Monthly Tutorial: Gijung Kim

Speaker: Gijung Kim, Issadore and Lee Labs

Title: Liquid-like surfaces for fouling resistive microfluidic manufacturing of RNA–lipid nanoparticles

Location: Amy Gutmann Hall, Room 414 (Penn), and via Zoom (email Annie for link)

Lunch will be provided for in-person attendees at Penn (please bring your own drinks)!

Abstract: Lipid nanoparticles (LNPs) are essential carriers for RNA-based therapeutics, including mRNA vaccines and gene-silencing agents. However, conventional bulk mixing suffers from poor size control, heterogeneity, and limited encapsulation efficiency, hindering large-scale manufacturing. Microfluidic mixing offers precise size control and scalability through parallelization, yet its broader adoption is limited by fouling, where lipid precursors and nascent LNPs accumulate on channel walls, causing clogging and performance loss. Current antifouling approaches—such as  poly(ethylene glycol)-, zwitterionic-, or fluorinated silane coatings—fail to function effectively in ethanol-rich conditions. Another approach, lubricant-infused surfaces initially mitigate fouling but fail under high shear flow due to lubricant depletion, while also raising contamination and safety concerns. To address this, we developed Tethered Liquid-Like Surfaces (TLLS): covalently anchored, liquid-like interfacial layers that retain molecular mobility without lubricant depletion. TLLS resists fouling under high-shear, ethanol-rich environments, enabling stable and reproducible LNP production. By integrating TLLS with microfluidic platforms, we aim to establish a scalable, GMP-compatible technology for continuous manufacturing of RNA therapeutics.