Abstract

Understanding Three-Dimensional Microfluidic Design to Optimize Lipid Nanoparticle Fabrication

Noah Malmstadt, Professor of Chemical Engineering and Materials Science, University of Southern California

3D printing brings with it a plethora of advantages for microfluidic applications. Principle among these are rapid prototyping, iterative design, and the ability to avoid the cost and overhead of cleanrooms. However, there is also an inherent advantage in being able to design and build devices in a truly three-dimensional, rather than layer-by-layer, geometry. One simple domain in which the advantages of true 3D routing are clear is in mixing. Control over a 3D geometry allows for multiple complex mixing configurations--herringbones, relamination mixers, chaotic advection--to be trivially constructed and recombined. We have deployed these principles of 3D design to design simple, compact devices for the high-throughput manufacture of lipid nanoparticles (LNPs). LNPs are drug delivery vehicles of increasing importance: they have demonstrate effectiveness and scalability as the delivery vehicles for mRNA-based vaccines against SARS-CoV-2 and emerging research is demonstrating that they have broad applications in vaccine delivery and beyond. This talk discusses how microfluidic mixing controls the size, structure, and uniformity of LNPs with several drug-like payloads including mRNA and therapeutic peptides.