Lab on a chipMar 31, 2026

Vertical stacking design for making consistent lipid nanoparticles at scale

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A vertically stacked microfluidic cartridge produced lipid nanoparticles at higher throughput while preserving particle quality in platform testing.

Evidence

This formulation and platform experiment tested a five-layer polycarbonate VeSMiC device, achieving 0.96 L per hour flow, 7-fold higher throughput than a single channel, 100-150 nm LNP size, PDI below 0.12, and encapsulation efficiency above 96%.

Caveat

Industrial-scale performance is partly projected from an 80-cartridge platform, and the reported therapeutic efficacy comes from a wound model rather than human manufacturing or clinical outcomes.

Simplified

Lipid nanoparticles (LNPs) are a key platform for nucleic acid delivery, but their industrial-scale production remains a critical bottleneck. While microfluidics ensures high-quality LNP production, conventional single layer strategies suffer from low throughput. Existing scaling strategies, like parallel or 3D devices, face limitations in flow distribution and fabrication complexity, failing to balance throughput with LNP quality. Here, we report a robust, vertically stacked microfluidic cartridge (VeSMiC) fabricated using polycarbonate (PC) that successfully addresses the flow distribution challenge. This platform integrates a hydrodynamic tapered inlet structure, ensuring uniform flow partitioning across layers, with re-Tesla mixers for rapid synthesis. A five-layer device was scalably fabricated using a two-step surface modification and a robust bonding method. This device enabled stable operation at a high total flow rate (0.96 L per hour) operation and increased LNP throughput 7-fold compared to a single channel. Critically, this high throughput did not compromise quality; LNPs consistently maintained an average size of 100-150 nm, a low polydispersity index (PDI) below 0.12, and high encapsulation efficiency above 96%. Furthermore, they also demonstrated significant therapeutic efficacy in anwound model. Notably, an 80-cartridge platform is projected to achieve a production flow rate of approximately 80 L per hour, validating this platform as a viable solution for industrial-scale LNP manufacturing. in vitro