Date of Completion

7-8-2016

Embargo Period

7-7-2017

Keywords

Cancer diagnostics, Biomarkers, Microfluidics, Electrochemical, Immunoassay, Magnetic beads, On-line capture

Major Advisor

Dr. James F. Rusling

Associate Advisor

Dr. Douglas Adamson

Associate Advisor

Dr. Alfedo-Angeles M. Boza

Field of Study

Chemistry

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Early cancer diagnoses promise to improve treatment outcomes and patient survival rates. However, current cancer diagnostics often rely on finding a tumor, making early detection difficult and possibly compromising therapy outcomes. Screening for cancer without tumor detection can be based on assays of body fluids such as serum or plasma for cancer biomarker proteins to provide an instantaneous record of a patient’s disease status. Measurement of these biomarker proteins should be accurate, sensitive, cheap and preferably at point-of-care (POC) for translation to the clinic. In addition, due to low predictive power of some biomarker proteins and their over-expression by multiple cancer types, it is essential to measure panels of biomarker proteins as opposed to a single biomarker for reliable diagnosis of cancer. Simultaneous measurement of the levels of a panel of biomarker proteins can lead to more accurate diagnoses and offer clarity about disease characteristics and progression that may help guide treatment strategies.

The long-term goal of this thesis research is to provide multiple biomarker-based diagnostics to enable accurate early detection of cancer and therapy monitoring. A simple, low-cost, 8-electrode semi-automated modular microfluidic system for on-line capture and electrochemical detection of panels of cancer protein biomarkers was designed and validated. Proteins that were validated include oral cancer biomarkers (IL-6 & IL-8) and oral mucositis biomarkers (IL-6, TNF-α, IL-1β and CRP). This thesis also describes our first electrochemical assay for parathyroid hormone related peptide (PTHrP); a paraneoplastic peptide responsible for hypercalcemia in cancer patients and also implicated in cancer metastasis. Also described in the dissertation, is a novel 16-electrode electrochemical set up for simultaneous detection of upto 8-prostate cancer biomarkers, many of which are thought to be specific for aggressive prostate cancer. Measurement of these small panels of selective biomarkers holds remarkable promise for future cancer diagnostics and personalized cancer therapies and most importantly in identifying aggressive vs indolent forms of prostate cancer.

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