A digital microfluidic single-cell manipulation system optimized by extending-depth-of-field device

Author:

Chen Qiushu1ORCID,Meng Qi2,Liu Yuzhe1,Long Xiangan3,Kong Yawei1,Yao Longfang14,Chen Liwen15,Wu Chuanyong6,Chu Kaiqin27,Mi Lan1ORCID,Ma Jiong138ORCID

Affiliation:

1. Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), School of Information Science and Technology, Fudan University, Shanghai 200433, P. R. China

2. Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei 230027, Anhui, P. R. China

3. Institute of Biomedical Engineering and Technology, Academy for Engineering and Technology, Fudan University, Shanghai 200433, P. R. China

4. Institute of Photonic Chips, Centre for Artificial-Intelligence Nanophotonics, School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China

5. Ruidge Biotech Co. Ltd., No. 888, Huanhu West 2nd Road, Lin-Gang Special Area, China (Shanghai) Pilot Free Trade Zone, Shanghai 200131, P. R. China

6. Shanghai Hengxin BioTechnology, Ltd., 1688 North Guo Quan Rd, Bldg A8, Rm 801, Shanghai 200438, P. R. China

7. Centre for Artificial-Intelligence Nanophotonics, School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China

8. Shanghai Engineering Research Center of Industrial Microorganisms, The Multiscale Research Institute of Complex Systems (MRICS), School of Life Sciences, Fudan University, Shanghai 200433, P. R. China

Abstract

Microfluidic systems have been widely utilized in high-throughput biology analysis, but the difficulties in liquid manipulation and cell cultivation limit its application. This work has developed a new digital microfluidic (DMF) system for on-demand droplet control. By adopting an extending-depth-of-field (EDoF) phase modulator to the optical system, the entire depth of the microfluidic channel can be covered in one image without any refocusing process, ensuring that 95% of the particles in the droplet are captured within three shots together with shaking processes. With this system, suspension droplets are generated and droplets containing only one yeast cell can be recognized, then each single cell is cultured in the array of the chip. By observing their growth in cell numbers and the green fluorescence protein (GFP) production via fluorescence imaging, the single cell with the highest production can be identified. The results have proved the heterogeneity of yeast cells, and showed that the combined system can be applied for rapid single-cell sorting, cultivation, and analysis.

Funder

National Natural Science Foundation of China

National Key R&D Program of China

Anhui Province Key R&D Project

Shanghai Natural Science Foundation

Science and Technology Research Program of Shanghai

Shanghai key discipline construction plan

Shanghai Engineering Technology Research Center of Hair Medicine

Medical Engineering Fund of Fudan University

Pioneering Project of Academy for Engineering and Technology, Fudan University

Publisher

World Scientific Pub Co Pte Ltd

Subject

Biomedical Engineering,Atomic and Molecular Physics, and Optics,Medicine (miscellaneous),Electronic, Optical and Magnetic Materials

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