Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS
Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS
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DOI：
10.1021/ja057720w
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发表时间：
2006-03-01
影响因子：
15
通讯作者：
Ismagilov, RF
中科院分区：
文献类型：
--
作者：
Hatakeyama, T;Chen, DL;Ismagilov, RF
本文介绍了一种在亚微克尺度上筛选和优化有机反应条件的微流控系统。该系统使用离散液滴（塞）作为微反应器，通过氟化载液的连续相分离和输送。在此之前，我们演示了使用微制造的PDMS plug-based微流体系统在水溶液中进行光学检测的分析和结晶实验。在这里，我们开发了一种不需要微流体装置微加工的方法，适用于有机溶剂中的合成反应，并使用MALDI-MS检测。作为示范，测试了选择性脱乙酰化的条件，并确定了单、双、三脱乙酰化的最佳条件。通过放大反应和分离这些潜在的神经毒性产物，验证了这些条件。单脱乙酰和双脱乙酰产物是脱乙酰反应中不稳定的中间产物，是首次分离得到的产物。该系统能够无损失地处理含有几微克化合物的亚微升体积。它可以用于研究或优化宝贵底物的反应（例如，长合成序列的产物和只能少量分离的天然产物）。
This paper describes a microfluidic system to screen and optimize organic reaction conditions on a submicrogram scale. The system uses discrete droplets (plugs) as microreactors separated and transported by a continuous phase of a fluorinated carrier fluid. Previously, we demonstrated the use of a microfabricated PDMS plug-based microfluidic system to perform assays and crystallization experiments in aqueous solutions with optical detection. Here, we developed an approach that does not require microfabrication of microfluidic devices, is applicable to synthetic reactions in organic solvents, and uses detection by MALDI-MS. As a demonstration, conditions for selective deacetylation of ouabain hexaacetate were tested, and the optimum conditions for mono-, bis-, or trisdeacetylation have been identified. These conditions were validated by scale-up reactions and isolating these potentially neurotoxic products. Mono- and bisdeacetylated products are unstable intermediates in the deacetylation and were isolated for the first time. This system enables no-loss handling of submicroliter volumes containing a few micrograms of a compound of interest. It could become valuable for investigating or optimizing reactions of precious substrates (e.g., products of long synthetic sequences and natural products that can be isolated only in small quantities).