Advanced Mass Spectrometry Kit for Controlling Chemical Robots and Exploring Complex Chemical Systems

Lead Research Organisation: University of Glasgow
Department Name: School of Chemistry

Abstract

We will use this kit to help us establish a world leading and unique capability for exploring real-time feedback control driven by very high resolution MS in the area of chemical cybernetics / chemical robotics. The emerging field of Chemical Cybernetics aims to build upon existing expertise in chemical robotics, complex networks, supramolecular self-assembly and automation, combined with newly available state-of-the-art chromatographic and mass spectrometric techniques to drive feedback control and artificial intelligence in complex chemical systems. The equipment requested in this proposal will allow the construction of a truly unique platform where advanced spectrometric techniques, usually only seen in metabolomics, are applied to chemical problems of low-abundance analyte identification and differentiation of complex mixtures over a broad spectrum of research, from optimisation of automated synthesis for a 'dial-a-molecule' devices to sequence specification in origins of life research to manufacturing and chemical discovery.

Planned Impact

We aim to enable our advanced mass spec kit for chemical robotic control to be adopted not only by other researchers and academics, but to transform the current world of chemistry by embracing digital technology and our developments in configurable chemical-robotic platforms for the discovery, optimisation, scale-up and control of chemistry. The outputs which will be made possible by the new platform will create also impacts in advanced proteomics, biopharma and metabolomics applications, including quantitation using isobaric tags, low level PTM analysis, data independent acquisition (DIA), and top down proteomics.

The Cronin group is also engaged with a number of industrial collaborators through our EPSRC programme grant and we will use these collaborations to help explore the use of the new kit and the robotic interface to problems set by our industrial collaborators.

Publications

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Doran D (2017) A recursive microfluidic platform to explore the emergence of chemical evolution. in Beilstein journal of organic chemistry

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Marshall SM (2017) A probabilistic framework for identifying biosignatures using Pathway Complexity. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

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Surman AJ (2019) Environmental control programs the emergence of distinct functional ensembles from unconstrained chemical reactions. in Proceedings of the National Academy of Sciences of the United States of America

 
Description We have shown it is possible to use mass spec to explore and rank the complexity or information content of small molecules and use this to build a calibration curve for our PATH life detection system (PATH = pathway assembly technosignature heuristic]. Our findings have shown a key difference in the complexity of molecules which are known to arise from living systems and those which are formed from non-living processes. This will impact Origins of Life research and the search for extraterrestrial life.

We have also now expanded this methodology to utilise NMR as a measure of molecular complexity.
Exploitation Route NASA are using our findings to build new types of space probe for life detection. Breakthrough Prize are designing a space mission to Titan and possibly Europa for life detection using mass spec.
Sectors Aerospace, Defence and Marine,Chemicals,Digital/Communication/Information Technologies (including Software),Education,Manufacturing, including Industrial Biotechology,Culture, Heritage, Museums and Collections

 
Description We are using the kit to help develop a new life detection system to be used in conjunction with NASA and BreakthroughPrize to plan a space mission to search for life in the outer solar system.
First Year Of Impact 2017
Sector Aerospace, Defence and Marine,Chemicals,Digital/Communication/Information Technologies (including Software),Education,Healthcare
Impact Types Cultural,Societal

 
Title The Chemputer 
Description A universal modular robotic synthesiser which can undertake ca. 60% of the batch reactions in the chemical literature. This also includes the XDL language and ontology for translating chemical procedures into universally readable actionable code which can potentially be implemented in any robotic system. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact 19 News outlets have reported on this discovery. Plans are underway to setup a spinout and patent aspects of the discovery. https://www.altmetric.com/details/45198487/news https://www.altmetric.com/details/51967737/news 
URL http://www.chem.gla.ac.uk/cronin/chemify/
 
Description Integrated Discovery Chemputer Toward Addiction Free Opiates 
Organisation Arizona State University
Department School of Earth and Space Exploration
Country United States 
Sector Academic/University 
PI Contribution The Cronin group are experts in chemical robotics, database development, ELNs, machine learning for chemistry, theory, robotics, in particular the development of closed-loop engines capable of building databases, populating chemistry notebooks, programming chemistry robots, and developing real-time closed loop assays for assessing the real time spectroscopy, structure, and molecular diversity of chemical reactions. We have previously shown that the synthesis of a wide range of organic molecules is possible using our automated Chemputer reactor and that in-line analysis can provide real time data for optimisation algorithms. The main aim of this challenge is to develop and integrate components from multiple platforms into a unified chemical synthesis platform. To do this we have developed Chemical Description Language (XDL) to formalise the way chemists execute and report chemical protocols and synthesis procedures. This language allows the modular use of a wide range of hardware to carry out bespoke chemical synthesis.
Collaborator Contribution The team at ASU are experts in theory developing the networks for retrosynthetic analysis, exploring chemical space, and developing information measures to target novel opiate targets in chemical space using a network theory approach. We will use the Chemputer system and XDL language to search for novel molecules with target properties. To quantify the similarity of the search results to the intended goal we require a fitness function. This function is a mathematical description of the distance from the desired properties. The fitness function could, for example, compare two absorption spectra. We will design sensors so that the directly update the fitness function. This means that new discoverable molecules will be used to update the database and that potential new virtual libraries of accessible molecules will be fed into the database in real time.
Impact Proc. Natl. Acad. Sci. USA, 2019, 116, 5387-5392; Astrobiology, 2018, 18, 779-824
Start Year 2018