A facile cell-involved microfluidic platform for assessing risk of hepatotoxic chemicals via on-line monitoring of multi-indexes

A facile cell-involved microfluidic platform for assessing risk of hepatotoxic chemicals via on-line monitoring of multi-indexes
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一种简便的细胞参与微流控平台,用于通过多指标在线监测评估肝毒性化学物质的风险

DOI:
10.1016/j.snb.2021.129938
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发表时间:
2021-04-22
影响因子:
8.4
通讯作者:
Li, Yingchun
Li, Yingchun
中科院分区:
化学1区
文献类型:
--
作者:
Lu, Wei;Huang, Bingtong;Li, Yingchun

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毒性评估在许多领域都是必要的,但常见的动物实验和传统的基于细胞的生物分析是终点试验,在成本、操作复杂、个体差异等方面受到限制。本文基于电化学生物传感和微流体技术,建立了一个涉及细胞的化学品风险便捷评估平台。通过原位监测传感器室培养的活细胞对外部化学刺激的反应,初步分类了化学物质对细胞损伤可逆性的影响。该装置由两个核心单元组成:生物反应器和细胞代谢监测芯片(CMMC)。该生物反应器用于培养活细胞,同时通过内置的数字间电极提供细胞的实时电化学阻抗。CMMC连接到生物反应器上,安装的酶丝网印刷电极(spe)可以在线检测从生物反应器流出的葡萄糖(Glu)和乳酸(LA)。阻抗值与细胞生长繁殖有关,而Glu和LA的量反映细胞的呼吸状态。为了验证平台的有效性,在生物反应器中培养HepG2细胞并用五种化学物质处理。通过监测和分析细胞粘附、Glu摄取和LA生成三个信号的变化,研究了这些化学物质的影响。整个系统可以初步了解化学物质作用于细胞的毒性和可能的机制,并有望应用于生态安全、生物医学等各个领域。
Toxicity assessment is necessary in many fields, but the common animal experiments and traditional cell-based bioassays are endpoint tests and limited in the aspects of cost, complex operation, individual difference, etc. Herein, a cell-involved platform for facilely assessing risk of chemicals was established based on electrochemical biosensing and microfluidic technology. Through in situ monitoring responses of live cells cultivated in sensor chamber towards exterior chemical stimuli, a preliminary categorization of chemicals on reversibility of cell injury has been achieved. The device consists of two core units: a bioreactor and a cell metabolism monitoring chip (CMMC). The bioreactor is for culturing live cells and meanwhile delivering real-time electrochemical impedance of cells via a built-in interdigital electrode. The CMMC is connected to the bioreactor and the installed enzymatic screen-printed electrodes (SPEs) fulfill on-line detection of glucose (Glu) and lactic acid (LA) flowing out of the bioreactor. Impedance values have to do with cell growth and reproduction, while the amounts of Glu and LA reflect respiration state of cells. To test validity of the platform, HepG2 cells were cultured in the bioreactor and treated with five chemicals. The influence induced by these chemicals was studied by monitoring and analyzing the variations of three signals (cell adhesion, Glu uptake and LA generation). The whole system allows for preliminary understanding of toxicity and possible mechanism of chemicals acting on cells, which is also expected to be applied in varied fields including ecological safety, biomedicine, etc.