Abstract

Microfluidic Immunoengineering

Abraham Lee, William J. Link Professor and Chair, University of California-Irvine

The COVID-19 pandemic, and the subsequent successful development of the mRNA vaccine has ushered in an era of immunoengineering. Immunoengineering involves the “reprogramming” of the immune system to overcome limitations of the innate or adaptive immune responses that the body naturally produces. Recent developments of microfluidics for precision medicine applications such as liquid biopsy, cell therapy, single cell analysis, and microphysiological systems have contributed to the general field of immunoengineering. Specifically, adoptive cell therapy (ACT) is a type of immunotherapy that involves the processing of blood from a donor to isolate immune cells (e.g. T cells) for genetic manipulation followed by reinfusion of the cells into patients. This process that starts from blood drawn from one person and ends with specialized engineered cells delivered to the patient includes multiple tedious and costly steps, and can require a long time that the patient may not have. Microfluidic technologies can address most steps of this complex cell manufacturing process, including cell harvesting, cell isolation, cell activation and expansion, and cell transfection. In this talk I will introduce two microfluidic platforms in my lab applied to the cellular engineering processes, one is the lateral cavity acoustic transducer (LCAT) and the other is droplet microfluidics. Based on LCAT, we developed the acoustic electric shear orbiting poration (AESOP) device to uniformly deliver genetic cargos into a large population of cells simultaneously. We demonstrate high quality transfected cells with controlled dosage delivery as well as serial delivery of different genetic cargos. These capabilities can be used to optimize the therapeutic efficacy of the engineered cells and also combine it with promising gene editing tools to further condition the cells for more specific in vivo targeting. Based on droplet microfluidics we constructed bottom-up artificial antigen presenting cells (aAPCs) for antigen-specific T cell activation. By trapping single cells in microfluidic droplet compartments, we are able to study the 3D cell morphology of both the cell surface and also its intracellular constituents to further understand immune cell activation and immune cell synapses.