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基于深度学习的数字微流控无标记并行细胞分选

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

作者信息

Guo Zongliang, Li Fenggang, Li Hang, Zhao Menglei, Liu Haobing, Wang Haopu, Hu Hanqi, Fu Rongxin, Lu Yao, Hu Siyi, Xie Huikai, Ma Hanbin, Zhang Shuailong

机构信息

Beijing Advanced Innovation Center for Intelligent Robots and Systems, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, 100081, China.

School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China.

出版信息

Adv Sci (Weinh). 2025 Jan;12(1):e2408353. doi: 10.1002/advs.202408353. Epub 2024 Nov 5.


DOI:10.1002/advs.202408353
PMID:39497614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11906218/
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.

摘要

从异质样本中筛选特定细胞对于研究和临床应用至关重要。在这项工作中,提出了一种新型的无标记细胞分选方法,该方法将深度学习图像识别与微流控操作相结合,以根据形态区分细胞。使用有源矩阵数字微流控(AM-DMF)平台,YOLOv8目标检测模型确保精确的液滴分类,安全间隔路径规划算法管理多目标、无碰撞的液滴路径规划。模拟和实验表明,检测模型精度、浓度比和分选周期显著影响回收率和纯度。以HeLa细胞和聚苯乙烯珠为样本,该方法在三个周期内实现了98.5%的分选精度、96.49%的纯度和80%的回收率。经过一系列实验验证,该方法还可用于从红细胞中筛选HeLa细胞、从白细胞中筛选癌细胞(以HeLa和Jurkat细胞为代表)以及区分白细胞亚型(以HL-60细胞和Jurkat细胞为代表)。使用该方法分选的细胞可以在其所在的液滴内直接在芯片上裂解,确保最小的样本损失并适用于下游生物分析。这种创新的AM-DMF细胞分选技术在推进细胞生物学的诊断、治疗和基础研究方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/e21a43491a51/ADVS-12-2408353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/51b30c36ca40/ADVS-12-2408353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/c2421bcfe1f9/ADVS-12-2408353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/7cae8efbe8da/ADVS-12-2408353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/ebc442ffe7cf/ADVS-12-2408353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/ccca50865fa7/ADVS-12-2408353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/e21a43491a51/ADVS-12-2408353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/51b30c36ca40/ADVS-12-2408353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/c2421bcfe1f9/ADVS-12-2408353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/7cae8efbe8da/ADVS-12-2408353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/ebc442ffe7cf/ADVS-12-2408353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/ccca50865fa7/ADVS-12-2408353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3d2/11906218/e21a43491a51/ADVS-12-2408353-g006.jpg

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[1]
Deep Learning-Assisted Label-Free Parallel Cell Sorting with Digital Microfluidics.

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[4]
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引用本文的文献

[1]
Nucleic acid amplification tests in digital microfluidics: the promise of next-generation point-of-care diagnostics.

Microsyst Nanoeng. 2025-8-18

[2]
Intelligent single-cell manipulation: LLMs- and object detection-enhanced active-matrix digital microfluidics.

Microsyst Nanoeng. 2025-7-7

本文引用的文献

[1]
Rapid automated extracellular vesicle isolation and miRNA preparation on a cost-effective digital microfluidic platform.

Anal Chim Acta. 2024-4-1

[2]
High-precision rapid testing of omicron SARS-CoV-2 variants in clinical samples using AI-nanopore.

Lab Chip. 2023-11-7

[3]
Advanced design and applications of digital microfluidics in biomedical fields: An update of recent progress.

Biosens Bioelectron. 2023-12-15

[4]
Sub-5-Minute Ultrafast PCR using Digital Microfluidics.

Biosens Bioelectron. 2023-12-15

[5]
DIRECT: Digital Microfluidics for Isolation-Free Shared Library Construction of Single-Cell DNA Methylome and Transcriptome.

Small Methods. 2024-1

[6]
Is AI essential? Examining the need for deep learning in image-activated sorting of .

Lab Chip. 2023-9-26

[7]
Digital-scRRBS: A Cost-Effective, Highly Sensitive, and Automated Single-Cell Methylome Analysis Platform via Digital Microfluidics.

Anal Chem. 2023-9-5

[8]
Computer Vision-Based Artificial Intelligence-Mediated Encoding-Decoding for Multiplexed Microfluidic Digital Immunoassay.

ACS Nano. 2023-7-25

[9]
Large-Area Electronics-Enabled High-Resolution Digital Microfluidics for Parallel Single-Cell Manipulation.

Anal Chem. 2023-5-2

[10]
Cell damage evaluation by intelligent imaging flow cytometry.

Cytometry A. 2023-8

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