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

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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.