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An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening

BACKGROUND: Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techn...

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Autores principales: Wang, Biao, He, Bang-Shun, Ruan, Xiao-Lan, Zhu, Jiang, Hu, Rui, Wang, Jie, Li, Ying, Yang, Yun-Huang, Liu, Mai-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494811/
https://www.ncbi.nlm.nih.gov/pubmed/36131323
http://dx.doi.org/10.1186/s40779-022-00409-9
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author Wang, Biao
He, Bang-Shun
Ruan, Xiao-Lan
Zhu, Jiang
Hu, Rui
Wang, Jie
Li, Ying
Yang, Yun-Huang
Liu, Mai-Li
author_facet Wang, Biao
He, Bang-Shun
Ruan, Xiao-Lan
Zhu, Jiang
Hu, Rui
Wang, Jie
Li, Ying
Yang, Yun-Huang
Liu, Mai-Li
author_sort Wang, Biao
collection PubMed
description BACKGROUND: Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions. METHODS: We developed a new microfluidics-based “SMART” platform that is Simple to operate, able to generate a Massive single-cell array and Multiplex drug concentrations, capable of keeping cells Alive, Retainable and Trackable in the microchambers. These features are achieved by integrating a Microfluidic chamber Array (4320 units) and a six-Concentration gradient generator (MAC), which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way. RESULTS: A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity. The statistic results reveal that Imatinib (Ima) and Resveratrol (Res) combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment, indicated by the markedly reduced half maximal inhibitory concentration (IC(50)). Additionally, single-cell derived clones demonstrate a higher IC(50) in each drug treatment compared to single cells. Moreover, primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC. CONCLUSION: This microfluidics-based “SMART” platform allows high-throughput single-cell capture and culture, dynamic drug-gradient treatment and cell response monitoring, which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40779-022-00409-9.
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spelling pubmed-94948112022-09-23 An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening Wang, Biao He, Bang-Shun Ruan, Xiao-Lan Zhu, Jiang Hu, Rui Wang, Jie Li, Ying Yang, Yun-Huang Liu, Mai-Li Mil Med Res Research BACKGROUND: Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions. METHODS: We developed a new microfluidics-based “SMART” platform that is Simple to operate, able to generate a Massive single-cell array and Multiplex drug concentrations, capable of keeping cells Alive, Retainable and Trackable in the microchambers. These features are achieved by integrating a Microfluidic chamber Array (4320 units) and a six-Concentration gradient generator (MAC), which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way. RESULTS: A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity. The statistic results reveal that Imatinib (Ima) and Resveratrol (Res) combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment, indicated by the markedly reduced half maximal inhibitory concentration (IC(50)). Additionally, single-cell derived clones demonstrate a higher IC(50) in each drug treatment compared to single cells. Moreover, primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC. CONCLUSION: This microfluidics-based “SMART” platform allows high-throughput single-cell capture and culture, dynamic drug-gradient treatment and cell response monitoring, which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40779-022-00409-9. BioMed Central 2022-09-22 /pmc/articles/PMC9494811/ /pubmed/36131323 http://dx.doi.org/10.1186/s40779-022-00409-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Biao
He, Bang-Shun
Ruan, Xiao-Lan
Zhu, Jiang
Hu, Rui
Wang, Jie
Li, Ying
Yang, Yun-Huang
Liu, Mai-Li
An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title_full An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title_fullStr An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title_full_unstemmed An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title_short An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
title_sort integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494811/
https://www.ncbi.nlm.nih.gov/pubmed/36131323
http://dx.doi.org/10.1186/s40779-022-00409-9
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