研究动态
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用于癌症球体药物筛选的简单液滴微流体平台。

Simple droplet microfluidics platform for drug screening on cancer spheroids.

发表日期:2023 Nov 09
作者: Caroline Parent, Kiran Raj Melayil, Ya Zhou, Vivian Aubert, Didier Surdez, Olivier Delattre, Claire Wilhelm, Jean-Louis Viovy
来源: LAB ON A CHIP

摘要:

3D 体外生物系统正在逐步取代 2D 系统,以提高细胞研究的生理相关性。基于微流体的方法可以成为此类仿生系统的强大工具,但通常需要高端复杂且昂贵的工艺和设备进行微加工。在此,提出了一种药物筛选平台,最大限度地减少技术细节和制造步骤。它提供了在管中液滴中生成球体的另一种方法。然后,液滴微流体在可编程时间引发多个液滴合并事件,将球体依次提交化疗和细胞毒性筛选试剂。在对液滴内的肿瘤发生进行全面研究后,该系统通过癌细胞系以及来自患者异种移植物 (PDX) 的细胞的化疗药物筛选 (IC50) 进行验证。与微量滴定板方法相比,我们的系统将初始细胞数量减少了多达 10 倍,并为原发性肿瘤药物筛选方法开辟了新途径。
3D in vitro biological systems are progressively replacing 2D systems to increase the physiological relevance of cellular studies. Microfluidics-based approaches can be powerful tools towards such biomimetic systems, but often require high-end complicated and expensive processes and equipment for microfabrication. Herein, a drug screening platform is proposed, minimizing technicality and manufacturing steps. It provides an alternate way of spheroid generation in droplets in tubes. Droplet microfluidics then elicit multiple droplets merging events at programmable times, to submit sequentially the spheroids to chemotherapy and to reagents for cytotoxicity screening. After a comprehensive study of tumorogenesis within the droplets, the system is validated for drug screening (IC50) with chemotherapies in cancer cell lines as well as cells from a patient-derived-xenografts (PDX). As compared to microtiter plates methods, our system reduces the initial number of cells up to 10 times and opens new avenues towards primary tumors drug screening approaches.