A Rapid Method for Accurately Determining Lipid Nanoparticle Size Using Nano-Flow Cytometry

Lipid nanoparticles (LNPs) are small particles composed of lipids that can be used to encapsulate and deliver therapeutic substances like mRNA or other drugs to specific cells or tissues. LNPs are specifically designed to protect the payload from degradation, enhance payload stability, and improve delivery to target cells and tissues. When developing LNPs for nucleic acid-based therapeutics, there are two characteristics that are often analyzed to determine the quality of the formulations: size distribution and loading efficiency. Various techniques are used to determine the size of nanoparticles, with each providing different details and having specific advantages and limitations. In this study, we evaluated the use of nanoparticle tracking analysis, dynamic light scattering, and two different nano cytometers to determine LNP size. We compared the results obtained from these four methods to the particle size determined using cryogenic transmission electron microscopy. Our findings showed that nano-flow cytometry instrumentation, like NanoFCM and CytoFLEX nano, offers a robust and accurate method for sizing LNPs with measurements in high concordance to those obtained by conventional cryogenic transmission electron microscopy.