European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, CB10 1SD, Cambridge, United Kingdom.
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117, Heidelberg, Germany.
Nat Commun. 2018 Jun 22;9(1):2434. doi: 10.1038/s41467-018-04919-w.
Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
在实体瘤患者活检上进行药物筛选具有巨大的潜力，但由于可供使用的材料数量有限，这具有挑战性。为了解决这个问题，我们在这里提出了一种基于插件的微流控平台，用于药物组合的功能筛选。集成的盲文阀允许按需改变插件组成，并能够为每个活检收集超过 1200 个数据点（56 种不同条件，每种条件至少有 20 个重复）。在为两种遗传上不同的胰腺癌细胞系和异种移植小鼠模型推导出并验证了有效和特异的药物组合后，我们还无需进行离体培养步骤即可对来自人体实体瘤的活细胞进行筛选，并获得高度特异的敏感性谱。整个工作流程可以在 48 小时内完成，每个患者的检测成本低于 150 美元。我们相信这可以为快速确定最佳的个性化癌症治疗方法铺平道路。
