Chen Po-Hung, Cheng Yu-Ting, Ni Bing-Syuan, Huang Jen-Huang
Department of Chemical Engineering, National Tsing Hua University, No. 101, Sec. 2, Kuang-Fu Rd., Hsinchu, 30013, Taiwan.
Appl Biochem Biotechnol. 2020 May;191(1):151-163. doi: 10.1007/s12010-020-03288-9. Epub 2020 Feb 21.
The development of a continuous process for cell separation is growing rapidly due to the current trend of cost-effective manufacturing in biological industries. The continuous cell separation process has a significant reduction in capital equipment costs and facility size compared to the conventional batch process. In the study, a multi-layered microfluidic-based device integrated with the porous membranes was fabricated for continuous size-based isolation of the cells based on the mechanism of restrictive cross-flow filtration, allowing the biological sample entered in a single inlet of the device and separated into two outlet streams. One stream which contained the cells returned back to the original sample fluid, while another stream with conditioned medium only was collected for later applications. The membrane fouling issue was overcome by introducing the alternative flow rate consisted of a set of higher and lower flows. The device integrated with the controllable flow restriction allows to increase the permeate flow rate, and alternative boosted flow demonstrates the high permeate flow rate (0.3 mL/min), high cell viability (> 98%), and increase of cell concentration (48%). As a result, we believe that the microfluidic-based continuous cell separation system is a promising tool for downstream bioprocess.
由于生物产业当前具有成本效益的制造趋势，细胞分离连续过程的发展正在迅速增长。与传统的分批过程相比，连续细胞分离过程在资本设备成本和设施规模方面有显著降低。在该研究中，基于限制错流过滤机制，制造了一种集成有多孔膜的多层微流控装置，用于基于尺寸的细胞连续分离，使生物样品从装置的单个入口进入并分离成两个出口流。一个包含细胞的流返回原始样品流体，而另一个仅含有条件培养基的流被收集以供后续应用。通过引入由一组较高和较低流速组成的交替流速，克服了膜污染问题。集成有可控流阻的装置能够提高渗透流速，交替增压流显示出高渗透流速（0.3 mL/分钟）、高细胞活力（>98%）以及细胞浓度增加（48%）。因此，我们认为基于微流控的连续细胞分离系统是下游生物过程中一种很有前景的工具。
