A 30.3 fA/√Hz Biosensing Current Front-End With 139 dB Cross-Scale Dynamic Range

This paper presents an 8-channel array of low-noise (30.3 fA/√Hz) current sensing front-ends with on-chip microelectrode electrochemical sensors. The analog front-end (AFE) consists of a 1st-order continuous-time delta-sigma (CT ΔΣ) modulator that achieves 123 fA sensitivity over a 10 Hz bandwidth and 139 dB cross-scale dynamic range with a 2-bit programmable current reference. A digital predictor and tri-level pulse width modulated (PWM) current-steering DAC realize the equivalent performance of a multi-bit ΔΣ in an area- and power-efficient manner. The AFE consumes 50.3 µW and 0.11 mm2 per readout channel. The proposed platform was used to observe protein-ligand interactions in real-time using transient induced molecular electronic spectroscopy (TIMES), a label- and immobilization-free biosensing technique.

[1]  Drew A. Hall,et al.  Current Sensing Front-Ends: A Review and Design Guidance , 2021, IEEE Sensors Journal.

[2]  Shao-Yung Lu,et al.  A 19 μW, 50 kS/s, 0.008-400 V/s Cyclic Voltammetry Readout Interface With a Current Feedback Loop and On-Chip Pattern Generation , 2021, IEEE Transactions on Biomedical Circuits and Systems.

[3]  Drew A. Hall,et al.  A 2-in-1 Temperature and Humidity Sensor With a Single FLL Wheatstone-Bridge Front-End , 2020, IEEE Journal of Solid-State Circuits.

[4]  Y. Lo,et al.  Detecting Protein-Ligand Interaction from Integrated Transient Induced Molecular Electronic Signal (i-TIMES). , 2020, Analytical chemistry.

[5]  Albert Yen-Chih Chiou,et al.  9.1 A Current-Sensing Front-End Realized by A Continuous-Time Incremental ADC with 12b SAR Quantizer and Reset-Then-Open Resistive DAC Achieving 140dB DR and 8ppm INL at 4kS/s , 2020, 2020 IEEE International Solid- State Circuits Conference - (ISSCC).

[6]  Y. Lo,et al.  Measuring Electric Charge and Molecular Coverage on Electrode Surface from Transient Induced Molecular Electronic Signal (TIMES) , 2019, Scientific Reports.

[7]  Ross M. Walker,et al.  Low-Noise Integrated Potentiostat for Affinity-Free Protein Detection With 12 nV/rt-Hz at 30 Hz and 1.8 pArms Resolution , 2019, IEEE Solid-State Circuits Letters.

[8]  Drew A. Hall,et al.  A Sub-pA Current Sensing Front-End for Transient Induced Molecular Spectroscopy , 2019, 2019 Symposium on VLSI Circuits.

[9]  Chung-Lun Hsu,et al.  A current-measurement front-end with 160dB dynamic range and 7ppm INL , 2018, 2018 IEEE International Solid - State Circuits Conference - (ISSCC).

[10]  Andrew J. Mason,et al.  Ultracompact Microwatt CMOS Current Readout With Picoampere Noise and Kilohertz Bandwidth for Biosensor Arrays , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[11]  Giovanni De Micheli,et al.  A Differential Electrochemical Readout ASIC With Heterogeneous Integration of Bio-Nano Sensors for Amperometric Sensing , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[12]  Hwasuk Cho,et al.  A Low-Power Wide Dynamic-Range Current Readout Circuit for Ion-Sensitive FET Sensors , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[13]  B. Peterson,et al.  Quantification of Small Molecule–Protein Interactions using FRET between Tryptophan and the Pacific Blue Fluorophore , 2016, ACS omega.

[14]  Y. Lo,et al.  Protein–Ligand Interaction Detection with a Novel Method of Transient Induced Molecular Electronic Spectroscopy (TIMES): Experimental and Theoretical Studies , 2016, ACS central science.

[15]  Y. Lo,et al.  Transient Induced Molecular Electronic Spectroscopy (TIMES) for study of protein-ligand interactions , 2016, Scientific Reports.

[16]  Andrew J. Mason,et al.  CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring , 2016, IEEE Transactions on Biomedical Circuits and Systems.

[17]  R. W. Hansen,et al.  Innovation in the pharmaceutical industry: New estimates of R&D costs. , 2016, Journal of health economics.

[18]  Pavan Kumar Hanumolu,et al.  A Highly Digital VCO-Based ADC Architecture for Current Sensing Applications , 2015, IEEE Journal of Solid-State Circuits.

[19]  Nan Sun,et al.  Predicting ADC: A new approach for low power ADC design , 2014, 2014 IEEE Dallas Circuits and Systems Conference (DCAS).

[20]  Roman Genov,et al.  CMOS Neurotransmitter Microarray: 96-Channel Integrated Potentiostat With On-Die Microsensors , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[21]  Amy E Herr,et al.  Microfluidic Western blotting , 2012, Proceedings of the National Academy of Sciences.

[22]  A. Manz,et al.  Revisiting lab-on-a-chip technology for drug discovery , 2012, Nature Reviews Drug Discovery.

[23]  Bingling Li,et al.  A fully-electronic charge-based DNA sequencing CMOS biochip , 2012, 2012 Symposium on VLSI Circuits (VLSIC).

[24]  Jacob D. Durrant,et al.  Molecular dynamics simulations and drug discovery , 2011, BMC Biology.

[25]  J. Hafner,et al.  Localized surface plasmon resonance sensors. , 2011, Chemical reviews.

[26]  Yuyuan Tian,et al.  Study of single particle charge and Brownian motions with surface plasmon resonance. , 2010, Applied physics letters.

[27]  Daehwa Paik,et al.  A low-noise self-calibrating dynamic comparator for high-speed ADCs , 2008, 2008 IEEE Asian Solid-State Circuits Conference.

[28]  Kok Lim Chan,et al.  Segmented Dynamic Element Matching for High-Resolution Digital-to-Analog Conversion , 2008, IEEE Transactions on Circuits and Systems I: Regular Papers.

[29]  L. Hellman,et al.  Electrophoretic mobility shift assay (EMSA) for detecting protein–nucleic acid interactions , 2007, Nature Protocols.

[30]  Kartikeya Murari,et al.  VLSI Potentiostat Array With Oversampling Gain Modulation for Wide-Range Neurotransmitter Sensing , 2007, IEEE Transactions on Biomedical Circuits and Systems.

[31]  Kevin W Plaxco,et al.  Biosensors based on binding-modulated donor-acceptor distances. , 2005, Trends in biotechnology.

[32]  Gabor C. Temes,et al.  Understanding Delta-Sigma Data Converters , 2004 .

[33]  Bernabé Linares-Barranco,et al.  On the design and characterization of femtoampere current-mode circuits , 2003, IEEE J. Solid State Circuits.

[34]  S. Schreiber,et al.  Printing proteins as microarrays for high-throughput function determination. , 2000, Science.

[35]  John Choma,et al.  A continuous-time common-mode feedback circuit (CMFB) for high-impedance current-mode applications , 2000 .

[36]  J. Drews.  Drug discovery: a historical perspective. , 2000, Science.

[37]  A. Hassibi,et al.  A CMOS Electrochemical Biochip With 32×32 Three-Electrode Voltammetry Pixels , 2019 .

[38]  Woojun Choi,et al.  A Compact Resistor-Based CMOS Temperature Sensor With an Inaccuracy of 0.12 C (3) and a Resolution FoM of 0.43 pJ,,K in 65-nm CMOS , 2018 .

[39]  Kofi A. A. Makinwa,et al.  Delft University of Technology A Resistor-Based Temperature Sensor With a 0.13 pJ·K2 Resolution FoM , 2016 .

[40]  K. Jalink,et al.  Fluorescence resonance energy transfer microscopy (FRET). , 2015, Methods in molecular biology.

[41]  K. Foley,et al.  Measuring surface charge density and particle height using surface plasmon resonance technique. , 2010, Analytical chemistry.

[42]  Francisco Colodro Ruiz,et al.  New Continuous-Time Multibit Sigma–Delta Modulators With Low Sensitivity to Clock Jitter , 2009, IEEE Transactions on Circuits and Systems I: Regular Papers.

[43]  Maurits Ortmanns,et al.  Continuous time sigma-delta A/D conversion : fundamentals, performance limits and robust implementations , 2006 .