Molecular imprinted nanoelectrodes for ultra sensitive detection of ovarian cancer marker.

The relentless discovery of cancer biomarkers demands improved methods for their detection. In this work, we developed protein imprinted polymer on three-dimensional gold nanoelectrode ensemble (GNEE) to detect epithelial ovarian cancer antigen-125 (CA 125), a protein biomarker associated with ovarian cancer. CA 125 is the standard tumor marker used to follow women during or after treatment for epithelial ovarian cancer. The template protein CA 125 was initially incorporated into the thin-film coating and, upon extraction of protein from the accessible surfaces on the thin film, imprints for CA 125 were formed. The fabrication and analysis of the CA 125 imprinted GNEE was done by using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. The surfaces of the very thin, protein imprinted sites on GNEE are utilized for immunospecific capture of CA 125 molecules, and the mass of bound on the electrode surface can be detected as a reduction in the faradic current from the redox marker. Under optimal conditions, the developed sensor showed good increments at the studied concentration range of 0.5-400 U mL(-1). The lowest detection limit was found to be 0.5 U mL(-1). Spiked human blood serum and unknown real serum samples were analyzed. The presence of non-specific proteins in the serum did not significantly affect the sensitivity of our assay. Molecular imprinting using synthetic polymers and nanomaterials provides an alternative approach to the trace detection of biomarker proteins.

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

[2]  Chien Chou,et al.  Diagnostic detection of human lung cancer-associated antigen using a gold nanoparticle-based electrochemical immunosensor. , 2010, Analytical chemistry.

[3]  David M. Rissin,et al.  Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations , 2010, Nature Biotechnology.

[4]  J. Ho,et al.  Disposable electrochemical immunosensor for carcinoembryonic antigen using ferrocene liposomes and MWCNT screen-printed electrode. , 2009, Biosensors & bioelectronics.

[5]  Ren-Shyan Liu,et al.  Early detection of recurrent ovarian cancer in patients with low-level increases in serum CA-125 levels by 2-[F-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography. , 2011, Cancer biotherapy & radiopharmaceuticals.

[6]  Adrian M Ionescu,et al.  Nanowire transistors made easy. , 2010, Nature nanotechnology.

[7]  C. G. Zoski,et al.  Fabrication of 3D gold nanoelectrode ensembles by chemical etching. , 2005, Analytical chemistry.

[8]  Sudhir Srivastava,et al.  Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens , 2011, Cancer Prevention Research.

[9]  Maëlle Perfézou,et al.  Cancer detection using nanoparticle-based sensors. , 2012, Chemical Society reviews.

[10]  Song Zhang,et al.  Protein chips and nanomaterials for application in tumor marker immunoassays. , 2009, Biosensors & bioelectronics.

[11]  Shana O Kelley,et al.  Protein detection using arrayed microsensor chips: tuning sensor footprint to achieve ultrasensitive readout of CA-125 in serum and whole blood. , 2011, Analytical chemistry.

[12]  Changming Mao,et al.  A label-free immunosensor based on modified mesoporous silica for simultaneous determination of tumor markers. , 2011, Biosensors & bioelectronics.

[13]  Dan Wu,et al.  Nanoporous gold film based immunosensor for label-free detection of cancer biomarker. , 2011, Biosensors & bioelectronics.

[14]  B. Jena,et al.  Gold nanoelectrode ensembles for the simultaneous electrochemical detection of ultratrace arsenic, mercury, and copper. , 2008, Analytical chemistry.

[15]  A. Verbeek,et al.  Considering Early Detection of Relapsed Ovarian Cancer: A Review of the Literature , 2011, International Journal of Gynecologic Cancer.

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

[17]  James Noble,et al.  The rational development of molecularly imprinted polymer-based sensors for protein detection. , 2011, Chemical Society reviews.

[18]  B. Rigas,et al.  Potentiometric sensors based on surface molecular imprinting: Detection of cancer biomarkers and viruses , 2010 .

[19]  Jeffrey H. Chuang,et al.  A molecular-imprint nanosensor for ultrasensitive detection of proteins. , 2010, Nature nanotechnology.

[20]  Celia Arnaud INFLAMMATION STOKES CANCER: WHEN IT GOES AWRY, this defense mechanism can contribute to all stages of cancer progression , 2011 .

[21]  Sudhir Srivastava,et al.  A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer , 2011, Cancer Prevention Research.

[22]  James F Rusling,et al.  Microfluidic electrochemical immunoarray for ultrasensitive detection of two cancer biomarker proteins in serum. , 2011, Biosensors & bioelectronics.

[23]  S. Yau,et al.  Field-effect amperometric immuno-detection of protein biomarker. , 2011, Biosensors & bioelectronics.