AN8006: In-line monitoring of liposome size by RT-MALS

In liposome and lipid nanoparticle (LNP) drug-delivery applications, particle size is a critical quality attribute (CQA) that impacts bioaccessibility, retention time and bio-distribution. Current on-line and off-line control methods do not sample the entire lot, and only provide average sizes, potentially hiding pockets of out-of-spec material. Real-time multi-angle light scattering (RT-MALS) ensures batch consistency by in-line monitoring for size of the entire batch; the collection stream can be diverted to waste if the particle size falls out of specification.

Extracellular vesicle isolation

Preparative anion-exchange chromatography is seen as a scalable solution for isolation of extracellular vesicles (EVs), derived from human bone marrow mesenchymal stromal cells, for delivery of therapeutics. While traditional, UV-only detection during elution indicates a single peak which does not actually contain EVs, the addition of RT-MALS inline reveals a second peak (with very low UV extinction) that holds the desired product. Thus real-time monitoring of scattering intensity and particle size by RT-MALS will be critical in developing, scaling, and eventually full GMP production with this process.

See preprint - Dehghani et al., “Orthogonal and Robust Analytics Enable Reproducible and Scalable Manufacturing of High Purity Extracellular Vesicles Derived from Mesenchymal Stromal Cells” https://doi.org/10.1101/2025.08.26.672476