Nanotechnology Community

Dear Nanotechnology community members,

Given the inherent heterogeneity in lipid nanoparticle (LNP) populations, I'm curious to learn more about the analytical tools or high-throughput methods currently available to deconvolute structure–activity relationships at the single-particle level.

What approaches have you found effective in resolving this complexity? Are there emerging technologies or platforms you would recommend exploring?

Thank you!

Best Regards,

Hi Mittal,

Cry-EM is the most widely used conventional tool to analyze the LNP morphology for a structure-activity type of study. 

Here are some emerging tools to evaluate the structure of LNPs

1. Single-Particle Spectroscopic Chromatography: this instrument combines the strength of single-fluorophore sensitivity and absolute quantification by confocal fluorescence spectroscopy with unbiased chromatographic nanoparticle size, with high resolution and high throughput. More info can be found here: https://pubs.acs.org/doi/10.1021/acsnano.4c02341
2. AF4: Asymmetric-flow field-flow fractionation (AF4) is a powerful technique used to study lipid nanoparticle (LNP) structure by separating them based on size and other properties, often coupled with detectors like small-angle X-ray scattering (SAXS) or multi-angle light scattering (MALS) to provide detailed information on size distributions, morphology, and internal structure. More info can be found here: https://www.nature.com/articles/s41598-023-42274-z.

Dear Nanotechnology community members,

Given the inherent heterogeneity in lipid nanoparticle (LNP) populations, I'm curious to learn more about the analytical tools or high-throughput methods currently available to deconvolute structure–activity relationships at the single-particle level.

What approaches have you found effective in resolving this complexity? Are there emerging technologies or platforms you would recommend exploring?

Thank you!

Best Regards,