Hello,

I'm planning on performing experiments to investigate the lifespan of a membrane used for the concentration and diafiltration of a protein product. In the literature, there is a recommendation to perform blank runs with the solution matrix (without the protein product) at regular intervals to determine product carryover between runs.

As part of the blank runs, I'm wondering about what samples are worth taking and which analytical techniques are best to detect small traces of protein (that is if any is in fact present). Is it enough to measure the final retentate sample (which is usually the product) or do those with relevant experience also perform testing on the permeate samples? One method I've come across is TOC (total organic carbon) analysis which is used for protein concentration determination. Since my sample is initially in a guanidine matrix, would this impact the analyses? It is important to mention that the product becomes exchanged into a low salt buffer during diafiltration.

Any guidance on this topic would be very much appreciated!

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