Department of Chemical and Biological Engineering, University of Colorado, Room: ECCH 111, Campus Box 0424, 1111 Engineers Dr, Boulder, Colorado 80309-0424, USA.
Biotechnol Bioeng. 2010 Jan 1;105(1):121-9. doi: 10.1002/bit.22525.
Stainless steel is a ubiquitous surface in therapeutic protein production equipment and is also present as the needle in pre-filled syringe biopharmaceutical products. Stainless steel microparticles can cause the aggregation of a monoclonal antibody (mAb). The initial rate of mAb aggregation was second order in steel surface area and zero order in mAb concentration, generally consistent with a bimolecular surface aggregation being the rate-limiting step. Polysorbate 20 (PS20) suppressed the aggregation yet was unable to desorb the firmly bound first layer of protein that adsorbs to the stainless steel surface. Also, there was no exchange of mAb from the first adsorbed layer to the bulk phase, suggesting that the aggregation process actually occurs on subsequent adsorption layers. No oxidized Met residues were detected in the mass spectrum of a digest of a highly aggregated mAb, although there was a fourfold increase in carbonyl groups due to protein oxidation.
不锈钢在治疗性蛋白生产设备中无处不在，也是预填充注射器生物制药产品中的针头。不锈钢微粒会引起单克隆抗体（mAb）聚集。mAb 聚集的初始速率在钢表面积上为二级，在 mAb 浓度上为零级，通常与双分子表面聚集成为限速步骤一致。聚山梨酯 20（PS20）抑制了聚集，但不能解吸牢固结合到不锈钢表面的第一层蛋白质。此外，没有 mAb 从第一层吸附层到本体相的交换，这表明聚集过程实际上发生在随后的吸附层上。在高度聚集的 mAb 的消化物的质谱中未检测到氧化的 Met 残基，尽管由于蛋白质氧化，羰基增加了四倍。
