Cyclo Olefin Polymer (COP) based microbioreactors on a microfluidic chip were produced in house by hot-embossing and thermo-compression bonding methods. The chip allows two different experiments to be performed on trapped cells at the same time. On one side of the chip, red fluorescent protein (RFP) tagged nucleolar Nop56 protein was used to track changes in cell cycle as well as protein synthesis within the yeast cells under the application of the anti-tumor agent hydroxyurea (HU). Simultaneously, on the other side of the chip, the response of yeast cells to the drug metformin, mTOR inhibitor, was investigated to reveal the role of TOR signaling in ribosome biogenesis and cell proliferation. The results of 20 h long experiments are captured by taking brightfield and fluorescent microscopy images of the trapped cells every 9 min. The expression of Nop56 protein of ribosome assembly and synthesis was densely observed during G1 phase of cell cycle, and later towards the end of cell cycle the ribosomal protein expression slowed down. Under HU treatment, the morphology of yeast cells changed, but after cessation of HU, the biomass synthesis rate was sustained as monitored by the cell perimeter. Under metformin treatment, the perimeters of single cells were observed to decrease, implying a decrease in biomass growth; however these cells continued their proliferation during and after the drug application. The relation between ribosome biogenesis and cell cycle was successfully investigated on single cell basis, capturing cell-to-cell variations, which cannot be tracked by regular macroscale bioreactors.

中文翻译：

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由环烯烃聚合物制成的细胞捕获微流控芯片可同时进行两个具有长期耐久性的细胞生物学实验

在微流控芯片上的基于环烯烃聚合物（COP）的微生物反应器是通过热压印和热压粘合方法在室内生产的。该芯片允许对捕获的细胞同时进行两个不同的实验。在芯片的一侧，在抗肿瘤剂羟基脲（HU）的作用下，红色荧光蛋白（RFP）标记的核仁Nop56蛋白用于跟踪酵母细胞内细胞周期的变化以及蛋白质合成。同时，在芯片的另一侧，研究了酵母细胞对药物二甲双胍mTOR抑制剂的反应，以揭示TOR信号在核糖体生物发生和细胞增殖中的作用。每隔9分钟通过对捕获细胞进行明场和荧光显微镜图像捕获20小时的实验结果。在细胞周期的G1期密集地观察到核糖体组装和合成的Nop56蛋白的表达，后来到细胞周期结束时，核糖体蛋白的表达减慢。在HU处理下，酵母细胞的形态发生了变化，但是在HU停止后，通过细胞周长监测，生物质合成速率得以维持。在二甲双胍处理下，观察到单个细胞的周长减少，这意味着生物量的增长减少了。然而，这些细胞在药物施用期间和之后继续增殖。核糖体生物发生与细胞周期之间的关系已成功地在单细胞基础上进行了研究，捕获了细胞间的差异，而常规的大型生物反应器无法追踪这种差异。