Date of Award

2026

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Biological Sciences (PhD)

Administrative Home Department

Department of Biological Sciences

Advisor 1

Caryn L. Heldt

Advisor 2

Paul D. Goetsch

Committee Member 1

Rupali Datta

Committee Member 2

Zhiying Shan

Committee Member 3

Ashutosh Tiwari

Abstract

Cancer treatments and survival outcomes have improved significantly in the last couple of decades, with survival rates increasing in the U.S. Despite improvements in treatment outcomes, early detection and treatment are crucial for improving cancer prognosis and survival rates. The standard cancer diagnostic procedure of tissue biopsy is highly invasive, leading to the further spread of cancer in some cases. Alternatively, the extraction of biofluids from cancer patients, also called a liquid biopsy, is increasingly popular because it is less invasive and more representative of the tumor microenvironment, which contains cancer cells, tumor genetic material, and extracellular vesicles, including small extracellular vesicles (sEVs). sEVs are lipid bilayer vesicles released from cells containing cargo (e.g., DNA, RNA, and proteins) unique to their parent cell. sEVs are found in most bodily fluids (e.g., saliva, blood, urine) and are released by many cell types, including cancer cells. Tumor-derived sEVs contribute to cancer progression by promoting metastasis; thus, they are valuable biomarkers for cancer diagnosis due to their circulation in various body fluids. However, sEV heterogeneity hinders the isolation and purification needed for accurate diagnostics. Therefore, improved biophysical characterization of sEVs at the single-particle level could improve diagnostic sensitivity for tumor-derived sEVs. Thus, this dissertation used atomic force microscopy (AFM) and chemical force microscopy (CFM) to investigate the effects of covalent immobilization on sEV morphology, evaluate the influence of isolation methods on downstream analysis of sEVs, and characterize the biophysical and chemical properties of tumor-derived sEVs. This work establishes AFM and CFM as complementary single-particle characterization techniques to improve the efficacy of tumor-derived sEVs for cancer screening and disease monitoring.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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