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Another approach is multi-angle light scattering, or MALS. This is also
a light-scattering based approach, but collects the scattered light at
multiple angles, which deconvolutes additional information about the
protein. Most notably, the added benefit of MALS is the ability to tell you
the absolute molar mass of your sample. While MALS offers many of the
benefits of DLS, it requires accurate concentration input along with the
sample, as well as very pure sample for accurate MW determination. It is
routinely coupled to size-exclusion chromatography (SEC) to ensure the
measurement is done on purified sample.
An alternative method for getting very accurate molecular weights
is analytical ultracentrifugation. There are some drawbacks
to this method: it is low throughput and you need a high level
of expertise to perform the experiment and analyze the results
correctly. Researchers have coupled AUC to fluorescence-based
methods to learn more about their proteins and biologics,
particularly in complexes. As yet, the process cannot be standardized
to be compliant with Good Manufacturing Practices (GMP), which
represents a drawback for industrial pharmaceutical researchers.
Multi-angle light scattering
Analytical ultracentrifugation
