Yu Nianzuo, Zhang Feiran, Tang Xiaoduo, Liu Yongshun, Zhang Junhu, Yang Bai, Wang Quan
Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130031, PR China; Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun, 130031, PR China; State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China.
Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun, 130031, PR China.
Acta Biomater. 2023 Apr 15;161:144-153. doi: 10.1016/j.actbio.2023.02.036. Epub 2023 Mar 2.
2D cell cultures are suitable for rapid exploration of the factors in the extracellular matrix affecting the development of cells. The technology of the micrometre-sized hydrogel array provides a feasible, miniaturized, and high-throughput strategy for the process. However, current microarray devices lack a handy and parallelized methodology in sample treatment, which makes the process of high-throughput cell screening (HTCS) expensive and inefficient. Here, based on the functionalization of micro-nano structures and the fluid control capability of microfluidic chips, we build a microfluidic spotting-screening platform (MSSP). The MSSP can print 20000 microdroplet spots within 5 min, coupled with a simple strategy for parallel addition of compound libraries. Compared with open microdroplet arrays, the MSSP can control the evaporation rate of nanoliter droplets, providing a stable fabrication platform for hydrogel-microarray-based materials. As a proof-of-concept demonstration, the MSSP successfully controlled the adhesion, adipogenic, and osteogenic differentiation behavior of mesenchymal stem cells by rationally designing the substrate stiffness, adhesion area, and cell density. We anticipate that the MSSP may provide an accessible and promising tool for hydrogel-based HTCS. STATEMENT OF SIGNIFICANCE: High-throughput screening of cells is a common approach to improve the efficiency of biological experiments, and one challenge of the existing technologies is to achieve rapid and precise cell screening with a low-cost and simple strategy. Through the integration of the microfluidic and micro-nanostructure technologies, we fabricated a microfluidic spotting-screening platforms. Benefiting from the flexible control of the fluids, the device can print 20000 microdroplet spots within 5 min, coupled with a simple procedure for parallel addition of compound libraries. High-throughput screening of stem cell lineage specification has also been achieved by the platform, which provides a high-throughput, high-content information extraction strategy for cell-biomaterial interaction research.
二维细胞培养适用于快速探索细胞外基质中影响细胞发育的因素。微米级水凝胶阵列技术为该过程提供了一种可行、小型化且高通量的策略。然而，当前的微阵列设备在样品处理方面缺乏便捷且并行化的方法，这使得高通量细胞筛选（HTCS）过程昂贵且低效。在此，基于微纳结构的功能化和微流控芯片的流体控制能力，我们构建了一个微流控点样筛选平台（MSSP）。该MSSP能够在5分钟内打印20000个微滴点，并结合一种简单的策略用于并行添加化合物库。与开放微滴阵列相比，MSSP能够控制纳升级液滴的蒸发速率，为基于水凝胶微阵列的材料提供了一个稳定的制造平台。作为概念验证演示，MSSP通过合理设计底物刚度、黏附面积和细胞密度，成功地控制了间充质干细胞的黏附、成脂和成骨分化行为。我们预计，MSSP可能为基于水凝胶的HTCS提供一种便捷且有前景的工具。意义声明：细胞的高通量筛选是提高生物学实验效率的常用方法，现有技术的一个挑战是用低成本且简单的策略实现快速精确的细胞筛选。通过整合微流控和微纳结构技术，我们制造了一个微流控点样筛选平台。受益于对流体的灵活控制，该设备能够在5分钟内打印20000个微滴点，并结合一种简单的程序用于并行添加化合物库。该平台还实现了干细胞谱系定向的高通量筛选，为细胞 - 生物材料相互作用研究提供了一种高通量、高内涵信息提取策略。
