Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics

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....

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Main Authors: Zongliang Guo, Fenggang Li, Hang Li, Menglei Zhao, Haobing Liu, Haopu Wang, Hanqi Hu, Rongxin Fu, Yao Lu, Siyi Hu, Huikai Xie, Hanbin Ma, Shuailong Zhang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202408353
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author Zongliang Guo
Fenggang Li
Hang Li
Menglei Zhao
Haobing Liu
Haopu Wang
Hanqi Hu
Rongxin Fu
Yao Lu
Siyi Hu
Huikai Xie
Hanbin Ma
Shuailong Zhang
author_facet Zongliang Guo
Fenggang Li
Hang Li
Menglei Zhao
Haobing Liu
Haopu Wang
Hanqi Hu
Rongxin Fu
Yao Lu
Siyi Hu
Huikai Xie
Hanbin Ma
Shuailong Zhang
author_sort Zongliang Guo
collection DOAJ
description 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.
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institution Kabale University
issn 2198-3844
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publishDate 2025-01-01
publisher Wiley
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spelling doaj-art-a6818cee027f40d4966a3d5b5f84e9d72025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202408353Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital MicrofluidicsZongliang Guo0Fenggang Li1Hang Li2Menglei Zhao3Haobing Liu4Haopu Wang5Hanqi Hu6Rongxin Fu7Yao Lu8Siyi Hu9Huikai Xie10Hanbin Ma11Shuailong Zhang12Beijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering Beijing Institute of Technology Beijing 100081 ChinaBeijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering Beijing Institute of Technology Beijing 100081 ChinaSchool of Medical Technology Beijing Institute of Technology Beijing 100081 ChinaBeijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering Beijing Institute of Technology Beijing 100081 ChinaBeijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering Beijing Institute of Technology Beijing 100081 ChinaSchool 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 ChinaSchool of Medical Technology Beijing Institute of Technology Beijing 100081 ChinaSchool of Medical Technology Beijing Institute of Technology Beijing 100081 ChinaSchool 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 ChinaCAS Key Laboratory of Bio‐Medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou 215163 ChinaSchool 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 ChinaCAS Key Laboratory of Bio‐Medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou 215163 ChinaBeijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering Beijing Institute of Technology Beijing 100081 ChinaAbstract 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.https://doi.org/10.1002/advs.202408353artificial intelligencecell sortingdigital microfluidicsdropletsingle cell researchlabel‐free
spellingShingle Zongliang Guo
Fenggang Li
Hang Li
Menglei Zhao
Haobing Liu
Haopu Wang
Hanqi Hu
Rongxin Fu
Yao Lu
Siyi Hu
Huikai Xie
Hanbin Ma
Shuailong Zhang
Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
Advanced Science
artificial intelligence
cell sorting
digital microfluidics
droplet
single cell research
label‐free
title Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
title_full Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
title_fullStr Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
title_full_unstemmed Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
title_short Deep Learning‐Assisted Label‐Free Parallel Cell Sorting with Digital Microfluidics
title_sort deep learning assisted label free parallel cell sorting with digital microfluidics
topic artificial intelligence
cell sorting
digital microfluidics
droplet
single cell research
label‐free
url https://doi.org/10.1002/advs.202408353
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