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Demand-driven active droplet generation and sorting based on positive pressure-controlled fluid wall

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Abstract

Droplet microfluidics is a rapidly advancing area of microfluidic technology, which offers numerous advantages for cell analysis, such as isolation and accumulation of signals, by confining cells within droplets. However, controlling cell numbers in droplets is challenging due to the uncertainty of random encapsulation which result in many empty droplets. Therefore, more precise control techniques are needed to achieve efficient encapsulation of cells within droplets. Here, an innovative microfluidic droplet manipulation platform had been developed, which employed positive pressure as a stable and controllable driving force for manipulating fluid within chips. The air cylinder, electro-pneumatics proportional valve, and the microfluidic chip were connected through a capillary, which enabled the formation of a fluid wall by creating a difference in hydrodynamic resistance between two fluid streams at the channel junction. Lowering the pressure of the driving oil phase eliminates hydrodynamic resistance and breaks the fluid wall. Regulating the duration of the fluid wall breakage controls the volume of the introduced fluid. Several important droplet microfluidic manipulations were demonstrated on this microfluidic platform, such as sorting of cells/droplets, sorting of droplets co-encapsulated cells and hydrogels, and active generation of droplets encapsulated with cells in a responsive manner. The simple, on-demand microfluidic platform was featured with high stability, good controllability, and compatibility with other droplet microfluidic technologies.

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Funding

We gratefully acknowledge the financial supports from the National Key R&D Program of China (2017YFA0700403 and 2021YFA1101500), the National Natural Science Foundation of China (22074047), and the Fundamental Research Funds for the Central Universities (2020kfyXJJS034).

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  1. Yiwei Zhang and Yiwei Lin contributed equally to this work.

Authors and Affiliations

  1. 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

    Yiwei Zhang, Yiwei Lin, Xianzhe Hong, Chao Di, Yuelai Xin, Xinru Wang, Shuhong Qi, Bi-Feng Liu, Zhihong Zhang & Wei Du

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  1. Yiwei Zhang
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Zhang, Y., Lin, Y., Hong, X. et al. Demand-driven active droplet generation and sorting based on positive pressure-controlled fluid wall. Anal Bioanal Chem 415, 5311–5322 (2023). https://doi.org/10.1007/s00216-023-04806-4

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