Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Biotechnol Bioeng. 1989 Aug 20;34(5):629-38. doi: 10.1002/bit.260340507.
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.
悬浮细胞培养物的回收单元操作可以通过细胞絮凝来改善。进行了絮凝剂搜索，发现强阳离子聚合物对细胞有严重毒性，而中性和阴离子聚合物则无毒且对絮凝细胞无效。弱且水溶性差的聚阳离子聚-L-组氨酸能够絮凝 CHO、HeLa、U-937 和 CRL 1606 杂交瘤细胞的培养物，而对大多数细胞没有毒性。除了降低急性毒性外，聚合物处理还使细胞处于可回收的生长状态。发现絮凝是通过聚合物的沉淀物介导的。聚-L-组氨酸的低毒性可能归因于其在生理 pH 下的低溶解度和电荷。非静电相互作用也可能起作用。
