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Modular operation of microfluidic chips for highly parallelized cell culture and liquid dosing via a fluidic circuit board
Microsystems & Nanoengineering ( IF 7.3 ) Pub Date : 2020-11-30 , DOI: 10.1038/s41378-020-00216-z
A R Vollertsen 1 , D de Boer 2 , S Dekker 1 , B A M Wesselink 1 , R Haverkate 1 , H S Rho 3 , R J Boom 4 , M Skolimowski 4 , M Blom 4 , R Passier 5 , A van den Berg 1 , A D van der Meer 5 , M Odijk 1
Affiliation  

Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a single, monolithic device as a “one size fits all” solution. However, this approach limits the end users’ (re)design flexibility and complicates the addition of new functions to the system. To address this challenge, we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs), whereby both the FCB and the MFBBs contain integrated valves. A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures. The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint. We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs, each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control. We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB. Moreover, we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range. Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB. Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.



中文翻译:

微流控芯片的模块化操作,用于通过流控电路板进行高度并行的细胞培养和液体定量

微流体系统能够以低体积和确定的液体剂量实现自动化和高度并行的细胞培养。为了实现这一点,系统通常将所有功能集成到一个单一的单片设备中,作为“一刀切”的解决方案。然而,这种方法限制了最终用户的(重新)设计灵活性并使向系统添加新功能变得复杂。为了应对这一挑战,我们提出并展示了一种模块化和标准化的即插即用流体电路板 (FCB),用于操作微流体构建块 (MFBB),其中 FCB 和 MFBB 都包含集成阀门。单个 FCB 最多可以并行化三个相同设计的 MFBB,或者操作具有完全不同架构的 MFBB。MFBB 通过 FCB 的操作是完全自动化的,不会产生额外的外部足迹成本。我们使用这个模块化平台来控制三个微流体大规模集成 (mLSI) MFBB,每个都有 64 个微室,适用于具有高时空控制的细胞培养。我们证明了我们可以在这个 MFBB 的腔室中培养人脐静脉内皮细胞 (HUVEC) 多天的原则证明。此外,我们还使用相同的 FCB 来控制 MFBB,用于具有高动态范围的液体计量。我们的结果表明,可以在单个 FCB 上控制和组合具有不同设计的 MFBB。我们为并行细胞培养操作自动化微流体系统的新型模块化方法将实现更大的实验灵活性并促进来自不同实验室的不同芯片的合作。

更新日期:2020-12-01
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