Lipid Nanoparticles (LNPs) have become a leading non-viral delivery system for therapeutics and vaccines. LNP size, size distribution, lamellarity, cargo encapsulation, and stability are critical factors which influence their in vivo effectiveness. Cryo-TEM can be used to assess all of these factors, as well as provide confidence in sample uniformity and purity, and evaluate the influence of storage conditions such as pH, temperature, and time on lipid nanoparticle morphology.
Cryo-TEM can be used to reveal sample information at multiple levels - from the LNP population as a whole, down to minute structural details, such as the leaflets of lipid bilayers. In addition, cryo-TEM can visualize bleb formation in LNPs and the lamellarity of your lipid nanoparticle, showing if your LNP is unilamellar or multilamellar.
To read an in-depth study showing how cryo-TEM per-particle analysis of LNPs can reveal subtle structural changes including bleb formations, that other analytical methods can not, download the whitepaper here.
Visualize the unexpected with cryo-EM.
While typically spherical and ~20-100 nm in diameter, lipid nanoparticles (LNPs) could unexpectedly be produced in a variety of shapes and sizes, as seen in the image. Along with particle size distribution, the fraction of particles which have multiple bilayers, multiple compartments (pink arrows), or contain other vesicles (green arrow) can be determined.
When a detailed 3-dimensional understanding of particle morphology and contents is required, cryo-electron tomography is used to image a small subset of particles.
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Frequently Asked Questions
Can I see an example report for lipid nanoparticle (LNP) characterization and analysis?
How many particles do you count, or images do you analyze per sample or grid?
What additional information about LNPs can cryo-TEM detect that DLS cannot?
How well does cryo-TEM data correlate with DLS data for particle size distribution analysis of LNPs?
What additional information about LNPs can cryo-TEM detect that the RiboGreen assay cannot?
How do you currently measure payload distribution for lipid nanoparticles?
Can you tell the difference between RNA or DNA encapsulation in my LNPs?
Can we measure RNA outside/inside/on the individual lipid nanoparticles?
Is it possible to distribute between mRNA-loaded and aqueous blebs with cryo-TEM?
Is the ability to detect and report an accurate percentage of blebbed areas more difficult as the particles become smaller?
How do you measure the PEG layer in lipid nanoparticle samples?
Are you able to see the PEG layer on LNPs with cryo-TEM? If so, how can you tell the difference between the PEG layer and lipid bilayer?
Can cryo-TEM determine the number of antibodies conjugated on LNP surfaces?
