Mitosis is a crucial biological process where a parental cell undergoes precisely controlled functional phases and divides into two daughter cells. Some drugs can inhibit cell mitosis, for instance, the anti-cancer drugs interacting with the tumor cell proliferation and leading to mitosis arrest at a specific phase or cell death eventually. Combining machine learning with microfluidic impedance flow cytometry (IFC) offers a concise way for label-free and high-throughput classification of drug-treated cells at single-cell level. IFC-based single-cell analysis generates a large amount of data related to the cell electrophysiology parameters, and machine learning helps establish correlations between these data and specific cell states. This work demonstrates the application of machine learning for cell state classification, including the binary differentiations between the G1/S and apoptosis states and between the G2/M and apoptosis states, as well as the classification of three subpopulations comprising a subgroup insensitive to the drug beyond the two drug-induced states of G2/M arrest and apoptosis. The impedance amplitudes and phases used as input features for the model training were extracted from the IFC-measured datasets for the drug-treated tumor cells. The deep neural network (DNN) model was exploited here with the structure (e.g., hidden layer number and neuron number in each layer) optimized for each given cell type and drug. For the H1650 cells, we obtained an accuracy of 78.51% for classification between the G1/S and apoptosis states and 82.55% for the G2/M and apoptosis states. For HeLa cells, we achieved a high accuracy of 96.94% for classification between the G2/M and apoptosis states, both of which were induced by taxol treatment. Even higher accuracy approaching 100% was achieved for the vinblastine-treated HeLa cells for the differentiation between the viable and non-viable states, and between the G2/M and apoptosis states. We also demonstrate the capability of the DNN model for high-accuracy classification of the three subpopulations in a complete cell sample treated by taxol or vinblastine.
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January 2024
Research Article|
January 23 2024
Machine learning classification of cellular states based on the impedance features derived from microfluidic single-cell impedance flow cytometry

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Jian Wei;
Jian Wei
(Data curation, Software, Writing – original draft)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
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Wenbing Gao
;
Wenbing Gao
(Formal analysis, Methodology, Validation)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
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Xinlong Yang;
Xinlong Yang
(Methodology, Resources)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
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Zhuotong Yu
;
Zhuotong Yu
(Writing – original draft, Writing – review & editing)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
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Fei Su;
Fei Su
(Formal analysis, Funding acquisition)
2
Department of Integrative Oncology, China-Japan Friendship Hospital
, No. 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
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Chengwu Han;
Chengwu Han
(Funding acquisition, Investigation, Supervision)
3
Department of Clinical Laboratory, China-Japan Friendship Hospital
, No. 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
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Xiaoxing Xing
Xiaoxing Xing
a)
(Funding acquisition, Methodology, Supervision, Writing – original draft, Writing – review & editing)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
a)Author to whom correspondence should be addressed: [email protected]
Search for other works by this author on:
Jian Wei
1
Wenbing Gao
1
Xinlong Yang
1
Zhuotong Yu
1
Fei Su
2
Chengwu Han
3
Xiaoxing Xing
1,a)
1
College of Information Science and Technology, Beijing University of Chemical Technology
, No. 15 North 3rd Ring Road, Chaoyang District, Beijing 100029, China
2
Department of Integrative Oncology, China-Japan Friendship Hospital
, No. 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
3
Department of Clinical Laboratory, China-Japan Friendship Hospital
, No. 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
a)Author to whom correspondence should be addressed: [email protected]
Biomicrofluidics 18, 014103 (2024)
Article history
Received:
October 16 2023
Accepted:
December 19 2023
Connected Content
A companion article has been published:
Machine learning meets cytometry for anti-cancer drug performance analysis
Citation
Jian Wei, Wenbing Gao, Xinlong Yang, Zhuotong Yu, Fei Su, Chengwu Han, Xiaoxing Xing; Machine learning classification of cellular states based on the impedance features derived from microfluidic single-cell impedance flow cytometry. Biomicrofluidics 1 January 2024; 18 (1): 014103. https://doi.org/10.1063/5.0181287
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