The growing demand for biological therapeutics has increased interest in large‐volume perfusion bioreactors, but the operation and scalability of perfusion membranes remain a challenge. This study evaluates perfusion cell culture performance and monoclonal antibody (mAb) productivity at various membrane fluxes (1.5–5 LMH), utilizing polyvinylidene difluoride (PVDF), polyethersulfone (PES), or polysulfone (PS) membranes in tangential flow filtration mode. At low flux, culture with PVDF membrane maintained higher cell culture growth, permeate titer (1.06–1.34 g/L) and sieving coefficients (≥83%) but showed lower permeate volumetric throughput and higher transmembrane pressure (TMP) (>1.50 psi) in the later part of the run compared to cultures with PES and PS membrane. However, as permeate flux increased, the total mass of product decreased by around 30% for cultures with PVDF membrane, while it remained consistent with PES and PS membrane, and at the highest flux studied, PES membrane generated 12% more product than PVDF membrane. This highlights that membrane selection for large‐volume perfusion bioreactors depends on the productivity and permeate flux required. Since operating large‐volume perfusion bioreactors at low flux would require several cell retention devices and a complex setup, PVDF membranes are suitable for low‐volume operations at low fluxes whereas PES membranes can be a desirable alternative for large‐volume higher demand products at higher fluxes.

中文翻译：

---

评估不同通量下的各种膜以实现大容量一次性灌注生物反应器

对生物疗法不断增长的需求增加了人们对大容量灌注生物反应器的兴趣，但灌注膜的操作和可扩展性仍然是一个挑战。本研究利用聚偏二氟乙烯 (PVDF)、聚醚砜 (PES) 或聚砜 (PS) 膜以切向流过滤模式评估不同膜通量 (1.5–5 LMH) 下的灌注细胞培养性能和单克隆抗体 (mAb) 生产率。在低通量下，使用 PVDF 膜进行的培养保持了较高的细胞培养物生长、渗透物滴度 (1.06–1.34 g/L) 和筛分系数 (≥83%)，但表现出较低的渗透物体积通量和较高的跨膜压力 (TMP) (>1.50 psi)在运行的后期与使用 PES 和 PS 膜的培养物进行比较。然而，随着渗透通量的增加，使用 PVDF 膜的培养物的产物总质量减少了约 30%，而与 PES 和 PS 膜保持一致，并且在研究的最高通量下，PES 膜比 PVDF 膜产生的产物多 12% 。这凸显了大容量灌注生物反应器的膜选择取决于所需的生产率和渗透通量。由于在低通量下操作大容量灌注生物反应器需要多个细胞保留装置和复杂的设置，PVDF 膜适用于低通量下的小容量操作，而 PES 膜可能是大容量高需求产品的理想替代品。通量。