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One of the most reliable approaches for accurately sizing particles are structural biology-
based methods. This generally refers to X-ray crystallography, nuclear magnetic resonance
(NMR), or cryo-electron microscopy (CryoEM). Each of these techniques provides you with
detailed pictures of your protein or antibody, down to the amino acid. With full structures,
it is possible to get accurate and detailed sizing information down to the angstrom (10
-10
m)
resolution.
However, there are drawbacks to using these approaches. They require purified and stable
samples, which requires a lot of time and effort from lab scientists. Additionally, they all
require expensive instrumentation that is generally best outsourced to CROs or rented from
large institutions. They also require expertise in decoding the data. X-ray crystallography
and CryoEM do not reflect behavior in solution, which is o en a key component for biologics
formulation. Finally, NMR has a practical size limitation of about 35 kDa, which makes it less
useful for larger proteins such as antibodies.
Structural biology methods
