Dynamic Light Scattering (DLS) is a powerful, non-destructive, fast technique to measure both particle size and evaluate the presence of aggregation. It also analyzes vastly more particles than cryo-TEM. However, DLS results are heavily affected by factors such as buffer, temperature and the presence of air bubbles, dust, or other impurities in the sample. In addition, DLS measures the hydrodynamic radius of the particles and doesn't do well with heterogeneous samples as the signal of the larger particles weigh more than that of smaller particles resulting in over-estimation of the particle size. Cryo-TEM captures the particles in their native state enabling the determination of true particle size. Cryo-TEM is also well-equipped to deal with heterogeneous samples. Cryo-TEM captures specimens in their natural hydrated state and is forgiving of heterogeneous mixtures of particles, making cryo-TEM an important analysis technique to measure particle size and size distribution, as well as lamellarity, drug encapsulation, and more, with as little as 3 microliters of sample. Cryo-TEM provides more answers than any other nanoparticle characterization technique in only one study.
Read the paper in Science Direct describing the differences between lipid nanoparticle characterization done by DLS and cryo-TEM, including imaging of lipid nanoparticles (LNP’s) done by NIS.
Read a paper in the Journal of Physics: Conference Series comparing TEM and DLS methods to characterize size distribution of ceramic nanoparticles.