Contactless Microfluidic Cell Stretching Enables High Throughput Genetic Modification

Abstract: Cell and gene therapies are being explored for many disease areas, but face challenges associated with safety and efficacy as well as manufacturing time and cost. Intracellular delivery of genes and gene editing complexes such as CRISPR-Cas9 are essential to manufacturing, but low yield and process heterogeneity still characterize clinically available delivery methods. To address this need, we have investigated microfluidic systems that leverage the nonlinear stress behavior of viscoelastic fluids to apply sub-millisecond pulses of mechanical tension to the plasma membrane of cells without surface contact. This creates reversible pores in the membrane, allowing mRNA and CRISPR-Cas9 ribonucleoproteins to diffuse into the cytosol within seconds. This uniquely fast and effective intracellular delivery platform has several promising applications in cell and gene therapy manufacturing, for example in T cell editing for CAR T production.

Bio: Derin Sevenler joined the Carnegie Mellon University Department of Chemical Engineering as an assistant professor in 2024. His research addresses problems at the interface of biotechnology and fluid mechanics. His interests include microfluidics, non-Newtonian and complex fluids, biomaterials, gene & drug delivery, nano-optics, and molecular diagnostics.

Sevenler received his Ph.D. in biomedical engineering from Boston University and his BS in mechanical and aerospace engineering from Cornell University. From 2018 to 2022, he was a postdoctoral fellow in the laboratory of Mehmet Toner at Massachusetts General Hospital. Before joining Carnegie Mellon University, he was an instructor in the Center for Engineering in Medicine & Surgery at Massachusetts General Hospital and Harvard Medical School. Sevenler is a recipient of the NIH Pathway to Independence Award.

Host: Ipsita Banerjee