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A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

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Abstract

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells. However, state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds, sample loss, and labor-intensive preparation procedures. Here, we demonstrate the development of a novel microfluidic chip that integrates droplet generation, on-demand electrostatic droplet charging, and high-throughput sorting. The charging electrode is a copper wire buried above the nozzle of the microchannel, and the deflecting electrode is the phosphate buffered saline in the microchannel, which greatly simplifies the structure and fabrication process of the chip. Moreover, this chip is capable of high-frequency droplet generation and sorting, with a frequency of 11.757 kHz in the drop state. The chip completes the selective charging process via electrostatic induction during droplet generation. On-demand charged microdroplets can arbitrarily move to specific exit channels in a three-dimensional (3D)-deflected electric field, which can be controlled according to user requirements, and the flux of droplet deflection is thereby significantly enhanced. Furthermore, a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal. This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

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Acknowledgements

The authors acknowledge the financial support from the National Natural Science Foundation of China (No. 52275562) and the Technology Innovation Fund of Huazhong University of Science and Technology (No. 2022JYCXJJ015). The authors would like to express gratitude to the Analytical and Testing Center, Flexible Electronics Research Center, Measurement Laboratory of Collaborative Innovation Center, and the Wuhan National Laboratory for Optoelectronics of Huazhong University of Science and Technology for their assistance with lithography, coating, bonding, and characterization.

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  1. Jinhui Yao and Chunhua He have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Intelligent Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Jinhui Yao, Chunhua He, Jianxin Wang, Canfeng Yang, Ye Jiang, Zhiyong Liu, Guanglan Liao & Tielin Shi

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  1. Jinhui Yao
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Contributions

JHY and CHH designed the experiments. JHY fabricated the microfluidic chip and integrated the chip with experimental observations and the detection device. JHY performed the simulation of the microstructure used for droplet generation and optimized the structural parameters of the microfluidic channel with the help of CHH. With the help of CHH and JXW, JHY conducted the experimental tests of droplet generation and deflection and summarized the laws and influencing factors of droplet generation and deflection. Together with CFY, JHY built a real-time droplet frequency detection system to improve the accuracy of droplet deflection. JHY compiled experimental data and wrote this manuscript together with CHH and YJ. GLL, TLS, and ZYL carefully guided the experimental tests and the writing of the manuscript. All authors reviewed the final version of the manuscript prior to submission.

Corresponding authors

Correspondence to Zhiyong Liu or Guanglan Liao.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary Information

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42242_2023_257_MOESM1_ESM.eps

Supplementary file1 (EPS 3786 kb). Fig. S1 Schematic diagram of the fabrication process of the chip. (a) We dropped the photoresist on a silicon wafer; (b) we spun coating the photoresist to 50–60 μm and prebaked; (c) the photoresist was exposed under the mask and UV-light for 15 s; (d) development operation with subsequent hardening and hydrophobic treatment; (e) we poured PDMS and embedded the copper wire; (f) we cut and drilled the PDMS to obtain the microchannel; (g) oxygen plasma treatment; (h) changes of surface chemical bonds between glass and PDMS after oxygen plasma treatment; and (i) the final microfluidic chip.

42242_2023_257_MOESM2_ESM.tif

Supplementary file2 (TIF 17579 kb). Fig. S2 We attached the PDMS insulation layer to a piece of glass and then measured its thickness under an optical microscope. The measurement result shows that the thickness value is around 200 μm.

42242_2023_257_MOESM3_ESM.eps

Supplementary file3 (EPS 5844 kb). Fig. S3 The diagram of the gradual increase in the volume of the droplet at the nozzle until it broke during one cycle (7 frames taken with a high-speed camera). The droplet was generated at a flow rate of 10 μL/min for the dispersed phase and 90 μL/min for the continuous phase at a frequency of approximately 11.757 kHz or a period of 85 μs.

Supplementary file5 (MP4 2431 kb). Video S1 Dynamic video of droplet generation in the squeeze type. At this time, the flow rate of the dispersed phase was 10 μL/min, the flow rate of the continuous phase was 40 μL/min, the frequency of droplet generation was about 2.859 kHz, and the diameter of the droplet was about 63 μm, corresponding to Fig. 4b in the manuscript

Supplementary file6 (MP4 2433 kb). Video S2 Dynamic video of droplet generation in the drop type. At this time, the flow rate of the dispersed phase was 10 μL/min, the flow rate of the continuous phase was 90 μL/min, the frequency of droplet generation was about 11.757 kHz, and the diameter of the droplet was about 33 μm, corresponding to Fig. 4c in the manuscript.

Supplementary file7 (MP4 2434 kb). Video S3 Dynamic video of droplet generation in the jet type. At this time, the flow rate of the dispersed phase was 10 μL/min, the flow rate of the continuous phase was 120 μL/min, the frequency of droplet generation was about 13.124 kHz, and the diameter of the droplet was about 28.4 μm, corresponding to Fig. 4d in the manuscript.

Supplementary file8 (MP4 2426 kb). Video S4 Dynamic video of one droplet moving toward the upper channel and one droplet moving toward the lower channel, corresponding to Fig. 5c in the manuscript.

Supplementary file9 (MP4 2619 kb). Video S5 Dynamic video of one droplet moving toward the upper channel and two droplets moving toward the lower channel, corresponding to Fig. 5d in the manuscript.

Supplementary file10 (MP4 2611 kb). Video S6 Dynamic video of one droplet moving toward the upper channel and three droplets moving toward the lower channel, corresponding to Fig. 5e in the manuscript.

Supplementary file11 (MP4 2370 kb). Video S7 Dynamic video of four droplets moving toward the upper channel and one droplet moving toward the lower channel, corresponding to Fig. 5f in the manuscript.

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Yao, J., He, C., Wang, J. et al. A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting. Bio-des. Manuf. 7, 31–42 (2024). https://doi.org/10.1007/s42242-023-00257-z

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