We frequently purify proteins from mammalian cells using HPLC, which requires a clarified lysate free from cell-debris. Our current method is to centrifuge the cell lysate at 33,000xg and then to filter it through .45 micron syringe filters followed by .22 micron filters. This is wildly inefficient and time consuming because the filters clog so fast and it takes upwards of 20 to clear one 60 mL sample. I'm sure there has to be a better way, but I haven't been able to find any good information. Does anyone know of a better method?
*We've tried using a vacuum system in the past, but still had the same problem of the filter clogging too fast