FAQ: Molecular weight estimate from DLS?

Here is a question I recently encountered that I thought might be worthwhile to post here:

“I would like to use the particle size data to calculate an estimate for molecule weight. Would you please send me some information on that. For example, do I use mean size by number or by volume or by intensity?”

If you want to use the size data to predict/estimate molecular weight I would recommend using the size from the intensity distribution. However, if you have a broad peak, then using the volume distribution can also provide useful insight. Very often, if there is a distribution of several different species the molecular weight estimated from the volume distribution will give you an idea of what the smallest part of the distribution is.  For example, for proteins if there is a monomer-dimer equilibrium, the estimate from intensity will give an average molecular weight somewhere between the two, however when using the estimate from volume, this will be very close to the molecular weight from the monomer.

Screenshot of molecular weight estimate calculator in the Zetasizer software

 You can then put those numbers into the molecular weight estimator within the Zetasizer software under Tools → Calculators → tab MW & Shape Estimates to obtain the molecular weight, for example for the radius of 8nm. In the screenshot, the calculator is shown for 8nm radius. Here, the estimate for the molecular weight of a molecule similar to a linear polysaccharide would be expected to be 88kDa. If the molecule was expected to be more like a branched polysaccharide, the 8nm would correspond to an estimated 207kDa. This is an estimate, and typically this is good to within ~20%, however there may be cases of larger deviation for other molecular shapes.

The technical note titled ‘Introduction to the calculators in the Zetasizer software‘ shows some of the background and references behind the various calculators available in the software, a summary of the information is also available in the summary titled “FAQ Can MW be measured with DLS?”

The units for the molecular weight (or more correctly: the molar mass) in the calculator are kilo Dalton [kDa] which is the same as kg/mol. 1 kDa is the same as 1000 Da or 1000 g/mol.

Previously

If you have any questions, please email me at ulf.nobbmann@malvern.com. Thanks!
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