Madadkar P, Selvaganapathy P R, Ghosh R
Department of Chemical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4L7, Canada.
Department of Mechanical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario L8S 4L7, Canada.
Biomicrofluidics. 2018 Aug 20;12(4):044114. doi: 10.1063/1.5030984. eCollection 2018 Jul.
PEGylation is increasingly being utilized to enhance the therapeutic efficacy of biopharmaceuticals. Various chemistries and reaction conditions have been established to synthesize PEGylated proteins and more are being developed. Both the extent of conversion and selectivity of protein PEGylation are highly sensitive to process variables and parameters. Therefore, microfluidic-based high-throughput screening platforms would be highly suitable for optimization of protein PEGylation. As part of this study, a poly-dimethylsiloxane-based continuous flow microreactor system was designed and its performance was compared head-to-head with a batch reactor. The reactants within the microreactor were contacted by passive micromixing based on chaotic advection generated by staggered herringbone grooves embedded in serpentine microchannels. The microreactor system was provided with means for on-chip reaction quenching. Lysozyme was used as the model protein while methoxy-polyethylene glycol-(CH)COO-NHS was used as the PEGylation reagent. Full mixing was achieved close to the microreactor inlet, making the device suitable for protein PEGylation. The effect of mixing type, i.e., simple stirring versus chaotic laminar mixing on PEGylation, was investigated. Higher selectivity (as high as 100% selectivity) was obtained with the microreactor while the conversion was marginally lower.
聚乙二醇化越来越多地被用于提高生物制药的治疗效果。已经建立了各种化学方法和反应条件来合成聚乙二醇化蛋白质，并且更多的方法正在开发中。蛋白质聚乙二醇化的转化率和选择性对工艺变量和参数高度敏感。因此，基于微流控的高通量筛选平台非常适合优化蛋白质聚乙二醇化。作为本研究的一部分，设计了一种基于聚二甲基硅氧烷的连续流微反应器系统，并将其性能与间歇式反应器进行了直接比较。微反应器内的反应物通过基于嵌入蛇形微通道中的交错人字形凹槽产生的混沌平流的被动微混合进行接触。微反应器系统具备芯片上反应淬灭的手段。以溶菌酶作为模型蛋白，以甲氧基聚乙二醇-(CH)COO-NHS作为聚乙二醇化试剂。在微反应器入口附近实现了完全混合，使得该装置适用于蛋白质聚乙二醇化。研究了混合类型，即简单搅拌与混沌层流混合对聚乙二醇化的影响。微反应器获得了更高的选择性（高达100%的选择性），而转化率略低。
