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E-raamat: Emerging CMOS Capacitive Sensors for Biomedical Applications: A multidisciplinary approach

(York University, Lassonde School of Engineering, Department of Electrical Engineering and Computer Science, Toronto, Canada), (York University, Lassonde School of Engineering, Department of Electrical Engineering and Computer Science, )
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  • Sari: Materials, Circuits and Devices
  • Ilmumisaeg: 22-Oct-2021
  • Kirjastus: Institution of Engineering and Technology
  • Keel: eng
  • ISBN-13: 9781785619168
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  • Formaat: EPUB+DRM
  • Sari: Materials, Circuits and Devices
  • Ilmumisaeg: 22-Oct-2021
  • Kirjastus: Institution of Engineering and Technology
  • Keel: eng
  • ISBN-13: 9781785619168
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CMOS-based sensors offer significant advantages to life science applications, such as non-invasive long-term recordings, fast responses and label-free processes. They have been widely applied in many biological and medical fields for the study of living cell samples such as neural cell recording and stimulation, monitoring metabolic activity, cell manipulation, and extracellular pH monitoring. Compared to other sensing techniques, capacitive sensors are low-complexity, high-precision, label-free sensing methods for monitoring cellular activities such as cell viability, proliferation and morphology.

The development of capacitive sensors for use in life sciences requires thorough knowledge of both the intended biological applications and CMOS circuitry. This book addresses the principles, design, implementation and testing, and packaging of CMOS circuits for these applications. Existing applications, markets, and potential future developments are also covered, plus the relevant biological protocols.

Emerging CMOS Capacitive Sensors for Biomedical Applications provides information and guidance for researchers and advanced students in the field of microelectronics who are looking to specialise in biological applications. It is also relevant to academic and industrial researchers already working in the biosensors field, who wish to expand their knowledge and keep abreast of new developments.



Developing capacitive sensors for use in life sciences requires thorough knowledge of both the intended biological applications and CMOS circuitry. This book addresses the principles, design, implementation and testing, and packaging of CMOS circuits for biomedical applications, plus relevant biological protocols.

About the authors xi
Table of terminology and definitions xiii
List of frequently used acronyms and abbreviations xxix
Parameters xxxv
1 Introduction 1(18)
1.1 CMOS sensors
1(12)
1.1.1 Optical
3(4)
1.1.2 Magnetic
7(3)
1.1.3 Electrochemical
10(3)
1.2 CMOS capacitive sensor
13(3)
1.2.1 LoC-based versus MEMS-based capacitive sensors
14(2)
1.3 Organization of this book
16(3)
2 Design, implementation, and characterization of CMOS capacitive biosensors 19(16)
2.1 Design metrics
19(8)
2.1.1 Applicability
19(1)
2.1.2 Noise immunity
20(1)
2.1.3 Linearity
21(1)
2.1.4 Limit of detection
22(1)
2.1.5 Resolution
22(1)
2.1.6 Input dynamic range
22(1)
2.1.7 Sensitivity
23(1)
2.1.8 Detection time
23(1)
2.1.9 Selectivity
23(2)
2.1.10 Reproducibility
25(1)
2.1.11 Multiplexing
25(1)
2.1.12 Reusability
25(1)
2.1.13 Miniaturization and integration capabilities
26(1)
2.1.14 Complexity
26(1)
2.1.15 Power consumption
26(1)
2.1.16 Biostability and lifetime
27(1)
2.1.17 Biocompatibility
27(1)
2.2 Design, implementation, and test steps
27(6)
2.2.1 Electrode design and biointerface layer
28(2)
2.2.2 Circuit design, modeling, and fabrication
30(1)
2.2.3 Sample preparation
30(1)
2.2.4 Microfluidics
31(1)
2.2.5 Experimental setup and test
31(1)
2.2.6 Calibration
32(1)
2.3 Summary
33(2)
3 Microelectrodes 35(18)
3.1 Electrode-solution interfaces
35(2)
3.2 Capacitive transducers and their models
37(4)
3.2.1 Floating electrodes
37(1)
3.2.2 Interdigitated electrodes
38(2)
3.2.3 Surface stress-based devices
40(1)
3.3 CMOS-based integrated electrodes
41(10)
3.3.1 Passivated electrodes
42(2)
3.3.2 High-sensitivity passivated electrodes
44(1)
3.3.3 Quasi IDE
44(1)
3.3.4 AL/Al2O3 electrodes
45(1)
3.3.5 Polymer-coated electrodes
46(1)
3.3.6 Au-coated electrodes
46(3)
3.3.7 Pt-coated electrodes
49(1)
3.3.8 TiN electrodes
50(1)
3.4 Summary
51(2)
4 CMOS interface circuits of capacitive biosensors 53(48)
4.1 Different CMOS interface circuits of capacitive biosensors
53(18)
4.1.1 Charge-sharing method
53(1)
4.1.2 Charge-sensitive amplifier-based and SC techniques
54(3)
4.1.3 CFC using a comparator-based relaxation oscillator
57(1)
4.1.4 RO-based CFC
58(1)
4.1.5 VCO-based sensors
59(3)
4.1.6 Lock-in detection
62(3)
4.1.7 Triangular voltage analysis
65(1)
4.1.8 Charge-based capacitance measurement
66(2)
4.1.9 Comparison of different capacitive sensors
68(3)
4.2 Some nonidealities of CBCM
71(2)
4.3 Core-CBCM interface circuits
73(27)
4.3.1 Core-CBCM capacitive biosensors using discrete components
75(1)
4.3.2 Current mirror integrated with CBCM structure
76(2)
4.3.3 Non-differential CVCs
78(1)
4.3.4 The CVCs based on differential voltage
79(2)
4.3.5 The single-ended circuits based on differential current
81(7)
4.3.6 The fully differential circuits based on differential current
88(4)
4.3.7 Core-CBCM CFC
92(5)
4.3.8 Core-CBCM capacitance sensor with nanoelectrodes
97(3)
4.4 Summary
100(1)
5 Microfluidic packaging 101(28)
5.1 Materials and challenges
101(2)
5.2 IC-microfluidic packaging techniques
103(19)
5.2.1 Rapid prototyping methods
103(6)
5.2.2 Soft lithography
109(6)
5.2.3 Direct-write fabrication process
115(1)
5.2.4 Other microfabrication methods
116(6)
5.3 Discussion on IC-microfluidic packaging
122(5)
5.4 Summary
127(2)
6 Biological/chemical applications 129(26)
6.1 Chemical sensing
129(2)
6.2 Cell monitoring and toxicity test
131(5)
6.3 Selective sensing
136(18)
6.3.1 Nucleic acid-based methods
137(4)
6.3.2 Antibody-based assays
141(7)
6.3.3 Other selective techniques and artificial BREs
148(6)
6.4 Summary
154(1)
7 Current technology and future work 155(8)
7.1 Conventional impedimetric and capacitive measurement systems
155(3)
7.2 Handheld impedance or capacitance measurement systems
158(1)
7.3 Toward fully integrated capacitive sensing LoC
158(3)
7.3.1 Capacitance characterization
159(1)
7.3.2 Multiphysics modeling of LoC-based capacitive biosensors
159(1)
7.3.3 Generic LoC-based capacitive biosensor
160(1)
7.3.4 Cleaning procedure
160(1)
7.3.5 Packaging
160(1)
7.4 Summary
161(2)
Appendix A: Simulation of electrodes 163(2)
Appendix B: Fabrication techniques 165(10)
Appendix C: Simulation of single-ended and fully differential core-CBCM CVCs 175(4)
Appendix D: Simulation of a core-CBCM CFC 179(8)
Appendix E: Cell culture 187(4)
References 191(32)
Index 223
Ebrahim Ghafar-Zadeh received his B.Sc. and M.Sc. in Electrical Engineering from the KNT University of Technology (Tehran, Iran) and University of Tehran (Tehran, Iran), respectively. He then continued his studies in Polytechnique of Montreal (Montreal, Canada), where he received his Ph.D. degree in Electrical Engineering in 2008. His graduate studies focused on complementary metal-oxide semiconductor (CMOS)-based sensors for lab-on-chip applications. In recognition of his research achievements, he received several fellowship awards including a Postdoctoral Fellowship (PDF) from the Natural Sciences and Engineering Research Council of Canada (NSERC). Then he continued his PDF research studies in Electrical Engineering at the McGill University (Montreal, Canada) and in Bioengineering, at the University of California, Berkeley. As Assistant Professor, in 2013, Ebrahim joined the Department of Electrical Engineering and Computer Science (EECS) in the Lassonde School of Engineering at York University where currently he is Associate Professor, Member of Graduate Programs of Departments of EECS and Biology, and Director of Biologically Inspired Sensors and Actuators (BioSA) research laboratory. His research is aimed at exploring novel integrated sensors and actuators for life science applications. Since 2013, Professor Ghafar-Zadeh has published more than 100 journal and conference articles and trained more than 40 highly qualified personnel (HQP) in the fields of Electrical Engineering and Biology. He is Senior Member of the IEEE and a licensed Professional Engineer in the province of Ontario.



Saghi Forouhi is a postdoctoral researcher at York University (Department of Electrical Engineering and Computer Science (EECS), Biologically Inspired Sensors and Actuators (BioSA) Laboratory), Canada. She received the B.Sc. and M.Sc. degrees in Electrical Engineering from Guilan University, Iran, in 2010 and 2012, respectively. Then, she completed her Ph.D. at Isfahan University of Technology (IUT) in 2019 in an active collaboration between IUT and York University. Her research interests lie in the area of biologically inspired micro-systems, CMOS sensors, circuits, and systems.