Author: Michael Yeh
Date/Time: February 3rd, 2026 at 1:00PM EST
Location: AJC 5104
Committee Members:
Dr. Don L. DeVoe, Chair
Dr. Cecilia Huertas Cerdeira
Dr. Ryan Sochol
Dr. Kenneth Kiger
Dr. Ian White, Dean’s Representative
Title of Dissertation: Large Scale Integration of Microfluidic Trap Arrays for Probing T-Cell Activation in Nanoliter Tumor Co-cultures
Abstract: Immune responses against cancer are inherently stochastic, with small numbers of individual T cells within a larger ensemble of lymphocytes initiating the molecular cascades that lead to tumor cytotoxicity. A potential source of this intra-tumor variability is the differential ability of immune cells to respond to tumor cells. Classical microwell co-cultures of T cells and tumor cells are inadequate for reliably culturing and analyzing low cell numbers needed to probe this variability, and are unable to recapitulate the heterogeneous small domains observed in tumors.
Microfluidics is leveraged to overcome limitations of conventional microwell plates for immunodynamic studies. Membrane Displacement Traps (MDTs), dynamic nanowells originally developed for droplet manipulation, are adapted as an enabling technology for a single-phase perfusion cell culture platform. Using an optimized MDT array, interactions between small numbers of T cells and tumor cells with differential expression of antigens associated with immune activation are investigated. This data is correlated with off-chip immune cell profiling by flow cytometry to highlight the strengths and limitations of the novel platform.
The primary limitation of the MDT array technology is reliance on independent fluidic channels for actuation, which are cumbersome to integrate and significantly delay time-sensitive experimental steps. To address the need for scalable fluidic interfacing with the MDT arrays and allow for higher-density cell cultures to be performed, a fabrication process is developed and refined to produce thin membranes that can be patterned as in conventional soft lithography, but with the novel ability to also integrate through-holes seamlessly into the channel network. MDT array devices with integrated ports, such as a fluidic ribbon cable, were made using this process to demonstrate the novel capability to rapidly make highly parallel connections.
A modular pneumatic multiplexer is developed to take advantage of this interface, enabling individual control of each MDT nanowell while externalizing complexity from the cell culture device. The extended platform, operated by programmable multiplexed control over a fluidic ribbon cable, is used to perform simple MDT operations to demonstrate the feasibility of the MDT array technology for investigating stochastic immune signaling and activation processes as originally envisioned. Ultimately, the platform could be used for identifying and isolating high-performing T cells for adoptive cell immunotherapies.