A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell

Semiconductor genetics is now disrupting the field of healthcare owing to the rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect transistors (ISFETs) fabricated using commercial complementary metal -oxide semiconductor technology. The enabling concept of DNA reaction monitoring introduced by Toumazou has made this a reality and we are now seeing relentless scaling with Moore's law ultimately achieving the $100 genome. In this paper, we present the next evolution of this technology through the creation of the gene-sensitive integrated cell (GSIC) for label-free real-time analysis based on ISFETs. This device is derived from the traditional metal-oxide semiconductor field-effect transistor (MOSFET) and has electrical performance identical to that of a MOSFET in a standard semiconductor process, yet is capable of incorporating DNA reaction chemistries for applications in single nucleotide polymorphism microarrays and DNA sequencing. Just as application-specific integrated circuits, which are developed in much the same way, have shaped our consumer electronics industry and modern communications and memory technology, so, too, do GSICs based on a single underlying technology principle have the capacity to transform the life science and healthcare industries.

[1]  Kazuo Nakazato,et al.  An Integrated ISFET Sensor Array , 2009, Sensors.

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

[3]  Christofer Toumazou,et al.  PG-ISFET based DNA-logic for reaction monitoring , 2010 .

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

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

[6]  A. Sibbald,et al.  A miniature flow-through cell with a four-function chemfet integrated circuit for simultaneous measurements of potassium, hydrogen, calcium and sodium ions , 1984 .

[7]  David R. S. Cumming,et al.  The development of scalable sensor arrays using standard CMOS technology , 2004 .

[8]  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).

[9]  Christofer Toumazou,et al.  An adaptive ISFET chemical imager chip , 2008, 2008 IEEE International Symposium on Circuits and Systems.

[10]  A. A. Shul'ga,et al.  Overall characterization of ISFET-based glucose biosensor , 1992 .

[11]  C. Toumazou,et al.  64 pH-ISFET averaging array employing global negative current feedback , 2009 .

[12]  D. R. S. Cumming,et al.  High-Speed Imaging of 2-D Ionic Diffusion Using a 16$\,\times\,$16 Pixel CMOS ISFET Array on the Microfluidic Scale , 2012, IEEE Sensors Journal.

[13]  Christofer Toumazou,et al.  Apparatus and method for detecting ionic charge localized fluctuations during a chemical reaction by using field effect transistors ion sensitive , 2002 .

[14]  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 .

[15]  M. J. Milgrew,et al.  A large transistor-based sensor array chip for direct extracellular imaging , 2005 .

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

[17]  Christofer Toumazou,et al.  An ISFET based sensing array with sensor offset compensation and pH sensitivity enhancement , 2010, Proceedings of 2010 IEEE International Symposium on Circuits and Systems.

[18]  G.E. Moore,et al.  Cramming More Components Onto Integrated Circuits , 1998, Proceedings of the IEEE.

[19]  C. Domínguez,et al.  Investigation of chloride sensitive ISFETs with different membrane compositions suitable for medical applications , 2004 .

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

[21]  Christofer Toumazou,et al.  Semiconductors for early detection and therapy , 2011 .

[22]  Marvin H. White,et al.  A self-contained CMOS integrated pH sensor , 1988, Technical Digest., International Electron Devices Meeting.

[23]  M. J. Milgrew,et al.  Matching the Transconductance Characteristics of CMOS ISFET Arrays by Removing Trapped Charge , 2008, IEEE Transactions on Electron Devices.

[24]  F. Van Steenkiste,et al.  A CMOS multi-parameter biochemical microsensor with temperature control and signal interfacing , 2001, 2001 IEEE International Solid-State Circuits Conference. Digest of Technical Papers. ISSCC (Cat. No.01CH37177).

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

[26]  Sunil Purushothaman,et al.  Protons and single nucleotide polymorphism detection: A simple use for the Ion Sensitive Field Effect Transistor , 2006 .

[27]  S. Purushothaman Iyer,et al.  Towards fast solid state DNA sequencing , 2002, 2002 IEEE International Symposium on Circuits and Systems. Proceedings (Cat. No.02CH37353).

[28]  T. Lee,et al.  A Programmable 0.18-$\mu\hbox{m}$ CMOS Electrochemical Sensor Microarray for Biomolecular Detection , 2006, IEEE Sensors Journal.

[29]  C. Toumazou,et al.  A TDC based ISFET readout for large-scale chemical sensing systems , 2012, 2012 IEEE Biomedical Circuits and Systems Conference (BioCAS).

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