Open-Source Automated Platform for Microfluidic Synthesis and Purification in Flow Chemistry

In recent years, automated and integrated platforms in flow chemistry have been of particular interest, as they enable high experimental throughput and generate process data for further optimization studies. However, these platforms are often based on commercial, proprietary, and fully integrated systems, including sensors, actuators, and reactors that cannot be easily complemented by other process steps. Therefore, the demand for open-source lab automation in combination with 3D-printed lab ware and tailored flow reactors is becoming increasingly important. This work presents the development of an automated platform consisting mainly of open-source components for microfluidic synthesis and purification in flow chemistry using the transfer of manual discontinuous stepwise chemistry to automated continuous flow chemistry as an application. This includes DNA-encoded chemistry for synthesizing DNA-encoded screening libraries (DELs) to identify potential bioactive molecules based on a DNA barcode that does not participate in the chemical reaction. To fulfill the specific requirements of DNA-tagged substrates, helically coiled capillary flow reactors were constructed as photoreactors and coiled flow inverter (CFI) reactors. Single-phase liquid capillary flow limitations with DNA-tagged substrates were evaluated, and two-phase liquid-liquid capillary flow systems were successfully applied. This enables automated continuous flow photoredox and amide coupling reactions with DNA-tagged substrates for the first time. In addition to the flow reactor design, the purification process after reaction and prior to analysis was also transferred to automated flow chemistry with the same DNA recovery as in manual handling. Furthermore, 3D-printed sensor flow cells were applied to model reactions to control and measure process parameters. The developed automated and integrated platform demonstrates the feasibility of profiling and screening studies in continuous flow.