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A versatile fabrication route for screening block copolymer membranes for bioprocessing
ChemRxiv Pub Date : 2024-04-25 , DOI: 10.26434/chemrxiv-2024-9vqjf
Ke Meng 1 , Alberto Alvarez-Fernandez 1, 2 , Stefan Guldin 1 , Daniel G. Bracewell 1
Affiliation  

Traditional polyethersulfone (PES) filters, widely used for sterile, viral and ultrafil- tration often exhibit limited selectivity-permeability due to the heterogenous pore size distribution. Such limitations have sparked interest in developing novel isoporous mem- brane materials and fabrication techniques to overcome the selectivity-permeability upper bound. Among several promising candidates, block copolymer membranes pro- duced via the self-assembly and non-solvent induced phase separation (SNIPS) method offer distinct advantages, such as customisable pore size, narrow dispersity, high poros- ity and mechanical flexibility. However, achieving the desired structure formation in SNIPS remains a complex optimisation procedure, rendering this approach unsuitable for the rapid screening of new block copolymer candidates. This study explores a direct spin coating method to fabricate a poly(styrene)-block- poly(methyl methacrylate) (PS-b-PMMA) thin film composite membrane, integrating a block copolymer layer with rigid anodic aluminium oxide (AAO) support. The pro- cess involves depositing the polymer solution onto a water-filled AAO substrate via spin coating. Compared with the SNIPS method, this fabrication process greatly re- duces the complexity of optimisation to yield an isoporous membrane structure for filtration purposes. We present this approach as a straightforward and reliable plat- form method for the rapid screening and evaluation of block copolymer membranes in their initial development stages. When compared to commercial PES membranes with similar molecular weight cut-offs, these novel PS-b-PMMA thin film composite membranes showed similar transmission rates for Bovine Serum Albumin and a Mon- oclonal Antibody while providing a 9 fold enhancement in Thyroglobulin rejection. This indicates a superior performance in terms of cut-off precision. The membranes demonstrate potential for the removal of viruses and antibody aggregates in the down- stream processing of monoclonal antibody production, which could reduce the burden of chromatographic polishing steps. An advance which offers promise for improving efficiency and reducing costs in biopharmaceutical manufacturing.

中文翻译:

用于筛选生物加工用嵌段共聚物膜的通用制造途径

广泛用于无菌、病毒和超滤的传统聚醚砜(PES)过滤器由于孔径分布不均匀,通常表现出有限的选择性渗透性。这些限制引发了人们对开发新型等孔膜材料和制造技术以克服选择性渗透率上限的兴趣。在几种有前途的候选膜中,通过自组装和非溶剂诱导相分离(SNIPS)方法生产的嵌段共聚物膜具有明显的优势,例如可定制的孔径、窄分散性、高孔隙率和机械灵活性。然而,在 SNIPS 中实现所需的结构形成仍然是一个复杂的优化过程,使得该方法不适合快速筛选新的嵌段共聚物候选物。本研究探索了一种直接旋涂方法来制造聚(苯乙烯)-嵌段-聚甲基丙烯酸甲酯(PS-b-PMMA)薄膜复合膜,将嵌段共聚物层与刚性阳极氧化铝(AAO)支撑体集成在一起。该过程包括通过旋涂将聚合物溶液沉积到充满水的 AAO 基板上。与 SNIPS 方法相比,这种制造工艺大大降低了优化的复杂性,以产生用于过滤目的的等孔膜结构。我们将这种方法作为一种简单可靠的平台方法,用于在嵌段共聚物膜的初始开发阶段进行快速筛选和评估。与具有相似截留分子量的商用 PES 膜相比,这些新型 PS-b-PMMA 薄膜复合膜对牛血清白蛋白和单克隆抗体表现出相似的透过率,同时甲状腺球蛋白排斥增强了 9 倍。这表明在切割精度方面具有优越的性能。该膜显示出在单克隆抗体生产的下游处理中去除病毒和抗体聚集体的潜力,这可以减轻色谱精制步骤的负担。这一进步有望提高生物制药制造的效率并降低成本。
更新日期:2024-04-25
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