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首页> 外文期刊>Lab on a chip >An integrated microfluidic cell culture system for high-throughput perfusion three-dimensional cell culture-based assays: effect of cell culture model on the results of chemosensitivity assayst
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An integrated microfluidic cell culture system for high-throughput perfusion three-dimensional cell culture-based assays: effect of cell culture model on the results of chemosensitivity assayst

机译：基于高通量灌注三维细胞培养测定的集成微流细胞培养系统：细胞培养模型对化学敏感性测定结果的影响

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Although microfluidic cell culture systems are versatile tools for cellular assays, their use has yet to set in motion an evolutionary shift away from conventional cell culture methods. This situation is mainly due to technical hurdles: the operational barriers to the end-users, the lack of compatible detection schemes capable of reading out the results of a microfluidic-based cellular assay, and the lack of fundamental data to bridge the gap between microfluidic and conventional cell culture models. To address these issues, we propose a high-throughput, perfusion, three-dimensional (3-D) microfluidic cell culture system encompassing 30 microbior-eactors. This integrated system not only aims to provide a user-friendly cell culture tool for biologists to perform assays but also to enable them to obtain precise data. Its technical features include (i) integration of a heater chip based on transparent indium tin oxide glass, providing stable thermal conditions for cell culturing; (ii) a microscale 3-D culture sample loading scheme that is both efficient and precise; (iii) a non-mechanical pneumatically driven multiplex medium perfusion mechanism; and (iv) a microplate reader-compatible waste medium collector array for the subsequent high throughput bioassays. In this study, we found that the 3-D culture sample loading method provided uniform sample loading [coefficient of variation (CV): 3.2%]. In addition, the multiplex medium perfusion mechanism led to reasonably uniform (CV: 3.6-6.9%) medium pumping rates in the 30 microchannels. Moreover, we used the proposed system to perform a successful cell culture-based chemosensitivity assay. To determine the effects of cell culture models on the cellular proliferation, and the results of chemosensitivity assays, we compared our data with that obtained using three conventional cell culture models. We found that the nature of the cell culture format could lead to different evaluation outcomes. Consequently, when establishing a cell culture model for in vitro cell-based assays, it might be necessary to investigate the fundamental physiological variations of the cultured cells in different culture systems to avoid any misinterpretation of data. As a whole, we have developed an integrated microfluidic cell culture system that overcomes several technical hurdles commonly encountered in the practical application of microfluidic cell culture systems, and we have obtained fundamental information to reconcile differences found with data acquired using conventional methods.
机译：尽管微流体细胞培养系统是用于细胞测定的通用工具，但它们的使用尚未引起与常规细胞培养方法的进化转移。这种情况主要是由于技术上的障碍：最终用户的操作障碍，缺乏能够读取基于微流体的细胞测定结果的兼容检测方案以及缺乏弥合微流体之间差距的基本数据和常规的细胞培养模型。为了解决这些问题，我们提出了一个高通量，灌注，三维（3-D）微流体细胞培养系统，该系统包含30个微生物因子。这个集成的系统不仅旨在为生物学家提供用户友好的细胞培养工具，以进行测定，还使他们能够获得准确的数据。其技术特征包括：（i）基于透明铟锡氧化物玻璃的加热器芯片的集成，为细胞培养提供了稳定的热条件; （ii）高效且精确的微型3D培养样品装载方案; （iii）非机械气动驱动的多重介质灌注机构; （iv）可用于后续高通量生物测定的微孔板读取器兼容废液收集器阵列。在这项研究中，我们发现3-D培养样品加载方法提供了均匀的样品加载[变异系数（CV）：3.2％]。此外，多重介质灌注机制导致30个微通道中的介质泵送率相当均匀（CV：3.6-6.9％）。此外，我们使用提出的系统来执行成功的基于细胞培养的化学敏感性测定。为了确定细胞培养模型对细胞增殖的影响以及化学敏感性测定的结果，我们将我们的数据与使用三种常规细胞培养模型获得的数据进行了比较。我们发现细胞培养形式的性质可能导致不同的评估结果。因此，当建立用于体外基于细胞的测定的细胞培养模型时，可能有必要研究不同培养系统中培养细胞的基本生理变化，以避免对数据的任何误解。总体而言，我们开发了一种集成的微流体细胞培养系统，该系统克服了微流体细胞培养系统实际应用中通常遇到的几个技术障碍，并且我们已经获得了基本信息，以调和与使用常规方法获得的数据之间的差异。

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