Key Accomplishments in 2024: Lipid Nanoparticle (LNP) Characterization

19 January 2025

Tackling challenges in “quantitative cryo-EM” by specialty grids and orthogonal techniques such as MALLS.

One of the main challenges in quantitative cryo-EM is the effect of ice thickness variations on particle distribution. In cryo-EM images of LNPs, larger particles often accumulate near the edge of the hole, while smaller ones concentrate at the center. This bias impacts the statistical analysis of LNP samples, as oversized particles are removed during the blotting process. To address this issue, PUXANO tested novel grid types with ice thick enough to accommodate 80 nm particles. Initial tests with these specialty grids indicate a more uniform particle distribution, independent of size. Additionally, we integrate Multi-Angle Light Scattering (MALLS) with our automated nanoparticle size analysis, enabling reliable and quantitative cryo-EM.

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