Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis.
Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis.
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DOI：
10.1021/ac200267t
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发表时间：
2011-06-01
影响因子：
7.4
通讯作者：
Khademhosseini, Ali
中科院分区：
文献类型：
--
作者：
Kwon, Cheong Hoon;Wheeldon, Ian;Kachouie, Nezamoddin N.;Lee, Seung Hwan;Bae, Hojae;Sant, Shilpa;Fukuda, Junji;Kang, Jeong Won;Khademhosseini, Ali
传统的高通量筛选（HTS）是在需要大量机器人液体和板处理设备的集中设施中进行的。这种HTS模式是限制性的，因为许多研究人员无法使用这些设施。我们设计了一个简单的微阵列平台，可以在工作台上进行基于细胞的筛选。该设备以标准显微镜载玻片格式创建了2100个基于单个细胞的测定的微阵列。载有化学物质的水凝胶的微阵列解决了载有细胞的微孔的匹配阵列，从而创建了密封的微尺度细胞培养物的微阵列，每个微阵列具有独特的条件。我们通过筛选MCF-7乳腺癌细胞中细胞凋亡和坏死的程度来证明该设备的实用性，以响应暴露于一个小的化合物库。从一组筛选中，我们产生了优先诱导MCF-7细胞凋亡而非坏死的化学物质的等级顺序。与星形孢菌素、乙醇和过氧化氢相比，多柔比星处理诱导了高水平的细胞凋亡，而100 μM乙醇处理诱导了极轻微的细胞凋亡和高水平的坏死。我们预计该设备将广泛应用于各种研究和发现应用，因为它易于使用，可扩展，并且可以用最少的外围设备制造和操作。
Traditional high throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the bench top. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, while treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable and can be fabricated and operated with minimal peripheral equipment.
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