The present invention relates to a bimodal
polymer such as a
soluble polymer capable of irreversibly binding to insoluble
particulates and a subset of soluble impurities and also capable of reversibly binding to one or more desired biomolecules in an unclarified biological material containing
stream and the methods of using such a material to purify one or more desired biomolecules from such a
stream without the need for prior clarification. Such a
polymer comprises domains of charged pendant groups such as primary, secondary,
tertiary or
quaternary amines, (first mode) and is rendered insoluble and precipitates out of solution simply upon complexing with oppositely charged
solid particulates and a fraction of the soluble impurities in an amount sufficient to form an aggregate that can no longer be held in solution. The
polymer further comprises other domains of pendant groups that are charged or uncharged, hydrophilic or hydrophobic or have a ligand that is selective for the
biomolecule of interest depending on the
process conditions such as pH,
ionic strength, salts, and the like (second mode). When present in one mode, such as the uncharged form, said pendant groups are capable of binding to one or more desired biomolecules within the
stream (
protein, polypeptide, etc) in an unclarified
cell broth. The precipitate can then be removed from the stream, such as by being filtered out from the remainder of the stream and the desired
biomolecule is recovered such as by selective
elution.