PhD Oral Exam - Samuel Little, Electrical and Computer Engineering

When studying for a doctoral degree (PhD), candidates submit a thesis that provides a critical review of the current state of knowledge of the thesis subject as well as the student’s own contributions to the subject. The distinguishing criterion of doctoral graduate research is a significant and original contribution to knowledge.

Once accepted, the candidate presents the thesis orally. This oral exam is open to the public.

Abstract

Inserting foreign biomolecules into human cells is at the heart of cell engineering protocols. By taking nucleic acids or fully formed proteins and shuttling them across the cell membrane in a process known as transfection, cells can either temporarily or permanently gain or lose functionalities. This capability has been used extensively for applications including fundamental research into genetics, industrial production of high value biomolecules, and of interest to this thesis, the production of novel cell therapies – where human cells are repurposed to fight disease.

Numerous techniques have been developed to perform transfection on human cells with a specific focus on technologies that can engineer enough cells for clinical use (often > 109 cells are needed to treat a single patient). However, a currently unmet need in this field, is a miniaturized platform for the research and development of new cell therapies. For this application, large libraries of cellular modifications need to be tested in hopes of discovering one with clinical potential. To do this economically, testing each modification in the library must be done rapidly while consuming as few resources as possible.

Bulk microfluidics has emerged as an ideal technology for high throughput clinical cell therapy production; however, it is unsuited to processing numerous unique small-scale reactions in parallel. To address the unmet need, in this thesis we demonstrate that droplet microfluidics – the science of controllably manipulating sub-microliter volumes of liquid – can serve as the ideal platform for cell therapy R&D.