Deep Learning-Assisted Label-Free Parallel Cell Sorting with Digital Microfluidics.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
PMID:

Abstract

Sorting specific cells from heterogeneous samples is important for research and clinical applications. In this work, a novel label-free cell sorting method is presented that integrates deep learning image recognition with microfluidic manipulation to differentiate cells based on morphology. Using an Active-Matrix Digital Microfluidics (AM-DMF) platform, the YOLOv8 object detection model ensures precise droplet classification, and the Safe Interval Path Planning algorithm manages multi-target, collision-free droplet path planning. Simulations and experiments revealed that detection model precision, concentration ratios, and sorting cycles significantly affect recovery rates and purity. With HeLa cells and polystyrene beads as samples, the method achieved 98.5% sorting precision, 96.49% purity, and an 80% recovery over three cycles. After a series of experimental validations, this method can also be used to sort HeLa cells from red blood cells, cancer cells from white blood cells (represented by HeLa and Jurkat cells), and differentiate white blood cell subtypes (represented by HL-60 cells and Jurkat cells). Cells sorted using this method can be lysed directly on chip within their hosting droplets, ensuring minimal sample loss and suitability for downstream bioanalysis. This innovative AM-DMF cell sorting technique holds significant potential to advance diagnostics, therapeutics, and fundamental research in cell biology.

Authors

  • Zongliang Guo
    Beijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
  • Fenggang Li
    Beijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
  • Hang Li
    Beijing Academy of Quantum Information Sciences, Beijing 100193, China.
  • Menglei Zhao
    Beijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
  • Haobing Liu
  • Haopu Wang
    School of Integrated Circuits and Electronics, Engineering Research Center of Integrated Acousto-Opto-Electronic Microsystems (Ministry of Education of China), Beijing Institute of Technology, Beijing, 100081, China.
  • Hanqi Hu
    School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China.
  • Rongxin Fu
    Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.
  • Yao Lu
    Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo First Hospital, Ningbo, China.
  • Siyi Hu
    CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
  • Huikai Xie
    School of Integrated Circuits and Electronics, Engineering Research Center of Integrated Acousto-Opto-Electronic Microsystems (Ministry of Education of China), Beijing Institute of Technology, Beijing, 100081, China.
  • Hanbin Ma
    CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
  • Shuailong Zhang
    Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.