Emerging nanoproteomics approaches for disease biomarker detection: a current perspective.

Availability of genome sequence of human and different pathogens has advanced proteomics research for various clinical applications. One of the prime goals of proteomics is identification and characterization of biomarkers for cancer and other fatal human diseases to aid an early diagnosis and monitor disease progression. However, rapid detection of low abundance biomarkers from the complex biological samples under clinically relevant conditions is extremely difficult, and it requires the development of ultrasensitive, robust and high-throughput technological platform. In order to overcome several technical limitations associated with sensitivity, dynamic range, detection time and multiplexing, proteomics has started integrating several emerging disciplines such as nanotechnology, which has led to the development of a novel analytical platform known as 'nanoproteomics'. Among the diverse classes of nanomaterials, the quantum dots, gold nanoparticles, carbon nanotubes and silicon nanowires are the most promising candidates for diagnostic applications. Nanoproteomics offers several advantages such as ultralow detection, short assay time, high-throughput capability and low sample consumption. In this article, we have discussed the application of nanoproteomics for biomarker discovery in various diseases with special emphasis on various types of cancer. Furthermore, we have discussed the prospects, merits and limitations of nanoproteomics.

[1]  Arben Merkoçi,et al.  Enhanced gold nanoparticle based ELISA for a breast cancer biomarker. , 2010, Analytical chemistry.

[2]  Shalini Prasad,et al.  Iridium oxide nanomonitors: clinical diagnostic devices for health monitoring systems. , 2009, Biosensors & bioelectronics.

[3]  B D Malhotra,et al.  Sol-gel derived nano-structured zinc oxide film for sexually transmitted disease sensor. , 2009, The Analyst.

[4]  E. Diamandis,et al.  Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines* , 2009, Molecular & Cellular Proteomics.

[5]  Yasar Gurbuz,et al.  Label-free capacitive biosensor for sensitive detection of multiple biomarkers using gold interdigitated capacitor arrays. , 2010, Biosensors & bioelectronics.

[6]  T. Veenstra,et al.  Characterization of the Low Molecular Weight Human Serum Proteome*S , 2003, Molecular & Cellular Proteomics.

[7]  Sanjeeva Srivastava,et al.  Nanotechniques in proteomics: current status, promises and challenges. , 2010, Biosensors & bioelectronics.

[8]  A. Salvador,et al.  Clinical Quantitation of Prostate-specific Antigen Biomarker in the Low Nanogram/Milliliter Range by Conventional Bore Liquid Chromatography-Tandem Mass Spectrometry (Multiple Reaction Monitoring) Coupling and Correlation with ELISA Tests , 2009, Molecular & Cellular Proteomics.

[9]  Sze Chuen Cesar Wong,et al.  Advanced proteomic technologies for cancer biomarker discovery , 2009, Expert review of proteomics.

[10]  S. Hanash Disease proteomics : Proteomics , 2003 .

[11]  E. Petricoin,et al.  The blood peptidome: a higher dimension of information content for cancer biomarker discovery , 2006, Nature Reviews Cancer.

[12]  H. Klocker,et al.  Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy , 2009, Proceedings of the National Academy of Sciences.

[13]  S. Prasad,et al.  Biogenic nanoporous silica-based sensor for enhanced electrochemical detection of cardiovascular biomarkers proteins. , 2010, Biosensors & bioelectronics.

[14]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[15]  Gavin Brooks,et al.  The use of proteomics to identify novel therapeutic targets for the treatment of disease , 2007, The Journal of pharmacy and pharmacology.

[16]  Do Won Hwang,et al.  In vitro derby imaging of cancer biomarkers using quantum dots. , 2009, Small.

[17]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[18]  Adam Wax,et al.  Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles. , 2009, AJR. American journal of roentgenology.

[19]  E. Petricoin,et al.  Clinical proteomics: translating benchside promise into bedside reality , 2002, Nature Reviews Drug Discovery.

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

[21]  M. Porter,et al.  Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels. , 2003, Analytical chemistry.

[22]  Shenghong Hu,et al.  Detection of multiple proteins on one spot by laser ablation inductively coupled plasma mass spectrometry and application to immuno- microarray with element-tagged antibodies. , 2007, Analytical chemistry.

[23]  Moon-Ho Jo,et al.  Electrical detection of VEGFs for cancer diagnoses using anti-vascular endotherial growth factor aptamer-modified Si nanowire FETs. , 2009, Biosensors & bioelectronics.

[24]  Bong Hyun Chung,et al.  Quantum dot‐based protein micro‐ and nanoarrays for detection of prostate cancer biomarkers , 2008, Proteomics.

[25]  James F Rusling,et al.  Attomolar detection of a cancer biomarker protein in serum by surface plasmon resonance using superparamagnetic particle labels. , 2011, Angewandte Chemie.

[26]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[27]  Emanuel F Petricoin,et al.  Mass spectrometry-based protein biomarker discovery: solving the remaining challenges to reach the promise of clinical benefit. , 2010, Clinical chemistry.

[28]  Hongying Zhu,et al.  Rapid and label-free detection of breast cancer biomarker CA15-3 in clinical human serum samples with optofluidic ring resonator sensors. , 2009, Analytical chemistry.

[29]  Jeong-Yeol Yoon,et al.  Microfluidic immunosensor with integrated liquid core waveguides for sensitive Mie scattering detection of avian influenza antigens in a real biological matrix , 2010, Analytical and bioanalytical chemistry.

[30]  A Paul Alivisatos,et al.  Semiconductor quantum rods as single molecule fluorescent biological labels. , 2007, Nano letters.

[31]  Sandip Niyogi,et al.  Comparison of analytical techniques for purity evaluation of single-walled carbon nanotubes. , 2005, Journal of the American Chemical Society.

[32]  Nuo Duan,et al.  Sensitive immunoassay of Listeria monocytogenes with highly fluorescent bioconjugated silica nanoparticles probe. , 2010, Journal of microbiological methods.

[33]  César Fernández-Sánchez,et al.  One-step immunostrip test for the simultaneous detection of free and total prostate specific antigen in serum. , 2005, JIM - Journal of Immunological Methods.

[34]  Sai Bi,et al.  Multilayers enzyme-coated carbon nanotubes as biolabel for ultrasensitive chemiluminescence immunoassay of cancer biomarker. , 2009, Biosensors & bioelectronics.

[35]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[36]  S. Carr,et al.  Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution*S , 2007, Molecular & Cellular Proteomics.

[37]  G. Hortobagyi,et al.  The Role of Serum CEA as a Prognostic Indicator in Stage II and III Breast Cancer Patients Treated With Adjuvant Chemotherapy , 1989, Cancer.

[38]  Hongjie Dai,et al.  Protein microarrays with carbon nanotubes as multicolor Raman labels , 2008, Nature Biotechnology.

[39]  Yasar Gurbuz,et al.  A novel interdigitated capacitor based biosensor for detection of cardiovascular risk marker. , 2009, Biosensors & bioelectronics.

[40]  J. Phair,et al.  Detection of HIV-1 p24 Gag in plasma by a nanoparticle-based bio-barcode-amplification method. , 2008, Nanomedicine.

[41]  J. Oesterling,et al.  Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. , 1991, The Journal of urology.

[42]  Sanjeeva Srivastava,et al.  Proteomic technologies for the identification of disease biomarkers in serum: Advances and challenges ahead , 2011, Proteomics.

[43]  Sanjeeva Srivastava,et al.  Applications of protein microarrays for biomarker discovery , 2008, Proteomics. Clinical applications.

[44]  Priyabrata Mukherjee,et al.  Gold nanoparticles: opportunities and challenges in nanomedicine , 2010, Expert opinion on drug delivery.

[45]  Shekhar Bhansali,et al.  Ultrasensitive electrochemical detection of cytokeratin-7, using Au nanowires based biosensor , 2008 .

[46]  M. Ferrari,et al.  Clinical proteomics: Written in blood , 2003, Nature.

[47]  Kornelia Polyak,et al.  Identification of CD44v6+/CD24− breast carcinoma cells in primary human tumors by quantum dot-conjugated antibodies , 2009, Laboratory Investigation.

[48]  N. Lee,et al.  Organic electrochemical transistor based immunosensor for prostate specific antigen (PSA) detection using gold nanoparticles for signal amplification. , 2010, Biosensors & bioelectronics.

[49]  Monica Simion,et al.  Nanostructured silicon particles for medical applications. , 2010, Journal of nanoscience and nanotechnology.

[50]  John Gohring,et al.  Detection of HER2 breast cancer biomarker using the optofluidic ring resonator biosensor , 2010, Defense + Commercial Sensing.

[51]  Gautham Kumar Ahirwal,et al.  Gold nanoparticles based sandwich electrochemical immunosensor. , 2010, Biosensors & bioelectronics.

[52]  George Alexeeff,et al.  Nanotechnology and nanomaterials: toxicology, risk assessment, and regulations. , 2010, Journal of nanoscience and nanotechnology.

[53]  Gregor Kijanka,et al.  Protein arrays as tools for serum autoantibody marker discovery in cancer. , 2009, Journal of proteomics.

[54]  Ruo Yuan,et al.  Ultrasensitive amperometric immunosensor for the determination of carcinoembryonic antigen based on a porous chitosan and gold nanoparticles functionalized interface , 2009 .

[55]  Sophie Lanone,et al.  Potential uses of carbon nanotubes in the medical field: how worried should patients be? , 2007, Nanomedicine.

[56]  C. Mirkin,et al.  Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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

[58]  Abraham Fuks,et al.  Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule , 1989, Cell.

[59]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[60]  Shusheng Zhang,et al.  Detection of prostate specific antigen with 3,4-diaminobenzoic acid (DBA)-H(2)O(2)-HRP voltammetric enzyme-linked immunoassay system. , 2007, Talanta.

[61]  Monty Liong,et al.  Mesoporous Silica Nanoparticles for Cancer Therapy: Energy-Dependent Cellular Uptake and Delivery of Paclitaxel to Cancer Cells , 2007, Nanobiotechnology : the journal at the intersection of nanotechnology, molecular biology, and biomedical sciences.

[62]  Rebecca Sutphen,et al.  Surface-enhanced Raman scattering detection of lysophosphatidic acid , 2005, Analytical and bioanalytical chemistry.

[63]  Jianlong Zhao,et al.  Novel colorimetric enzyme immunoassay for the detection of carcinoembryonic antigen. , 2010, Talanta.

[64]  Amit K Jain,et al.  Carbon nanotubes in cancer theragnosis. , 2010, Nanomedicine.

[65]  Sung-Hyun Lee,et al.  A novel approach to ultrasensitive diagnosis using supramolecular protein nanoparticles , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[66]  Sanjiv S Gambhir,et al.  Cys-diabody quantum dot conjugates (immunoQdots) for cancer marker detection. , 2009, Bioconjugate chemistry.

[67]  Yoshikazu Matsuda,et al.  Proteomics-based safety evaluation of multi-walled carbon nanotubes. , 2010, Toxicology and applied pharmacology.

[68]  Ying Wang,et al.  Rapid and sensitive detection of protein biomarker using a portable fluorescence biosensor based on quantum dots and a lateral flow test strip. , 2010, Analytical chemistry.

[69]  Brian C. Heinze,et al.  Microfluidic immunosensor for rapid and sensitive detection of bovine viral diarrhea virus , 2009 .

[70]  Ping He,et al.  Nanosilver-doped DNA polyion complex membrane for electrochemical immunoassay of carcinoembryonic antigen using nanogold-labeled secondary antibodies. , 2010, Analytica chimica acta.

[71]  Amanda Paulovich,et al.  Cancer biomarkers: a systems approach , 2006, Nature Biotechnology.

[72]  Yuri D. Ivanov,et al.  Nanotechnologies in proteomics , 2006, Proteomics.

[73]  Gwo-Bin Lee,et al.  An integrated microfluidic system for rapid diagnosis of dengue virus infection , 2009, Biosensors and Bioelectronics.

[74]  Richard N Zare,et al.  Single-molecule spectroscopy using microfluidic platforms. , 2010, Methods in enzymology.

[75]  Maria Careri,et al.  Multiplexed determination of protein biomarkers using metal-tagged antibodies and size exclusion chromatography--inductively coupled plasma mass spectrometry. , 2009, Analytical chemistry.

[76]  Shulin Zhao,et al.  Noncompetitive immunoassay for carcinoembryonic antigen in human serum by microchip electrophoresis for cancer diagnosis. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[77]  E. Petricoin,et al.  Nanoparticle technology: addressing the fundamental roadblocks to protein biomarker discovery. , 2010, Current molecular medicine.

[78]  Makoto Hashizume,et al.  Gold nanoparticle-based colorimetric assay for cancer diagnosis. , 2010, Biosensors & bioelectronics.

[79]  Weidong Zhou,et al.  Core-Shell Hydrogel Particles Harvest, Concentrate and Preserve Labile Low Abundance Biomarkers , 2009, PloS one.

[80]  James F Rusling,et al.  Protein immunosensor using single-wall carbon nanotube forests with electrochemical detection of enzyme labels. , 2005, Molecular bioSystems.

[81]  Shuming Nie,et al.  Multiplexed detection and characterization of rare tumor cells in Hodgkin's lymphoma with multicolor quantum dots. , 2010, Analytical chemistry.

[82]  C. Fan,et al.  Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. , 2010, ACS nano.

[83]  Steven C Kazmierczak,et al.  From diagnostics to therapy: prospects of quantum dots. , 2007, Clinical biochemistry.

[84]  Joseph D. Gong,et al.  Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers. , 2006, Journal of the American Chemical Society.

[85]  Seung-Hee Ryu,et al.  Immunosensors for detection of Annexin II and MUC5AC for early diagnosis of lung cancer. , 2009, Biosensors & bioelectronics.

[86]  S. Byrne,et al.  Analysis of Bordetella pertussis pertactin and pertussis toxin types from Queensland, Australia, 1999–2003 , 2006, BMC infectious diseases.

[87]  Joon Won Park,et al.  Nanotechnology for Early Cancer Detection , 2010, Sensors.

[88]  Sailing He,et al.  Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells. , 2007, Nano letters.

[89]  A. J. Nijdam,et al.  Selective binding and enrichment for low‐molecular weight biomarker molecules in human plasma after exposure to nanoporous silica particles , 2006, Proteomics.

[90]  Young Mee Jung,et al.  QUANTITATIVE ANALYSIS OF A PROSTATE-SPECIFIC ANTIGEN IN SERUM USING FLUORESCENCE IMMUNOCHROMATOGRAPHY , 2010, Journal of immunoassay & immunochemistry.

[91]  E. Tamiya,et al.  Label-free immunosensor for prostate-specific antigen based on single-walled carbon nanotube array-modified microelectrodes. , 2007, Biosensors & bioelectronics.

[92]  Sang Jun Sim,et al.  Preparation of highly stable oligo(ethylene glycol) derivatives-functionalized gold nanoparticles and their application in LSPR-based detection of PSA/ACT complex. , 2007, Journal of nanoscience and nanotechnology.

[93]  Ying Zhuo,et al.  Study on an amperometric immunosensor based on Nafion-cysteine composite membrane for detection of carcinoembryonic antigen. , 2010, Analytical biochemistry.

[94]  R. Aebersold,et al.  Proteomics: the first decade and beyond , 2003, Nature Genetics.

[95]  Chad A Mirkin,et al.  Microarray-based multiplexed scanometric immunoassay for protein cancer markers using gold nanoparticle probes. , 2009, Analytical chemistry.

[96]  John Gohring,et al.  Detection of HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor , 2010 .

[97]  Kaiyang Li,et al.  Immunofluorescence detection with quantum dot bioconjugates for hepatoma in vivo. , 2007, Journal of biomedical optics.

[98]  Yan Liu,et al.  Novel potentiometric immunosensor for determination of diphtheria antigen based on compound nanoparticles and bilayer two-dimensional sol–gel as matrices , 2005, Analytical and bioanalytical chemistry.

[99]  Emanuel F Petricoin,et al.  Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml. , 2004, The Journal of urology.

[100]  L. C. Gunn,et al.  Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators. , 2009, Analytical chemistry.

[101]  Sanjeeva Srivastava,et al.  Protein microarrays and novel detection platforms , 2011, Expert review of proteomics.

[102]  Jaebum Choo,et al.  Optoelectrofluidic sandwich immunoassays for detection of human tumor marker using surface-enhanced Raman scattering. , 2010, Analytical chemistry.

[103]  Trairak Pisitkun,et al.  Discovery of Urinary Biomarkers* , 2006, Molecular & Cellular Proteomics.

[104]  Sadia Afrin Khan,et al.  Multifunctional oval-shaped gold-nanoparticle-based selective detection of breast cancer cells using simple colorimetric and highly sensitive two-photon scattering assay. , 2010, ACS nano.

[105]  Sanjeeva Srivastava,et al.  Cell‐free synthesis‐based protein microarrays and their applications , 2010, Proteomics.

[106]  Shaoyi Jiang,et al.  Label-free biomarker sensing in undiluted serum with suspended microchannel resonators. , 2010, Analytical chemistry.

[107]  James F Rusling,et al.  Single-wall carbon nanotube forest arrays for immunoelectrochemical measurement of four protein biomarkers for prostate cancer. , 2009, Analytical chemistry.

[108]  Paresh Chandra Ray,et al.  Ultrasensitive and highly selective detection of Alzheimer's disease biomarker using two-photon Rayleigh scattering properties of gold nanoparticle. , 2009, ACS nano.

[109]  Bing Li,et al.  An on-nanoparticle rolling-circle amplification platform for ultrasensitive protein detection in biological fluids. , 2010, Small.

[110]  Yun Xiang,et al.  Sensitive label-free immunoassay of carcinoembryonic antigen based on Au-TiO2 hybrid nanocomposite film. , 2010, Journal of colloid and interface science.

[111]  Mengsu Yang,et al.  A microfluidic device with microbead array for sensitive virus detection and genotyping using quantum dots as fluorescence labels. , 2010, Biosensors & bioelectronics.

[112]  Sang Jun Sim,et al.  Homogenous growth of gold nanocrystals for quantification of PSA protein biomarker. , 2009, Biosensors & bioelectronics.

[113]  Jiangqin Zhao,et al.  Detection of Anthrax Toxin by an Ultrasensitive Immunoassay Using Europium Nanoparticles , 2009, Clinical and Vaccine Immunology.

[114]  Richard D. Smith,et al.  Advances and Challenges in Liquid Chromatography-Mass Spectrometry-based Proteomics Profiling for Clinical Applications* , 2006, Molecular & Cellular Proteomics.

[115]  Harshini Mukundan,et al.  Quantitative multiplex detection of pathogen biomarkers on multichannel waveguides. , 2010, Analytical chemistry.

[116]  H. Haick,et al.  Detecting simulated patterns of lung cancer biomarkers by random network of single-walled carbon nanotubes coated with nonpolymeric organic materials. , 2008, Nano letters.

[117]  Xiaoyan Yang,et al.  Luminol/antibody labeled gold nanoparticles for chemiluminescence immunoassay of carcinoembryonic antigen. , 2010, Analytica chimica acta.

[118]  Jesse V Jokerst,et al.  Nano-bio-chips for high performance multiplexed protein detection: determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. , 2009, Biosensors & bioelectronics.

[119]  Zhimin Zhang,et al.  Nanogold-enwrapped graphene nanocomposites as trace labels for sensitivity enhancement of electrochemical immunosensors in clinical immunoassays: Carcinoembryonic antigen as a model. , 2010, Biosensors & bioelectronics.

[120]  Emanuel F Petricoin,et al.  Clinical applications of proteomics. , 2003, The Journal of nutrition.

[121]  M. Tyers,et al.  From genomics to proteomics , 2003, Nature.

[122]  Yefu Wang,et al.  Rapid and simultaneous detection of human hepatitis B virus and hepatitis C virus antibodies based on a protein chip assay using nano-gold immunological amplification and silver staining method , 2005, BMC infectious diseases.

[123]  Maureen R. Gwinn,et al.  Nanoparticles: Health Effects—Pros and Cons , 2006, Environmental health perspectives.

[124]  Shusheng Zhang,et al.  Sensitive amperometric immunosensor for alpha-fetoprotein based on carbon nanotube/gold nanoparticle doped chitosan film. , 2009, Analytical biochemistry.

[125]  Joseph Wang,et al.  Electrochemical biosensors: towards point-of-care cancer diagnostics. , 2006, Biosensors & bioelectronics.

[126]  Huiling Gao,et al.  An electrochemical immunosensor for carcinoembryonic antigen enhanced by self-assembled nanogold coatings on magnetic particles. , 2010, Analytica chimica acta.

[127]  Kyu-Sik Shin,et al.  Quantitative measurements of C-reactive protein using silicon nanowire arrays , 2008, International journal of nanomedicine.

[128]  Yuehe Lin,et al.  Nanomaterial labels in electrochemical immunosensors and immunoassays. , 2007, Talanta.

[129]  Ruo Yuan,et al.  A novel electrochemical immunoassay based on diazotization-coupled functionalized bioconjugates as trace labels for ultrasensitive detection of carcinoembryonic antigen. , 2011, Biosensors & bioelectronics.

[130]  Beverly A Rzigalinski,et al.  Cadmium-containing nanoparticles: perspectives on pharmacology and toxicology of quantum dots. , 2009, Toxicology and applied pharmacology.

[131]  Emanuel F Petricoin,et al.  Nanoparticles: potential biomarker harvesters. , 2006, Current opinion in chemical biology.

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

[133]  T. Giorgio,et al.  Quantum dot self-assembly for protein detection with sub-picomolar sensitivity. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[134]  Gilberto Brambilla,et al.  A microfluidic refractometric sensor based on gratings in optical fibre microwires. , 2009, Optics express.

[135]  Ming Zhao,et al.  Prostate specific antigen detection in patient sera by fluorescence-free BioCD protein array. , 2011, Biosensors & bioelectronics.

[136]  E. Petricoin,et al.  Early detection: Proteomic applications for the early detection of cancer , 2003, Nature Reviews Cancer.

[137]  David Sidransky,et al.  Emerging molecular markers of cancer , 2002, Nature Reviews Cancer.

[138]  Zhouping Wang,et al.  Sensitive detection of Salmonella with fluorescent bioconjugated nanoparticles probe , 2011 .

[139]  G. Oberdörster,et al.  Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology , 2010, Journal of internal medicine.

[140]  T Laurell,et al.  Reverse-phase versus sandwich antibody microarray, technical comparison from a clinical perspective. , 2007, Analytical chemistry.

[141]  Wentao Yue,et al.  Label-free detection of p53 antibody using a microcantilever biosensor with piezoresistive readout , 2009, 2009 IEEE Sensors.

[142]  Indira Hewlett,et al.  Nanoparticle-based immunoassays for sensitive and early detection of HIV-1 capsid (p24) antigen. , 2010, The Journal of infectious diseases.

[143]  Abdallah S. Daar,et al.  State of Academic Knowledge on Toxicity and Biological Fate of Quantum Dots , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[144]  R. V. Van Duyne,et al.  Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor. , 2005, Journal of the American Chemical Society.

[145]  Harold G. Craighead,et al.  Detection of prostate specific antigen with nanomechanical resonators. , 2009, Lab on a chip.

[146]  Yu Qin,et al.  Functional Nanoprobes for Ultrasensitive Detection of Biomolecules , 2011 .

[147]  Miriam Colombo,et al.  Femtomolar detection of autoantibodies by magnetic relaxation nanosensors. , 2009, Analytical biochemistry.

[148]  A. Kozitsina,et al.  Hybrid Electrochemical/Magnetic Assay for Salmonella Typhimurium Detection , 2010, IEEE Sensors Journal.

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

[150]  Qian Wang,et al.  An investigation of the mechanisms of electronic sensing of protein adsorption on carbon nanotube devices. , 2004, Journal of the American Chemical Society.

[151]  Young Soo Park,et al.  Measurements of serum C-reactive protein levels in patients with gastric cancer and quantification using silicon nanowire arrays. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[152]  Y. Perera,et al.  Development and validation of a quantitative ELISA for the measurement of PSA concentration. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[153]  Shusheng Zhang,et al.  Investigation of voltammetric enzyme-linked immunoassay system based on N-heterocyclic substrate of 2,3-diaminopyridine. , 2009, Talanta.

[154]  Iulia M Lazar,et al.  Microfluidic chips for protein differential expression profiling , 2009, Electrophoresis.

[155]  Joshua LaBaer,et al.  Nanotubes light up protein arrays , 2008, Nature Biotechnology.

[156]  Sanjeeva Srivastava,et al.  Label‐free detection techniques for protein microarrays: Prospects, merits and challenges , 2009, Proteomics.

[157]  Olle Nilsson,et al.  Amperometric immunosensor for carcinoembryonic antigen in colon cancer samples based on monolayers of dendritic bipodal scaffolds. , 2010, Analytical chemistry.

[158]  Dianping Tang,et al.  In situ amplified electrochemical immunoassay for carcinoembryonic antigen using horseradish peroxidase-encapsulated nanogold hollow microspheres as labels. , 2008, Analytical chemistry.

[159]  Arun Majumdar,et al.  Label-free protein recognition two-dimensional array using nanomechanical sensors. , 2008, Nano letters.

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

[161]  Giovanni Pellacani,et al.  A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum , 2011, Experimental dermatology.

[162]  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.

[163]  P. Abrahamsson,et al.  Prostate specific antigen and human glandular kallikrein 2 in early detection of prostate cancer. , 2003, The Journal of urology.

[164]  Wei Wang,et al.  A disposable electrochemical immunosensor for carcinoembryonic antigen based on nano-Au/multi-walled carbon nanotubes-chitosans nanocomposite film modified glassy carbon electrode. , 2010, Analytica chimica acta.

[165]  Judit M Nagy,et al.  Proteomics, nanotechnology and molecular diagnostics , 2008, Proteomics.

[166]  O John Semmes,et al.  Serum, salivary and tissue proteomics for discovery of biomarkers for head and neck cancers , 2005, Expert review of molecular diagnostics.

[167]  Shalini Prasad,et al.  Nanomonitors: Electrical immunoassays for protein biomarker profiling , 2008 .

[168]  Hui Chen,et al.  A one-step homogeneous immunoassay for cancer biomarker detection using gold nanoparticle probes coupled with dynamic light scattering. , 2008, Journal of the American Chemical Society.

[169]  Weidong Zhou,et al.  Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology , 2010, The AAPS Journal.

[170]  D. T. Wong,et al.  Human body fluid proteome analysis , 2006, Proteomics.

[171]  Bo Zhang,et al.  Carbon nanotubes in cancer diagnosis and therapy. , 2010, Biochimica et biophysica acta.

[172]  Jing Li,et al.  MCE enzyme immunoassay for carcinoembryonic antigen and alpha‐fetoprotein using electrochemical detection , 2009, Electrophoresis.

[173]  J. Vaqué,et al.  Ultrasensitive electrochemical immunosensor for oral cancer biomarker IL-6 using carbon nanotube forest electrodes and multilabel amplification. , 2010, Analytical chemistry.

[174]  Hua-Zhong Yu,et al.  Aptamer-based detection of epithelial tumor marker mucin 1 with quantum dot-based fluorescence readout. , 2009, Analytical chemistry.

[175]  Chad A Mirkin,et al.  Multiplexed detection of protein cancer markers with biobarcoded nanoparticle probes. , 2006, Journal of the American Chemical Society.

[176]  K Kostarelos,et al.  Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. , 2009, Nature nanotechnology.

[177]  Kathryn Ziegler-Graham,et al.  Forecasting the global burden of Alzheimer’s disease , 2007, Alzheimer's & Dementia.

[178]  C. Lenz,et al.  Multiple reaction monitoring cubed for protein quantification at the low nanogram/milliliter level in nondepleted human serum. , 2009, Analytical chemistry.

[179]  Fang Wang,et al.  A novel method for D-arabinitol determination based on a nano-structured sensing film by one-step electrodeposition , 2010 .

[180]  Virginia Espina,et al.  Concentration and preservation of very low abundance biomarkers in urine, such as human growth hormone (hGH), by Cibacron Blue F3G-A loaded hydrogel particles , 2008, Nano research.

[181]  Jeffrey T La Belle,et al.  Development of a novel single sensor multiplexed marker assay. , 2011, The Analyst.

[182]  Shuming Nie,et al.  Multicolor quantum dots for molecular diagnostics of cancer , 2006, Expert review of molecular diagnostics.

[183]  K. Hung,et al.  Proteomic approaches to cancer biomarkers. , 2010, Gastroenterology.

[184]  Chad A Mirkin,et al.  A bio-barcode assay for on-chip attomolar-sensitivity protein detection. , 2006, Lab on a chip.

[185]  Emanuel F Petricoin,et al.  Serum proteomics in cancer diagnosis and management. , 2004, Annual review of medicine.

[186]  Guo-Li Shen,et al.  Silver-enhanced colloidal gold metalloimmunoassay for Schistosoma japonicum antibody detection. , 2005, Journal of immunological methods.

[187]  H. Dai,et al.  Peptide-coated nanotube-based biosensor for the detection of disease-specific autoantibodies in human serum. , 2008, Biosensors & bioelectronics.

[188]  Xiaohu Gao,et al.  Plasmonic fluorescent quantum dots. , 2009, Nature nanotechnology.

[189]  J. Choo,et al.  Highly sensitive immunoassay of lung cancer marker carcinoembryonic antigen using surface-enhanced Raman scattering of hollow gold nanospheres. , 2009, Analytical chemistry.

[190]  C. Keating,et al.  Nanoscience enables ultrasensitive detection of Alzheimer's biomarker. , 2005, Proceedings of the National Academy of Sciences of the United States of America.