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

小规模化学制造（SSCM）用于生产药品、研究试剂、纳米材料等。SSCM目前集成了批量合成和批量纯化。批处理的“走走停停”特性阻碍了它们的流线型化：它们难以控制和自动化。对于一种能够促进流线型SSCM的连续合成/纯化/分析技术的需求尚未得到满足。虽然近年来在毛细管微反应器中进行的连续流微合成取得了重大进展，但没有相应的微净化和分析技术。由于制药行业对简化SSCM的兴趣，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。我们的净化取决于这样一个事实，即所有分子都具有电荷、大小和结合其他分子的能力的独特组合。这些特性将用于使产品在电场中分离。在我们提出的方法中，毛细管微反应器的出口将插入一个薄而宽的分离室，在这个分离室中，溶剂将保持稳定的均匀流动，为分离提供介质。该腔室将包含电极，以形成与气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，当气流通过微反应器时，反应将继续进行。产品的混合物将被连续地转移到室中，在那里它们将被连续地分离成单个化合物的流。产品流将通过光学光谱和/或质谱分析，以促进合成和纯化的自动化控制。最后，我们的产品将通过从腔室的远端并联输出连续出口，并收集到单独的管中。FLOWSTREAM有望成为第一个强大的流线型SSCM平台。AB Sciex和Alphora Research预计FLOWSTREAM将带来直接的经济收益。此外，该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.