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An autonomous portable platform for universal chemical synthesis

Nature Chemistry volume 14, pages 1311–1318 (2022)Cite this article

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Abstract

Robotic systems for synthetic chemistry are becoming more common, but they are expensive, fixed to a narrow set of reactions, and must be used within a complex laboratory environment. A portable system that could synthesize known molecules anywhere, on demand, and in a fully automated way, could revolutionize access to important molecules. Here we present a portable suitcase-sized chemical synthesis platform containing all the modules required for synthesis and purification. The system uses a chemical programming language coupled to a digital reactor generator to produce reactors and executable protocols based on text-based literature syntheses. Simultaneously, the platform generates a reaction pressure fingerprint, used to monitor processes within the reactors and remotely perform a protocol quality control. We demonstrate the system by synthesizing five small organic molecules, four oligopeptides and four oligonucleotides, in good yields and purities, with a total of 24,936 base steps executed over 329 h of platform runtime.

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Fig. 1: Schematic representation of any synthesis carried out in the compact/portable platform.
Fig. 2: Summary of the implemented reaction and platform operations.
Fig. 3: Physical implementation of the portable platform.
Fig. 4: Synthetic schemes of five different APIs prepared using the platform.
Fig. 5: Fingerprinting and validation of phenelzine sulfate synthesis using the pressure profile.
Fig. 6: Schematic representation of the oligopeptides and oligonucleotides synthesized in the platform.

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Data availability

The Supplementary Information includes full details to reproduce this work. This consists of full details to reproduce the electronic and mechanical construction of the platform. The XDL files (.xdl), along with the respective graph (.json) and 3D reactor design (.stl), and full analytical data are provided, including our pneumatic fingerprint for the reactions, at https://doi.org/10.5281/zenodo.5248762.

Code availability

Code is available from https://doi.org/10.5281/zenodo.5248762.

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Acknowledgements

We thank D. Caramelli for producing the Supplementary Video and S. Rohrbach and M. Siauciulis for helpful comments on the manuscript. We gratefully acknowledge financial support from the EPSRC (grants nos. EP/L023652/1, EP/R020914/1, EP/S030603/1, EP/R01308X/1, EP/S017046/1 and EP/S019472/1), the ERC (project no. 670467 SMART-POM), the EC (project no. 766975 MADONNA) and DARPA (projects nos. W911NF-18-2-0036, W911NF-17-1-0316 and HR001119S0003). The views, opinions and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the US Government.

Author information

Authors and Affiliations

  1. School of Chemistry, the University of Glasgow, University Avenue, Glasgow, UK

    J. Sebastián Manzano, Wenduan Hou, Sergey S. Zalesskiy, Przemyslaw Frei, Hsin Wang, Philip J. Kitson & Leroy Cronin

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  1. J. Sebastián Manzano
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  2. Wenduan Hou
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  3. Sergey S. Zalesskiy
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  4. Przemyslaw Frei
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  5. Hsin Wang
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  6. Philip J. Kitson
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  7. Leroy Cronin
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Contributions

L.C. invented the concept and devised the project and the digitization approach, with help from J.S.M., S.S.Z. and P.J.K. S.S.Z. developed the initial system design and built the first prototype together with J.S.M. W.H. carried out reactionware synthetic routes for the small organic molecules, and P.F. and H.W. helped with method development for the synthesis of oligopeptides and oligonucleotides. J.S.M. carried out all the automated synthesis and developed the necessary code for the platform. J.S.M. and P.J.K. wrote the paper, with help from L.C.

Corresponding author

Correspondence to Leroy Cronin.

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Competing interests

The work described here has been filed as a patent GB 2213747.5 filed by the University of Glasgow.

Peer review

Peer review information

Nature Chemistry thanks Melodie Christensen, Kerry Gilmore and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–44, Tables 1–15, building instructions, methods, results and discussions.

Supplementary Video 1

Animation of a typical literature to cartridge to synthesis process.

Supplementary Data 1

stl, .xdl, .json for all the syntheses executed in the portable platform.

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Manzano, J.S., Hou, W., Zalesskiy, S.S. et al. An autonomous portable platform for universal chemical synthesis. Nat. Chem. 14, 1311–1318 (2022). https://doi.org/10.1038/s41557-022-01016-w

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