Automated Particle Classification Analysis

Protein and lipid-based nanoparticles have been widely used in clinical applications, such as drug and gene delivery and vaccine development. Their unique physical and chemical properties at the nanoscale level have paved the way for various breakthroughs in medicine and healthcare. Characterizing the homogeneity of nanoparticles is crucial for ensuring their safety, efficacy, and performance in clinical settings.

Cryo-TEM imaging is a powerful technique used to directly visualize nanoparticles, such as liposomes and lipid nanoparticles (LNPs), viruses and virus like particles (VLPs), in their near-native state. This technique can evaluate the size, morphology, internal structure, and surface features of the nanoparticles. Therefore, cryo-TEM imaging is immensely valuable in categorizing nanoparticles based on specific properties of interest.

NIS provides the following types of fraction counting analysis services using cryo-TEM direct imaging and automated analysis of nanoparticles:

• Payload Location and Density
• Lamellarity Analysis
• Antigen Distribution
• Virus Maturation State

payload encapsulation within nanoparticles such as virus and virus-like particle (VLP) capsids, particularly adeno-associated virus (AAV), adenovirus (AV), lipid nanoparticles (LNPs), and liposomes. 

In the case of AAV, it is possible to determine the empty/full ratio of a formulation using automated image analysis. Please contact us to see an example report of our automated capsid ratio analysis.

Lamellarity of lipid nanoparticles (LNPs) refers to the various arrangements of lipid bilayer within the particle, which is an important factor in determining their effectiveness as drug delivery vehicles. Similar to size, morphology, and encapsulation state, lamellarity is a critical attribute that can affect their bioavailability, stability, and therapeutic outcome.

Researchers work on optimizing the lamellarity of lipid nanoparticles to improve their performance as drug carriers. LNP and liposome lamellarity evaluation with cryo-TEM imaging is a valuable tool to differentiate between for example unilamellar, multilamellar, multicompartmental (or “blebbing” when looking at LNPs), and multivesicular particles.

vaccine formulation, leading to a stronger and more durable immune response. 

Characterizing the antigen spatial distribution on the nanoparticle surface using cryo-TEM images into classes such as densely decorated, sparsely decorated, or no antigen decorated nanoparticles, can help optimize nanoparticle-based vaccine design. In addition, cryo-TEM imaging can also capture conformational variations of the surface-expressed antigens.

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