 1. A. Romani et al Capacitive sensor array for localization of bioparticles in CMOS lab-on-achip, Digest of Technical Papers, IEEE ISSCC Conf., 2004, pp D. Sylvester et al, Investigation of interconnect capacitance characterization using CBCM technique and three-dimensional simulation, IEEE JSSC, Vol. 33, no. 3, C. Guiducci, C. Stagni, G. Zuccheri, "DNA detection by integrable electronics," J.. Biosensors and Bioelectronics, vol. 19, no. 9, A. Hierlemann, Integrated Chemical Microsensor Systems in CMOS Technology, New York: Springer-Verlag, E. Ghafar-Zadeh, M. Sawan and D. Therriault, Novel direct-write CMOS-based laboratoryon-chip: Design, assembly and experimental results, Sensors and Actuators A: Physical, Volume 134, Issue 1, 28 February 2007, Pages E. Ghafar-Zadeh, M. Sawan, A Core-CBCM Sigma Delta Capacitive Sensor Array Dedicated to Lab-on-Chip Applications, In press in Sensors & Actuators: A. Physical 7. E. Ghafar-Zadeh, M. Sawan and D. Therriault, A Microfluidic Packaging Technique for Labon-Chip Applications, In press IEEE Trans. on Advanced Packaging. 8. E. Ghafar-Zadeh, M. Sawan, Charge-Based Capacitive Sensor Array for CMOS-Based Laboratory-On-Chip Applications, IEEE Sensors, Vol. 8, No. 4, April 2008, pp E. Ghafar-Zadeh, M. Sawan, A Hybrid Microfluidic/CMOS Capacitive Sensor Dedicated to Lab-on-Chip Applications, IEEE TBioCAS, Vol. 1, No. 4, December 2007, pp GBM Dispositifs Médicaux Intelligents 31

32 Quizz 1. Capacitive sensor is optimized to: a. Mesure a single value of the capacitance b. Mesure a capacitance change c. Mesure liquid concentration d. Mesure liquid concentration change GBM Dispositifs Médicaux Intelligents 32

33 Quizz 1. Capacitive sensor is optimized to: a. Mesure a single value of the capacitance b. Mesure a capacitance change c. Mesure liquid concentration d. Mesure liquid concentration change GBM Dispositifs Médicaux Intelligents 33

34 Quiz 2. CBCM measures: a. Capacitance change b. Current change c. Voltage change d. Resistance change GBM Dispositifs Médicaux Intelligents 34

35 Quiz 2. CBCM measures: a. Capacitance change b. Current change c. Voltage change d. Resistance change GBM Dispositifs Médicaux Intelligents 35

36 Quiz 3. When you design interdigitited electrodes on the top of a CMOS chip: a. You have to remove the passivation layer b. You have to add an isolation layer c. You have to add Poly layer d. (a,b and c) GBM Dispositifs Médicaux Intelligents 36

37 Quiz 3. When you design interdigitited electrodes on the top of a CMOS chip: a. You have to remove the passivation layer b. You have to add an isolation layer c. You have to add Poly layer d. (a,b and c) GBM Dispositifs Médicaux Intelligents 37

38 Quiz 4. LoC contains a. Only microfluidic chip b. Only Microelectronic chip c. Only MEMS device d. (a,b and c ) GBM Dispositifs Médicaux Intelligents 38

39 Quiz 4. LoC contains a. Only microfluidic chip b. Only Microelectronic chip c. Only MEMS device d. (a,b and c ) GBM Dispositifs Médicaux Intelligents 39

I. Introduction II. Biochemistry III. Microfluidic Packaging IV. Capacitive Sensors V. Cells Manipulation and Detection.

March 2011 Laboratory-on-hip : Outline I. Introduction II. Biochemistry III. Microfluidic Packaging IV. apacitive Sensors V. ells Manipulation and Detection. GBM8320 - Dispositifs Médicaux Intelligents