Date of Award

Spring 6-7-2023

Document Type

Thesis (Undergraduate)

Department

Engineering

First Advisor

John X.J. Zhang

Abstract

Drug delivery is a key area of therapeutic development that focuses on delivery of active agents to target tissues while minimizing off-target toxicities. Current methods have drawbacks including immunogenicity and suboptimal tissue targeting. Exosomes have gained attention as an ideal delivery molecule due to their high biocompatibility, cargo agnostic nature, and innate targeting ability. The current roadblock for exosomes as a therapeutic modality is the unscalable and inefficient manufacturing paradigm.

We validate a developed microfluidic device for integrated isolation and therapeutic loading of exosomes from native biofluid. The developed system captures exosomes by use of anti-exosome antibodies conjugated to magnetic, iron oxide nanoparticles. The captured exosomes are irradiated with LED light to generate photothermal heating of the iron oxide; the rapid heating induces temporary membrane proration such that therapeutic cargo can be loaded. This system was optimized for loading of COLO-1 exosomes with doxorubicin. Biochemical parameters such as conjugate ratios, exosome surface markers, and elution system have been optimized. Additionally, system parameters such as optical power output, pulse length, and pulsing has been optimized. With an optimized protocol, we demonstrate isolation of exosomes and subsequent loading from clinical plasma samples obtained from pancreatic cancer patients.

This study generates proof of concept data for a novel microfluidic platform that leverages magnetic nanoparticles and photothermal heating for exosome processing. Economic analysis indicates a 53% reduction in unit costs of this platform relative to current standard. Additionally, we discuss the significance of using this platform for autologous exosomes, opening consideration for personalized medicine.

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