Date of Award

Spring 2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Sandra Zivanovic

Abstract

Prostate cancer (PC) affects elderly men more than young men. The currently used cancer biomarker, prostate-specific antigen (PSA), highly overestimates PC population. Men with high PSA levels often have to go through unnecessary, but physically painful, and expensive prosesses, such as prostate biopsies. Finding a prostate cancer marker that is produced selectively by cancer, but not by normal prostate cells will increase the reliability of PC test. In 2006, our collaborator (Dr. Girish Shah) discovered a novel protein, referred as neuroendocrine marker (NEM), secreted only by malignant prostate cells and released in blood circulation.

To examine whether the combined NEM-PSA test can improve the reliability for early PC detection, we have developed a nanoporous thin film sensor that can reliably detect PSA and NEM in patient samples. The thin film sensor is fabricated from nanoporous anodic aluminum oxide and uses an optical Fabry-Perot intereferometric technique. This optical sensor has been tested for several assay paradigms, including nonspecific binding, reliability, accuracy, precision, and sensitivity. The results demonstrate that the optical nanoporous thin film sensor is reliable and extremely sensitive when used with only 0.5 µl of patient serum (or even less) to measure levels of the PSA and NEM, even in a non-cancer individual. When compared with the traditional ELISA test for PSA, the nanosensor assay is several-fold more sensitive, and it elimnates the need for labeled antigen, sample processing, complex equipment, and highly experienced individuals. These benefits, along with the low cost, should make the technology suitable for Point-of-Care application to accurately screen elderly male populations for PC and to monitor the progress of patients undergoing PC treatment. Nanoporous thin-film sensor was able to detect prostate cancer markers concentrations as low as 1 pg/ml for NEM and 20 pg/ml for PSA.

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