Date of Award

Spring 2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Engineering

Committee Director

Gymama Slaughter

Committee Member

Barbara Hargrave

Committee Member

Krishnanand Kaipa

Committee Member

Nancy Xu

Abstract

Prostate cancer is a prevalent malignancy and the second leading cause of cancer-related deaths among men globally. The early detection and monitoring of prostate cancer are crucial for improving patient outcomes and reducing unnecessary treatments. Traditional diagnostic methods, such as prostate specific antigen (PSA) blood testing and biopsies, are invasive, costly, and can lead to overdiagnosis. Additionally, PSA tests often yield false positives or negatives, and biopsies carry significant side-effects and discomforts. Therefore, there is a pressing need for novel, non-invasive diagnostic approaches. MicroRNAs (miRNAs) have emerged as promising biomarkers for prostate cancer due to their dysregulation in malignant cells and their presence in urine.

However, conventional miRNA detection is hindered by low sensitivity, complex procedures, and expensive equipment. Electrochemical biosensors, utilizing readily available electrode substrates, offer a cost-effective, rapid, and highly sensitive alternative for miRNA detection. Paper substrates are advantageous due to their low cost, accessibility, and compatibility with inkjet printing, which allows for rapid and scalable production of high-resolution electrode patterns. By incorporating these advancements in paper-based electrodes, electrochemical biosensors can offer a highly sensitive, cost-effective, and user-friendly platform for the early detection and monitoring of prostate cancer.

This study introduces an innovative electrochemical paper-based biosensor that leverages gold inkjet printing for the quantitative detection of miRNAs. The biosensor, aimed at developing cost-effective POC devices for low-resource settings, uses thiolated self-assembled monolayers to immobilize single-stranded DNA (ssDNA) on electrodeposited gold nanoparticles (AuNPs) on the printed gold surface, facilitating specific miRNA capture and enhancing sensitivity. The hybridization of ssDNA with miRNA increases the anionic barrier density, impeding electron transfer from the redox probe and resulting in a current suppression that correlates with miRNA concentration. The biosensor exhibited a linear detection range from 1 fM to 1 μM miR-141 with a sensitivity of 73.13 fM μA-1 cm-2 and a rapid response time (15 min). With a low detection limit of 2.31 fM miR-141 in synthetic urine, the biosensor also demonstrates excellent selectivity against interferent species. This innovative device highlights the potential for the development of cost-effective electrode substrates accessible for cancer diagnostics.

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DOI

10.25777/nwjw-5q69

ISBN

9798280748705

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