# Unique Aerofoil‐Structured Microfluidics for High Throughput Lipid Nanoparticle Formulation Screening and Scale‐up

## TL;DR

A new microfluidic platform with aerofoil structures enables efficient, high-throughput lipid nanoparticle formulation and scalable production for drug delivery.

## Contribution

Introduces a novel aerofoil-structured microfluidic platform for LNP formulation screening and scale-up with high reproducibility and quality.

## Key findings

- The aerofoil structures enhance mixing and LNP formation across flow rates from 0.2 to 50 mL/min.
- MiNANO-form enables simultaneous synthesis of multiple LNP formulations with size 38–150 nm and PDI < 0.2.
- MiNANO-scale supports continuous LNP production at up to 50 mL/min with validated mRNA, pDNA, and siRNA delivery.

## Abstract

Herein, a high‐throughput microfluidic platform is presented that addresses the challenges in lipid nanoparticles (LNPs) formulation screening and scale‐up through the design of micromixers with unique aerofoil structures. These structures are optimized to enhance mixing and LNP formation across a wide flow rate range (0.2–50 mL min−1), using minimal reagent volumes (as low as 0.1 mL) up to liter‐scale production. A high‐throughput formulation screening instrument named MiNANO‐form and a microfluidic cartridge with eight parallel channels is introduced, which enables simultaneous synthesis of multiple LNP formulations with excellent quality (size 38–150 nm and polydispersity index (PDI), PDI < 0.2) and reproducibility. In addition, for a seamless scale‐up, the platform consists of a custom‐made modular microfluidic unit, named MiNANO‐scale, capable of continuous LNP production at up to 50 mL min−1. The platform's performance is validated through mRNA and pDNA transfection, as well as siRNA uptake studies in HEK293, A549, and CFBE cells.

This study presents aerofoiled microfluidic structures optimized for efficient mixing and lipid nanoparticle (LNP) formation across broad flow rates. Based on this design, two dedicated systems are introduced: MiNANO‐form for high‐throughput formulation screening and MiNANO‐scale for continuous large‐scale production, enabling reproducible, high‐quality LNPs validated with mRNA, pDNA, and siRNA delivery.