An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening.
An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening.
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一个集成的微流体平台，具有高通量单细胞克隆阵列和浓度梯度发生器，用于高效的癌症药物效应筛选。
DOI：
10.1186/s40779-022-00409-9
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发表时间：
2022-09-22
影响因子：
21.1
通讯作者：
Liu, Mai-Li
中科院分区：
文献类型：
--
作者：
Wang, Biao;He, Bang-Shun;Ruan, Xiao-Lan;Zhu, Jiang;Hu, Rui;Wang, Jie;Li, Ying;Yang, Yun-Huang;Liu, Mai-Li
肿瘤细胞异质性介导的耐药已被认为是癌症治疗的绊脚石。因此，在单细胞水平上高通量地阐明抗癌药物的细胞毒性对开发精准治疗具有重要价值。然而，目前的技术在动态表征数千个单细胞或细胞克隆对多种药物条件的反应方面存在局限性。我们开发了一种新的基于微流体的“SMART”平台，操作简单，能够产生大量的单细胞阵列和多重药物浓度，能够在微室中保持细胞存活，可保留和可跟踪。这些功能是通过集成微流控室阵列（4320个单元）和六浓度梯度发生器（MAC）来实现的，它能够以高通量的方式高效分析白血病药物对单细胞和细胞克隆的影响。一个简单的程序产生6个芯片上的药物梯度来治疗3000多个单细胞或单细胞衍生克隆，从而允许有效和精确的细胞异质性分析。统计结果显示，伊马替尼（Ima）和白藜芦醇（Res）联合治疗对单细胞或克隆的效果明显优于伊马替尼或Res单药治疗，其最大抑制浓度（IC50）显著降低一半。此外，与单细胞相比，单细胞衍生克隆在每种药物治疗中表现出更高的IC50。此外，从两名白血病患者身上分离的原代细胞在MAC上也发现了明显的异质性。这种基于微流体的“SMART”平台可以实现高通量单细胞捕获和培养，动态药物梯度治疗和细胞反应监测，这代表了一种有效研究抗癌药物作用的新方法，应该有助于白血病和其他癌症的药物发现。在线版本包含补充材料，可在10.1186/s40779-022-00409-9获得。
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. 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. 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 (IC50). Additionally, single-cell derived clones demonstrate a higher IC50 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. 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. The online version contains supplementary material available at 10.1186/s40779-022-00409-9.
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影响因子：
5.5
作者：
Guo H;Qian L;Cui J
通讯作者：
Cui J
用于药物评价的单一 CTC 表型相关药物敏感性分析
影响因子：
8.4
作者：
Pei H;Yu M;Dong D;Wang Y;Li Q;Li L;Tang B
通讯作者：
Tang B
影响因子：
4
作者：
Novakovic B;Gordon L;Wong NC;Moffett A;Manuelpillai U;Craig JM;Sharkey A;Saffery R
通讯作者：
Saffery R
影响因子：
4.1
作者：
Li, Ying;Jang, Joon Hee;Qin, Lidong
通讯作者：
Qin, Lidong
使用集成微流体进行单细胞衍生肿瘤球形成和耐药性测定
影响因子：
7.4
作者：
Pang, Long;Ding, Jing;Fan, Shih-Kang
通讯作者：
Fan, Shih-Kang