Multi-angle DLS helps measure protein aggregation

Multi-angle DLS helps measure protein aggregation

A variety of new pharmaceutical preparations of protein-based drugs have been made commercially available in recent years.

Being complicated macromolecules, proteins tend to undergo a variety of interactions between molecules and within the same molecule. Such interactions lead to de-naturation and aggregation, changes to the protein particle size distribution that may affect a protein-drug’s efficacy. These larger particles range from 0.1 to 1 micron. Dynamic Light Scattering (DLS) is a particle size analysis technique that works exceptionally well in that size range. As the amount of aggregation might tend to be low in concentration, performing Dynamic Light Scattering at a forward scattering angle is advised in order to increase the sensitivity of the measurement to these larger particles. The Nicomp N3000 has multi-angle capability that can be used make measurements at 90 degrees as well as forward and backward scattering angles all in the same instrument. Figure A contains a PSD of Bovine Serum Albumin (BSA) measured at a 90 degree scattering angle. The PSD consists of two peaks, the one at 6 nm is the primary protein. The large diameter peak is from protein aggregation. The primary protein peak dominates the PSD. Figure B contains a PSD of Bovine Albumin Serum measured at a forward angle of 20 degrees. Now the aggregate peak dominates. Clearly, a DLS instrument with multi-angle capability is better capable of characterizing a protein.