The future is capsule chemistry

The future is capsule chemistry
01 April 2022 - Automation

Quick word on the future of automated organic synthesis as envisioned by Gao, Raghavan and Coley in a recent comment in Nature Communications (DOI). Thankfully open-access which relieves me of the job having to provide a summary. According to the authors the future is bright and just like with a coffee maker al you have to do is punch a few buttons and out comes your brew. Internally the automated synthesis machine would be machine trained for synthesis prediction, self-learning, equipped with the software to calculate reaction conditions for each step, contain a massive amount of containers holding the building blocks and reagents, the necessary pumps, connectors, robotic arms, conveyer belts, reactors, spectrometers and separating units. Out of the dispenser comes your ordered chemical compound, of course in a recyclable container and physical manifestation permitting, a smiley imprinted on the surface.

A machine that can produce any chemical compound, from a fixed amount of building blocks? Regardless of the number of steps at takes? The number of common reagents for organic synthesis is in the hundreds but include many very water and oxygen sensitive compounds. How do you handle butyllithium solutions? My estimate of the number of basic building blocks relevant to pharma is 50 thousand. Of course DNA synthesizers exist and polypeptide synthesizers exist and we also have combinatorial chemistry that can be automated but these are just machine parts.

Will not keep people from trying, in this blog we have already featured the robotic chemist (link), IBM RXN (link) and the chemputer (link). To the list can now be added several companies such as SynFini by RSI (link) , the SMOLE by Chemspeed (link) and Coley’s own Entos (link) . The Chemspeed solution is intriguing. In their machine, different sealed glass capsules containing the reagents are combined in a vessel that each burst at a specific pressure. Glass melting and sealing is incorporated in the process. Solves the too-difficult-to-handle chemical problem! Capsule chemistry is also at the core of company Synple (link) , based on the work done by Jeffrey Bode in 2021 (DOI).

However, today’s prize winner must be Eli Lilly with their Life Sciences Study. Their smart youtube video will convert any skeptic into a believer (link). This studio looks more like a car assembly line than a laboratory and again we can see the glass capsules whisking by. Laboratory automator Strateos, who helped building the plant, has it’s own R&D Cloud Automation Platform.

Back to the comment by Connor Coley and colleagues, a fully automated data-driven synthesis machine? An outrageous idea at first sight but then there were these capsules...