Induced flocculation of animal cells in suspension culture.

Recycle unit operations for suspension cell cultures may be improved by flocculation of the cells. A flocculant search was conducted, and it was found that where strongly cationic polymers were severly toxic to the cells, neutral and anionic polymers were nontoxic and ineffective at flocculating the cells. A weak and poorly soluble polycation, poly-L-histidine, was capable of flocculating cultures of CHO, HeLa, U-937, and CRL 1606 hybridoma cells with no toxicity to the majority of cells. In addition to the lowered acute toxicity, the polymer treatment left the cells in a growing state for recycle. Flocculation was found to be mediated by precipitates of the polymer. The low toxicity of poly-L-histidine is probably due to its low solubility and charge at physiological pH. Nonelectrostatic interactions may also play a role.