Direct ultrasensitive electrical detection of prostate cancer biomarkers with CMOS-compatible n- and p-type silicon nanowire sensor arrays.

Sensitive and quantitative analysis of proteins is central to disease diagnosis, drug screening, and proteomic studies. Here, a label-free, real-time, simultaneous and ultrasensitive prostate-specific antigen (PSA) sensor was developed using CMOS-compatible silicon nanowire field effect transistors (SiNW FET). Highly responsive n- and p-type SiNW arrays were fabricated and integrated on a single chip with a complementary metal oxide semiconductor (CMOS) compatible anisotropic self-stop etching technique which eliminated the need for a hybrid method. The incorporated n- and p-type nanowires revealed complementary electrical response upon PSA binding, providing a unique means of internal control for sensing signal verification. The highly selective, simultaneous and multiplexed detection of PSA marker at attomolar concentrations, a level useful for clinical diagnosis of prostate cancer, was demonstrated. The detection ability was corroborated to be effective by comparing the detection results at different pH values. Furthermore, the real-time measurement was also carried out in a clinically relevant sample of blood serum, indicating the practicable development of rapid, robust, high-performance, and low-cost diagnostic systems.

[1]  R. Williams,et al.  Journal of American Chemical Society , 1979 .

[2]  Minhee Yun,et al.  Investigation of a single Pd nanowire for use as a hydrogen sensor. , 2006, Small.

[3]  Dusan Losic,et al.  Protein electrochemistry using aligned carbon nanotube arrays. , 2003, Journal of the American Chemical Society.

[4]  Guo-Jun Zhang,et al.  Silicon nanowire biosensor and its applications in disease diagnostics: a review. , 2012, Analytica chimica acta.

[5]  Pengfei Dai,et al.  Silicon-nanowire-based CMOS-compatible field-effect transistor nanosensors for ultrasensitive electrical detection of nucleic acids. , 2011, Nano letters.

[6]  V. Latora,et al.  Complex networks: Structure and dynamics , 2006 .

[7]  Eric N. Dattoli,et al.  Tin oxide nanowire sensor with integrated temperature and gate control for multi-gas recognition. , 2012, Nanoscale.

[8]  O. Tabata,et al.  Anisotropic etching of silicon in TMAH solutions , 1992 .

[9]  J. Kang,et al.  Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers. , 2005, Biosensors & bioelectronics.

[10]  Chao Li,et al.  Complementary detection of prostate-specific antigen using In2O3 nanowires and carbon nanotubes. , 2005, Journal of the American Chemical Society.

[11]  Sukwon Jung,et al.  Fabrication of suspended silicon nanowire arrays. , 2008, Small.

[12]  Peng Chen,et al.  Ultra-sensitive detection of adipocytokines with CMOS-compatible silicon nanowire arrays. , 2009, Nanoscale.

[13]  I. Park,et al.  Top-down fabricated silicon nanowire sensors for real-time chemical detection , 2010, Nanotechnology.

[14]  Charles M. Lieber,et al.  Nanoelectronics from the bottom up. , 2007, Nature materials.

[15]  Ajay Agarwal,et al.  Silicon nanowire sensor array using top–down CMOS technology , 2008 .

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

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

[18]  Gengfeng Zheng,et al.  Nanowire sensors for medicine and the life sciences. , 2006, Nanomedicine.

[19]  Pengfei Dai,et al.  Enhanced sensing of nucleic acids with silicon nanowire field effect transistor biosensors. , 2012, Nano letters.

[20]  K. Hidajat,et al.  Adsorption of bovine serum albumin on nanosized magnetic particles. , 2004, Journal of colloid and interface science.

[21]  Charles M. Lieber,et al.  Nanowire-based biosensors. , 2006, Analytical chemistry.

[22]  Junhong Chen,et al.  Single-walled carbon nanotube field-effect transistors with graphene oxide passivation for fast, sensitive, and selective protein detection. , 2013, Biosensors & bioelectronics.

[23]  Gerd Ritter,et al.  Real-Time, label-free monitoring of tumor antigen and serum antibody interactions. , 2004, Journal of biochemical and biophysical methods.

[24]  T. Thundat,et al.  Bioassay of prostate-specific antigen (PSA) using microcantilevers , 2001, Nature Biotechnology.

[25]  Pengfei Dai,et al.  Signal-to-noise ratio enhancement of silicon nanowires biosensor with rolling circle amplification. , 2013, Nano letters.

[26]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[27]  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.

[28]  B. Kramer,et al.  Trends in biomarker research for cancer detection. , 2001, The Lancet. Oncology.

[29]  H. Xie,et al.  Electric-field-assisted growth of functionalized poly(3,4-ethylenedioxythiophene) nanowires for label-free protein detection. , 2009, Small.

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

[31]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[32]  Gengfeng Zheng,et al.  Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species , 2006, Nature Protocols.

[33]  Ilkka Tittonen,et al.  The fabrication of silicon nanostructures by focused-ion-beam implantation and TMAH wet etching , 2010, Nanotechnology.

[34]  M. Reed,et al.  Semiconducting Nanowire Field-Effect Transistor Biomolecular Sensors , 2008, IEEE Transactions on Electron Devices.

[35]  M. Shim,et al.  Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. J. Rost,et al.  Pushing the limits of SPM , 2005 .

[37]  Li Zhang,et al.  Silicon nanowire biosensor for highly sensitive and rapid detection of Dengue virus , 2010 .

[38]  Peng Chen,et al.  Nanoelectronic detection of triggered secretion of pro-inflammatory cytokines using CMOS compatible silicon nanowires. , 2011, Biosensors & bioelectronics.

[39]  F. Bruggeman,et al.  Cancer: a Systems Biology disease. , 2006, Bio Systems.

[40]  C. Mirkin,et al.  Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins , 2003, Science.

[41]  James E. Cherry D & C , 2000 .

[42]  D. Armbruster,et al.  Prostate-specific antigen: biochemistry, analytical methods, and clinical application. , 1993, Clinical chemistry.

[43]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[44]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[45]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[46]  Di Li,et al.  A silicon nanowire-based electrochemical glucose biosensor with high electrocatalytic activity and sensitivity. , 2010, Nanoscale.

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

[48]  W. Marsden I and J , 2012 .

[49]  T. Soukka,et al.  Supersensitive time-resolved immunofluorometric assay of free prostate-specific antigen with nanoparticle label technology. , 2001, Clinical chemistry.

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

[51]  Fred J Sigworth,et al.  Importance of the Debye screening length on nanowire field effect transistor sensors. , 2007, Nano letters.

[52]  T. Fromherz,et al.  Inverted Ge islands in {111} faceted Si pits—a novel approach towards SiGe islands with higher aspect ratio , 2010 .

[53]  David J. Mooney,et al.  Label-free biomarker detection from whole blood , 2009, 2010 10th IEEE International Conference on Solid-State and Integrated Circuit Technology.

[54]  J. Weinstein,et al.  Biomarkers in Cancer Staging, Prognosis and Treatment Selection , 2005, Nature Reviews Cancer.

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

[56]  C. Sander,et al.  Genomic medicine and the future of health care. , 2000, Science.

[57]  A M Ward,et al.  Prostate specific antigen: biology, biochemistry and available commercial assays , 2001, Annals of clinical biochemistry.

[58]  Jing-Min Hwang,et al.  Development of an immunosensor for human ferritin, a nonspecific tumor marker, based on surface plasmon resonance. , 2004, Biosensors & bioelectronics.