Bio-protocolSep 26, 2025

Affordable and Reliable Method to Make mRNA-Carrying Lipid Nanoparticles Using Standard Lab Microfluidics

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

A low-cost laboratory microfluidic setup produced mRNA-loaded lipid nanoparticles with reported quality metrics similar to commercial systems.

Evidence

This was a protocol and platform-optimization report using syringe pumps, Y-shaped glass microfluidic chips, and silicone tubing to make mRNA-LNPs at 12 mL/min and a 3:1 lipid-to-aqueous ratio.

Caveat

The protocol reports manufacturing attributes such as at least 80% encapsulation, 100-120 nm size, PDI at most 0.2, and at least 7 days of 4 °C storage, not biological delivery efficacy or clinical performance.

Simplified

This protocol describes a standardized and economically accessible method for synthesizing mRNA-encapsulated lipid nanoparticles using routine laboratory equipment, including precision syringe pumps, Y-shaped glass microfluidic chips, and silicone tubing. Designed to address the cost and accessibility limitations of commercial microfluidic platforms, the system achieves performance metrics comparable to high-end devices while reducing equipment costs by 90%. By systematically optimizing hydrodynamic parameters (total flow rate: 12 mL/min; lipid-to-aqueous phase ratio: 3:1), the protocol enables consistent production of lipid nanoparticles with key quality attributes: high mRNA encapsulation efficiency (≥ 80%), narrow particle size distribution (100-120 nm, polydispersity index ≤ 0.2), and excellent storage performance (≥ 7 days at 4 °C). Key features • A low-cost mRNA@LNPs synthesis method is developed using common lab equipment, cutting costs by 90% while matching commercial systems' performance. • The LNP synthesis platform allows researchers to flexibly adjust hydrodynamic parameters to screen various lipid formulations.