Automation Chemist NIH/NCATS -ASPIRE, California, United States
Indigo Reactor is an advanced chemical synthesis platform capable of running in an automated environment with 8 independently controlled reactors, allowing conventional thermal control up to 150 °C with or without an upper cooled reflux zone or under complete cryo-controlled temperatures down to -40 °C, plus controllable magnetic stirring, vessel inerting via vacuum application and dry nitrogen backfill, and/or under applied nitrogen pressure application as high as 20 bar. Equipped with interchangeable adapters, it can either run 10 mL or 20 mL reaction vessels. These reaction vessels can be interchangeably used with Biotage (brand) microwave reactor instruments as well. This presentation will review the various functional capabilities of the Indigo reactor. It will cover the system testing and development that has been completed thus far. Through the testing, we get a better understanding of the thermal profile, and the ability to adjust and control the pressure inside the reaction. Equipped with an automated cleaning cycle, the reactor will wash the chemically resistant reactor seal with acetone and water after each reaction is finished to eliminate any possible cross-contamination in subsequent use. It is also possible to monitor the reaction progress under certain conditions by controlling the lidding mechanism while the reaction is underway. The system first will release the pressure and reduce the temperature to make it safe for the operator to take the sample for LC/MS or UPLC. After sampling, the reaction can be returned to a sealed state to complete the incubation cycle automatically. A key part of this project has been to conduct a series of tests through execution of a diverse set of chemical reactions to serve as a standardized set of benchmarks to characterize the functionality of the system but will also serve as a quantitative comparator as such system's functionality and capabilities evolve. Also demonstrated will be how to transfer different complex chemical reaction conditions into a recipe that will play an important role in automated chemistry synthesis, and how to use it for running parallel reactions, tracking the reaction progress, and reproducing chemistry reactions repeatedly. Since this development effort of the Indigo Reactor was initiated, both the hardware and software have seen significant upgrades guided by this development effort. The UI is now easier to use for a first-time user. With the hardware upgrade, the automation system has become more reliable and key components more durable. The web server also gives the chemist the option to log in to the system remotely. The Indigo Reactor can provide a practical option for chemistry labs looking to further automate their chemical synthesis with a more compact design, flexibility for different scale reactions, and useful integration options.