CMOS high density electrical impedance biosensor array for tumor cell detection

Abstract We present a high-throughput label-free electrical-impedance spectroscopy (EIS) platform composed of a 96 × 96 microelectrode array for counting and analysis of breast tumor cells (MCF-7). These Au-electrodes are densely packed within a 3.5 mm × 3.5 mm interrogation region. Each Au-electrode has an edge-length of 25 μm designed to detect single tumor cell by electrical impedance spectroscopy. The detected signal is read out via an integrated circuit (IC) of addressable electrode-selection-switch array manufactured with 0.18 μm CMOS technology. The independently addressable microelectrode array is integrated onto a printed circuit board (PCB) containing associated circuitry for electrode switching and readout. MCF-7 cells were dispensed onto the chip surface and EIS measurements were recorded before and after the cell dispensation. On an average 20% increase in impedance was found associated with cell occupancy on the electrode surface. A positive correlation was observed between cell detection with optical microscopy and with electrical scanning.

[1]  P. Paterlini-Bréchot,et al.  Circulating tumor cells (CTC) detection: clinical impact and future directions. , 2007, Cancer letters.

[2]  Neal J Meropol,et al.  Circulating tumor cells: evolving evidence and future challenges. , 2009, The oncologist.

[3]  Tanja Fehm,et al.  HER-2 gene amplification can be acquired as breast cancer progresses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Alberto Yufera,et al.  A CMOS bio-impedance measurement system , 2009, 2009 12th International Symposium on Design and Diagnostics of Electronic Circuits & Systems.

[5]  Ivar Giaever,et al.  A Whole Cell Biosensor Based On Cell-substrate Interactions , 1990, [1990] Proceedings of the Twelfth Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[6]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[7]  K. Pienta,et al.  Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer , 2008, Clinical Cancer Research.

[8]  Pamela Abshire,et al.  CMOS contact imager for monitoring cultured cells , 2005, 2005 IEEE International Symposium on Circuits and Systems.

[9]  Richard D. Beach,et al.  Towards a miniature implantable in vivo telemetry monitoring system dynamically configurable as a potentiostat or galvanostat for two- and three-electrode biosensors , 2005, IEEE Transactions on Instrumentation and Measurement.

[10]  Ruud H. Brakenhoff,et al.  Detection, clinical relevance and specific biological properties of disseminating tumour cells , 2008, Nature Reviews Cancer.

[11]  Arjang Hassibi,et al.  A CMOS Electrochemical Impedance Spectroscopy (EIS) Biosensor Array , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[12]  N. Manaresi,et al.  A CMOS chip for individual cell manipulation and detection , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[13]  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).

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

[15]  Sabine Riethdorf,et al.  Advancing personalized cancer therapy by detection and characterization of circulating carcinoma cells , 2010, Annals of the New York Academy of Sciences.

[16]  Xingqun Jiang,et al.  Electrochemical impedance biosensor with electrode pixels for precise counting of CD4+ cells: a microchip for quantitative diagnosis of HIV infection status of AIDS patients. , 2010, Biosensors & bioelectronics.

[17]  Sunil K Arya,et al.  Breast tumor cell detection at single cell resolution using an electrochemical impedance technique. , 2012, Lab on a chip.

[18]  W. Grody,et al.  The Clinical Significance of Circulating Tumor Cells in the Peripheral Blood , 2006, Diagnostic molecular pathology : the American journal of surgical pathology, part B.