Highly sensitive detection of HER2 extracellular domain in the serum of breast cancer patients by piezoelectric microcantilevers.

Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection; however, their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/mL). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection.

[1]  Joseph A. Capobianco,et al.  Label free detection of white spot syndrome virus using lead magnesium niobate-lead titanate piezoelectric microcantilever sensors. , 2010, Biosensors & bioelectronics.

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

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

[4]  W. Shih,et al.  Enhanced Detection Resonance Frequency Shift of a Piezoelectric Microcantilever Sensor by a DC Bias Electric Field in Humidity Detection. , 2009, Sensors and actuators. B, Chemical.

[5]  D. Villemain,et al.  Evaluation of a manual ELISA kit for determination of HER2/neu in serum of breast cancer patients. , 2008, Anticancer research.

[6]  R. Bast,et al.  Early Detection of Ovarian Cancer , 2007, Disease markers.

[7]  S Gori,et al.  Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  Koutilya R Buchapudi,et al.  Microcantilever biosensors based on conformational change of proteins. , 2008, The Analyst.

[9]  John T. Woosley,et al.  Circulating levels of inflammatory cytokines and risk of colorectal adenomas. , 2008, Cancer research.

[10]  Wei-Heng Shih,et al.  In situ detection of Bacillus anthracis spores using fully submersible, self-exciting, self-sensing PMN-PT/Sn piezoelectric microcantilevers. , 2007, The Analyst.

[11]  B-W. Park,et al.  Resveratrol downregulates acetyl-CoA carboxylase alpha and fatty acid synthase by activating AMP-activated protein kinase and suppressing the mammalian target of rapamycin signal pathway , 2007, Breast Cancer Research.

[12]  E. Lee,et al.  Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer. , 2006, Clinical chemistry.

[13]  M. Pawlita,et al.  Suppression of non-specific binding in serological Luminex assays. , 2006, Journal of immunological methods.

[14]  G. Adams,et al.  Isolation of scFvs to in vitro produced extracellular domains of EGFR family members. , 2005, Cancer biotherapy & radiopharmaceuticals.

[15]  Farooq Ghani,et al.  Serum levels of shed Her2/neu protein in men with prostate cancer correlate with disease progression. , 2005, The Journal of urology.

[16]  S. Kritchevsky,et al.  Circulating Levels of Inflammatory Markers and Cancer Risk in the Health Aging and Body Composition Cohort , 2005, Cancer Epidemiology Biomarkers & Prevention.

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

[18]  D Robert Siemens,et al.  Prostatitis and prostate cancer: implications for prostate cancer screening. , 2004, Urology.

[19]  Christiane Ziegler,et al.  Cantilever-based biosensors , 2004, Analytical and bioanalytical chemistry.

[20]  W. Wilczak,et al.  Prognostic and Predictive Impact of the HER-2/neu Extracellular Domain (ECD) in the Serum of Patients Treated with Chemotherapy for Metastatic Breast Cancer , 2004, Breast Cancer Research and Treatment.

[21]  R. Neumann,et al.  Monitoring of Serum Her-2/neu Predicts Response and Progression-Free Survival to Trastuzumab-Based Treatment in Patients with Metastatic Breast Cancer , 2004, Clinical Cancer Research.

[22]  R. Neumann,et al.  Potential clinical utility of serum HER-2/neu oncoprotein concentrations in patients with breast cancer. , 2003, Clinical chemistry.

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

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

[25]  Y. Yarden,et al.  The basic biology of HER2. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[26]  A. Dnistrian,et al.  Monitoring Therapy by Serum HER-2/Neu , 2000, The International journal of biological markers.

[27]  R. Kashyap,et al.  Extremely Elevated Serum CA125 Due To Endometriosis , 1999, The Australian & New Zealand journal of obstetrics & gynaecology.

[28]  L. A. Currie,et al.  Nomenclature in evaluation of analytical methods including detection and quantification capabilities (IUPAC Recommendations 1995) , 1995 .

[29]  S. Ménard,et al.  The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. , 1993, Oncogene.