Avi Gupta

BioE Ph.D. Proposal Presentation

12 PM on Mon, May 5, 2025

Location: UA Whitaker 1232

https://gatech.zoom.us/j/92625832569?pwd=eMGUo0PIdygUcSThODIXDeMRI5YBna.1&from=addon

Advisor: Todd Sulchek, Ph.D. (ME, Georgia Institute of Technology)

Committee:

Alexander Alexeev, Ph.D. (ME, Georgia Institute of Technology)

Scott Danielsen (MSE, Georgia Institute of Technology)

David Myers, Ph.D. (BME, Georgia Institute of Technology)

Guillem Pratx, Ph.D. (Radiology and Medical Physics, Stanford University) 

Optimization of Forces, Loading Rates and Strain Rates for Cytosolic Delivery using Mechanoporation  

Intracellular delivery of biomolecules such as mRNA, radiotracers, and gene-editing tools is a critical to advance gene therapy, diagnostics, and regenerative medicine. Microfluidic mechanoporation uses physical deformation of cells to transiently open membrane pores offering a scalable and reagent-free alternative to traditional delivery methods. Its broader adoption is limited by unpredictable delivery outcomes and incomplete understanding of how mechanical forces impact cells. This research aims to establish a force-informed framework for designing microfluidic systems that can consistently and efficiently deliver biomolecules directly into cytosol, bypassing endocytic degradation. By studying how cells respond to dynamic adhesion, loading rate, and strain state across microsecond to millisecond time scales, this work seeks to make delivery outcomes more predictable and tunable. In Aim 1, we will investigate how adhesion and mechanical properties influence cell behavior under flow using atomic force microscopy (AFM) and microfluidic ridge geometries. Aim 2 focuses on developing and validating analytical models that isolate and quantify the mechanical forces driving membrane poration using custom channel designs that modulate shear loading rate. In Aim 3, we will evaluate the biological fate of delivered molecules by comparing cytosolic versus endosomal colocalization using fluorescent and radiolabeled cargo. Together, this work will provide key design principles for the next generation of intracellular delivery platforms, enabling more precise and effective delivery for time-sensitive and therapeutically potent molecules.