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Tutorial: Circuits and Systems for Lab-on-Chip Integration

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Tutorial on Circuits and Systems for Lab-on-Chip Integration by Dr. Wael Badawy, ATIPS Associate, Associate Professor, Dept. ECE, University of Calgary, Calgary, Alberta, Canada …

Tutorial on Circuits and Systems for Lab-on-Chip Integration by Dr. Wael Badawy, ATIPS Associate, Associate Professor, Dept. ECE, University of Calgary, Calgary, Alberta, Canada
And Dr. Yehya Ghallab, ATIPS Research Associate University of Calgary, Calgary, Alberta, Canada

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  • 1. Circuits and Systems for Lab-on-Chip Integration Dr. Yehya Ghallab ATIPS Research Associate University of Calgary Calgary, Alberta, Canada Dr. Wael Badawy ATIPS Associate Associate Professor, Dept. ECE University of Calgary Calgary, Alberta, Canada CCIT Calgary Center for Innovative Technologies ICT Information and Communication Technologies
  • 2. Acknowledgement •  National Science and Engineering research Council (NSERC) strategic grant, STPGP 258024-02. •  Canadian Microelectronics Corporation (CMC). •  Macralyne Company. •  Dr. Karan Kaler, University of Calgary, for his advice and academic help. 2
  • 3. Outline •  •  •  Introduction Main parts of the Lab-on-a-chip 1. Actuation part 2. Sensing part 3. Read-out circuit 4. Other Circuitry (A/D, Filters,Amplifiers,….etc) Summary 3
  • 4. Motivation Fluorescence detector Cell Suspension Detector of forward scattered light LASER Electrodes - + Fluorescence Labelling Technique Optical Technique Flow Profile Cell AC Current Lines Electrodes A B C Impedance sensing Technique Yehya H. Ghallab, and Wael Badawy "Sensing methods of Dielectrophorieses from Bulky instruments to Lab-on-a-chip", IEEE Circuit and Systems Magazine, Q3 issue, vol. 4, pp.5-15, 2004. 4
  • 5. •  biological cell systems 5
  • 6. Background v Bio-species (cells and genes) have a determined behavior in response to stimuli. v The integration of a stimuli within a micro fluidics chip produces what we call lab-on-a-chip. v The current Lab-on-a-chip technology lacks the integration of on-chip sensor that accurately measure the response of the biospecies. v Dielectrophoresis (DEP) is a suitable candidate to be used for wide lab-on-a-chip applications. 6
  • 7. •  Dielectrophoresis (DEP) •  Effective mechanism for manipulating cells •  Dielectric difference exploited for various applications •  Cell characteristics from the cell dynamics HENCE REAL-TIME TRACKING REQUIRED 7
  • 8. •  Conventional intensity-based and edge-detection techniques do not produce closed contours. •  Biological cell cannot be extracted. Original Image Gradient Edge detection using Sobel operator Canny’s edge detection 8
  • 9. Sequence captured Fixed Camera Segmentation Tracking Sequence replayed Object characteristics Tracking display 9
  • 10. Microbead Sequence Mesh construction 10
  • 11. Daudi blood cell sequences Mesh construction 11
  • 12. Yeast cell sequences Mesh construction 12
  • 13. Target The proposed Imager Read and Control •  Electric field imager can be used in sensing, real time monitoring, counting, detecting • In many applications Visual Image is better replaced by the Electric field Image 13
  • 14. The Roadmap Imager /sensor Ctrl M icro-Fluidic SOC Special Filter & Lens Systems M EM S DRV M icroe le ctronics SOC Platform DRV Ctrl Processing Memories Buff User-defined IP-Blocks User-defined IP-Blocks Clas s ification S ys tem Valve Pump Mix Imager /sensor P roces s ing S ys tem M EM S ARM DSP Special Filter & Lens Systems Valve Pump Valve Processing Chamber Chamber Elevation view Bio-cells Characterisation Separation and control system A A B C B 1 Plan view Bio-cells PCR and Electropherisis Module for DNA or Molecular Analysis C Dispose Unit Glass Substrate 14
  • 15. Movie Time •  Switch to external player 15
  • 16. Part 1: Actuation Part Many techniques can be used to manipulate biocells: •  Optical tweezers •  Ultrasound •  Magnetic Field (Magnetophoresis) •  Electric field (Electrophoresis or Dielectrophoresis) 16
  • 17. Dielectrophoresis Ø  Dielectrophoresis (DEP) is defined as the motion of an uncharged (neutral) particles caused by polarization effect in a nonuniform electric field. + A A + (-) (+) (+) (-) - B + + + + + + - B A is a positive particle Fig.1a B is a neutral particle Fig.1b 17
  • 18. Electrophoresis Electrophoresis manipulates charged particles in a dissipative medium with electric fields + + + + + + + + + + + + + + + + + - - Charged body-moves along field lines Fig.2 Charged particles under the Electrophoresis effect 18
  • 19. Dielectrophoresis Vs Electrophoresis •  DEP does not require the particle to be charged in order to manipulate it. •  The particle must only differ electrically from the medium that it is in. •  DEP works with AC fields, whereas no net electrophoretic movement occurs in such a field. u r •  DEP forces increase with the gradient of the square of the electric field, ∇ | E | whereas electrophoretic forces increase linearly with the electric field. 2 •  DEP can avoid problems such as: a) Electrode polarization effects and electrolysis at electrodes. b) The use of AC fields reduces membrane charging of biological cells. 19
  • 20. Dielectrophoresis Vs Electrophoresis + + + + + + + + + + + + + + + + + - + + + - Charged bodymoves along field lines Neutral body-merely polarized Fig.3 Uniform Electric field applied to neutral and charged bodies 20
  • 21. DEP Features •  Particles experience DEP force only when the electric field is nonuniform. •  The DEP Force does not depend on the polarity of the applied electric field and is observed with AC as well as DC excitation. •  There are two kinds of DEP forces: 1. Positive DEP for εm < εp. In this case, particles are attracted to regions of stronger electric field. 2. Negative DEP for εm > εp. In this case, particles are repelled from regions of stronger electric field. •  DEP is most readily observed for particles with diameters ranging from approximately 1-1000 µm. 21
  • 22. Applications of DEP 1.  Separation of living biological cells. 2.  Cell fusion. 3.  Basic cell studies. 4.  Mineralogical separation. 5.  DNA molecules manipulation. 22
  • 23. Dielectrophoresis Force •  •  r r r u E (r + d ) Independent on the polarity of the applied electric field. Dipole Two DEP forces: +q + u r r E (r ) FDEP ε 2 − ε1 = 2πε1 R [ ]∇E 2 ε 2 + 2ε1 3 q y - x Positive DEP ( ε2 > ε1) Negative DEP ( ε2 < ε1) z where ε1and ε2 is the permittivity of the suspended medium and particles. R is the radius of the particle. E is the electric field intensity. 23
  • 24. Negative DEP Available at www.dielectrophoresis.org 24
  • 25. Positive DEP Available at www.dielectrophoresis.org 25
  • 26. Dielectrophoretic Levitation •  Dielectrophoretic levitation fulfills a somewhat specialized need among the scientific and technical applications for DEP. •  The DEP levitation technique is based on the balance of the gravitational force and the DEP force to suspend a particle stably in a fluid of known properties. radius = a 2 Fz 3Q ≅− Re [ K 2 ] GQUAD ( z ) 5 πε1 a K2 = * 10(ε * − ε m ) p * p 2ε + 3ε * m GQUAD(z) collects the geometric dependencies +Q (0, -b, 0) -Q (b, 0, 0) (0, 0, z) -Q (-b, 0, 0) +Q (0, b, 0) Fig. 4 The Quadrupole point charge model 26
  • 27. Dielectrophoretic Levitation •  Two levitations mechanism: 1.  Passive levitation 2.Feedback-controlled levitation. Ring Electrode V Plane Electrode Fig.5 Electrode for passive levitation [18] FDEP+ Fg Fig.6 Electrode for feedback-controlled levitation [18] 27
  • 28. Electrorotation •  A phase varying non-uniform electric field causes particle rotation and particle conveyance. •  When such a field is implemented in a rotating configuration, it causes the particle to rotate. Fig. 7 Schematic of a dipole moment P in a rotating field with field strength E [70] 28
  • 29. Electrorotation Available at www.dielectrophoresis.org 29
  • 30. Travelling Wave Dielectrophoretic (TWD) •  A travelling wave electric field will be produced when a 90-degree phase shifted signal sequence is applied to a parallel electrode array Fig.13 A schematic of parallel electrode array connected to a 90-degree phase shifted signal sequence [71] FTWD = Where ) −4π R3ε m Im[ K e ]E02 ( rms ) ⋅ γ 0 λ λ is the wavelength of the travelling electric field 30
  • 31. Travelling Wave Dielectrophoretic (TWD) Available at www.dielectrophoresis.org 31
  • 32. Actuations Courtesy of Prof. Graham Jullien – ATIPS 32
  • 33. Part 2: Sensing Part •  Electrical Model of the BioCells a) Single shell model b) Double shell model •  Techniques for Sensing 1. Optical technique 2. Fluorescent labeling 3. Impedance sensing technique •  Currently used Lab-on-a-Chip 33
  • 34. BioCells Models (1/2) Fig.8 A single shell model for the Biocells [18] 34
  • 35. BioCells Models (2/2) Fig.9 A double shell model for Biocells [18] 35
  • 36. Optical Technique for Sensing (1/2) Fig.10 The overall electronic design of the dual DEP spectrometer [20] 36
  • 37. Optical Technique for Sensing (2/2) •  The disadvantages of this technique from the lab-ona-chip point of view can be summarized as follows: (a) It requires bulky and expensive equipment, (b) It needs complex sampling preparation and (c) It is not suitable for miniaturization. 37
  • 38. Fluorescence-activated cell sorter (FACS) (1/4) Fig.11 Schematic representation of the fluorescence-activated cell sorter (FACS) [24] 38
  • 39. Fluorescence-activated cell sorter (µFACS)device (2/4) Fig.12 Optical micrograph of the µFACS device [25]. 39
  • 40. Cell Sorting Apparatus (3/4) Fig.13 Schematic diagram of the cell sorting apparatus [25]. 40
  • 41. Advantages and Disadvantages of Fluorescent labeling (4/4) Advantage •  High sensitivity •  Impressive efficient sorting. Disadvantages •  Require cell modification by markers or antibody, •  Equipments are rather expensive, bulky, and complex. •  It’s not suitable for miniaturization. 41
  • 42. Impedance Sensing Technique (1/3) Flow Profile Fig.14 Side schematic view of the microchannel [26] Cell AC Current Lines Electrodes C B A Cell signal ZAC - ZBC ttr Fig.15 Impedance difference signal [26] 0 0.5 1 1.5 2 t(ms) 42
  • 43. Impedance Sensing Technique (2/3) Cell Flow Profile Cm Membrane RC Cm RSol2 Cytoplasm Cdl RSol1 A Cdl B Cdl Electrodes C Fig.16 An electrical model of the impedance change [26] 43
  • 44. Advantages and Disadvantages of the Impedance Sensing Technique (3/3) Advantage: •  It can be used in many tasks, e.g. counting, sizing, and population study. •  Suitable for miniaturization. Disadvantage: •  Doesn’t provide integration actuation capabilities •  Require microfluidics to move cells in the device. 44
  • 45. CMOS lab-on-a-chip Based DEP (1/3) vin RF CM RM CF - vout + Fig.17 DEP Cage [15] Fig.18 Sensing part [31] Medoro et al., in 2002, proposed the 1st lab-on-a-chip integrated microsystem 45
  • 46. CMOS lab-on-a-chip Based DEP (2/3) Fig.19 Microsites array [16] Fig.20 One microsite [16] Actuation part Sensing part Manaresi et al., In 2003, proposed a CMOS lab-on-a-chip microsystem. 46
  • 47. Advantages and Disadvantages CMOS lab-on-a-chip Based DEP (3/3) •  •  Advantages: 1. The first PCB and CMOS labs on a chip. 2. They can trap, concentrate, and quantify biocells. Disadvantages: 1. We cannot sense the actual intensity of the nonuniform electric field that produces the DEP force. 2. There is no real time detection of the cell response under the effect of the nonuniform electric field, as we halted the actuation part and activate the sensing part. 3. This sensing approach depends on an external factor, which is the inertia of the levitated cells. 47
  • 48. A Novel Lab-on-a-Chip For Biomedical applications Movie shows A real time tracking of BioCells 48
  • 49. Quadrapole Configuration Quadrupole Electrodes Biocell Fig.4 Quadrapole Levitator DeFETs Quadrupole Electrodes Fz 3Q 2 ≅− Re [ K 2 ] GQUAD ( z ) 5 πε1 a * 10(ε * − ε m ) 5 p FDEP α (radius) K 2 = * * radius=a GQUAD(z) collects the geometric dependencies 2ε p + 3ε m •  Quadrapole levitator comprises an axis symmetric electrode arrangement capable of sustaining passive stable particle levitation. 49
  • 50. Electric Field Sensor (eFET) •  Novel MOSFET-based structure is proposed and termed “Electric Field Sensitive FET (eFET)” Gate 2 Drain 2 VDD Source Drain 1 n+ Gate 1 Gate 1 + n MD1 VDD Drain 2 MD2 Gate 2 n+ SiO2 P-Sub Drain 1 Fig.8 Physical structure of an eFET Source Fig.9 Equivalent circuit of an eFET 50
  • 51. DeFET for Lab-on-a-Chip •  Novel MOSFET-based structure is proposed and termed “ Differential Electric Field Sensitive FET (DeFET)” VDD Nonuniform E IOUT Vin1 Vin2 VSS Fig.10 The DeFET’s circuit symbol Fig.11 An equivalent circuit of a DeFET 51
  • 52. DeFET’s SPICE Model Fig.12 DeFET’s SPICE Model 52
  • 53. Simulation Results (1/4) Fig.13 Iout with input voltage variation 53
  • 54. Simulation Results (2/4) Fig.14 Iout versus Electric field intensity 54
  • 55. Simulation Results (3/4) Fig.15 Circuit for Simulation 55
  • 56. Simulation Results (4/4) Fig.16 Spectre DC simulation results 56
  • 57. Effect of DeFET on the applied Electric Field Profile (1/2) Fig. 17 Electrostatic Simulation result shows that we can trap the biocell above the sensors with the existence of the DeFETs sensors 57
  • 58. Effect of DeFET on the applied Electric Field Profile (2/2) Fig.18 Result of the Electrostatic simulation shows the improvement due to using DeFE 58
  • 59. The Proposed Micrsystem Fig.18 The microscopic picture of the Die The Die size is 0.7mm x 0.6mm 59
  • 60. The DeFET 60
  • 61. Experimental Results (DC Response) 1.2 Output current (mA) 1 0.8 0.6 Experimental result 0.4 Simulation Results Vin1=Vin2 (Uniform Electric Field) 0.2 -6x106 -4x106 -2x106 0x100 2x106 Electric field Intensity (V/m) 4x106 6x106 Fig.19 The DC response of the microsystem 61
  • 62. Experimental Results (AC Response) The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Fig.57 Spectrum analyzer graph shows the frequency response of the DeFET and confirms the measured values in Fig.56 Fig. 56 The measured frequency response of the DeFET in different media 62
  • 63. Experimental Results (Different Media and Electric field profile) 1600 1200 1600 Response of the DeFETs with diffrent media Air Silicon Rubber 1200 800 800 550 400 400 188 110 116 138 140 116 112 3 400 148 0 2 Ac Response of DeFET Air Silicon Rubber 800 400 0 1 Output Current peak to peak(µA) Output Current peak to peak(µA) 1200 4 5 6 7 DeFET Sensor number 8 9 10 Fig.20 The measured output current for different DeFET sensor with the configuration Electrode 1 and 3= -5 p-p, and Electrode 2 and 4= +5V p-p (i.e. Quadrupole Configuration) and the frequency is 10 MHz 0 1 2 3 4 5 6 Sensor Number 7 8 9 10 Fig.21 The measured output current for different DeFET sensor with the configuration: Electrode 1 and 4= 5V p-p, Electrode 2 = -5V p-p, electrode 3 is not connected and the frequency is 10 MHz 63
  • 64. Experimental Results (Noise Measurements) -140 -141 -142 Noise Spectral (dBm/Hz) -143 -144 -145 -146 -147 -148 -149 -150 -151 -152 0x100 5x107 1x108 2x108 2x108 3x108 3x108 Frequency (Hz) 4x108 4x108 5x108 5x108 Fig.22 The measured noise floor using Spectrum analyzer 64
  • 65. Experimental Results (Signal to Noise Ratio) S/N= 78 dB Fig.23 Spectrum Analyzer picture shows the Signal to noise Ratio 65
  • 66. Experimental Results (Light Effect) (a) (b) Fig. 61 (a) The response of the DeFET at a room light (b) The response of the DeFET at a very close light source 66
  • 67. Experimental Results (Light Effect) Light Floating Gate Electric field Source Light Drain ++++++++++++++++++++++++++ ++++++++++++++++++++++++++ p+ + - holes p+ n-well + - Electric field + - + - + - Depletion Region p-Substrate electron-hole pairs Fig.62 Cross section view of the P eFET 67
  • 68. Summary of the DeFET features Parameter Value Unit Die Area 0.0005 mm2 Supply voltage +/- 3.3 Volt Sensitivity 71.6 µA/V/µm Signal/noise ratio >78.2 dB Offset voltage 25 µV Bandwidth Band pass with BW=11 MHz Quality factor = 2.12 1.23 mW Rise Time 17 ns Fall Time 15 ns Noise Level Very low DC power consumption 68
  • 69. The Electric Field Imager The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. 69
  • 70. Experimental Results (Different Media and Electric field profile) 1600 1200 1600 Response of the DeFETs with diffrent media Air Silicon Rubber 1200 800 800 550 400 400 188 110 116 138 140 116 112 3 400 148 0 2 Ac Response of DeFET Air Silicon Rubber 800 400 0 1 Output Current peak to peak(µA) Output Current peak to peak(µA) 1200 4 5 6 7 DeFET Sensor number 8 9 10 Fig.20 The measured output current for different DeFET sensor with the configuration Electrode 1 and 3= -5 p-p, and Electrode 2 and 4= +5V p-p (i.e. Quadrupole Configuration) and the frequency is 10 MHz 0 1 2 3 4 5 6 Sensor Number 7 8 9 10 Fig.21 The measured output current for different DeFET sensor with the configuration: Electrode 1 and 4= 5V p-p, Electrode 2 = -5V p-p, electrode 3 is not connected and the frequency is 10 MHz 70
  • 71. Biocells Manipulation (1/3) Levitated cell Levitated cell Fig. 24 Levitated Polystrine cells with diameters 8.9 and 20.9 µm 71
  • 72. Biocells Manipulation (2/3) 3000 DeFET Response with cells Air (No cells) Cells (8.9 µm) Output Current (µA peak-to-peak)) 2500 Cells (20.9 µm) 2000 1500 1000 500 0 0 1 2 3 4 5 6 7 8 DeFET sensor number 9 10 11 12 Fig.25 The DeFET sensors response in air and in fluid contains different cell sizes 72
  • 73. Applications of the proposed micrsystem v Characterize the biocells §  Cancer Detection §  Antibodies Selection §  DNA Molecules Manipulation §  Sorting and manipulation of microorganism v Real Time Monitoring §  Impedance sensor §  Electric Field Imager 73
  • 74. Summary •  DEP based lab-on-a-chip is a state of the art that promises more functionality to bio-cell analysis. •  Surveying the literature (no real time sensing DEP-based integrated bio-system exists). •  A novel electric field imager for integrated biocell lab-on-a chip is proposed. •  Simulation and Experimental results are presented and discussed. 74
  • 75. Part 3: Read-out Circuit •  Introduction. •  The Operational Floating Current Conveyor (OFCC) •  The Proposed Current-Mode Instrumentation Amplifier (CMIA) •  Experimental and Simulation Results •  Comparison between the Proposed and other CMIA •  Conclusion 75
  • 76. Introduction(1/4) •  Instrumentation amplifier (IA) has many applications in the biomedical field such as: bioimpedance measurement, read-out circuits for biosensors, …etc. •  Voltage-mode instrumentation amplifier (VMIA) exhibits a narrow bandwidth, which also is dependent on the gain. Also, VMIA requires precise resistors matching to achieve high common-mode rejection ratio (CMRR). •  Current-mode instrumentation amplifier (CMIA) has better performance with respect to CMRR and frequency range of operation. Today, most of the CMIA topologies are formed around the second-generation current conveyor (CCII+). 76
  • 77. Introduction(2/4) Vin1 Y RX Vout Z CCII (1) C X RL RG RX Z X CCII (2) Vin2 Y Fig.21 Wilson’s Current-mode instrumentation amplifier CMIA [1990] Ad = vo RL 1 = . vin1 -vin2 R G +2R X 1+sCR L Where: RL is the load resistance Rx is the equivalent input resistance at the X terminal (Rx=50-65Ω) RG is the gain determined resistor C is the effective CCII output capacitance 77
  • 78. Introduction(3/4) The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Fig.22 Khan et all’s CMIA [1995] The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Where: RL is the load resistance. Rx is the equivalent input resistance at the X terminal. RG is the gain determined resistor. C is the effective CCII output capacitance. 78
  • 79. Introduction(4/4) Vin1 + - OP1 Y Vout Z CCII (1) RL X RG Z X Vin2 + OP2 - CCII (2) Y Fig.23 Gift’s CMIA [2000] vo R 1 Ad = = L. vin1 -vin2 R G 1+ sT 1+Kβ β= Where: RG 2R X +R G RL is the load resistance, Rx is the equivalent input resistance at the X terminal. RG is the gain determined resistor, T is the time constant of the op-amp. K is the low frequency gain. 79
  • 80. The Operational Floating Current Conveyor (OFCC) Vx ix W X OFCC Vy iy Y iW Vw Z- Vz- Z+ iz- V z+ iz+ Fig.24 Block diagram representation of the OFCC • Terminal characteristics of ideal OFCC vx= vy iy=0 iw=iz+ iw=-izThere is a voltage tracking at the input between X and Y . There is a current tracking at the output between W,Z+ and Z-. 80
  • 81. OFCC Circuit Implementation The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Fig.25 OFCC implementation scheme 81
  • 82. Feedback Effect on OFCC’s input resistance (Rx) RW i1 Vin vx X iin Vy Y ii x e i=0 iy Cy X + Rx Buffer Ry Z- OFCC vw=-ie.Zt Y v2 iW W - Z+ iz+ CZ+ RZ+ CZ- RZ- Vw W Vz- RX = 50 Ω, RY = 50 kΩ | RZ+ = RZ- = 5 MΩ iz+ CX = 2pF, Cy = 2pF Z- OFCC Fig.26 Simple model of OFCC and Circuit for measuring Rx Where: vin = | Current-mirror Parameters iz- V z+ Z+ iZ- R in = CFB Parameters | CZ+ = CZ- = 6pF Zt=200 MΩ Table.1 OFCC’s model parameters R XR W i in R X +Z t +R W Rx is the equivalent input resistance at the X terminal Rw is the feedback resistance between W and X terminals. Zt represents the impedance between X and W. Typical values of these resistors are: Rx = 50 Ω, Rw =1KΩ, and Zt = 200MΩ. So Rin=0.025Ω. 82
  • 83. The New CMIA Based on OFCC Z- Y Vin1 OFCC (1) Z+ X W I1 RW1 IX RG R W2 W X OFCC (2) Z+ I2 Y Vin2 Fig.27 The Proposed CMIA Ad = Where: Vo Z- CZ RL vo 2R L = vin1 -vin2 R G (1+jωC Z R L ) RL is the load resistance. RG is the gain determined resistor. CZ is the effective OFCC output capacitance. 83
  • 84. Experimental and Simulation Results (1/3) 40 Gain=40, BW=1.2 MHz (RG=50 Ω , RL= 1kΩ ) 30 Gain (dB) Gain=20, BW=1.2 MHz (RG=100 Ω , RL= 1kΩ ) Simulation 20 Experimental Gain=4, BW=1.2 MHz (RG=500 Ω , RL= 1kΩ ) 10 Gain=2, BW=1.2 MHz (RG=1 kΩ , RL= 1kΩ ) 0 1x100 1x101 1x102 1x103 1x104 Frequency (Hz) 1x105 1x106 Fig.28 The frequency response of the proposed CMIA 84
  • 85. Experimental and Simulation Results (2/3) 80 Proposed Khan CMRR (dB) Wilson, Gift 60 40 20 1E+1 1E+2 1E+3 1E+4 1E+5 1E+6 Frequency (Hz) Fig.29 CMRR for different CMIA 85
  • 86. Experimental and Simulation Results (3/3) 78 76 CMRR (dB) 74 72 CMRR for Different gains Gain=2 Gain=4 Gain=20 Gain=40 70 68 66 64 1x10 0 1x10 1 1x10 2 3 1x10 Frequency (Hz) 4 1x10 1x10 5 6 1x10 Fig.30 CMRR for different gain values 86
  • 87. Noise Analysis (1/3) 2 inn 2 vn X Y + W | | OFCC Z+ Noise sources values: Z- | inp = 6 pA / Hz 2 inp vn = 2 nV / Hz inn = 20 pA / Hz Fig. 31 Simplified noise model of the OFCC 87
  • 88. Noise Analysis (2/3) 2 inn1 RS Y Z- X Z+ OFCC(1) + W 2 v n1 2 inp1 RW1 RG RW2 2 inn 2 2 vn 2 X + W RS OFCC(2) ZZ+ Y Vo RL 2 inp 2 Fig. 32 Equivalent circuit for analyzing OFCC noise effects on proposed CMIA 88
  • 89. Noise Analysis (3/3) 24 Equivalent input noise voltage (nV/√ Hz) 22 20 Noise Results RG=50 Ω 18 RG=100 Ω RG=500 Ω RG=1 kΩ 16 14 1x100 1x101 1x102 1x103 1x104 Frequency (Hz) 1x105 1x106 1x107 Fig.33 Input noise spectral density versus frequency for different RG 89
  • 90. Characteristics of the proposed CMIA Characteristics Value Condition Settling Time 180ns To 0.01% for a step input for gains of 2 to 40 Input Offset Voltage 90 µV Gain=40 Slew rate 395 V/µs Bandwidth 1.2 MHz Independent of gain CMRR 76 dB With -3dB frequency = 185 kHz , it is independent of gain Table 1 The Dynamic and Static characteristics of the proposed CMIA 90
  • 91. Comparison between the Proposed and Other CMIA CMIA Circuit Differential Gain For RL/RG=10 CMRR For RL/RG=10 Magnitude (Value) -3dB Frequency (Bandwidth) Gain varies with BW Wilson 9.09 2 MHz Yes Gift 10 2 MHz Yes Khan 17.8 1.4Mhz Proposed 20 1.2 MHz Magnitude (dB) -3dB Frequency (Bandwidth) Number of building blocks used 16 KHz 2 CCII 65 16 KHz 2CCII 2 Op-amp No 73 65 KHz 3 CCII No 76 185 KHz 2 OFCC 65 Table.2 Comparison between the proposed and other CMIA 91
  • 92. Conclusion Ø  A new CMIA based on OFCC has been analyzed, implemented and the experimental results have been presented. Ø  The new circuit has a wider bandwidth independent of the gain. Moreover, it has higher CMRR without the use of matched resistors associated with the OFCC. Ø  The voltage gain of the proposed circuit is independent of Rx. Ø  The experimental results show that the proposed CMIA will be suitable for the Lab-on-chip applications. 92
  • 93. A pH Sensor and Its Current Mode Read-out-Circuits
  • 94. Outline •  •  •  •  •  •  Introduction The Ion sensitive Field Effect Transistor (ISFET) The proposed current mode read-out circuit Experimental and simulation results Comparison with different pH read-out circuits Conclusion 94
  • 95. Introduction v  Lab-on-Chip is one of the hottest area of research these days. v  Lab-on-a-chip, holds the promise of cheaper, better and faster biological analysis. v  Current-mode circuits have the superior large signal handling capabilities, wider dynamic range and inherent wide bandwidth. v  Simpler circuity, lower power consumption and greater linearity over the voltage-mode circuits are also advantages 95
  • 96. The Ion sensitive Field Effect Transistor (ISFET) VT = K1+ψo (pH) Vref Electrolyte solution IDS ≈ K [(VGS -VT)] VDS Reference Electrode pH sensitive insulating dielectric (Gate) Passivation layer Metal Oxide n+ Source n+ Drain p-Si Substrate VGS = I DS KVDS + K1 + ψ o (pH) where: K1 summarize all the pH independent quantities. ψo(pH) represents the potential difference between the insulator surface exposed to the electrolyte and the bulk of the electrolyte itself. IDS is the drain current. Fig.34 Schematic cross-sectional view of The ISFET VDS is the drain to source voltage K = µn Ci W / L 96
  • 97. The Differential Ion Sensitive Field Effect Transistor (DISFET) Technique Sensor Effect (e.g. pH-measurement) Vm ISFET V1=Vdis+Vm Vdis Common-mode disturbance: Signal difference Vdif= V1 - V2 =Vm -Unstable liquid-metal interface voltage Vdis -Leakage Current V2=Vdis -Temperature Dependence REFET Fig.35 Differential measurement setup 97
  • 98. The proposed current mode read-out circuit VDD VDD Rw Rw IS1 Z+ X Z- + OFCC(1) W IS1 Y + R1 VGS = I DS KVDS VDS1 VDS1 + K1 + ψ o (pH) VA - IDS1 D Z- OFCC(2) D Vref Rw ISFET + W Y + R VDS VDS VO Vss Reference Electrode S ISFET REFET - Rw VDD - I Y out Iout= Iout1-Iout2 Z+ OFCC(3) X ZW IS3 D S OFCC(1) W 2 R Z+ Y IS2 Vref Z X ZW Part 1 X Iout1 + OFCC(3)- - X S Z+Z Y VO1 IDS2 Z+ X Z- + OFCC(4) W VA Z+ Y Y OFCC(2) + R3 VDS2 VDS2 VO2 - VB OFCC(5) IS4 Rw W Z ZW R1 Part 2 Iout2 IS2 R4 ZW X X + OFCC(6) X Z+ Y Y Z- Rw Vss Vss Fig.36 New differential ISFET current mode read-out circuit 98
  • 99. Simulation results (1/3) VDD Rw IS1 + X Z Z- + OFCC(1) W Y + R1 VDS1 VDS1 VO1 VA Z+ Y IDS1 Part 1 IS2 Rw ISFET Vref Iout= Iout1-Iout2 Vss Reference Electrode VDD REFET Rw IS3 D S Iout1 W X S Z+ ZW R2 Z- OFCC(2) D OFCC(3) X - Y IDS2 Z+ X Z- + OFCC(4) W Y + R3 VDS2 VDS2 VO2 - VB Z+ Y OFCC(5) Z- Y OFCC(6) X Z+ ZW Part 2 Iout2 R4 W X IS4 Rw Vss Fig.37 New differential ISFET current mode read-out circuit 99
  • 100. Simulation results (2/3) 3.2 2.8 Output voltage (V) Vo1 Slope=52 mV/pH 2.4 2.0 Slope=36 mV/pH 1.6 Vo2 1.2 2 4 6 pH 8 10 12 Fig.38 Plot of the output voltage Vo1 and Vo2 versus solution pH 100
  • 101. Simulation results (3/3) 850 800 Iout (µ A) 750 700 650 600 1.00 1.05 1.10 1.15 1.20 Vout1-Vout2 (V) Fig.39 Plot of the output current (Iout) versus the differential output voltage (Vout1-Vout2) 101
  • 102. Comparison with different pH read-out circuits Type of active elements used Kind of output Reference Sensitive layer used pH sensitivity mV/pH Chin (2001) SnO2 58 1(Op-Amp) Voltage Palan (1998) Si3N4 52 2 Current Ivars (2001) Si3N4 58 1(Op-Amp) Voltage Presented circuit Si3N4 52 1 Current Table 3 Comparison with other pH sensors’ read-out circuits 102
  • 103. The Ion sensitive Field Effect Transistor (ISFET) VT = K1-ψo (pH) Vref Electrolyte solution IDS ≈ K [(VGS -VT)] VDS Reference Electrode pH sensitive insulating dielectric (Gate) Passivation layer Metal Oxide n+ Source n+ Drain If VGS and VDS is constant: IDS =K 2 +K3 ψo (pH) where: K1 summarize all the pH independent quantities. K2=K VDS (VGS-K1), and K3= KVDS p-Si Substrate Fig.40 Schematic cross-sectional view of The ISFET ψo(pH) represents the potential difference between the insulator surface exposed to the electrolyte and the bulk of the electrolyte itself. IDS is the drain current. VDS is the drain to source voltage 103
  • 104. Another Read-out Circuit Configuration RW1 X + If VGS is constant: W VDD Z+ OFCC (1) I1 Y Z- IDS =K 2 +K3 ψo (pH) Iout D2 Reference Electrode D1 IDS2 RL IDS1 Z- Y S2 S1 REFET I2 OFCC (2) ISFET Z+ VREf=0.8V X W RW2 Fig.41 The proposed current-mode read out circuit using 2 OFCC Only 104
  • 105. Simulation Results 80 100 80 60 Slope=7.2 µA/pH 60 Iout (µA) Output Current (µ Α ) IDS1(Output Current of ISFET) 40 40 20 IDS1-IDS2 IDS2(Output Current of REFET) 20 Iout Slope=1.7 µA/pH 0 0 2 4 6 pH 8 10 12 Fig.42 The output currents of the ISFET and REFET 2 4 6 pH 8 10 12 Fig.43 The Difference output currents 105
  • 106. Part 3/B: The Current Mode Whetastone Bridge (CMWB) • The Voltage-Mode Wheatstone Bridge (VMWB) •  The Current-Mode Whetastone Bridge based CCII • The Proposed Current-Mode Whetastone Bridge (CMWB) • Experimental and Simulation Results • Comparison between the Proposed and other CMWB • Conclusion 106
  • 107. The Voltage-Mode Wheatstone Bridge (VMWB) R1 R3 + Vin - + V1 • Traditional voltage-mode Wheatstone bridge (VMWB) offers a good method for measuring small resistance changes accurately. Vo R2 V2 - •  The Wheatstone bridges are used for sensing temperature, strain, pressure, fluid flow, and dew point humidity,…. etc. R4 Vo =( Fig.1 Traditional voltagemode Wheatstone bridge R2 R4 )Vin R1 +R 2 R 3 +R 4 Null Condition (Vo = 0): R1R 4 =R 2 R 3 R1 =R 4 =R o mΔR R 2 =R 3 =R o ±ΔR If and Vo =V1 -V2 =± ΔR .Vin Ro 107
  • 108. The Current Mode Whetastone Bridge Based CCII (CMWB) R1 From circuit duality concept X I1 CCII+ Z IREF R1 =R o mΔR If Y and Iout =± ΔG .Iin Go R 2 =R o ±ΔR Iout RL Y I2 CCII- Z X R2 Fig.2 The CMWB based on CCII Iout =I1 -I 2 = ±ΔR .I ref Ro The advantage of the CMWB are: (1)  Reduction of passive sensing elements. (2) Superposition principle can be applied without adding any signal conditioning circuitry (3) It has a higher common-mode cancellation. 108
  • 109. The Current Mode Whetastone Bridge Based CCII (CMWB) R1 X RX If X Ideal CCII+ Y Z Z IREF Iout Iout =I1 -I 2 = RL I2 Y Y Ideal CCIIX R2 Z X RX Fig.3 Practical CMWB based on the equivalent circuit of CCII R 2 =R o ±ΔR and Taking into consideration the equivalent input resistance at X terminal (Rx) of the CCIIs. Y I1 R1 =R o mΔR ±ΔR .I ref R o +R x When R1 =R o mΔR and R 2 =R o Z Io =I x = ±ΔR+R x .I ref 2R o +R x The disadvantages 1.  The limited accuracy 2.  The need of more circuitry for linearization. 109
  • 110. The Proposed Current Mode Whetastone Bridge (CMWB) RW2 If R1 I1 X VA Z+ OFCC (2) Y X Z- Iin OFCC (1) Y (1)  Reduction of passive sensing elements. Z+ Z- Iout I4 Z+ Y Vin RL OFCC (3) VB I2 R 2 =R o ±ΔR The advantage of the proposed CMWB are: I3 W and ±ΔR Iout = .Iin Ro W RW1 R1 =R o mΔR X Z- W R2 RW3 The proposed CMWB based on OFCC (2) Superposition principle can be applied without adding any signal conditioning circuitry. (3) It has a higher common-mode cancellation. (4) No need for more circuitry for linearization (just reconfigure the proposed CMWB). 110
  • 111. Experimental Results 0.0008 0.004 R2=4K Ohm, BW=50Meg Hz R2=4K Ohm R2=3K Ohm, BW=50Meg Hz 0.003 0.0006 R2=3K Ohm R2=2K Ohm, BW=50Meg Hz 0.002 Iout (A) iout (A) R2=2K Ohm 0.0004 R2=1.5K Ohm, BW=50Meg Hz R2=1.5K Ohm 0.001 0.0002 R2=1K Ohm Simulation Results 0 Simulation Results Experimental Results Experimental Results 0 -0.001 0 1 2 Vin(V) 3 4 The Dc response of the proposed CMWB with R1=1K Ω and R2 varies 5 1x102 1x103 1x104 1x105 Frequency (Hz) 1x106 1x107 1x108 The Frequency response for the proposed CMWB with R1=1K Ohm and R2 varies 111
  • 112. Experimental Results 0.0005 0.0004 iout(A) 0.0003 CMWB based CCII [4] 0.0002 Proposed based on OFCC 0.0001 0 1x102 1x103 1x104 1x105 Frequency (Hz) 1x106 1x107 1x108 Experimental results for R1=R2=1K Ω to compare between the CMR of the proposed CMWB and the CMWB based on CCII 112
  • 113. The Proposed Linearization Technique RW1 If X Z- Y RW1 Z+ I2 Iin X Rin I3 W OFCC (1) Iout =± RW1 Z- R1 Y Z+ I4 IX X W ΔR ΔR .Iin ≈ ± 2R o +ΔR 2R o V1 1 I1 The proposed linearization circuit With the linearization circuit Iout OFCC (3) R2 R 2 =R o ±ΔR 2 V2 Vin and The proposed CMWB based on OFCC (Without the linearization circuit ) W OFCC (2) R1 =R o mΔR Y Z+ Z- RL R2 Iout =( -1)Iin R1 m ΔR Iout = Iin Ro 113
  • 114. Conclusion •  The proposed CMWB is not complicated. •  We can add the sensor effects, superposition ability, without using complicated circuitry. •  We can reduce the number of sensing passive elements. •  Contrary to the CMWB based on CCII, the output current of our CMWB is independent of Rx and dependent only on the external resistors. •  The proposed CMWB would be a suitable candidate for integration in an IC process. Thus, it can be used in many applications, such as biomedical and lab-on-a-chip. •  Finally, we have proved that the linearization technique may be much easier than the VMWBs. 114
  • 115. A pH Sensor and Its Current Mode Read-out-Circuits
  • 116. Outline •  •  •  •  •  •  Introduction The Ion sensitive Field Effect Transistor (ISFET) The proposed current mode read-out circuit Experimental and simulation results Comparison with different pH read-out circuits Conclusion 116
  • 117. Introduction v  Lab-on-Chip is one of the hottest area of research these days. v  Lab-on-a-chip, holds the promise of cheaper, better and faster biological analysis. v  Current-mode circuits have the superior large signal handling capabilities, wider dynamic range and inherent wide bandwidth. v  Simpler circuity, lower power consumption and greater linearity over the voltage-mode circuits are also advantages 117
  • 118. The Ion sensitive Field Effect Transistor (ISFET) VT = K1+ψo (pH) Vref Electrolyte solution IDS ≈ K [(VGS -VT)] VDS Reference Electrode pH sensitive insulating dielectric (Gate) Passivation layer Metal Oxide n+ Source n+ Drain p-Si Substrate Fig.34 Schematic cross-sectional view of The ISFET VGS = I DS KVDS + K1 + ψ o (pH) where: K1 summarize all the pH independent quantities. ψo(pH) represents the potential difference between the insulator surface exposed to the electrolyte and the bulk of the electrolyte itself. IDS is the drain current. VDS is the drain to source voltage K = µn Ci W / L 118
  • 119. The Differential Ion Sensitive Field Effect Transistor (DISFET) Technique Sensor Effect (e.g. pH-measurement) Vm ISFET V1=Vdis+Vm Vdis Common-mode disturbance: Signal difference Vdif= V1 - V2 =Vm -Unstable liquid-metal interface voltage Vdis -Leakage Current V2=Vdis -Temperature Dependence REFET Fig.35 Differential measurement setup 119
  • 120. The proposed current mode read-out circuit VDD VDD Rw Rw IS1 Z+ X Z- + OFCC(1) W IS1 Y + R1 VGS = I DS KVDS VDS1 VDS1 + K1 + ψ o (pH) VA - IDS1 D Z- OFCC(2) D Vref Rw ISFET + W Y + R VDS VDS VO Vss Reference Electrode S ISFET REFET - Rw VDD - Y I out Iout= Iout1-Iout2 Z+ OFCC(3) X ZW IS3 D S OFCC(1) W 2 R Z+ Y IS2 Vref Z X ZW Part 1 X Iout1 + OFCC(3)- - X S Z+Z Y VO1 IDS2 Z+ X Z- + OFCC(4) W VA Z+ Y Y OFCC(2) + R3 VDS2 VDS2 VO2 - VB OFCC(5) IS4 Rw W Z ZW R1 Part 2 Iout2 IS2 R4 ZW X X + OFCC(6) X Z+ Y Y Z- Rw Vss Vss Fig.36 New differential ISFET current mode read-out circuit 120
  • 121. Simulation results (1/3) VDD Rw IS1 + X Z Z- + OFCC(1) W Y + R1 VDS1 VDS1 VO1 VA Z+ Y IDS1 Part 1 IS2 Rw ISFET Vref Iout= Iout1-Iout2 Vss Reference Electrode VDD REFET Rw IS3 D S Iout1 W X S Z+ ZW R2 Z- OFCC(2) D OFCC(3) X - Y IDS2 Z+ X Z- + OFCC(4) W Y + R3 VDS2 VDS2 VO2 - VB Z+ Y OFCC(5) Z- Y OFCC(6) X Z+ ZW Part 2 Iout2 R4 W X IS4 Rw Vss Fig.37 New differential ISFET current mode read-out circuit 121
  • 122. Simulation results (2/3) 3.2 2.8 Output voltage (V) Slope=52 mV/pH 2.4 2.0 Slope=36 mV/pH 1.6 1.2 2 4 6 pH 8 10 12 Fig.38 Plot of the output voltage Vo1 and Vo2 versus solution pH 122
  • 123. Simulation results (3/3) 850 800 Iout (µ A) 750 700 650 600 1.00 1.05 1.10 1.15 1.20 Vout1-Vout2 (V) Fig.39 Plot of the output current (Iout) versus the differential output voltage (Vout1-Vout2) 123
  • 124. Comparison with different pH read-out circuits Type of active elements used Kind of output Reference Sensitive layer used pH sensitivity mV/pH Chin (2001) SnO2 58 1(Op-Amp) Voltage Palan (1998) Si3N4 52 2 Current Ivars (2001) Si3N4 58 1(Op-Amp) Voltage Presented circuit Si3N4 52 1 Current Table 3 Comparison with other pH sensors’ read-out circuits 124
  • 125. The Ion sensitive Field Effect Transistor (ISFET) VT = K1-ψo (pH) Vref Electrolyte solution IDS ≈ K [(VGS -VT)] VDS Reference Electrode pH sensitive insulating dielectric (Gate) Passivation layer Metal Oxide n+ Source n+ Drain If VGS and VDS is constant: IDS =K 2 +K3 ψo (pH) where: K1 summarize all the pH independent quantities. K2=K VDS (VGS-K1), and K3= KVDS p-Si Substrate Fig.40 Schematic cross-sectional view of The ISFET ψo(pH) represents the potential difference between the insulator surface exposed to the electrolyte and the bulk of the electrolyte itself. IDS is the drain current. VDS is the drain to source voltage 125
  • 126. Another Read-out Circuit Configuration RW1 X + If VGS is constant: W VDD Z+ OFCC (1) I1 Y Z- IDS =K 2 +K3 ψo (pH) Iout D2 Reference Electrode D1 IDS2 RL IDS1 Z- Y S2 S1 REFET I2 OFCC (2) ISFET Z+ VREf=0.8V X W RW2 Fig.41 The proposed current-mode read out circuit using 2 OFCC Only 126
  • 127. Simulation Results 80 100 80 60 Slope=7.2 µA/pH 60 Iout (µA) Output Current (µ Α ) IDS1(Output Current of ISFET) 40 40 20 IDS1-IDS2 IDS2(Output Current of REFET) 20 Iout Slope=1.7 µA/pH 0 0 2 4 6 pH 8 10 12 Fig.42 The output currents of the ISFET and REFET 2 4 6 pH 8 10 12 Fig.43 The Difference output currents 127
  • 128. Conclusion •  A differential ISFET technique reduces the ISFET sensor dependence on parameter fluctuations and environment conditions. •  A read-out circuit based on the current-mode technique provides a linear sensitivity to pH of 52mV/pH at room temperature (i.e. 27oC) in the consideration range 2-12. •  This read-out circuit uses only one type of active element (i.e. OFCC) that makes this circuit easier to be both integrated and fabricated. •  Simulation results demonstrate that the read-out circuit works reliably and can be suitably used for lab-on-a-chip applications. 128
  • 129. Conclusion •  A differential ISFET technique reduces the ISFET sensor dependence on parameter fluctuations and environment conditions. •  A read-out circuit based on the current-mode technique provides a linear sensitivity to pH of 52mV/pH at room temperature (i.e. 27oC) in the consideration range 2-12. •  This read-out circuit uses only one type of active element (i.e. OFCC) that makes this circuit easier to be both integrated and fabricated. •  Simulation results demonstrate that the read-out circuit works reliably and can be suitably used for lab-on-a-chip applications. 129
  • 130. References 1.  2.  3.  4.  5.  6.  7.  H.A. Pohl, Dielectrophoresis, Cambridge University Press, Cambridge, 1978. M. Washizu, and O. Kurosawa “Electrostatic manipulation of DNA in microfabricated structures “, IEEE Transactions on Industry Applications, vol. 26, no.6, pp. 1165-1172, 1990. R. Casanella, J. Samitier, A. Errachid, C. Madrid, S. Paytubi, and A. Juarez,” Aggregation profile characterisation in dielectrophoretic structures using bacteria and submicron latex particles,” IEE Proceedings-Nanobiotechnnology, vol. 150, pp. 70- 74, 2003. D. J.Bennett, B. Khusid, C. D. James, P. C. Galambos, M. Okandan, D. Jacqmin, and A. Acrivos, ” Combined field-induced dielectrophoresis and phase separation for manipulating particles in microfluidics,” Journal of Applied Physics Letters, vol. 83, pp. 4866-4868, 2003. E. V. Tsiper, Z.G. Soos," Electronic polarization at surfaces and thin films of organic molecular crystal:PTCDA," chemical physics letters 360(1-2): pp. 47-52 JUL 3 2002. M. P. Hughes et al., “Strategies for dielectrophoretic separation in laboratory-on-a-chip systems,” Electrophoresis, vol. 23, no. 16, pp. 2569–2582, 2002. P.T. Gaynor, and P.S. Bodger, “Electrofusion processes: theoretical evaluation of high electric field effects on cellular transmembrane potentials”, IEE Proceedings-Science, Measurement and Technology, vol. 142, no.2 , pp. 176-182, 1995. 130
  • 131. References 8.  9.  10.  11.  12.  13.  14.  15.  16.  L. Benguigui, A.L. Shalom, and I.J. Lin, “Influence of the sinusoidal field frequency on dielectrophoretic capture of a particle on a rod”, Journal of Physics D (Applied Physics), vol.19, no.10, pp. 1853-1861, 1986. P. Fortina, S. Surrey, and Lj. Kricka, “Molecular diagnostics: hurdles for clinical implementation,” Trends Mol. Med., vol. 8, pp. 264–266, 2002. Internet web site, www.lab-on-a-chip.com. K. K. Jain, “Pharmacogenomics,” in Cambridge Healthtech Inst. Third Annual. Conf. Labon-a-Chip and Microarrays, vol. 2, Zurich K. K. Jain, “Pharmacogenomics,” in Cambridge Healthtech Inst. Third Annual. Conf. Labon-a-Chip and Microarrays, vol. 2, Zurich, Switzerland, 2001, pp. 73–77. Lj. Kricka, “Microchips, microarrays, biochips and nanochip: personal laboratories for the 21st century,” Clin. Chim. Acta, vol. 307, pp. 219–223, 2001. Internet web site, http://www.healthtech.com/2003/mfe/index.asp, G. Medoro, N. Manaresi, M. Tartagni, and R. Guerrieri,” CMOS-only Sensors and Manipulation for microorganisms”, Proc. IEDM, pp. 415-418, 2000. N. Manaresi, A. Romani, G. Medoro, L. Altomare, A. Leonardi, M. Tartagni, and R. Guerrieri,” A CMOC Chip for Individual Manipulation and Detection”, IEEE International Solid-State Circuits Conference, ISSCC 03, pp. 486-488. 2003. 131
  • 132. Acknowledgement •  National Science and Engineering research Council (NSERC) strategic grant, STPGP 258024-02. •  Canadian Microelectronics Corporation (CMC). •  Macralyne. •  Dr. Karan Kaler, University of Calgary, for his advice and academic help. 132
  • 133. References 17.  18.  19.  20.  21.  22.  23.  24.  Gianni Medoro, Nicoló Manaresi, Andrea Leonardi, Luigi Altomare, Marco Tartagni, and Roberto Guerrieri,” A Lab-on-a-Chip for Cell Detection and Manipulation,” IEEE Sensors Journal, vol. 3, no. 3, pp. 317-325, June 2003. T.B. Jones, Electromechanics of Particles, Cambridge Univ. Press, Cambridge, 1995. Joel Voldman, “A Microfabricated Dielectrophoretic Trapping array for Cell-based Biological assays,” PhD thesis, Massachusetts Institute of Technology, June 2001. M. S. Talary and R. Pethig, “Optical technique for measuring the positive and negative dielectrophoretic behavior of cells and colloidal suspensions,” Proc. Inst. Elect. Eng.—Sci. Meas. Technol., vol. 14, no. 5,Sept. 1994. J.P.H Burt, T.A.K Al-Ameen, R. Pethig, and X. Wang,” An optical dielectrophoresis spectrometer for low frequency measurements on colloidal suspensions,” J. Physics E: Sci. Instr. Vol.22, pp. 952-957, 1989. J.A.R. Price, J.P.H Burt and R. Pethig,” Applications of a new optical technique for measuring the dielectrophoretic behavior of microorganism,” Biochim. Biophy. Acta, vol. 964, pp. 221-230, 1988. Shulamit Eyal, and Stephen R. Quake,” Velocity-independent microfluidic flow cytometry,” Electrophoresis, vol.23, pp. 2653-2657, 2002. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/F/FACS.html, internet website 133
  • 134. References 25.  26.  27.  28.  29.  30.  31.  A. Y. Fu, C. Spence, A. Scherer, F. H. Arnold, and S. R. Quake, “A microfabricated fluorescence-activated cell sorter,” Nat. Biotech., vol.17, Nov. 1999. S. Gawad, L. Schild, and Ph. Renaud, “Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing,” Lab on a Chip, vol. 1, pp. 76–82, 2001. K. C. Fuller, J. Hamilton, H. Ackler, P. Krulevitch, B. Boser, A. Eldredge, F. Becker, J. Yang, and P. Gascoyne, “Microfabricated multi-frequency particle [1] impedance characterization systems,” in Micro Total Analysis Systems. Enschede, The Netherlands: Kluwer, 2000. L. L. Sohn, O. A. Saleh, G. R. Facer, A. J. Beavis, R. S. Allan, and D. A. Notterman, “Capacitance cytometry: measuring biological cells one by one,” in Proc. Nat. Acad. Sci. USA, vol. 97, 2002, pp. 10 687–10 690. H. E. Ayliffe, A. B. Frazier and R. D. Rabbitt, IEEE J. Microelectromech. Syst., 8(1), 50-57, 1999. S. Gawad, L. Schildb and Ph. Renauda, “Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing,” Lab on a Chip, vol. 1, pp. 76–82, 2001. G. Medoro, N. Manaresi, A. Leonardi, L. Altomare, M. Tartagni, and R. Guerrieri,” A labon-a-chip for cell detection and manipulation”, Proceedings of IEEE SENSORS 2002, vol. 1, pp.472-475, 2002. 134
  • 135. References 32.  33.  34.  35.  36.  37.  38.  J. Szynowski,ʺ″CMRR analysis in instrumentation amplifiers, Elect..Let., vol. 19, no. 14, pp. 547-549, 1983. R.P. Areny and J. G. Webster, ʺ″Common-mode rejection ratio in differential amplifier stages,ʺ″ IEEE Trans. Instr. Meas., vol. 40, no. 4, pp. 669-676, 1991. R.P. Areny and J. G. Webster, ʺ″Common mode rejection ratio for cascaded differential amplifier stages, ʺ″,ʺ″ IEEE Trans. Instr. Meas., vol. 40, no. 4, pp. 677-681, 1991. A. A. Khan, M. A. Al-Turaigi and M. Abou El-Ela, ʺ″An Improved Current-mode Instrumentation Amplifier with Bandwidth Independent of gain, ʺ″ IEEE Trans. Instr. Meas., vol. 44, no. 4, 1995. C. Galanis and I. Haritantis, ʺ″An Improved Current-mode Instrumentation Amplifier,ʺ″ ICECS '96, vol.1, pp. 65-68, 1996. T. Kaulberg, ʺ″ A CMOS Current-Mode Operational Amplifier, ʺ″ IEEE Journal of Solid State circuits, vol. 28, no. 7, pp. 849-852, 1993. B. Wilson, ʺ″ Universal Conveyor Instrumentation Amplifier, ʺ″ Elect. Let., vol. 25, no.7, pp. 470-471, 1989. 135
  • 136. References 39.  40.  41.  42.  43.  44.  45.  46.  47.  48.  C. Toumazou and F. J. Lidgey, ʺ″Novel Current-Mode Instrumentation Amplifier, ʺ″ Elect. Let., vol. 25, no. 3, pp. 228-230, 1989. S. J. Azhari and H. Fazalipoor, ʺ″ A Novel Current-Mode Instrumentation Amplifier (CMIA) Topology, ʺ″ IEEE Trans. Instr. Meas., vol. 49, no. 6, pp. 1272-1277, 2000. S. J. G. Gift, ʺ″ An Enhanced Current-Mode Instrumentation Amplifier, ʺ″IEEE Trans. Instr. Meas., vol. 50, no. 1, pp. 85-88, 2001. I. Gkotsis, G. Souliotis and I. Haritantis, ʺ″ Instrumentation Amplifier Based Analogue Interface,” ICECS '98, vol.1, pp. 317-320, 1998. K. Koli and K. A. I. Halonen, ʺ″ CMRR Enhancement Techniques for Current-Mode Instrumentation Amplifiers,ʺ″IEEE Trans. on Circuits and Systems, vol. 47, no. 5, pp. 622-632, 2000. Q. S. Zhu, F.J. Lidgey and W. J. Su,ʺ″ High CMRR, Second generation Current-Mode Instrumentation Amplifier,ʺ″ ISCAS93, vol.2, pp. 1326-1328, 1993. B. Wilson," Recent Developments in Current Conveyors and Current-mode Circuits" IEEE Proc., Circuit Devices and Systems., vol. 137, (12), pp. 63 – 77, 1990. A.S. Sedra, G.W. Roberts and F. Gohn, "The Current Conveyor: History Progress and New Results," Proc. IEEE on Instr. Elect. Eng., Circuit Devices and Systems, vol. 137, pp. 78 – 87, 1990. A.Khan, M. Al-Turiaia and M. Abo El-Ela, "Operational Floating Current Conveyor: Characteristics , Modeling and Applications," IMTC94, pp.788-790, Hamamtsu, Japan, 1994. Y. H. Ghallab, M. Abo El-Ela and M.Elsaid, "Operational Floating Current Conveyor: Characteristics, Modeling and Experimental results," ICM99, Kuwait, 1999. 136
  • 137. References 49.  50.  51.  52.  53.  54.  55.  S. Soclof, "Design and Applications of Analog Integrated Circuits", Englewood Cliffs, N. J Prentice Hall Inc. Chap.9, pp.443-460, 1991. Analog Devices Manual "450 V/µs, precision, current-feedback OpAmp (AD846)" pp. (2-307)-(2-317). Harris semiconductor "CA3096, CA3096A, CA3096C, NPN transistor arrays" File Number 595.4, December 1997. P. Begveld, "Development of an Ion-Sensitive Solid State Device for Neuropsychological Measurements", IEEE Trans. On Biomedical Eng., BE-17 pp.70-71, 1970. A. Lui, B.Margesin and M. Zen, "Chemical Sensors based on ISFET Transducers", International Conf. And Symposium on devices and Materials, Nova Gorica, Slovenia, pp. 51-72, 1996. K. Dzahini, F. gaffiot and M. Le Helley, "Using CMOS ASIC Technology for the Development of an Integrated ISFET Sensor", Euro ASIC '91, Paris, France, pp. 356-359, 1991. C. cane, I. Gracia, M. Lozano, E. Lora-Tamayo and J. steve, " Compatability of ISFET and CMOS Technologies for Smart Sensors", TRANSDUCERS '91, San Francisco, CA, USA, pp. 225-228, 1991. 137
  • 138. References 55.  56.  57.  58.  59.  60.  61.  62.  63.  P. Gimmel, K.D. Schierbaum, W. Gopel, H.H Van Den Vlekkert, and N. F. De Rooij, "Microstructure Solid-State Ion Sensitive Membranes by Thermal Oxidation of Ta", Sensors and Actuators, pp. 354-349, 1990. P. Gimmel, K.D. Schierbaum and W.Gopel, "Reduce Light Sensitivity in Optimized Ta2O5 ISFET Structures", Sensors and Actuators, pp.135-140, 1991. J. Janata and R.J Huber, Solid State Chemical Sensor, Academic Press, 1986. H. S. Wong and M. H. White, "A CMOS Integrated ISFET-Operational Amplifier Chemical Sensor Employing Differential Sensing", IEEE Trans. On Electron Devices, vol. 36(3), 1989. B.Palan , E.Santos and J.Karam, "A New ISFET Sensor Interface Circuit", Proc. Of the 1998 Eurosensors, Southhampton, UK. pp.1-3 , 1998. E. Muller, P. Woias, P. hein, S.Koch, "Differential ISFET/REFET as a reference system for Integrated ISFET-Sensor Arrays", Transducers 91, International conference on solid-state, pp. 467-470, 1991. L.Ravezzi, D. Stoppa, M. Corra, G. Soncini, G.F. Dalla Betta and L. Lorenzelli, "A CMOS ASIC For Differential Read-out of ISFET Sensor", ICECS 2001, Malta, pp. 1513-1516, 2001. Y. Chin,J. Chou, T.Sun , H. Liao , W. Chung and S. Hsiung, "A Novel SnO2/Al discrete gate ISFET pH sensor with CMOS standard process", Sensors and Actuators , B75, pp. 36-42 ,2001. L.Ravezzi and P.Conci, "ISFET sensor coupled with CMOS read-out circuit micrsystem", Electr. Letter, Vol. 341, pp.2234-2235. 1998. 138
  • 139. References 64.  65.  66.  67.  68.  69.  70.  71.  Ivars G. Finvers, Brent J. Maundy, Ibiyemi A. Omole and Peter Aronhime, "On the Design of CMOS Current Conveyors", Can. J. Elect.& Comp. Eng., Vol.26, No.1, Jan.2001. A.Khan , M. Al-Turiaia and M. Abo El-Ela, "Operational Floating Current Conveyor : Characteristics , Modeling and Applications", IEEE, IMTC94, pp.788-790, Hamamtsu, Japan, 1994. Y. H. Ghallab, M. Abo El-Ela and M.Elsaid, "Operational Floating Current Conveyor : Characteristics , Modeling and Experimental results", Proc. Of the international Conference on Microelectronics, ICM99, Kuwait, 1999. S. Martinoia, G. Massobrio and M. Grattarola, "Modeling H + -sensitive with SPICE", IEEE Transactions on Electron Devices, Vol.39 No.4, pp.813-819, 1992. P. Bergveld, "Future Applications of ISFETs", Sensors and Actuators, B4, pp.125-133, 1991. S. Soclof, "Design and Applications of Analog Integrated Circuits", Englewood Cliffs, N. J Prentice Hall Inc. Chap.9, pp.443-460, 1991. Pethig R., Application of a.c. electrical fields to the manipulation and characterization of cells, Automation in Biotechnology ed I Karube, 1991, pp. 159-85. X-B. Wang, Y. Huang, F. F. Becker and P.R.C. Gascoyne, A Unified Theory of Dielectrophoresis and Travelling Wave Dielectrophoresis, J.Phys D: Appl.Phys.27 (1994) pp. 1571-1574. 139
  • 140. References 72.  73.  74.  75.  76.  77.  Reinaldo J. Perez, Design of Medical Electronic devices, Academic press, USA, 2002. Joseph J. Carr, and John M. Brown, Introduction to Biomedical Equipment Technology, John Wiley and Sons, USA, 1981. L. P. Huelsman, Basic Circuit Theory, 3rd Edition, Prentice Hall, USA, 1991. S. Azhari, and H. Kaabi, “ AZKA Cell, the Current-Mode Alternative of Wheatstone Bridge,” IEEE Trans. Circuits and Systems-I, Vol. 47, No. 9, pp. 1277-1284, 2000. Analog Devices Manual "450 V/µs, precision, current-feedback OpAmp (AD846)" pp. (2-307)-(2-317). Harris semiconductor "CA3096, CA3096A, CA3096C, NPN transistor arrays" File Number 595.4, December 1997. 140