FLOWSTREAM: a technology that integrates continuous-flow micropurification with continuous-flow microsynthesis to streamline small-scale chemical manufacturing (SSCM)

小型化学制造(SSCM)用于药品、研究试剂、纳米材料等的生产。目前，SSCM集间歇合成和间歇提纯于一体。批处理过程的“走走停停”的性质阻碍了它们的简化：它们很难控制和自动化。对可促进简化SSCM的连续合成/提纯/分析技术的需求尚未得到满足。虽然最近在毛细管微反应器中进行的连续流动微合成取得了重大进展，但还没有与之相匹配的微纯化和分析技术。在制药行业对简化SSCM的兴趣的推动下，Krylov和Yudin与AB Sciex和Alphora Research合作开发了一个FLOWSTREAM平台，该平台集成了连续合成、纯化、在线分析和自动化过程控制。我们的提纯取决于这样一个事实，即所有分子都具有电荷、大小和与其他分子结合的能力的独特组合。这些功能将用于在电场中实现产品分离。在我们提出的方法中，毛细管微反应器的出口将被插入到一个薄而宽的分离室中，在该分离室中将保持稳定的均匀的溶剂流动，以提供分离的介质。该腔体将包含电极，以产生与水流成一定角度的均匀电场。反应物将被连续地送入微反应器，当流体通过它时，反应将继续进行。产品的混合物将被不断地转移到腔室中，在那里它们将被连续分离成单独的化合物流。产品流将通过光谱分析和/或质谱仪进行分析，以促进合成和提纯的自动化控制。最后，我们的产品将从腔体的远端通过并行输出连续输出，并收集到单独的管子中。FLOWSTREAM承诺成为简化SSCM的第一个强大的平台。AB Science ex和Alphora Research预计FLOWSTREAM将带来直接的经济收益。此外，这项技术将在制药行业找到多种用途。

Small-scale chemical manufacturing (SSCM) is used for the production of pharmaceuticals, research reagents, nanomaterials, etc. SSCM currently integrates batch synthesis and batch purification. The "stop-and-go" nature of batch processes prevents their streamlining: they are difficult to control and automate. There is an unmet need for a continuous synthesis/purification/analysis technology that could facilitate streamlined SSCM. While significant progress has been recently made in continuous-flow microsynthesis carried out in capillary microreactors, there are no matching micropurification and analysis techniques. Motivated by the interest in streamlined SSCM in the pharmaceutical industry, Krylov and Yudin teamed up with AB Sciex and Alphora Research to develop a FLOWSTREAM platform that integrates continuous synthesis, purification, on-line analysis, and automated process control. Our purification hinges on the fact that all molecules possess a unique combination of an electrical charge, size, and ability to bind other molecules. These features will be used to enable product separation in an electric field. In our proposed approach, the exit of the capillary microreactor will be inserted into a thin but wide separation chamber in which a steady-state uniform flow of solvent will be maintained to provide the media for separation. The chamber will contain electrodes to create a uniform electric field at an angle to the flow. The reactants will be fed continuously into the microreactor and the reaction will proceed while the flow moves through it. The mixture of products will be continuously transferred into the chamber, where they will undergo continuous separation into streams of individual compounds. The product streams will be analyzed by optical spectroscopy and/or mass spectrometry to facilitate automated control of both synthesis and purification. Finally, our products will exit continuously through parallel outputs from a distal end of the chamber and collected into individual tubes. FLOWSTREAM promises to become the first robust platform for streamlined SSCM. AB Sciex and Alphora Research expect direct economic gains from FLOWSTREAM. In addition, the technology will find multiple uses in the pharmaceutical industry.