The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Anal Chim Acta. 2020 Aug 15;1125:94-113. doi: 10.1016/j.aca.2020.05.065. Epub 2020 Jun 1.
Spatiotemporal manipulation of extracellular chemical environments with simultaneous monitoring of cellular responses plays an essential role in exploring fundamental biological processes and expands our understanding of underlying mechanisms. Despite the rapid progress and promising successes in manipulation strategies, many challenges remain due to the small size of cells and the rapid diffusion of chemical molecules. Fortunately, emerging microfluidic technology has become a powerful approach for precisely controlling the extracellular chemical microenvironment, which benefits from its integration capacity, automation, and high-throughput capability, as well as its high resolution down to submicron. Here, we summarize recent advances in microfluidics manipulation of the extracellular chemical microenvironment, including the following aspects: i) Spatial manipulation of chemical microenvironments realized by convection flow-, diffusion-, and droplet-based microfluidics, and surface chemical modification; ii) Temporal manipulation of chemical microenvironments enabled by flow switching/shifting, moving/flowing cells across laminar flows, integrated microvalves/pumps, and droplet manipulation; iii) Spatiotemporal manipulation of chemical microenvironments implemented by a coupling strategy and open-space microfluidics; and iv) High-throughput manipulation of chemical microenvironments. Finally, we briefly present typical applications of the above-mentioned technical advances in cell-based analyses including cell migration, cell signaling, cell differentiation, multicellular analysis, and drug screening. We further discuss the future improvement of microfluidics manipulation of extracellular chemical microenvironments to fulfill the needs of biological and biomedical research and applications.
利用微流控技术对细胞外化学微环境进行时空操控并同时监测细胞响应，对于探索基本生物过程和扩展对潜在机制的理解具有重要作用。尽管在操控策略方面取得了快速进展和有前景的成功，但由于细胞体积小和化学分子扩散迅速，仍然存在许多挑战。幸运的是，新兴的微流控技术已成为精确控制细胞外化学微环境的有力方法，这得益于其集成能力、自动化和高通量能力以及高达亚微米级的高分辨率。在这里，我们总结了微流控技术在细胞外化学微环境操控方面的最新进展，包括以下几个方面：i）基于对流流、扩散和液滴的微流控以及表面化学修饰实现的化学微环境的空间操控；ii）通过流切换/转移、细胞在层流中移动/流动、集成微阀/泵和液滴操控实现的化学微环境的时间操控；iii）通过耦合策略和开放空间微流控实现的化学微环境的时空操控；以及 iv）化学微环境的高通量操控。最后，我们简要介绍了上述技术进展在基于细胞的分析中的典型应用，包括细胞迁移、细胞信号转导、细胞分化、多细胞分析和药物筛选。我们进一步讨论了微流控技术对细胞外化学微环境的操控的未来改进，以满足生物和生物医学研究和应用的需求。
