This document proposes a novel lab-on-a-chip system for biomedical applications that integrates actuation, sensing, and real-time tracking of biocells. It discusses various actuation techniques including dielectrophoresis which can manipulate cells using nonuniform electric fields. It also covers different sensing methods like optical, fluorescence labeling, and impedance sensing. A new electric field sensor called DeFET is introduced that can detect the intensity of nonuniform fields for real-time monitoring of cell responses. Simulation results show that DeFET sensors can precisely trap cells above the sensor surface while monitoring the electric field profile. This innovative lab-on-a-chip has potential for advanced biomedical research and diagnostics with its integrated actuation

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)
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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
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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)
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the image and then insert it again.
Fig.22 Khan et all’s CMIA [1995]
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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
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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

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