Date Approved

6-10-2020

Embargo Period

6-11-2021

Document Type

Dissertation

Degree Name

PhD Doctor of Philosophy

Department

Biomedical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Shim, Jiwook

Committee Member 1

Byrne, Mark

Committee Member 2

Beachley, Vincent

Keywords

Biosensor, Nanopore, Nanotechnology, Precision Medicine, Single-molecule

Subject(s)

Nanopores; Cancer--Treatment

Disciplines

Biomedical Engineering and Bioengineering | Medicine and Health Sciences

Abstract

Currently, when patients are diagnosed with cancer, they often receive a treatment based on the type and stage of the tumor. However, different patients may respond to the same treatment differently, due to the variation in their genomic alteration profile. Thus, it is essential to understand the effect of genomic alterations on cancer drug efficiency and engineer devices to monitor these changes for therapeutic response prediction. Nanopore-based detection technology features devices containing a nanometer-scale pore embedded in a thin membrane that can be utilized for DNA sequencing, biosensing, and detection of biological or chemical modifications on single molecules. Overall, this project aims to evaluate the capability of the biological nanopore, alpha-hemolysin, as a biosensor for genetic and epigenetic biomarkers of cancer. Specifically, we utilized the nanopore to (1) study the effect of point mutations on C-kit1 G-quadruplex formation and its response to CX-5461 cancer drug; (2) evaluate the nanopore's ability to detect cytosine methylation in label-dependent and label-independent manners; and (3) detect circulating-tumor DNA collected from lung cancer patients' plasma for disease detection and treatment response monitoring. Compared to conventional techniques, nanopore assays offer increased flexibility and much shorter processing time.

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