Badinger Zachary, Behboudi Ali, Zydney Andrew L
Department of Chemical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
Membranes (Basel). 2025 Aug 11;15(8):245. doi: 10.3390/membranes15080245.
Recent advances in cell culture have led to significant increases in monoclonal antibody (mAb) titers, opening a new window of opportunity for developing a fully continuous downstream purification process based on the selective precipitation of the mAb from harvested cell culture fluid, with the precipitate dewatered and washed using single-pass tangential flow filtration (SPTFF) with microfiltration membranes.
Experiments were performed with precipitates of human serum immunoglobulin G formed using ZnCl and polyethylene glycol, both with and without added disodium malonate. SPTFF was conducted in both hollow fiber and screened cassette modules, with the critical flux identified using flux-stepping experiments.
Critical fluxes as high as 250 L/m/h were obtained in the screened cassette, significantly higher than what was possible in hollow fiber modules. A two-stage system was designed that provided up to 85% conversion in a single pass. This system could be operated continuously for 24 h with 80% conversion at a filtrate flux of 144 L/m/h without any significant fouling.
The results demonstrate the potential of using screened membrane cassettes for the continuous/intensified processing of precipitated proteins like monoclonal antibodies.
细胞培养技术的最新进展使单克隆抗体（mAb）滴度显著提高，为开发基于从收获的细胞培养液中选择性沉淀mAb的完全连续下游纯化工艺打开了新的机遇之窗，其中沉淀物通过使用微滤膜的单程切向流过滤（SPTFF）进行脱水和洗涤。
使用氯化锌和聚乙二醇形成的人血清免疫球蛋白G沉淀物进行实验，添加和不添加丙二酸钠。在中空纤维和筛网盒式模块中进行SPTFF，通过通量步进实验确定临界通量。
在筛网盒式模块中获得了高达250 L/m²/h的临界通量，显著高于中空纤维模块中的可能值。设计了一个两级系统，单次通过转化率高达85%。该系统可以在144 L/m²/h的滤液通量下连续运行24小时，转化率为80%，且无任何明显污染。
结果证明了使用筛网膜盒对单克隆抗体等沉淀蛋白进行连续/强化处理的潜力。
