Nucleic Acid-LNP Ultrafiltration And Diafiltration: TFF Flat Sheet Cassettes Vs Hollow Fiber Cartridges

Lipid nanoparticles have emerged as the leading non‑viral delivery system for nucleic acids, but downstream processing remains a critical bottleneck as programs scale from discovery to commercial manufacturing. Ultrafiltration and diafiltration are essential for concentrating LNPs, removing solvents, and enabling buffer exchange — yet process choices can directly impact particle integrity, recovery, and biological activity.

This analysis explores how tangential flow filtration performance differs between hollow fiber cartridges and flat sheet cassettes when applied to LNP formulations. Drawing on experimental data and case studies, it examines the influence of membrane chemistry, shear, transmembrane pressure, and membrane loading on key quality attributes such as particle size, polydispersity, encapsulation efficiency, and lipid recovery. Particular attention is given to challenges observed with hollow fiber systems during scale-up, including lipid precipitation and loss of product yield, and how flat sheet cassettes can mitigate these risks.

For teams developing mRNA vaccines, gene editing therapies, or other nucleic acid–based modalities, the insights offered here support more informed decisions around TFF format selection and process design. Access the full white paper to explore detailed data, experimental conditions, and practical considerations for robust LNP downstream processing.