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

FLOWSTREAM：一种将连续流微纯化与连续流微合成相结合的技术，可简化小规模化学品制造 (SSCM)

• 批准号: 463455-2014
• 负责人: Krylov, Sergey
• 金额: $ 18.97万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=558423
• 关键词: FLOWSTREAM; technology; integrates; continuous; flow

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.

小规模化学品制造（SSCM）用于生产药物，研究试剂，纳米材料等。SSCM目前集成了批量合成和批量纯化。间歇过程的“走走停停”的性质阻碍了它们的流线化：它们难以控制和自动化。对于可以促进流线型SSCM的连续合成/纯化/分析技术存在未满足的需求。虽然最近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，但没有匹配的微纯化和分析技术。出于对制药行业简化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。我们的纯化取决于这样一个事实，即所有分子都具有独特的电荷，大小和结合其他分子的能力。这些特征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但宽的分离室中，在该分离室中，溶剂的稳态均匀流动将被保持以提供用于分离的介质。腔室将包含电极，以产生与流体成一定角度的均匀电场。反应物将被连续地送入微反应器中，反应将在流动通过微反应器的同时进行。产物的混合物将被连续地转移到反应室中，在那里它们将被连续地分离成单个化合物的流。将通过光谱法和/或质谱法分析产物流，以促进合成和纯化的自动控制。最后，我们的产品将通过平行输出从腔室的远端连续排出，并收集到单独的管中。FLOWSTREAM有望成为简化SSCM的第一个强大平台。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中找到多种用途。