CMOS integrated lab-on-a-chip system for personalized biomedical diagnosis

289 Pages·2018·22.76 MB·English

by  Jiang, Yu

CMOS Integrated Lab‐on‐a‐Chip System for 
Personalized Biomedical Diagnosis
CMOS Integrated Lab‐on‐a‐Chip System for
Personalized Biomedical Diagnosis
Hao Yu
Southern University of Science and Technology
China
Mei Yan
Consultant
China
Xiwei Huang
Hangzhou Dianzi University
China
This edition first published 2018
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Library of Congress Cataloging‐in‐Publication Data
Names: Yu, Hao, 1976– author.
Title: CMOS integrated lab-on-a-chip system for personalized biomedical diagnosis / Hao Yu, Southern
University of Science and Technology, China, Mei Yan, Consultant, China, Xiwei Huang, Hangzhou
Dianzi University, China.
Description: Hoboken, NJ : Wiley, 2018. | Series: Wiley - IEEE | Includes bibliographical references
and index. |
Identifiers: LCCN 2017049248 (print) | LCCN 2017050886 (ebook) | ISBN 9781119218357 (pdf) |
ISBN 9781119218340 (epub) | ISBN 9781119218326 (hardback)
Subjects: LCSH: Medical instruments and apparatus–Research. | Metal oxide semiconductors,
Complementary.
Classification: LCC RA856.4 (ebook) | LCC RA856.4 .J53 2018 (print) | DDC 610.28/4–dc23
LC record available at https://lccn.loc.gov/2017049248
Cover Design: Wiley
Cover Image: © e-crow/Gettyimages
Set in 10/12pt Warnock by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1
v
Contents
Preface x
1 Introduction 1
1.1 P ersonalized Biomedical Diagnosis 1
1.1.1 Personalized Diagnosis 1
1.1.2 Conventional Biomedical Diagnostic Instruments 3
1.1.2.1 Optical Microscope 3
1.1.2.2 Flow Cytometer 4
1.1.2.3 DNA Sequencer 5
1.2 C MOS Sensor‐based Lab‐on‐a‐Chip for System Miniaturization 7
1.2.1 CMOS Sensor‐based Lab‐on‐a‐Chip 7
1.2.2 CMOS Sensor 8
1.2.2.1 CMOS Process Fundamentals 8
1.2.2.2 CMOS Sensor Technology 10
1.2.2.3 Multimodal CMOS Sensor 13
1.2.3 Microfluidics 14
1.2.3.1 Microfluidic Fundamentals 14
1.2.3.2 Microfluidics Fabrication 16
1.3 O bjectives and Organization of this Book 20
1.3.1 Objectives 20
1.3.2 Organization 20
References 21
2 CMOS Sensor Design 25
2.1 T op Architecture 25
2.2 N oise Overview 25
2.2.1 Thermal Noise 26
2.2.2 Flicker Noise 27
2.2.3 Shot Noise 28
2.2.4 MOSFET Noise Model 29
2.3 P ixel Readout Circuit 29
2.3.1 Source Follower 30
2.3.2 Sub‐threshold Gm Integrator 33
2.3.3 CTIA 35
2.4 C olumn Amplifier 38
vi Contents
2.5 C olumn ADC 39
2.5.1 Single‐Slope ADC 39
2.5.2 Sigma‐Delta ADC 43
2.6 C orrelated Sampling 49
2.6.1 Correlated Double Sampling 49
2.6.2 Correlated Multiple Sampling 51
2.7 T iming Control 52
2.7.1 Row Timing Control 52
2.7.2 Column Timing Control 55
2.8 L VDS Interface 57
References 59
3 CMOS Impedance Sensor 60
3.1 I ntroduction 60
3.2 CMOS Impedance Pixel 61
3.3 R eadout Circuit 63
3.4 A 96 × 96 Electronic Impedance Sensing System 65
3.4.1 Top Architecture 65
3.4.2 System Implementation 67
3.4.2.1 System Setup 67
3.4.2.2 Sample Preparation 68
3.4.3 Results 68
3.4.3.1 Data Fitting for Single Cell Impedance Measurement 69
3.4.3.2 Cell and Electrode Impedance Analysis 71
3.4.3.3 EIS for Single‐Cell Impedance Enumeration 71
References 74
4 CMOS Terahertz Sensor 76
4.1 I ntroduction 76
4.2 CMOS THz Pixel 76
4.2.1 Differential TL‐SRR Resonator Design 76
4.2.1.1 Stacked SRR Layout 76
4.2.1.2 Comparison with Single‐ended TL‐SRR Resonator 80
4.2.1.3 Comparison with Standing‐Wave Resonator 82
4.2.2 Differential TL‐CSRR Resonator Design 83
4.3 R eadout Circuit 84
4.3.1 Super‐regenerative Amplification 84
4.3.1.1 Equivalent Circuit of SRA 84
4.3.1.2 Frequency Response of SRA 86
4.3.1.3 Sensitivity of SRA 86
4.3.2 Super‐regenerative Receivers 87
4.3.2.1 Quench‐controlled Oscillation 87
4.3.2.2 SRX Design by TL‐CSRR 89
4.3.2.3 SRX Design by TL‐SRR 91
4.4 A 135 GHz Imager 94
4.4.1 135 GHz DTL‐SRR‐based Receiver 94
4.4.2 System Implementation 95
Contents vii
4.4.3 Results 95
4.5 P lasmonic Sensor for Circulating Tumor Cell Detection 98
4.5.1 Introduction of CTC Detection 98
4.5.2 SRR‐based Oscillator for CTC Detection 99
4.5.3 Sensitivity of SRR‐based Oscillator 101
References 103
5 CMOS Ultrasound Sensor 106
5.1 I ntroduction 106
5.2 C MUT Pixel 107
5.3 R eadout Circuit 109
5.4 A 320 × 320 CMUT‐based Ultrasound Imaging System 110
5.4.1 Top Architecture 110
5.4.2 System Implementation 111
5.4.2.1 Process Selection 111
5.4.2.2 High Voltage Pulser 112
5.4.2.3 Low‐Noise Preamplifier and High Voltage Switch 115
5.4.3 Results 116
5.4.3.1 Simulation Results 116
5.4.3.2 Two‐channel AFE IC Measurement Results 117
5.4.3.3 Acoustic Transmission Testing with AFE IC and CMUT 121
5.4.3.4 Acoustic Pulse‐echo Testing with AFE IC and CMUT 122
References 124
6 CMOS 3‐D‐Integrated MEMS Sensor 126
6.1 I ntroduction 126
6.2 M EMS Sensor 127
6.3 R eadout Circuit 127
6.4 A 3‐D TSV‐less Accelerometer 129
6.4.1 CMOS‐on‐MEMS Stacking 129
6.4.2 Bonding Reliability 132
6.4.2.1 Al–Au Thermo‐compression Shear Strength 132
6.4.2.2 Al–Au Thermo‐compression Hermeticity 134
6.4.3 Results 135
6.4.3.1 Standalone Validation of the Readout Circuit 135
6.4.3.2 Functionality Testing of CMOS‐on‐MEMS Chip 136
6.4.3.3 Reliability Testing of CMOS‐on‐MEMS Chip 138
References 141
7 CMOS Image Sensor 142
7.1 I ntroduction 142
7.2 C MOS Image Pixel 145
7.2.1 Structure 145
7.2.1.1 FSI 4 T Pixel 145
7.2.1.2 Back Side Illumination Pixel 147
7.2.1.3 Stack Pixel 148
7.2.2 Noise and Model 150
viii Contents
7.2.2.1 Photon Shot Noise 151
7.2.2.2 Reset Noise 152
7.2.2.3 Thermal Noise 152
7.2.2.4 Flicker Noise 154
7.2.2.5 Fixed Pattern Noise 154
7.3 R eadout Circuit 155
7.3.1 Global Serial Readout 156
7.3.2 Correlated Double Sampling 156
7.4 A 3.2 Mega CMOS Image Sensor 158
7.4.1 4‐way Shared Pixel Unit 158
7.4.2 Top Architecture 159
7.4.3 System Implementation 162
7.4.4 Results 164
7.4.4.1 System Characterization 164
7.4.4.2 Digital CDS for FPN Reduction 164
7.4.4.3 Blood Cell Imaging Experiments 165
References 167
8 CMOS Dual‐mode pH‐Image Sensor 169
8.1 I ntroduction 169
8.2 CMOS Dual‐mode pH‐Image Pixel 170
8.3 R eadout Circuit 172
8.3.1 CDS for Optical Sensing 174
8.3.2 CDS for Chemical Sensing 174
8.4 A 64 × 64 Dual‐mode pH‐Image Sensor 175
8.4.1 Top Architecture 175
8.4.2 System Implementation 177
8.4.3 Results 177
References 184
9 CMOS Dual‐mode Energy‐harvesting‐image Sensor 186
9.1 I ntroduction 186
9.2 C MOS EHI Pixel 187
9.3 R eadout Circuit 191
9.4 A 96 × 96 EHI Sensing System 195
9.4.1 Top Architecture 195
9.4.2 System Implementation 197
9.4.3 Results 203
References 211
10 DNA Sequencing 213
10.1 I ntroduction 213
10.2 CMOS ISFET‐based Sequencing 213
10.2.1 Overview 213
10.2.2 ISFET‐based Sequencing Procedure 215
10.3 CMOS THz‐based Genotyping 220
10.3.1 Overview 220