I. Introduction II. Biochemistry III. Microfluidic Packaging IV. Capacitive Sensors V. Cells Manipulation and Detection.
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1 March 2011 Laboratory-on-hip : Outline I. Introduction II. Biochemistry III. Microfluidic Packaging IV. apacitive Sensors V. ells Manipulation and Detection. GBM Dispositifs Médicaux Intelligents 2 Laboratory-on-hip : apacitive sensors GBM Dispositifs Médicaux Intelligents 3 1
2 Laboratory-on-hip : apacitor sensors apacitive sensors for Lo 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 ccelerometer Low complexity rray of capacitive sensors Offset cancellation Sandia National Laboratories, SUMMiT TM Technologyies apacitive sensor LO E.coli Bacteria Ghafar-Zadeh & Sawan, IEEE-IMST3W 2008 GBM Dispositifs Médicaux Intelligents 4 Lo : harge-based apacitive Measurement Interconnect or sensing capacitance can be retrieved/measured from the following equation: (I S! I R ) = f "V dd " # where Originated = s - 0, and 0 = R U Berkeley Year 1997 External tools Main application Resolution Frequency! D mmeter apacitance characterization Sub femtofarad <15 MHz! R M3 BM M1 Is B S M4 M2 GBM Dispositifs Médicaux Intelligents 5 Lo : BM-based capacitive sensor urrent mirror and integrating capacitor instead of dc mmeter. (! VTP ) S VS = (! VTP )! dv K x (! VTP ) t + S S 2 S = K x!( Vgs " VTP ) -Vs=Vgs 2 dt [(! VTP ) S ] K x I 1 I( S, t) " 2,! Low [ K x (! VTP ) t + S ] V d d V d d Is M 3 M 4 I(s,t) I S Is M 1 M 1 Vs in in s M 2 M 2 Ghafar-zadeh, Sawan, IEEE TBioS, 2007 GBM Dispositifs Médicaux Intelligents 6 2
3 Lo : BM-based capacitive sensor in d dt = I S dv S dt s = S I! + 0 = I " ( # VTP ) + V0 in ancellation of 0 (0 >>! ) ccurate reference current is needed. V out = I! s (V dd " V TP ) + V off in 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.! << p, the effect of p is almost cancelled by measuring S-R before converting to voltage. I M 1 M 2 V d d I S Is/I Reset mode harging mode Sampling Is GBM Dispositifs Médicaux Intelligents 7 Lo : BM-based capacitive sensor M3!! M5! 1.5!=3fF BM*! ID1!!! M1! S! M13!! Is! k5! int!! M10!! (V) 1.3!=2fF m!=1fF 700m!=0 500m 300m µ 200µ 300µ 400µ Time (s) GBM Dispositifs Médicaux Intelligents 8 Lo : BM-based capacitive sensor In agreement with the calculation and simulation; Higher dielectric constant of organic solvent, higher output voltage. M3! M5! Dichloromethane Injection!!! BM*! M1!!! M13!! ID1!! S!! Is! M7! Vb1!! int!! Is-! M10! Methanol Injection!!! GBM Dispositifs Médicaux Intelligents 9 3
4 M2 M1 Laboratory-on-hip : Outline Large interdigitated electrode BM structure. Sensing electrodes Microchannel M1!2 Process Outlet!1 Inlet!1!2 0.18!m MOS M2 Interdigitated electrode BM Sensing electrode 100"750 µm# Frequency (f) BM 1.8 Volt 100Hz-1MHz p1 s E1 E2 s/2 E2 p1 nalyte Passivation layers p1 E1 p1 s/2 p1 E2 p2 M-S BM p2 M-s p2 Ghafar-Zadeh, E., Sawan, M., IEEE TBioS, 2007 GBM Dispositifs Médicaux Intelligents 10 Lo : BM-based capacitive sensor Microscopic images of chip. Interdigitated electrodes Passivation layer removal Reference and sensing electrodes. Ghafar-Zadeh et al, Sensors and ctuators : Physical, 2008 GBM Dispositifs Médicaux Intelligents 11 Sensing capacitances values for different analytes; Parasitic capacitances of different chip samples; verage of recorded samples from 3 electrodes. $ (pf) Lo : BM-based capacitive sensor Dielectric constant 0 (pf) Measured chips Dichloromethane (D) 10.8 cetone () 20.0 Methanol (M) 32.0 Deionised water (W) 80.8 Saline water (S) conductive The recorded data for a particular organic solvent shows a decoded output of a 6-bit resolution. GBM Dispositifs Médicaux Intelligents 12 4
5 Lo : BM : Linearity & mismatch error Mismatch only affects an offset voltage M7 M4 M2 M5 IS M3 M1 Vb1 Vb1 M6 R M8 S int % change of 1100 W1 W2 W3 W4 (mv) 900 W5 W6 W7 W % change in Wi Reset mode Sampled voltage s (ff) GBM Dispositifs Médicaux Intelligents 13 Lo : BM-based capacitive sensor ancellation of Vos through Rp; replica of sensing circuit is employed to generate reference current. M8 R M7 M5 M6 M1 ID2 ID1 IS M2 s M4 M3 SR IS - in M10 M9 Rp FPG Vo GBM Dispositifs Médicaux Intelligents 14 Laboratory-on-hip : Outline Non-linearity of output voltage versus Rp1 and Rp Rp1 Rp2 Vo (V) 1.1 Rp2 M8 M7 M2 1.0 R B M Rp1/2 (kohms) M10 M9 GBM Dispositifs Médicaux Intelligents 15 5
6 Laboratory-on-hip : Outline djustable current mirror gain (D1-Dm) Three stages unity current mirror. M13 BM Q2 Q1 M 1 3 BM V d d B V a V b I s S 1 V c M 14 I M 5 V o u t B M 10 M c m M c 1 M 15 S W 1 M 6 M 9 D m D 1 M 8 M 7 GBM Dispositifs Médicaux Intelligents 16 Laboratory-on-hip : Outline djustable current mirror gain (D1-Dm) 1-bit D alibration circuit MD MM M1 M6 M4 M3 M5 SD SM S1 qn Dm D1 ID Vb1 M8 Vb2 M10 R ID1 Is BM M7 M2 M1 k1 Vb1 M13 M14 S k2 Vb2 M9 int M11 Is- k3 M12 I R = I R0 (1 + 2 m-1 D m-k D k + + D M ). M10 GBM Dispositifs Médicaux Intelligents 17 Laboratory-on-hip : Outline By adding a voltage comparator and a switch in series with a current source, a D input sigma delta can be realized. V R x n + LPF q n I x 1-bit D I s Xn q n = x I x Sw1 I x - + V R I(s, t) V o 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 6
7 Laboratory-on-hip : Sigma-Delta D Xn Post-layout simulation results Unique sequence. Sw1 I x - + V R I(s, t) V o i n Sw2 (output pulse) Q 1 Q 2 (V) $ = 0.22 ff 0 $ = 0.3 ff Time (msec) GBM Dispositifs Médicaux Intelligents 19 Laboratory-on-hip : Outline n array of capacitive sensors. djustable reference current. Sigma-Delta D /D converter Offset cancellation procedure ( FPG). O f f - c h i p F P G S y s t e m F 1 F 2 Stop calibration & recording D1-m S1 S2 S3 N o Reset U < V t h D 1 - m = D 1 - m + 1 Y e s D f s S1 V o u t UI1 S 1 B u f f e r VR S2 I s in R UI2 S 2 S3 UI3 S 3 I R justable urrent Mirror D 1-8 On-chip circuit GBM Dispositifs Médicaux Intelligents 20 Laboratory-on-hip : Measurement set-up GBM Dispositifs Médicaux Intelligents 21 7
8 Laboratory-on-hip : Outline ( I! I ) = f " V " # S R dd log( I! I ) = log f + log( V "# ) 2 1 dd % where s=%+0 Extraction of sensing capacitance variation 10 Log (I2-I1) Dichloromethane cetone Methanol DI water ( 0: Parasitic capacitance) -110 D -120 B E1 1E2 1E3 f(hz) 1E4 1E5 1E6 GBM Dispositifs Médicaux Intelligents 22 Laboratory-on-hip : Outline Microscopic image of fabricated chip (a) Die including the electrodes and sigma delta sensor, (b) Interdigitated electrode. Ghafar-Zadeh et al, Sensors and ctuators : Physical, 2008 GBM Dispositifs Médicaux Intelligents 23 Laboratory-on-hip : Bacteria growth monitoring GBM Dispositifs Médicaux Intelligents 24 8
9 Laboratory-on-hip : Outline Illustration of the proposed system for Bacteria-on- hip monitoring: LB : medium for bacteria Bacteria settles on the surface of chip which results in a capacitive element. GBM Dispositifs Médicaux Intelligents 25 Laboratory-on-hip : Bacteria growth monitoring 1 V = T Output of sensor versus parameters! 2t! t T RB1 RL B (1 / 2)! VTP e e # " I "(! 0 in RB RL = )dt T >> 0 ( / 2! /2) 1 B 1 (V dd! VTP )" I " + in + V Instead of Impedance measurement with R, we measure here only s. V OS OS GBM Dispositifs Médicaux Intelligents 26 Laboratory-on-hip : Bacteria growth monitoring GBM Dispositifs Médicaux Intelligents 27 9
10 Laboratory-on-hip : Magnetic manipulation arbon array of electrodes used to push the bacteria toward the sensing electrode for measurement. GBM Dispositifs Médicaux Intelligents 28 Laboratory-on-hip : ells Detection/manipulation Lo Implantable devices Neurotransmitter detection & separation High sensitivity / selectivity Intracortical neural ontrol Data acquisition Target diseases: Epilepsy lzheimer Parkinson GBM Dispositifs Médicaux Intelligents 29 Laboratory-on-hip : ells Detection/manipulation ctuation electrode matrix Sensing electrodes: capacitive sensor * DEP force Output signal referring to liquid concentration MOS chip ** (0.18!m) cquisition module: BM technique Quadrature signals MOS chip ** (0.18!m) ctuation module: Frequency / Magnitude control * Technology: Mixed MOS-Microfluidic ** The same MOS chip include both the acquisition and actuation module. GBM Dispositifs Médicaux Intelligents 30 10
11 Laboratory-on-hip : References 1.. Romani et al apacitive sensor array for localization of bioparticles in MOS lab-on-achip, Digest of Technical Papers, IEEE ISS onf., 2004, pp D. Sylvester et al, Investigation of interconnect capacitance characterization using BM technique and three-dimensional simulation, IEEE JSS, Vol. 33, no. 3, Guiducci,. Stagni, G. Zuccheri, "DN detection by integrable electronics," J.. Biosensors and Bioelectronics, vol. 19, no. 9, Hierlemann, Integrated hemical Microsensor Systems in MOS Technology, New York: Springer-Verlag, E. Ghafar-Zadeh, M. Sawan and D. Therriault, Novel direct-write MOS-based laboratoryon-chip: Design, assembly and experimental results, Sensors and ctuators : Physical, Volume 134, Issue 1, 28 February 2007, Pages E. Ghafar-Zadeh, M. Sawan, ore-bm Sigma Delta apacitive Sensor rray Dedicated to Lab-on-hip pplications, In press in Sensors & ctuators:. Physical 7. E. Ghafar-Zadeh, M. Sawan and D. Therriault, Microfluidic Packaging Technique for Labon-hip pplications, In press IEEE Trans. on dvanced Packaging. 8. E. Ghafar-Zadeh, M. Sawan, harge-based apacitive Sensor rray for MOS-Based Laboratory-On-hip pplications, IEEE Sensors, Vol. 8, No. 4, pril 2008, pp E. Ghafar-Zadeh, M. Sawan, Hybrid Microfluidic/MOS apacitive Sensor Dedicated to Lab-on-hip pplications, IEEE TBioS, Vol. 1, No. 4, December 2007, pp GBM Dispositifs Médicaux Intelligents 31 11
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