Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids.
Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids.
复制标题
用于肿瘤类器官动态和组合药物筛选的自动化微流控平台
DOI：
10.1038/s41467-020-19058-4
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发表时间：
2020-10-19
影响因子：
16.6
通讯作者：
Tay S
中科院分区：
文献类型：
--
作者：
Schuster B;Junkin M;Kashaf SS;Romero-Calvo I;Kirby K;Matthews J;Weber CR;Rzhetsky A;White KP;Tay S
三维（3D）细胞培养技术，如类器官，是基础和临床应用的生理相关模型。自动化微流体技术在细胞的高通量和精确分析方面具有优势，但尚未与类器官兼容。在这里，我们提出了一种自动化，高通量，微流体3D类器官培养和分析系统，以促进临床前研究和个性化治疗。我们的系统为数百种培养物提供了组合和动态药物治疗，并实现了类器官的实时分析。我们通过对人源性胰腺肿瘤类器官进行个体、组合和顺序药物筛选来验证我们的系统。我们观察到基于个体患者的类器官对药物治疗的反应存在显着差异，并发现临时修饰的药物治疗可能比体外恒定剂量的单药治疗或联合治疗更有效。该集成平台推进类器官模型，以筛选和反映真实的患者治疗过程，有可能促进个性化治疗的治疗决策。类器官在个性化医疗中的应用是有希望的，但需要高通量平台。在这里，作者开发了一种自动化、高通量、微流体3D类器官培养系统，可以进行组合和动态药物治疗以及类器官的实时分析。
Three-dimensional (3D) cell culture technologies, such as organoids, are physiologically relevant models for basic and clinical applications. Automated microfluidics offers advantages in high-throughput and precision analysis of cells but is not yet compatible with organoids. Here, we present an automated, high-throughput, microfluidic 3D organoid culture and analysis system to facilitate preclinical research and personalized therapies. Our system provides combinatorial and dynamic drug treatments to hundreds of cultures and enables real-time analysis of organoids. We validate our system by performing individual, combinatorial, and sequential drug screens on human-derived pancreatic tumor organoids. We observe significant differences in the response of individual patient-based organoids to drug treatments and find that temporally-modified drug treatments can be more effective than constant-dose monotherapy or combination therapy in vitro. This integrated platform advances organoids models to screen and mirror real patient treatment courses with potential to facilitate treatment decisions for personalized therapy. The use of organoids in personalized medicine is promising but high throughput platforms are needed. Here the authors develop an automated, high-throughput, microfluidic 3D organoid culture system that allows combinatorial and dynamic drug treatments and real-time analysis of organoids.
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影响因子：
23.9
作者：
Czerniecki SM;Cruz NM;Harder JL;Menon R;Annis J;Otto EA;Gulieva RE;Islas LV;Kim YK;Tran LM;Martins TJ;Pippin JW;Fu H;Kretzler M;Shankland SJ;Himmelfarb J;Moon RT;Paragas N;Freedman BS
通讯作者：
Freedman BS
影响因子：
64.5
作者：
Neal, James T.;Li, Xingnan;Kuo, Calvin J.
通讯作者：
Kuo, Calvin J.
影响因子：
6.1
作者：
Neils, C;Tyree, Z;Folch, A
通讯作者：
Folch, A
影响因子：
7.7
作者：
Kellogg, Ryan A.;Tian, Chengzhe;Tay, Savas
通讯作者：
Tay, Savas
影响因子：
6.1
作者：
Jensen EC;Stockton AM;Chiesl TN;Kim J;Bera A;Mathies RA
通讯作者：
Mathies RA