Toward High Throughput Core-CBCM CMOS Capacitive Sensors for Life Science Applications: A Novel Current-Mode for High Dynamic Range Circuitry

This paper proposes a novel charge-based Complementary Metal Oxide Semiconductor (CMOS) capacitive sensor for life science applications. Charge-based capacitance measurement (CBCM) has significantly attracted the attention of researchers for the design and implementation of high-precision CMOS capacitive biosensors. A conventional core-CBCM capacitive sensor consists of a capacitance-to-voltage converter (CVC), followed by a voltage-to-digital converter. In spite of their high accuracy and low complexity, their input dynamic range (IDR) limits the advantages of core-CBCM capacitive sensors for most biological applications, including cellular monitoring. In this paper, after a brief review of core-CBCM capacitive sensors, we address this challenge by proposing a new current-mode core-CBCM design. In this design, we combine CBCM and current-controlled oscillator (CCO) structures to improve the IDR of the capacitive readout circuit. Using a 0.18 μm CMOS process, we demonstrate and discuss the Cadence simulation results to demonstrate the high performance of the proposed circuitry. Based on these results, the proposed circuit offers an IDR ranging from 873 aF to 70 fF with a resolution of about 10 aF. This CMOS capacitive sensor with such a wide IDR can be employed for monitoring cellular and molecular activities that are suitable for biological research and clinical purposes.

[1]  J. Jacob Wikner,et al.  A highly sensitive, low-power, and wide dynamic range CMOS digital pixel sensor , 2015 .

[2]  Marco Carminati,et al.  28.7 CMOS monolithic airborne-particulate-matter detector based on 32 capacitive sensors with a resolution of 65zF rms , 2016, 2016 IEEE International Solid-State Circuits Conference (ISSCC).

[3]  Javed S. Gaggatur,et al.  High Gain Capacitance Sensor Interface for the Monitoring of Cell Volume Growth , 2017, 2017 30th International Conference on VLSI Design and 2017 16th International Conference on Embedded Systems (VLSID).

[4]  Mohamad Sawan,et al.  Novel direct-write CMOS-based laboratory-on-chip: Design, assembly and experimental results , 2007 .

[5]  Siddhartha Sen,et al.  A Differential Output Interfacing ASIC for Integrated Capacitive Sensors , 2018, IEEE Transactions on Instrumentation and Measurement.

[6]  C. Hu,et al.  Investigation of interconnect capacitance characterization using charge-based capacitance measurement (CBCM) technique and three-dimensional simulation , 1998 .

[7]  Giancarlo Ferrigno,et al.  Perspectives on MEMS in bioengineering: a novel capacitive position microsensor [and laser surgery and drug delivery applications] , 2000, IEEE Transactions on Biomedical Engineering.

[8]  Pamela Abshire,et al.  Real-Time Measurements of Cell Proliferation Using a Lab-on-CMOS Capacitance Sensor Array , 2018, IEEE Transactions on Biomedical Circuits and Systems.

[9]  Qing-An Huang,et al.  LC Wireless Sensitive Pressure Sensors With Microstructured PDMS Dielectric Layers for Wound Monitoring , 2018, IEEE Sensors Journal.

[10]  Zhiyu Wang,et al.  A New Capacitance-to-Frequency Converter for On-Chip Capacitance Measurement and Calibration in CMOS Technology , 2016, J. Electron. Test..

[11]  Madhurima Chattopadhyay,et al.  A new scheme for reducing breathing trouble through MEMS based capacitive pressure sensor , 2016 .

[12]  Jin Liu,et al.  Reduced setup time static D flip-flop , 2001 .

[13]  P. Abshire,et al.  On-Chip Capacitance Sensing for Cell Monitoring Applications , 2007, IEEE Sensors Journal.

[14]  Mohamad Sawan,et al.  A 0.18-μm CMOS capacitive sensor Lab-on-Chip , 2008 .

[15]  Pamela Abshire,et al.  Characterization of a high dynamic range lab-on-CMOS capacitance sensor array , 2017, 2017 IEEE International Symposium on Circuits and Systems (ISCAS).

[16]  J.C. Chen,et al.  An on-chip, attofarad interconnect charge-based capacitance measurement (CBCM) technique , 1996, International Electron Devices Meeting. Technical Digest.

[17]  An-Yu Chang,et al.  A CMOS magnetic microbead-based capacitive biosensor array with on-chip electromagnetic manipulation. , 2013, Biosensors & bioelectronics.

[18]  Yue Huang,et al.  Lab-on-CMOS: Integrating microfluidics and electrochemical sensor on CMOS , 2011, 2011 6th IEEE International Conference on Nano/Micro Engineered and Molecular Systems.

[19]  Marcelo Mulato,et al.  Highly sensitive dual mode electrochemical platform for microRNA detection , 2016, Scientific Reports.

[20]  Mohamad Sawan,et al.  A 64 pixel ISFET-based biosensor for extracellular pH gradient monitoring , 2015, 2015 IEEE International Symposium on Circuits and Systems (ISCAS).

[21]  Yutao Qin,et al.  A fully electronic microfabricated gas chromatograph with complementary capacitive detectors for indoor pollutants , 2016, Microsystems & Nanoengineering.

[22]  Jijun Xiong,et al.  Wireless flexible pressure sensor based on micro-patterned Graphene/PDMS composite , 2018, Sensors and Actuators A: Physical.

[23]  O. Wolfbeis,et al.  Capacitive monitoring of protein immobilization and antigen-antibody reactions on monomolecular alkylthiol films on gold electrodes. , 1997, Biosensors & bioelectronics.

[24]  Mohamad Sawan,et al.  A Core-CBCM sigma delta capacitive sensor array dedicated to lab-on-chip applications , 2008 .

[25]  E. Ghafar-Zadeh,et al.  Charge-Based Capacitive Sensor Array for CMOS-Based Laboratory-on-Chip Applications , 2006, IEEE Sensors Journal.

[26]  Fang Fang,et al.  A glass microfluidic chip for continuous blood cell sorting by a magnetic gradient without labeling , 2008, Analytical and bioanalytical chemistry.

[27]  Christoph Hagleitner,et al.  CMOS single-chip gas detection system comprising capacitive, calorimetric and mass-sensitive microsensors , 2002, IEEE J. Solid State Circuits.

[28]  M. Kraft,et al.  A high precision MEMS based capacitive accelerometer for seismic measurements , 2017, 2017 IEEE SENSORS.

[29]  Mohamad Sawan,et al.  A New Fully Differential CMOS Capacitance to Digital Converter for Lab-on-Chip Applications , 2015, IEEE Transactions on Biomedical Circuits and Systems.

[30]  R. Thewes,et al.  A Fully Electronic Label-Free DNA Sensor Chip , 2007, IEEE Sensors Journal.

[31]  R. Guerrieri,et al.  Capacitive sensor array for localization of bioparticles in CMOS lab-on-a-chip , 2004, 2004 IEEE International Solid-State Circuits Conference (IEEE Cat. No.04CH37519).

[32]  Denis Flandre,et al.  A 16 $\times$ 16 CMOS Capacitive Biosensor Array Towards Detection of Single Bacterial Cell , 2016, IEEE Transactions on Biomedical Circuits and Systems.

[33]  A. Matsuzawa,et al.  A 0.026mm2 capacitance-to-digital converter for biotelemetry applications using a charge redistribution technique , 2007, 2007 IEEE Asian Solid-State Circuits Conference.

[34]  Pamela Abshire,et al.  System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces , 2016, IEEE Transactions on Biomedical Circuits and Systems.

[35]  Marco Carminati,et al.  Multichannel 65 zF rms Resolution CMOS Monolithic Capacitive Sensor for Counting Single Micrometer-Sized Airborne Particles on Chip , 2016, IEEE Journal of Solid-State Circuits.

[36]  Yutaka Nonomura,et al.  Surface-mountable capacitive tactile sensors with flipped CMOS-diaphragm on a flexible and stretchable bus line☆ , 2016 .

[37]  Ebrahim Ghafar-Zadeh,et al.  Bacteria Growth Monitoring Through a Differential CMOS Capacitive Sensor , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[38]  C. Toumazou,et al.  Biocompatible encapsulation of CMOS based chemical sensors , 2009, 2009 IEEE Sensors.

[39]  John C. Batchelor,et al.  Two Solutions of Soil Moisture Sensing with RFID for Landslide Monitoring , 2018, Sensors.

[40]  L. Benini,et al.  CMOS DNA Sensor Array With Integrated A/D Conversion Based on Label-Free Capacitance Measurement , 2006, IEEE Journal of Solid-State Circuits.

[41]  F. S. Lai,et al.  Differential cascode voltage switch with the pass-gate (DCVSPG) logic tree for high performance CMOS digital systems , 1993, 1993 International Symposium on VLSI Technology, Systems, and Applications Proceedings of Technical Papers.

[42]  J. Jacob Wikner,et al.  A low-power wide tuning-range CMOS current-controlled oscillator , 2016, Integr..

[43]  J. Hruby Overview of LIGA Microfabrication , 2002 .

[44]  Andrew J. Mason,et al.  Post-CMOS parylene packaging for on-chip biosensor arrays , 2010, 2010 IEEE Sensors.

[45]  Khaled N. Salama,et al.  A Biosensor-CMOS Platform and Integrated Readout Circuit in 0.18-μm CMOS Technology for Cancer Biomarker Detection , 2017, Sensors.

[46]  Jeffrey R. Alcock,et al.  Micro-injection moulding of polymer microfluidic devices , 2009 .

[47]  Geoff Walker,et al.  A review of technologies for sensing contact location on the surface of a display , 2012 .

[48]  Antonio Baldi,et al.  Integration of microelectronic chips in microfluidic systems on printed circuit board , 2012 .

[49]  Luca Selmi,et al.  A CMOS Pixelated Nanocapacitor Biosensor Platform for High-Frequency Impedance Spectroscopy and Imaging , 2018, IEEE Transactions on Biomedical Circuits and Systems.

[50]  Erik Jensen,et al.  Modular integration of electronics and microfluidic systems using flexible printed circuit boards. , 2010, Lab on a chip.

[51]  Raghavendra B. Deshmukh,et al.  Dynamic capacitive sensing of droplet parameters in a low-cost open EWOD system , 2017 .

[52]  Michael S.-C. Lu,et al.  5×5 CMOS capacitive sensor array for detection of the neurotransmitter dopamine. , 2010, Biosensors & bioelectronics.

[53]  Ebrahim Ghafar-Zadeh,et al.  Towards High Throughput Cell Growth Screening: A New CMOS 8 $\times$ 8 Biosensor Array for Life Science Applications , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[54]  Gyu-Hyeong Cho,et al.  CMOS capacitive biosensor with enhanced sensitivity for label-free DNA detection , 2012, 2012 IEEE International Solid-State Circuits Conference.

[57]  Lin Li,et al.  Epoxy Chip-in-Carrier Integration and Screen-Printed Metalization for Multichannel Microfluidic Lab-on-CMOS Microsystems , 2018, IEEE Transactions on Biomedical Circuits and Systems.

[58]  Ebrahim Ghafar-Zadeh,et al.  A Hybrid Microfluidic/CMOS Capacitive Sensor Dedicated to Lab-on-Chip Applications , 2007, IEEE Transactions on Biomedical Circuits and Systems.

[59]  Douglas J. Thomson,et al.  Integrated 0.35 pm CMOS capacitance sensor with atto-farad sensitivity for single cell analysis , 2016, 2016 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[60]  Holger Becker,et al.  Hot embossing as a method for the fabrication of polymer high aspect ratio structures , 2000 .

[61]  Daniela De Venuto,et al.  Design of an integrated low-noise read-out system for DNA capacitive sensors , 2009, Microelectron. J..

[62]  T. Knowles,et al.  Microfluidic devices fabricated using fast wafer-scale LED-lithography patterning. , 2017, Biomicrofluidics.

[63]  Frédéric Reymond,et al.  Polymer microfluidic chips for electrochemical and biochemical analyses , 2002, Electrophoresis.

[64]  Marco Carminati,et al.  ZeptoFarad capacitance detection with a miniaturized CMOS current front-end for nanoscale sensors , 2011 .

[65]  Mona E. Zaghloul,et al.  Flexible packaging of solid-state integrated circuit chips with elastomeric microfluidics , 2013, Scientific Reports.

[66]  Mustafa Tahsin Guler,et al.  Capacitive detection of single bacterium from drinking water with a detailed investigation of electrical flow cytometry , 2018 .

[67]  Albert Folch,et al.  The upcoming 3D-printing revolution in microfluidics. , 2016, Lab on a chip.

[68]  Prem Pal,et al.  Various shapes of silicon freestanding microfluidic channels and microstructures in one-step lithography , 2009 .

[69]  Ali Hajimiri,et al.  A magnetic cell-based sensor. , 2012, Lab on a chip.

[70]  S.B. Prakash,et al.  A Fully Differential Rail-to-Rail Capacitance Measurement Circuit for Integrated Cell Sensing , 2007, 2007 IEEE Sensors.

[71]  M. Sawan,et al.  High accuracy differential capacitive circuit for bioparticles sensing applications , 2005, 48th Midwest Symposium on Circuits and Systems, 2005..

[72]  Pamela Abshire,et al.  A Fully Differential Rail-to-Rail CMOS Capacitance Sensor With Floating-Gate Trimming for Mismatch Compensation , 2009, IEEE Transactions on Circuits and Systems I: Regular Papers.

[73]  Khaled N. Salama,et al.  A Precision, Energy-Efficient, Oversampling, Noise-Shaping Differential SAR Capacitance-to-Digital Converter , 2019, IEEE Transactions on Instrumentation and Measurement.

[74]  Pamela Abshire,et al.  High resolution capacitance sensor array for real-time monitoring of cell viability , 2014, 2014 IEEE International Symposium on Circuits and Systems (ISCAS).

[75]  Pamela Abshire,et al.  Lab-on-CMOS capacitance sensor array for real-time cell viability measurements with I2C readout , 2016, 2016 IEEE International Symposium on Circuits and Systems (ISCAS).

[76]  Pamela Abshire,et al.  Tracking cancer cell proliferation on a CMOS capacitance sensor chip. , 2008, Biosensors & bioelectronics.

[77]  T. York,et al.  Microelectronic capacitance transducer for particle detection , 2004, IEEE Sensors Journal.

[78]  D. De Venuto,et al.  Design of an integrated low-noise read-out system for DNA capacitive sensors , 2007, 2007 2nd International Workshop on Advances in Sensors and Interface.