A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors.
A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors.
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DOI：
10.1039/c3lc51077h
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发表时间：
2014-03-07
期刊：
影响因子：
6.1
通讯作者：
Yoon E
中科院分区：
文献类型：
--
作者：
Lou X;Kim G;Yoon HK;Lee YE;Kopelman R;Yoon E
我们提出了一种新的高通量微流控平台，使光动力治疗（PDT）药物的抗癌疗效的评价超过多个微环境因素。PDT是独特的复杂性，源于其对三个独立但必需的元素的依赖：药物（或也称为光敏剂），氧气和光。因此，获得PDT疗效的可靠评估是非常具有挑战性的，需要相当大的努力和时间来评估所有三个相互依赖的参数。在本文中，我们报告了一个高通量功效筛选平台，我们通过开发单独控制基本PDT元素（光敏剂浓度，氧气水平和光通量）的微流体组件，然后将它们集成到一个单一的三层设备中来实现。集成的微流控芯片由一系列小隔间组成，每个隔间对应于这三个变量的特定组合。这允许并行测试1，000多种不同的条件。癌细胞在装置内培养，暴露于不同的PDT条件下，然后使用活/死荧光染色监测其活力。整个筛选试验仅需1小时，并且使用定制软件分析并报告用于组合筛选的收集的PDT结果（细胞活力）作为传统的剂量-反应曲线或3D气泡图。作为概念验证，采用亚甲蓝作为光敏剂，并使用制造的芯片在总共324个PDT条件下成功评估了其对C6胶质瘤细胞的药物功效。该平台不仅可以促进新光敏剂的开发，还可以优化现有的PDT方案。
We present a novel high-throughput microfluidic platform that enables the evaluation of the anticancer efficacy of photodynamic therapy (PDT) drugs over multiple microenvironmental factors. PDT is uniquely complex, originating from its dependence on three separate but essential elements: drug (or also called photosensitizer), oxygen, and light. Thus, obtaining a reliable evaluation of PDT efficacy is highly challenging, requiring considerable effort and time to evaluate all three interdependent parameters. In this paper, we report a high-throughput efficacy screening platform that we implemented by developing microfluidic components that individually control basic PDT elements (photosensitizer concentrations, oxygen levels, and light fluence), and then integrating them into a single triple-layer device. The integrated microfluidic chip consists of an array of small compartment, each corresponding to a specific combination of these three variables. This allows for more than 1,000 different conditions being tested in parallel. Cancer cells are cultured within the device, exposed to different PDT conditions, and then monitored for their viability using live/dead fluorescence staining. The entire screening assay takes only 1 hour, and the collected PDT outcomes (cell viability) for combinatorial screening are analysed and reported as traditional dose-response curves or 3D bubble charts using a custom software. As a proof of concept, methylene blue is adopted as a photosensitizer and its drug efficacy on C6 glioma cells has been successfully evaluated for total 324 PDT conditions using the fabricated chip. This platform can facilitate not only the development of new photosensitizers but also the optimization of current PDT protocols.
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影响因子：
6.1
作者：
Adler M;Polinkovsky M;Gutierrez E;Groisman A
通讯作者：
Groisman A
DOI：
10.1016/j.bbrc.2008.02.066
发表时间：
2008-05-02
影响因子：
3.1
作者：
Tang, Wei;Xu, Hao;Kopelman, Raoul
通讯作者：
Kopelman, Raoul
影响因子：
6.2
作者：
Jedrych, Elzbieta;Pawlicka, Zuzanna;Brzozka, Zbigniew
通讯作者：
Brzozka, Zbigniew
DOI：
10.1007/978-1-61779-052-2_11
发表时间：
2011-01-01
期刊：
BIOMEDICAL NANOETECHNOLOGY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Lee, Yong-Eun Koo;Kopelman, Raoul
通讯作者：
Kopelman, Raoul
影响因子：
6.1
作者：
Polinkovsky, Mark;Gutierrez, Edgar;Groisman, Alex
通讯作者：
Groisman, Alex