[CCoE Notice] Dissertation Announcement: Mohammad Sadman Mallick, "Advancements in Plasmonic Imaging for Quantitative Analysis and Molecular Profiling of Single Small Extracellular Vesicles towards Cancer Diagnosis"

[Greenwell, Stephen J]

[Dissertation Defense Announcement at the Cullen College of Engineering]
Advancements in Plasmonic Imaging for Quantitative Analysis and Molecular Profiling of Single Small Extracellular Vesicles towards Cancer Diagnosis
Mohammad Sadman Mallick
November 26, 2024; 10:00 AM - 12:00 PM (CST)
Location: W332 Eng Bld 2
Zoom: https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/82270910246?pwd=7Knq26XjFIB2HJwXvj2cfm3rm6zAbI.1__;!!LkSTlj0I!EmKSym0V_gGQM3NzUZyCIXbhz8drJsiP0rSY0unmrvdp-nZjqcnD52ymoPvAXQvvx-xs36YLVhsYHji6ATu_efOqGns$ <https://urldefense.com/v3/__https:/uh-edu-cougarnet.zoom.us/j/82270910246?pwd=7Knq26XjFIB2HJwXvj2cfm3rm6zAbI.1__;!!LkSTlj0I!DVTvMqp7n4k0bOq64_fviVrYd2aWuveZSjc1YK_koDQc67PqTv27YDixHSKD2u1rxFMQ7HRsaMjasijYMCs-GcL_2Q$>
Committee Chair:
Wei-Chuan Shih, Ph.D.
Committee Members:
John C. Wolfe, Ph.D. | Steven H. Lin, Ph.D. | Xiaonan Shan, Ph.D. | Rohith Reddy, Ph.D.
Abstract
Liquid biopsy, a minimally-invasive approach that examines tumor-derived biomarkers in body fluids, holds potential to enhance early diagnostics by identifying tumor components such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating tumor small extracellular vesicles (sEVs). Though CTDNA and CTC-based blood tests guide therapy by identifying tumor mutations, only dead cells can contribute to CTDNA and CTC. In contrast, blood circulating sEVs are constantly secreted by living cells, and both their surface proteins and cargo contents reflect the molecular composition of their parent cells. However, label-free characterization of these nanoscale vesicles is challenging, as they are virtually indistinguishable from similarly sized particles without labeling. This dissertation is primarily constructed on a foundational technology: PlAsmonic NanO-apeRture lAbel-free iMAging (PANORAMA), a narrow band bright-field imaging technique implemented on arrayed gold nanodisks on invisible substrates (AGNIS). PANORAMA enables high-resolution detection, quantification, and localization of individual nanoparticles as small as 25 nm with a limit of detection below 10 nm. It also introduces new developments in dynamic tracking of single exosomes, cluster formation monitoring, and 3D localization with ~21 nm lateral and ~7-9 nm axial accuracy. To enhance molecular specificity, PANORAMA is integrated with fluorescence imaging, allowing simultaneous detection of cancer-specific sEV cargo microRNAs (miRs), such as miR-21. This capability facilitates precise molecular targeting down to the single-sEV level. Testing on sEVs from cancer patient plasma demonstrated unique molecular signatures indicative of disease progression. PANORAMA's exquisite sensitivity for potential early cancer detection has been demonstrated in as little as 20 μl of plasma in both animal models and human subjects with consistent results. In a human subject study with over 300 individuals (multi-cancer, multi-stages), PANORAMA sEV counts can separate cancer from healthy individuals with a diagnostic sensitivity of 99.5%, a specificity of 97.3%, and an area under the curve (AUC) of 0.99 using a threshold of 3.5 absolute sEVs per μl for cancer detection. In another human subject study involving 156 individuals of 4 categories: hepatocellular carcinoma, cholangiocarcinoma, fatty liver disease (non-cancer), and healthy individuals, a molecular beacon (MB) panel was added together with the PANORAMA sEV counts and delivered 97% sensitivity, 95% specificity, and 0.94 AUC for cancer detection. The combination of PANORAMA with fluorescence imaging of sEV could significantly improve early detection accuracy in liquid biopsy.
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