Sampath Muthukumar, Shukla Anupam, Rathore Anurag S
Department of Chemical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India.
Bioengineering (Basel). 2014 Dec 8;1(4):260-277. doi: 10.3390/bioengineering1040260.
Filtration steps are ubiquitous in biotech processes due to the simplicity of operation, ease of scalability and the myriad of operations that they can be used for. Microfiltration, depth filtration, ultrafiltration and diafiltration are some of the most commonly used biotech unit operations. For clean feed streams, when fouling is minimal, scaling of these unit operations is performed linearly based on the filter area per unit volume of feed stream. However, for cases when considerable fouling occurs, such as the case of harvesting a therapeutic product expressed in , linear scaling may not be possible and current industrial practices involve use of 20-30% excess filter area over and above the calculated filter area to account for the uncertainty in scaling. In view of the fact that filters used for harvest are likely to have a very limited lifetime, this oversizing of the filters can add considerable cost of goods for the manufacturer. Modeling offers a way out of this conundrum. In this paper, we examine feasibility of using the various proposed models for filtration of a therapeutic product expressed in at constant pressure. It is observed that none of the individual models yield a satisfactory fit of the data, thus indicating that more than one fouling mechanism is at work. Filters with smaller pores were found to undergo fouling via complete pore blocking followed by cake filtration. On the other hand, filters with larger pores were found to undergo fouling via intermediate pore blocking followed by cake filtration. The proposed approach can be used for more accurate sizing of microfilters and depth filters.
过滤步骤在生物技术过程中无处不在，这是因为其操作简单、易于扩大规模，且可用于众多操作。微滤、深层过滤、超滤和渗滤是一些最常用的生物技术单元操作。对于清洁的进料流，当污垢极少时，这些单元操作的规模扩大是基于进料流每单位体积的过滤面积进行线性计算的。然而，对于出现大量污垢的情况，例如收获在……中表达的治疗性产品时，线性扩大规模可能不可行，当前的工业实践是在计算出的过滤面积之上使用20% - 30%的额外过滤面积，以考虑扩大规模时的不确定性。鉴于用于收获的过滤器可能使用寿命非常有限，这种过滤器的过大尺寸会给制造商增加相当大的商品成本。建模提供了摆脱这一难题的方法。在本文中，我们研究了在恒压下使用各种提议的模型对在……中表达的治疗性产品进行过滤的可行性。据观察，没有一个单独的模型能对数据给出令人满意的拟合，这表明不止一种污垢形成机制在起作用。发现孔径较小的过滤器会先通过完全的孔堵塞然后进行滤饼过滤而产生污垢。另一方面，发现孔径较大的过滤器会先通过中间孔堵塞然后进行滤饼过滤而产生污垢。所提出的方法可用于更精确地确定微滤器和深层过滤器的尺寸。
