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用于衰老细胞自动识别的无标记光片微流控细胞术

Label-free light-sheet microfluidic cytometry for the automatic identification of senescent cells.

作者信息

Lin Meiai, Liu Qiao, Liu Chao, Qiao Xu, Shao Changshun, Su Xuantao

机构信息

Institute of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong, 250061, China.

Department of Molecular Medicine and Genetics, School of Basic Medicine, Shandong University, Jinan, Shandong, 250012, China.

出版信息

Biomed Opt Express. 2018 Mar 14;9(4):1692-1703. doi: 10.1364/BOE.9.001692. eCollection 2018 Apr 1.

DOI:10.1364/BOE.9.001692
PMID:29675311
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5905915/
Abstract

Label-free microfluidic cytometry is of increasing interest for single cell analysis due to its advantages of high-throughput, miniaturization, as well as noninvasive detection. Here we develop a next generation label-free light-sheet microfluidic cytometer for single cell analysis by two-dimensional (2D) light scattering measurements. Our cytometer integrates light sheet illumination with a disposable hydrodynamic focusing unit, which can achieve 3D hydrodynamic focusing of a sample fluid to a diameter of 19 micrometer without microfabrication. This integration also improves the signal to noise ratio (SNR) for the acquisition of 2D light scattering patterns from label-free cells. Particle sizing with submicron resolution is achieved by our light-sheet flow cytometer, where Euclidean distance-based similarity measures are performed. Label-free, automatic classification of senescent and normal cells is achieved with a high accuracy rate by incorporating our light-sheet flow cytometry with support vector machine (SVM) algorithms. Our light-sheet microfluidic cytometry with a microfabrication-free hydrodynamic focusing unit may find wide applications for automatic and label-free clinical diagnosis.

摘要

无标记微流控细胞术因其高通量、小型化以及无创检测等优点,在单细胞分析中越来越受到关注。在此,我们开发了一种用于单细胞分析的下一代无标记光片微流控细胞仪,通过二维(2D)光散射测量进行分析。我们的细胞仪将光片照明与一次性流体动力聚焦单元集成在一起,无需微加工就能将样品流体实现三维流体动力聚焦至直径为19微米。这种集成还提高了从无标记细胞获取二维光散射图案时的信噪比(SNR)。我们的光片流式细胞仪通过基于欧几里得距离的相似性测量实现了亚微米分辨率的颗粒大小测定。通过将我们的光片流式细胞术与支持向量机(SVM)算法相结合,实现了衰老细胞和正常细胞的无标记自动分类,准确率很高。我们具有无需微加工的流体动力聚焦单元的光片微流控细胞术可能会在自动和无标记临床诊断中得到广泛应用。