Development of Electrochemical Immunosensors towards Point-of-care Cancer Diagnostics: Clinically Relevant Studies

Development of electrochemical biosensors towards cancer biomarker detection has been in the spot light for several decades. Electrochemical detection holds great promise for clinical applications because it offers several advantages including sensitive, fast, simple and low-cost. In addition, multiplexing capability for simultaneous detection of multiple biomarkers is feasible. Unfortunately, transition of biosensors from laboratories to the market is challenging. This review intends to summarize recent advances in the development of electrochemical immunosensors for the next generation cancer diagnostic devices. Clinically relevant details of cancer biomarkers such as threshold value and their diagnosis/prognosis application will be given in conjunction with the electrochemical detection platforms that have been validated using clinical samples. Finally, the critical aspects that require great attention in order to fulfill the criteria of biomedical diagnostics will be covered.

[1]  P. Humphrey,et al.  The early detection of prostate carcinoma with prostate specific antigen , 1997, Cancer.

[2]  Phil Gold,et al.  DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES , 1965, The Journal of experimental medicine.

[3]  H. Woo,et al.  Current Status of Biomarkers for Prostate Cancer , 2013, International journal of molecular sciences.

[4]  S. Campuzano,et al.  Electrochemical bioplatforms for the simultaneous determination of interleukin (IL)-8 mRNA and IL-8 protein oral cancer biomarkers in raw saliva. , 2016, Biosensors & bioelectronics.

[5]  Hongtao Zhang,et al.  Challenges in the clinical utility of the serum test for HER2 ECD. , 2012, Biochimica et biophysica acta.

[6]  Feng Yan,et al.  A disposable multianalyte electrochemical immunosensor array for automated simultaneous determination of tumor markers. , 2007, Clinical chemistry.

[7]  M. Tez,et al.  External metallic circle in hepaticojejunostomy , 2004, BMC surgery.

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

[9]  Carlo Montemagno,et al.  Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. , 2004, Archives of otolaryngology--head & neck surgery.

[10]  J Chang-Claude,et al.  Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. , 1998, American journal of human genetics.

[11]  M. Dowsett,et al.  Biomarkers for the clinical management of breast cancer: International perspective , 2013, International journal of cancer.

[12]  J. Izbicki,et al.  Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small-cell lung cancer. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  C. Delerue-Matos,et al.  Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD. , 2014, Talanta.

[14]  James T. Wu,et al.  Serum Alpha Fetoprotein (AFP) Levels in Normal Infants , 1981, Pediatric Research.

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

[16]  James F Rusling,et al.  Nanomaterials and biomaterials in electrochemical arrays for protein detection. , 2014, Journal of materials chemistry. B.

[17]  S. Kingsmore.  Multiplexed protein measurement: technologies and applications of protein and antibody arrays , 2006, Nature Reviews Drug Discovery.

[18]  I. Tothill.  Biosensors for cancer markers diagnosis. , 2009, Seminars in cell & developmental biology.

[19]  Feng Yan,et al.  Disposable reagentless electrochemical immunosensor array based on a biopolymer/sol-gel membrane for simultaneous measurement of several tumor markers. , 2008, Clinical chemistry.

[20]  R. Corn,et al.  Microarray methods for protein biomarker detection. , 2008, The Analyst.

[21]  Minghui Yang,et al.  Electrochemical immunosensors for cancer biomarker with signal amplification based on ferrocene functionalized iron oxide nanoparticles. , 2011, Biosensors & bioelectronics.

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

[23]  Joseph Wang,et al.  Point-of-care biosensor systems for cancer diagnostics/prognostics. , 2006, Biosensors & bioelectronics.

[24]  Jun Liu,et al.  Sensitive immunosensor for cancer biomarker based on dual signal amplification strategy of graphene sheets and multienzyme functionalized carbon nanospheres. , 2010, Analytical chemistry.

[25]  F. Balkwill.  TNF-α in promotion and progression of cancer , 2006, Cancer and Metastasis Reviews.

[26]  Andrew J. Vickers,et al.  Prostate-specific antigen and prostate cancer: prediction, detection and monitoring , 2008, Nature Reviews Cancer.

[27]  Yuzhong Zhang,et al.  Simultaneous electrochemical detection of multiple biomarkers using gold nanoparticles decorated multiwall carbon nanotubes as signal enhancers. , 2015, Analytical biochemistry.

[28]  P. Yáñez‐Sedeño,et al.  Electrochemical magnetoimmunosensor for the ultrasensitive determination of interleukin-6 in saliva and urine using poly-HRP streptavidin conjugates as labels for signal amplification , 2014, Analytical and Bioanalytical Chemistry.

[29]  F. Guadagni,et al.  CA 72-4 serum marker--a new tool in the management of carcinoma patients. , 1995, Cancer investigation.

[30]  María Pedrero,et al.  Electrochemical Biosensors for the Determination of Cardiovascular Markers: a Review , 2014 .

[31]  Na Liu,et al.  Platinum porous nanoparticles hybrid with metal ions as probes for simultaneous detection of multiplex cancer biomarkers. , 2014, Biosensors & bioelectronics.

[32]  M. Duffy,et al.  Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? , 2001, Clinical chemistry.

[33]  Jinghua Yu,et al.  Ultrasensitive electrochemical immunoassay for carcinoembryonic antigen based on three-dimensional macroporous gold nanoparticles/graphene composite platform and multienzyme functionalized nanoporous silver label. , 2013, Analytica chimica acta.

[34]  J. Brugge,et al.  IL-6 involvement in epithelial cancers. , 2007, The Journal of clinical investigation.

[35]  S. Muyldermans,et al.  Nanoimmunoassay onto a screen printed electrode for HER2 breast cancer biomarker determination. , 2014, Talanta.

[36]  G. Marrazza,et al.  An Electrochemical Immunoassay for HER2 Detection , 2012 .

[37]  P. Yager,et al.  Point-of-care diagnostics for global health. , 2008, Annual review of biomedical engineering.

[38]  M. Stoler,et al.  The clinical impact of using p16INK4a immunochemistry in cervical histopathology and cytology: An update of recent developments , 2015, International journal of cancer.

[39]  S. Campuzano,et al.  Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum. , 2014, Analytica chimica acta.

[40]  P. Sehgal,et al.  High levels of "complexed" interleukin-6 in human blood. , 1992, The Journal of biological chemistry.

[41]  P. Garcia-Lopez,et al.  Pre-clinical validation study of a miniaturized electrochemical immunoassay based on square wave voltammetry for early detection of carcinoembryonic antigen in human serum. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[42]  Minghui Yang,et al.  Prussian Blue-functionalized ceria nanoparticles as label for ultrasensitive detection of tumor necrosis factor-α , 2012 .

[43]  R. Mayeux.  Biomarkers: Potential uses and limitations , 2004, NeuroRX.

[44]  P. Kenemans,et al.  Comparison of seven immunoassays for the quantification of CA 125 antigen in serum. , 1998, Clinical chemistry.

[45]  Feng Yan,et al.  Biomedical and clinical applications of immunoassays and immunosensors for tumor markers , 2007 .

[46]  Dan Wu,et al.  Sandwich-type electrochemical immunosensor using dumbbell-like nanoparticles for the determination of gastric cancer biomarker CA72-4. , 2015, Talanta.

[47]  M. Duffy,et al.  Predictive markers in breast and other cancers: a review. , 2005, Clinical chemistry.

[48]  A. Yu,et al.  Enzymatically catalytic deposition of gold nanoparticles by glucose oxidase-functionalized gold nanoprobe for ultrasensitive electrochemical immunoassay. , 2015, Biosensors & bioelectronics.

[49]  M. Duffy,et al.  Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. , 2003, European journal of cancer.

[50]  Chunhai Fan,et al.  Development of electrochemical immunosensors towards point of care diagnostics. , 2013, Biosensors & bioelectronics.

[51]  Mahdi Emami,et al.  An electrochemical immunosensor for detection of a breast cancer biomarker based on antiHER2-iron oxide nanoparticle bioconjugates. , 2014, The Analyst.

[52]  John M S Bartlett,et al.  Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  R. Bast,et al.  Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. , 1996, Journal of the National Cancer Institute.

[54]  Jun‐Jie Zhu,et al.  A competitive electrochemical immunosensor for the detection of human interleukin-6 based on the electrically heated carbon electrode and silver nanoparticles functionalized labels. , 2014, Talanta.

[55]  Juan Tang,et al.  Graphene and Nanogold-Functionalized Immunosensing Interface with Enhanced Sensitivity for One-Step Electrochemical Immunoassay of Alpha-Fetoprotein in Human Serum , 2010 .

[56]  L. Mariani,et al.  Immunohistochemical expression of p16INK4a is predictive of HR-HPV infection in cervical low-grade lesions , 2006, Modern Pathology.

[57]  A. Haese*,et al.  Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range. , 2002, The Journal of urology.

[58]  Avraham Rasooly,et al.  Development of biosensors for cancer clinical testing. , 2006, Biosensors & bioelectronics.

[59]  James F Rusling,et al.  Ultrasensitive immunosensor for cancer biomarker proteins using gold nanoparticle film electrodes and multienzyme-particle amplification. , 2009, ACS nano.

[60]  M. Taketo,et al.  Significance and mechanism of lymph node metastasis in cancer progression. , 2011, Cancer research.

[61]  Cass J. Grandone,et al.  The Abbott IMx automated benchtop immunochemistry analyzer system. , 1988, Clinical chemistry.

[62]  A. Salimi,et al.  Highly sensitive immunosensing of prostate-specific antigen based on ionic liquid-carbon nanotubes modified electrode: application as cancer biomarker for prostate biopsies. , 2013, Biosensors & bioelectronics.

[63]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[64]  R. Kurzrock,et al.  Interleukin‐6 and its receptor in cancer , 2007, Cancer.

[65]  S. Barnhill,et al.  CA 125: The past and the Future , 1998, The International journal of biological markers.

[66]  J. Mauer,et al.  Versatile functions for IL-6 in metabolism and cancer. , 2015, Trends in immunology.

[67]  Yong Lin,et al.  Tumor necrosis factor and cancer, buddies or foes? , 2008, Acta Pharmacologica Sinica.

[68]  K. Syrigos,et al.  Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer , 2004, British Journal of Cancer.

[69]  A. Shelling,et al.  Predictive and prognostic molecular markers for cancer medicine , 2010, Therapeutic advances in medical oncology.

[70]  M. Hughes.  The Business of Self-Monitoring of Blood Glucose: A Market Profile , 2009, Journal of diabetes science and technology.

[71]  Svetlana Vinokurova,et al.  Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki‐67 in epithelial cells , 2012, International journal of cancer.

[72]  D. Wong.  Towards a simple, saliva-based test for the detection of oral cancer. , 2006, Expert review of molecular diagnostics.

[73]  Jeffrey S Ross,et al.  Breast cancer biomarkers and HER2 testing after 10 years of anti-HER2 therapy. , 2009, Drug news & perspectives.

[74]  James F Rusling,et al.  Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics. , 2013, Analytical chemistry.

[75]  Marta Sanchez-Carbayo,et al.  Antibody arrays: technical considerations and clinical applications in cancer. , 2006, Clinical chemistry.

[76]  Y. Yamazaki,et al.  Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[77]  F. Tas,et al.  Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer. , 2008, Lung cancer.

[78]  S. Sheen-Chen,et al.  Serum concentration of tumor necrosis factor in patients with breast cancer , 1997, Breast Cancer Research and Treatment.

[79]  S. Varnum,et al.  Elevated HGF levels in sera from breast cancer patients detected using a protein microarray ELISA. , 2002, Journal of proteome research.

[80]  Karl Hörmann,et al.  Serum levels of interleukin-6 in patients with primary head and neck squamous cell carcinoma. , 2005, Anticancer research.

[81]  A. Cuschieri,et al.  Comparison of serum CA 72-4 and CA 19-9 levels in gastric cancer patients and correlation with recurrence. , 1995, American journal of surgery.

[82]  P. Marques‐Vidal,et al.  Serum concentrations of TNF-alpha as a surrogate marker for malnutrition and worse quality of life in patients with gastric cancer. , 2007, Clinical nutrition.

[83]  Juan Tang,et al.  Gold-silver-graphene hybrid nanosheets-based sensors for sensitive amperometric immunoassay of alpha-fetoprotein using nanogold-enclosed titania nanoparticles as labels. , 2011, Analytica chimica acta.

[84]  J. Scheller,et al.  The pro- and anti-inflammatory properties of the cytokine interleukin-6. , 2011, Biochimica et biophysica acta.

[85]  Ž. Mihaljević,et al.  Serum HER2/ECD value in stage I and II early breast cancer – need of a lower cut-off? , 2011, Wiener klinische Wochenschrift.

[86]  P. Ugo,et al.  Nanoelectrode ensembles as recognition platform for electrochemical immunosensors. , 2008, Biosensors & bioelectronics.

[87]  James F Rusling,et al.  Measurement of biomarker proteins for point-of-care early detection and monitoring of cancer. , 2010, The Analyst.

[88]  S. Vera,et al.  Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma. , 2010, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[89]  René Bernards,et al.  Taming the dragon: genomic biomarkers to individualize the treatment of cancer , 2011, Nature Medicine.

[90]  A. Rajpal,et al.  Expanding the ProteOn XPR36 biosensor into a 36-ligand array expedites protein interaction analysis. , 2011, Analytical biochemistry.

[91]  Ning Gan,et al.  A Sandwich Electrochemical Immunosensor Using Magnetic DNA Nanoprobes for Carcinoembryonic Antigen , 2011, International journal of molecular sciences.

[92]  Jun‐Jie Zhu,et al.  Electrochemical immunoassay for the prostate specific antigen using ceria mesoporous nanospheres , 2014, Microchimica Acta.

[93]  A. Salimi,et al.  Ultrasensitive electrochemical immunosensor for PSA biomarker detection in prostate cancer cells using gold nanoparticles/PAMAM dendrimer loaded with enzyme linked aptamer as integrated triple signal amplification strategy. , 2015, Biosensors & bioelectronics.

[94]  C. Harris,et al.  A Combined Prognostic Serum Interleukin-8 and Interleukin-6 Classifier for Stage 1 Lung Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[95]  Juan Tang,et al.  Nanoparticle-based sandwich electrochemical immunoassay for carbohydrate antigen 125 with signal enhancement using enzyme-coated nanometer-sized enzyme-doped silica beads. , 2010, Analytical chemistry.

[96]  E. Diamandis,et al.  Strategies for discovering novel cancer biomarkers through utilization of emerging technologies , 2008, Nature Clinical Practice Oncology.

[97]  Zhipeng Sun,et al.  Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy , 2014, World Journal of Surgical Oncology.

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

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

[100]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[101]  D. Tang,et al.  Electrochemical immunosensor and biochemical analysis for carcinoembryonic antigen in clinical diagnosis , 2008 .

[102]  M. von Knebel Doeberitz,et al.  Screening for Cervical Cancer Precursors With p16/Ki-67 Dual-Stained Cytology: Results of the PALMS Study , 2013, Journal of the National Cancer Institute.

[103]  Hongyu Zhao,et al.  Serum protein markers for early detection of ovarian cancer. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[104]  S. Nock,et al.  Recent developments in protein microarray technology. , 2003, Angewandte Chemie.

[105]  S. Infusino,et al.  Serum concentrations of proinflammatory cytokines in advanced non small cell lung cancer patients. , 1998, Journal of experimental & clinical cancer research : CR.

[106]  Minghui Yang,et al.  Sensitive immunosensor for tumor necrosis factor α based on dual signal amplification of ferrocene modified self-assembled peptide nanowire and glucose oxidase functionalized gold nanorod. , 2013, Biosensors & bioelectronics.

[107]  A. Cuschieri,et al.  CA72–4: A new tumour marker for gastric cancer , 1990, The British journal of surgery.

[108]  Liyuan Wang,et al.  Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay , 2015, Scientific Reports.

[109]  A. Butch,et al.  Analytical performance of the Roche total and free PSA assays on the Elecsys 2010 immunoanalyzer. , 2002, Clinical biochemistry.

[110]  N. Morgan,et al.  Electrochemical immunosensors for detection of cancer protein biomarkers. , 2012, ACS nano.

[111]  M. O’Donovan,et al.  p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep™ smears , 2003, Journal of clinical pathology.

[112]  C. Kumar,et al.  Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. , 2011, Genes & cancer.

[113]  I. Tentes,et al.  Significance of Serum Tumor Necrosis Factor-Alpha and its Combination with Her-2 Codon 655 Polymorphism in the Diagnosis and Prognosis of Breast Cancer , 2010, The International journal of biological markers.

[114]  Yuquan Wei,et al.  Label-free alpha fetoprotein immunosensor established by the facile synthesis of a palladium-graphene nanocomposite. , 2014, Biosensors & bioelectronics.

[115]  Proespichaya Kanatharana,et al.  Ultrasensitive electrochemical immunosensor based on dual signal amplification process for p16(INK4a) cervical cancer detection in clinical samples. , 2015, Biosensors & bioelectronics.

[116]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[117]  E. Rose,et al.  Alpha-fetoprotein levels in normal adults. , 1992, The American journal of the medical sciences.

[118]  Niina J. Ronkainen,et al.  Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers , 2014, Materials.