Employment of omniphobic, thin-layer perfluorocarbon (TLP) coating to prevent fouling and clogging in microfluidic mixing devices during mRNA LNP formulations.

Lipid nanoparticle (LNP)-based delivery systems for mRNA and other therapeutics recently gained popularity because of their application in the Pfizer/BioNTech and Moderna COVID-19 vaccines. Compared to traditional bulk mixing and batch process approaches, microfluidic technology for mRNA-LNP manufacturing enables precision synthesis via rapid mixing and fluid flow control. However, fouling and clogging in microfluidic channels pose significant problems for LNP formulation as numerous existing hydrophilic/hydrophobic coatings only inhibit biomolecule adsorption and fouling in aqueous solutions, while the condition for LNP formation is a mixture of hydrophilic aqueous and amphiphilic ethanol (EtOH) solvents.

Coating a silicon (Si)/glass-based microfluidic mixing device with omniphobic, thin-layer perfluorocarbon (TLP) improves chemical resistance, suppresses non-specific biomolecule adsorption, and prevents nanoparticle aggregation.

The TLP layer consists of an immobilized tethered perfluorocarbon (TP) overlaid by a thin liquid perfluorocarbon (LP) layer, which is an FDA-approved material. Application of TLP coating to a Si/glass microfluidic mixing device repels water, EtOH, and water/EtOH mixture while suppressing non-specific adsorption of biomolecules such as BSA, glycine, and mRNA-LNP constituents. This prevents fouling of mRNA and LNP constituents.

• An antifouling resistant GMP compatible manufacturing platform using FDA-approved material.
• High-precision mRNA-LNP production (size < 100 nm, encapsulation efficiency > 90%).
• Robust mRNA-LNP production (operation t > 50 min without clogging).
• Prevents aggregation of nanoparticles, which expands its application to other nanomaterials and devices lined by anti-adsorption and antifouling surfaces.