Researcher(s)
- David Yun, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jason Gleghorn, Biomedical Engineering, University of Delaware
Abstract
Our group has developed a cell-mimetic drug delivery platform called T-cell Mimetic Membrane Wrapped Microparticles (T3MPs), using flow focusing generated alginate microparticle (MP) cores. The goal of this work is to validate manufacturing methods for an emulsion based MP generation system, to improve throughput and scalability. Current fabrication methods often produce polydisperse particles, while manual characterization is time-consuming and operator-dependent. Additionally, the negatively charged alginate surface may reduce T-cell membrane wrapping efficiency through electrostatic repulsion. This research aimed to develop a standardized workflow for alginate microparticle fabrication, characterization, storage, and surface modification to improve particle quality and support reproducible T3MP manufacturing. Brightfield microscopy images were analyzed using a custom machine learning autosegmentation pipeline to automate particle counting and size characterization. Sequential filtration strategies (40 µm, 40–20 µm, and 40–20–10 µm) were evaluated to remove oversized particles while maintaining particle yield of desired size regime. Poly-L-lysine (PLL) coatings were investigated to modify the negative surface charge of alginate MPs and improve membrane wrapping potential. Cryoprotectant formulations containing trehalose and sucrose were also evaluated to preserve particle recovery, morphology, and coating integrity during freezing and storage. Cascade filtration successfully reduced oversized particles while maintaining acceptable recovery, with the 40–20–10 µm cascade producing the greatest reduction in maximum particle size. Surface modification studies identified promising PLL coating conditions. The autosegmentation pipeline is currently being optimized, and cryoprotection studies are ongoing to identify storage conditions that maximize particle recovery and preserve morphology after freezing. Future work will validate the segmentation pipeline, optimize cryoprotectant formulations, improve coating stability, and integrate these processes into a complete T3MP manufacturing platform.