Multiplexed detection of cardiac biomarkers in serum with nanowire arrays using readout ASIC.

Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications.

[1]  Xuema Li,et al.  Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires , 2004 .

[2]  D. Rickwood,et al.  Gel electrophoresis of proteins: a practical approach , 1981 .

[3]  Ajay Agarwal,et al.  Label-free electrical detection of cardiac biomarker with complementary metal-oxide semiconductor-compatible silicon nanowire sensor arrays. , 2009, Analytical chemistry.

[4]  Zhiqiang Gao,et al.  Silicon nanowire arrays for label-free detection of DNA. , 2007, Analytical chemistry.

[5]  N Balasubramanian,et al.  Highly sensitive measurements of PNA-DNA hybridization using oxide-etched silicon nanowire biosensors. , 2008, Biosensors & bioelectronics.

[6]  N Balasubramanian,et al.  DNA sensing by silicon nanowire: charge layer distance dependence. , 2008, Nano letters.

[7]  K. Kato,et al.  Highly sensitive enzyme immunoassay for human creatine kinase MM and MB isozymes. , 1986, Clinica chimica acta; international journal of clinical chemistry.

[8]  Tobias Reichlin,et al.  Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. , 2009, The New England journal of medicine.

[9]  James R Heath,et al.  Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solution. , 2006, Journal of the American Chemical Society.

[10]  Mark A. Reed,et al.  Label-free immunodetection with CMOS-compatible semiconducting nanowires , 2007, Nature.

[11]  W. Gibler,et al.  The role of cardiac markers in the emergency department. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[12]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[13]  Charles M. Lieber,et al.  Direct ultrasensitive electrical detection of DNA and DNA sequence variations using nanowire nanosensors , 2004 .

[14]  Gengfeng Zheng,et al.  Electrical detection of single viruses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  George A Mensah,et al.  An overview of cardiovascular disease burden in the United States. , 2007, Health affairs.

[16]  Ajay Agarwal,et al.  Label-free direct detection of MiRNAs with silicon nanowire biosensors. , 2009, Biosensors & bioelectronics.

[17]  Nader Rifai,et al.  Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes: Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide , 2002, Circulation.

[18]  A. Baschirotto,et al.  A 160 dB Equivalent Dynamic Range Auto-Scaling Interface for Resistive Gas Sensors Arrays , 2007, IEEE Journal of Solid-State Circuits.

[19]  M. McQueen,et al.  Assessment of the accuracy of serial electrocardiograms in the diagnosis of myocardial infarction. , 1983, American heart journal.

[20]  A. Remppis,et al.  Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation. , 1997, Clinical chemistry.

[21]  C. Lieber,et al.  Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species , 2001, Science.