A CMOS Electrochemical Impedance Spectroscopy (EIS) Biosensor Array

In this paper, we present a fully integrated biosensor 10 × 10 array in a standard complementary metal-oxide semiconducor process, which takes advantage of electrochemical impedance spectroscopy (EIS). We also show that this system is able to detect various biological analytes, such as DNA and proteins, in real time and without the need for molecular labels. In each pixel of this array, we implement a biocompatible Au electrode transducer and embedded sensor circuitry which takes advantage of the coherent detector to measure the impedance of the associated electrode-electrolyte interface. This chip is capable of concurrently measuring admittance values as small as 10-8 Ω-1 within the array with the detection dynamic range of more than 90 dB in the frequency range of 10 Hz-50 MHz.

[1]  J. Homola.  Present and future of surface plasmon resonance biosensors , 2003, Analytical and bioanalytical chemistry.

[2]  A. Winkler,et al.  Characterization of alkanethiol self-assembled monolayers on gold by thermal desorption spectroscopy. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[3]  Woochang Lee,et al.  Detection of insulin-antibody binding on a solid surface using imaging ellipsometry. , 2004, Biosensors & bioelectronics.

[4]  K.L. Shepard,et al.  Active CMOS Sensor Array for Electrochemical Biomolecular Detection , 2008, IEEE Journal of Solid-State Circuits.

[5]  R A Normann,et al.  The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces. , 1997, Electroencephalography and clinical neurophysiology.

[6]  Ali Hajimiri,et al.  On noise processes and limits of performance in biosensors , 2007 .

[7]  Joseph Wang.  Nanomaterial-based electrochemical biosensors. , 2005, The Analyst.

[8]  J. A. Garber,et al.  Analysis of Impedance and Admittance Data for Solids and Liquids , 1977 .

[9]  Segyeong Joo,et al.  Chemical sensors with integrated electronics. , 2008, Chemical reviews.

[10]  Thomas H. Lee,et al.  The Design of CMOS Radio-Frequency Integrated Circuits: RF CIRCUITS THROUGH THE AGES , 2003 .

[11]  Leroy Hood,et al.  Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. , 2004, Journal of proteome research.

[12]  M. D. Rooij,et al.  Electrochemical Methods: Fundamentals and Applications , 2003 .

[13]  K R Rogers,et al.  Principles of affinity-based biosensors , 2000, Molecular biotechnology.

[14]  Justin C. Williams,et al.  Flexible polyimide-based intracortical electrode arrays with bioactive capability , 2001, IEEE Transactions on Biomedical Engineering.

[15]  P J Roberts-Thomson,et al.  Molecular size heterogeneity of immunoglobulins in health and disease , 1990, Clinical and experimental immunology.

[16]  Gavin MacBeath,et al.  Protein microarrays and proteomics , 2002, Nature Genetics.

[17]  Bong Hyun Chung,et al.  Self-directed and self-oriented immobilization of antibody by protein G-DNA conjugate. , 2007, Analytical chemistry.

[18]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[19]  R. Bruce Lennox,et al.  Insulating Properties of Self-Assembled Monolayers Monitored by Impedance Spectroscopy , 2000 .

[20]  Wei Zheng,et al.  Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. , 2004, Assay and drug development technologies.

[21]  Nikin Patel,et al.  Immobilization of Protein Molecules onto Homogeneous and Mixed Carboxylate-Terminated Self-Assembled Monolayers , 1997 .

[22]  Arjang Hassibi,et al.  A CMOS fluorescent-based biosensor microarray , 2009, 2009 IEEE International Solid-State Circuits Conference - Digest of Technical Papers.

[23]  B. Eversmann,et al.  A 128 × 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003 .

[24]  I. Willner,et al.  Probing Biomolecular Interactions at Conductive and Semiconductive Surfaces by Impedance Spectroscopy: Routes to Impedimetric Immunosensors, DNA‐Sensors, and Enzyme Biosensors , 2003 .

[25]  Antje J Baeumner,et al.  Biosensors for environmental pollutants and food contaminants , 2003, Analytical and bioanalytical chemistry.

[26]  L. Benini,et al.  Fully Electronic CMOS DNA Detection Array Based on Capacitance Measurement with On-Chip Analog-to-Digital Conversion , 2006, 2006 IEEE International Solid State Circuits Conference - Digest of Technical Papers.

[27]  James D. Plummer,et al.  Silicon VLSI Technology , 2008 .

[28]  Babak Hassibi,et al.  Real-time DNA microarray analysis , 2009, Nucleic acids research.

[29]  Igor M. Filanovsky,et al.  CMOS Schmitt trigger design , 1994 .

[30]  R. Thewes,et al.  A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion , 2004, IEEE Journal of Solid-State Circuits.

[31]  Marc Madou,et al.  DNA hybridization detection by label free versus impedance amplifying label with impedance spectroscopy , 2006 .

[32]  Andreas Hierlemann,et al.  CMOS Electro-Chemical DNA-Detection Array with On-Chip ADC , 2008, 2008 IEEE International Solid-State Circuits Conference - Digest of Technical Papers.

[33]  G. Marrazza,et al.  Carbon and gold electrodes as electrochemical transducers for DNA hybridisation sensors. , 2004, Biosensors & bioelectronics.

[34]  D. Schmitt-Landsiedel,et al.  A 128 /spl times/ 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[35]  Omowunmi A. Sadik,et al.  Impedance Spectroscopy: A Powerful Tool for Rapid Biomolecular Screening and Cell Culture Monitoring , 2005 .

[36]  B. Haab.  Methods and applications of antibody microarrays in cancer research , 2003, Proteomics.

[37]  L. Del Castillo,et al.  A miniaturized neuroprosthesis suitable for implantation into the brain , 2003, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[38]  A. El Gamal,et al.  CMOS image sensors , 2005, IEEE Circuits and Devices Magazine.

[39]  Itamar Willner,et al.  Enzyme-Linked Amplified Electrochemical Sensing of Oligonucleotide−DNA Interactions by Means of the Precipitation of an Insoluble Product and Using Impedance Spectroscopy , 1999 .

[40]  N. Pourmand,et al.  Label-Free Impedance Biosensors: Opportunities and Challenges. , 2007, Electroanalysis.

[41]  Hua Wang,et al.  A frequency-shift CMOS magnetic biosensor array with single-bead sensitivity and no external magnet , 2009, 2009 IEEE International Solid-State Circuits Conference - Digest of Technical Papers.

[42]  J. Rameau,et al.  Experimental pH Potential Diagram of Aluminum for Sea Water , 1981 .

[43]  R. Dutton,et al.  Biological shot-noise and quantum-limited signal-to-noise ratio in affinity-based biosensors , 2005 .