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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Anna Liu
BioEngineering PhD Proposal
January 12, 2018, 9 AM
Suddath Seminar Room 1128, Petit Institute for Bioengineering and Bioscience
Thesis Advisor:
Todd Sulchek, PhD
Georgia Institute of Technology, Woodruff School of Mechanical Engineering
Thesis Committee:
Alexander Alexeev, PhD
Georgia Institute of Technology, Woodruff School of Mechanical Engineering
Edmund K. Waller, MD, PhD
Emory University School of Medicine, Department of Medical Oncology
Mark Prausnitz, PhD
Georgia Institute of Technology, School of Chemical and Biomolecular Engineering
Krishnendu Roy, PhD
Georgia Institute of Technology, Coulter Department of Biomedical Engineering
CONVECTIVE INTRACELLULAR MACROMOLECULE DELIVERY BY CELL VOLUME EXCHANGE FOR CELL ENGINEERING APPLICATIONS
The rapidly growing field of cell manufacturing requires robust methods for intracellular delivery of cell engineering reagents. However, this field still lacks an intracellular delivery platform that is cost-effective, maintains high cell viability, and is broadly applicable for diverse cargoes and cell types. In this project, we discovered a unique biophysical phenomenon of transient cell volume exchange induced by rapid and sequential microfluidic cell compression. This behavior consists of iterations of brief, mechanically induced cell volume loss followed by rapid volume recovery. We found that cell volume exchange can convectively transfer a variety of macromolecules and particles into cells, including 2 MDa polysaccharides, 100 nm nanoparticles, and 2.5 MDa plasmids, without significantly impacting cell viability or other tested phenotypic properties. The ease of use and successful proof-of-concept transfections demonstrate great potential to address major challenges in intracellular delivery. The work first aims to understand the mechanisms of this technology, and then leverage the platform to impactfully address two growing needs in cell engineering: (1) test and evaluate a new immunotherapy manufacturing approach by delivering CD19 chimeric antigen receptor (CAR) mRNA to primary T cells and assessing CAR T cell expression and cytotoxicity against B cell lymphoma; (2) demonstrate induced pluripotent stem cell (iPSC) reprogramming by direct delivery of Yamanaka factor protein or mRNA.
