ORGS3-0269
High-Throughput LNP Production Using a 3D-Printed Continuous Mixing-Extrusion Platform
Topic
GS3. Graduate Student Oral Session III: Polymer Synthesis, Structure, Properties, and Processing
When and Where
Sep 28, 2026
15:12 - 15:24
Room 103
Session Chairs
Jiwon KIM
Junmin LEE
Youngwoon KO
Presenter(s)
Leekang Jeon (Pohang University of Science and Technology(POSTECH))
Co-Author(s)
Abstract
Lipid nanoparticles (LNPs) represent one of the most widely utilized platforms for nucleic acid delivery, with applications including mRNA vaccines, genetic medicines, and small-molecule therapeutics. LNP synthesis involves mixing aqueous nucleic acids and organic lipids to trigger spontaneous self-assembly, where rapid mixing kinetics are essential for uniform size and dispersity. While microfluidic mixing offers superior particle control, it faces operational hurdles like channel fouling and costly single-use chips. Bulk mixing with membrane extrusion has emerged as an alternative to avoid complex equipment, but it remains a discontinuous process requiring repeated steps. Consequently, maintaining consistent LNP quality while ensuring scalability and cost-effectiveness without compromising process stability remains a major hurdle in current manufacturing. Herein, we present a hybrid continuous synthesis platform that integrates a reusable, 3D-printed milli-fluidic mixing chamber with inline membrane extrusion, enabling a continuous extrusion process. By expanding channel dimensions to the milli-scale and engineering a robust 3D internal mixing architecture, this system achieves high mixing efficiency at elevated flow rates while mitigating clogging and surface fouling. Lipid and nucleic acid solutions are mixed within the chamber to generate a pre-mix suspension, which is immediately routed through an inline extrusion filter in a single pass, completely eliminating the need for repeated extrusion cycles. The durable and easy-to-clean 3D-printed mixer allows for repeated use without performance loss, enhancing reproducibility while reducing reliance on costly disposable systems. Using this integrated platform, we demonstrate continuous and contamination-resistant production of uniform, near-100 nm LNPs at flow rates up to 20 mL/min, offering a highly reproducible, cost-effective, and scalable route toward large-scale manufacturing.
