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通过机器学习增强的微流控全息流式细胞仪对上皮性卵巢癌细胞耐药性的无标记评估

Label-Free Assessment of the Drug Resistance of Epithelial Ovarian Cancer Cells in a Microfluidic Holographic Flow Cytometer Boosted through Machine Learning.

作者信息

Xin Lu, Xiao Wen, Che Leiping, Liu JinJin, Miccio Lisa, Bianco Vittorio, Memmolo Pasquale, Ferraro Pietro, Li Xiaoping, Pan Feng

机构信息

Key Laboratory of Precision Opto-mechatronics Technology, School of Instrumentation & Optoelectronic Engineering, Beihang University, Beijing 100191, China.

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.

出版信息

ACS Omega. 2021 Nov 12;6(46):31046-31057. doi: 10.1021/acsomega.1c04204. eCollection 2021 Nov 23.

Abstract

About 75% of epithelial ovarian cancer (EOC) patients suffer from relapsing and develop drug resistance after primary chemotherapy. The commonly used clinical examinations and biological tumor tissue models for chemotherapeutic sensitivity are time-consuming and expensive. Research studies showed that the cell morphology-based method is promising to be a new route for chemotherapeutic sensitivity evaluation. Here, we offer how the drug resistance of EOC cells can be assessed through a label-free and high-throughput microfluidic flow cytometer equipped with a digital holographic microscope reinforced by machine learning. It is the first time that such type of assessment is performed to the best of our knowledge. Several morphologic and texture features at a single-cell level have been extracted from the quantitative phase images. In addition, we compared four common machine learning algorithms, including naive Bayes, decision tree, K-nearest neighbors, support vector machine (SVM), and fully connected network. The result shows that the SVM classifier achieves the optimal performance with an accuracy of 92.2% and an area under the curve of 0.96. This study demonstrates that the proposed method achieves high-accuracy, high-throughput, and label-free assessment of the drug resistance of EOC cells. Furthermore, it reflects strong potentialities to develop data-driven individualized chemotherapy treatments in the future.

摘要

约75%的上皮性卵巢癌(EOC)患者在初次化疗后会复发并产生耐药性。常用的用于化疗敏感性的临床检查和生物肿瘤组织模型既耗时又昂贵。研究表明,基于细胞形态的方法有望成为化疗敏感性评估的新途径。在此,我们介绍如何通过配备数字全息显微镜并由机器学习增强的无标记高通量微流控流式细胞仪来评估EOC细胞的耐药性。据我们所知,这是首次进行此类评估。已从定量相位图像中提取了单细胞水平的几个形态和纹理特征。此外,我们比较了四种常见的机器学习算法,包括朴素贝叶斯、决策树、K近邻、支持向量机(SVM)和全连接网络。结果表明,SVM分类器实现了最佳性能,准确率为92.2%,曲线下面积为0.96。本研究表明,所提出的方法实现了对EOC细胞耐药性的高精度、高通量和无标记评估。此外,它还显示出未来开发数据驱动的个体化化疗治疗的强大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f21/8613806/a827c8594ed8/ao1c04204_0002.jpg

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