A 12.8 k Current-Mode Velocity-Saturation ISFET Array for On-Chip Real-Time DNA Detection

This paper presents a large-scale CMOS chemical-sensing array operating in current mode for real-time ion imaging and detection of DNA amplification. We show that the current-mode operation of ion-sensitive field-effect transistors in velocity saturation devices can be exploited to achieve an almost perfect linearity in their input–output characteristics (pH-current), which are aligned with the continuous scaling trend of transistors in CMOS. The array is implemented in a 0.35-<inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>m process and includes 12.8 k sensors configured in a 2T per pixel topology. We characterize the array by taking into account nonideal effects observed with floating gate devices, such as increased pixel mismatch due to trapped charge and attenuation of the input signal due to the passivation capacitance, and show that the selected biasing regime allows for a sufficiently large linear range that ensures a linear pH to current despite the increased mismatch. The proposed system achieves a sensitivity of 1.03 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>A/pH with a pH resolution of 0.101 pH and is suitable for the real-time detection of the NDM carbapenemase gene in <italic> E. Coli</italic> using a loop-mediated isothermal amplification.

[1]  Jan Van der Spiegel,et al.  Low Fixed Pattern Noise Current-mode Imager Using Velocity Saturated Readout Transistors , 2007, 2007 IEEE International Symposium on Circuits and Systems.

[2]  Eun Kyu Lee,et al.  Loop Mediated Isothermal Amplification of DNA , 2008 .

[3]  ChengCancan,et al.  Rapid detection of blaNDM, blaKPC, blaIMP, and blaVIM carbapenemase genes in bacteria by loop-mediated isothermal amplification. , 2014 .

[4]  C. Toumazou,et al.  Weak Inversion ISFETs for ultra-low power biochemical sensing and real-time analysis , 2005 .

[5]  Pantelis Georgiou,et al.  Impact of Technology Scaling on ISFET Performance for Genetic Sequencing , 2015, IEEE Sensors Journal.

[6]  Nicolas Moser,et al.  A 32 $\times$ 32 ISFET Chemical Sensing Array With Integrated Trapped Charge and Gain Compensation , 2017, IEEE Sensors Journal.

[7]  J. Eijkel,et al.  A novel description of ISFET sensitivity with the buffer capacity and double-layer capacitance as key parameters , 1995 .

[8]  Hao Feng,et al.  A High-Sensitivity Potentiometric 65-nm CMOS ISFET Sensor for Rapid E. coli Screening , 2018, IEEE Transactions on Biomedical Circuits and Systems.

[9]  Luca Selmi,et al.  Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint , 2016, Biosensors.

[10]  Pantelis Georgiou,et al.  Linear current-mode ISFET arrays , 2016, 2016 IEEE International Symposium on Circuits and Systems (ISCAS).

[11]  S. Jamasb.  An analytical technique for counteracting drift in ion-selective field effect transistors (ISFETs) , 2004, IEEE Sensors Journal.

[12]  Nicolas Moser,et al.  An ion imaging ISFET array for Potassium and Sodium detection , 2016, 2016 IEEE International Symposium on Circuits and Systems (ISCAS).

[13]  A. Errachid,et al.  ION-SENSITIVE FIELD-EFFECT TRANSISTORS FABRICATED IN A COMMERCIAL CMOS TECHNOLOGY , 1999 .

[14]  Nicolas Moser,et al.  A robust ISFET array with in-pixel quantisation and automatic offset calibration , 2016, 2016 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[15]  Hao Yu,et al.  A Dual-Mode Large-Arrayed CMOS ISFET Sensor for Accurate and High-Throughput pH Sensing in Biomedical Diagnosis , 2015, IEEE Transactions on Biomedical Engineering.

[16]  Christofer Toumazou,et al.  CMOS-based programmable gate ISFET , 2008 .

[17]  Yongyu Rui,et al.  Rapid detection of blaNDM, blaKPC, blaIMP, and blaVIM carbapenemase genes in bacteria by loop-mediated isothermal amplification. , 2014, Microbial drug resistance.

[18]  Bernard P. Puc,et al.  An integrated semiconductor device enabling non-optical genome sequencing , 2011, Nature.

[19]  Viktor Gruev,et al.  Current-Mode CMOS Imaging Sensor With Velocity Saturation Mode of Operation and Feedback Mechanism , 2014, IEEE Sensors Journal.

[20]  Christofer Toumazou,et al.  ISFETs in CMOS and Emergent Trends in Instrumentation: A Review , 2016, IEEE Sensors Journal.

[21]  Christofer Toumazou,et al.  Live demonstration: A CMOS-based ISFET array for rapid diagnosis of the Zika virus , 2017, 2017 IEEE International Symposium on Circuits and Systems (ISCAS).

[22]  Piet Bergveld,et al.  Thirty years of ISFETOLOGY ☆: What happened in the past 30 years and what may happen in the next 30 years , 2003 .

[23]  M. Fukuma,et al.  Effects of the velocity saturated region on MOSFET characteristics , 1994 .

[24]  C. Toumazou,et al.  A CMOS-Based ISFET Chemical Imager With Auto-Calibration Capability , 2011, IEEE Sensors Journal.

[25]  Eugenio Culurciello,et al.  Noise Analysis and Performance Comparison of Low Current Measurement Systems for Biomedical Applications , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[26]  Timothy G. Constandinou,et al.  A multichannel DNA SoC for rapid point-of-care gene detection , 2010, 2010 IEEE International Solid-State Circuits Conference - (ISSCC).

[27]  D. Cumming,et al.  High-resolution real-time ion-camera system using a CMOS-based chemical sensor array for proton imaging , 2012 .

[28]  M.J. Milgrew,et al.  A proton camera array technology for direct extracellular ion imaging , 2008, 2008 IEEE International Symposium on Industrial Electronics.

[29]  Christofer Toumazou,et al.  ISFET characteristics in CMOS and their application to weak inversion operation , 2009 .

[30]  Lin Li,et al.  CMOS Electrochemical Instrumentation for Biosensor Microsystems: A Review , 2016, Sensors.

[31]  C. Toumazou,et al.  Simultaneous DNA amplification and detection using a pH-sensing semiconductor system , 2013, Nature Methods.

[32]  Erika Check Hayden,et al.  Technology: The $1,000 genome , 2014, Nature.

[33]  C. Toumazou,et al.  An Extended CMOS ISFET Model Incorporating the Physical Design Geometry and the Effects on Performance and Offset Variation , 2011, IEEE Transactions on Electron Devices.

[34]  Franziska Hoffmann,et al.  Design Of Analog Cmos Integrated Circuits , 2016 .

[35]  Thierry Naas,et al.  Global Spread of Carbapenemase-producing Enterobacteriaceae , 2011, Emerging infectious diseases.

[36]  Melpomeni Kalofonou,et al.  Semiconductor technology for early detection of DNA methylation for cancer: From concept to practice , 2013 .

[37]  P. Bergveld,et al.  Operation of chemically sensitive field-effect sensors as a function of the insulator-electrolyte interface , 1983, IEEE Transactions on Electron Devices.

[38]  Pantelis Georgiou,et al.  A Robust ISFET pH-Measuring Front-End for Chemical Reaction Monitoring , 2014, IEEE Transactions on Biomedical Circuits and Systems.

[39]  S. D. Collins,et al.  A physical model for drift in pH ISFETs , 1998 .