Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening
Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening
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DOI：
10.1038/s41467-019-10685-0
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发表时间：
2019-06-28
影响因子：
16.6
通讯作者：
Levkin, Pavel A.
中科院分区：
文献类型：
--
作者：
Benz, Maximilian;Molla, Mijanur R.;Levkin, Pavel A.
药物开发通常依赖于基于高通量细胞的大化合物文库筛选。然而，化学上缺乏小型化和并行化的方法，以及生物活性化合物的合成与生物筛选的严格分离和不相容性，使得这一过程成本高，效率低。在这里，我们展示了一个结合了基于溶液的化合物文库合成和高通量生物筛选（chemBIOS）的片上平台。chemBIOS平台兼容合成所需的有机溶剂和生物筛选所需的水溶液。我们使用chemBIOS平台执行75个平行的三组分反应来合成类脂化合物库，然后通过MALDI-MS进行表征，在芯片上形成脂质体，并在芯片上筛选细胞。从文库合成到细胞筛选的整个过程只需要3天时间和大约1 mL的总溶液，这证明了chemBIOS技术在提高效率和加速筛选和药物开发方面的潜力。
Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.