A Fully-Automated Robotic System For Intelligent Chemical Reaction Screening
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
Robotic systems are changing the way in which we manipulate, control and manufacture materials that are of central importance to society at large. Here, we will take advantage of a state of the art robotic system (Chemspeed Technologies ISYNTH, a Swiss-based technology), based at the University of York to transform the way that chemists (and potentially other scientists) develop new reactions, drawing on its high-throughput reaction screening capability. The ISYNTH robotic system, alongside other analytical instrumentation, will support studies in (a) reaction mechanisms, (b) reaction optimisation, (c) novel route and compound discovery. Reliably capturing reaction data, and its statistical analysis, will be important in ensuring that our project is successful. All data generated from the project will be accessible through a common data repository, providing a rich source of information for future scientists to examine. We will provide a highly-instrumented and data intensive system that will accelerate workflow, productivity, accuracy, and precision in reaction screening for the Chemistry and Chemical Engineering communities.
Planned Impact
Funding this programme of research will provide academic researchers (and their industrial collaborators) access to a leading robotic system platform manufactured by Chemspeed Technologies (ISYNTH), which is linked to essential analytical instrumentation (GC/GC-MS, LC/LC-MS, IR and ESI-MS). Not only is the equipment provided as part of this programme of research, but also the expertise of using the robotic system, built-up over 6 years in York, since Chemspeed Technologies (UK hub) moved to York, with £750 K investment in robotic equipment. Our efforts will allow other researchers to benefit from both the key equipment and expertise, with focussed training given in the use of the equipment to suit the chemistry being examined.
We expect that academic and industrial laboratories stand to benefit from well-trained researchers in reaction optmisation, qualitative and quantitiative skills in mechanistic chemistry aligned with reaction developments (highlighted in a recent article by Hodges, Whitten and Ashworth as a key skills gap for industry moving forwards; Chemistry World 'Opinion Article' 2017, Nov. 9th).
Valuable (raw) open data will be made available to the scientific community on each reaction system optimised through use of the ISYNTH robotic system, which can be analysed by other groups (both academic and industrial) in the future. An example, would be optimisation of a key Suzuki-Miyaura cross-coupling reaction, the general outcome of which could lead others to know of the 'best optimised conditions' to molecules with structural similarity, molecular connectivity and/or functional group sensitivity.
A large volume of different reaction chemistries will potentially allow refinement of the ISYNTH robotic system, in addition to the inclusion of future data analysis tools. Creation of the latter in York, with collaborators, will be made freely available to the community where possible.
In the longer-term, we envisage that engagement with the ISYNTH robotic system in York, working synergistically alongside other recent EPSRC investments (ROAR at Imperial College and ASCL at Bristol) will lead to the broader adoption of automated approaches to chemical synthesis in the future.
We expect that academic and industrial laboratories stand to benefit from well-trained researchers in reaction optmisation, qualitative and quantitiative skills in mechanistic chemistry aligned with reaction developments (highlighted in a recent article by Hodges, Whitten and Ashworth as a key skills gap for industry moving forwards; Chemistry World 'Opinion Article' 2017, Nov. 9th).
Valuable (raw) open data will be made available to the scientific community on each reaction system optimised through use of the ISYNTH robotic system, which can be analysed by other groups (both academic and industrial) in the future. An example, would be optimisation of a key Suzuki-Miyaura cross-coupling reaction, the general outcome of which could lead others to know of the 'best optimised conditions' to molecules with structural similarity, molecular connectivity and/or functional group sensitivity.
A large volume of different reaction chemistries will potentially allow refinement of the ISYNTH robotic system, in addition to the inclusion of future data analysis tools. Creation of the latter in York, with collaborators, will be made freely available to the community where possible.
In the longer-term, we envisage that engagement with the ISYNTH robotic system in York, working synergistically alongside other recent EPSRC investments (ROAR at Imperial College and ASCL at Bristol) will lead to the broader adoption of automated approaches to chemical synthesis in the future.
People |
ORCID iD |
| Ian Fairlamb (Principal Investigator) |
Publications
Clarke G
(2023)
Deciphering Complexity in Pd-Catalyzed Cross-Couplings
Clarke G
(2023)
Deciphering Complexity in Pd-Catalyzed Cross-Couplings
Firth JD
(2020)
A Need for Caution in the Preparation and Application of Synthetically Versatile Aryl Diazonium Tetrafluoroborate Salts.
in Organic letters
Firth JD
(2021)
Light- and Manganese-Initiated Borylation of Aryl Diazonium Salts: Mechanistic Insight on the Ultrafast Time-Scale Revealed by Time-Resolved Spectroscopic Analysis.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Horbaczewskyj CS
(2022)
Pd-Catalyzed Cross-Couplings: On the Importance of the Catalyst Quantity Descriptors, mol % and ppm.
in Organic process research & development
| Description | We have fully validated a Chemspeed ISYNTH robotic system for use in the high throughput screening of various types of reaction chemistries. This now enables us to generate datasets of reaction outcomes, which can be subsequently examined and assessed by rich data analysis methods, including different types of mathematical procedures. We were able to pursue collaborative projects with regional academic groups (eg Lancaster, Leeds, Newcastle and York) and industrial groups (eg Astra-Zeneca, GlaxoSmithKline and Johnson-Matthey). From this we were able to grow new projects with several academic and industrial partners; projects supported by the EPSRC UK Catalysis Hub, EPSRC (responsive mode and strategic equipment), Astra-Zeneca, GlaxoSmithKline and Royal Society. |
| Exploitation Route | We have been successful in securing follow-on funding in several areas, including EPSRC (UK Catalysis Hub Science 3 funding, Horizon funding, responsive mode and equipment) funding. This research involves collaboration with UK academics and industrialists from the UK and USA. Our robotic system is being used to support collaborative efforts with Johnson-Matthey through a Royal Society Industry Fellowship (for Prof. Ian Fairlamb). We believe that the outcomes from this project can aid the development of other automated chemistry facilities, e.g. specifically those running at the University of Bristol and Imperial College (ROAR). |
| Sectors | Chemicals,Education,Pharmaceuticals and Medical Biotechnology |
| Description | We have been involved with outreach (general public) activities, with big audiences (up to 4000 participants, such as YorNIGHT). We have used Lego Robotic EV3 systems to simulate how higher-end robotic systems can be used in Chemistry research, particularly reaction understanding and optimisation. This has been a huge success and we will continue to deliver these activities to the general public. In 2023, we have started to go back into Schools with our Lego robotic systems. This involves taking bespoke Lego robotic serial dilution equipment into Schools and conducting high throughput experiments with light. Pupils plot graphs showing how the concentrations of certain dye molecules affect light absorbance. We also discuss the chemistry of Lego, particularly relating to polymer chemistry and dye chemistry, including sustainable new polymer materials. In 2022-23, we have created a new project on Automated Laboratory Experiments (which we are calling ALBERT), which is an interdisciplinary project involving Computer Science, Electronic Engineering, Physics, Sociology, Environmental Science and Mathematics. This is looking at the creation of the next generation robotic systems for Chemistry experiments. There are several dimensions to the project, including health and safety and an examination of regulations around autonomous systems in Chemistry. The University of York, and several Departments, have backed the project with several new PhD projects over two cohorts, beginning in October 2023. |
| First Year Of Impact | 2019 |
| Sector | Chemicals,Education,Environment,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Promotion of Digital Chemistry |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| URL | https://www.rsc.org/new-perspectives/discovery/digital-futures/ |
| Description | Catalytic Synthesis of Pharmaceutical Amides in Water |
| Amount | £442,674 (GBP) |
| Funding ID | EP/T01430X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2020 |
| End | 09/2023 |
| Description | Fit for Process: Pd Catalyst Control in Problematic Csp3-Csp2 Suzuki-Miyaura Cross-Couplings |
| Amount | £29,628 (GBP) |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2021 |
| End | 06/2025 |
| Description | Harnessing the Combined Power of IR Spectroscopy and Mass Spectrometry: Development of a New Instrument for Process Analytical Technology |
| Amount | £582,157 (GBP) |
| Funding ID | EP/X010724/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 03/2026 |
| Description | High throughput 2D-IR analysis of biomolecules under physiological conditions |
| Amount | £1,006,129 (GBP) |
| Funding ID | EP/W021404/1 |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2022 |
| End | 02/2024 |
| Description | Industrial CASE Account - University of York 2021 |
| Amount | £711,084 (GBP) |
| Funding ID | EP/W522296/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 09/2026 |
| Description | Mapping out the catalyst activation, turnover and deactivation pathways for critically important fine chemical industry Pd precatalysts, Royal Society Industry Fellowship with Johnson-Matthey |
| Amount | £186,780 (GBP) |
| Funding ID | INF\R2\202122 |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2021 |
| End | 02/2025 |
| Description | Seeing the Light with Manganese - Unveiling Catalysis by an Earth Abundant Metal |
| Amount | £1,052,768 (GBP) |
| Funding ID | EP/W031914/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2022 |
| End | 05/2026 |
| Description | Stereospecific Csp3-Csp2 Cross-Coupling of Saturated Heterocyclic Boronates: A Transformative Disconnection for Drug Discovery |
| Amount | £202,415 (GBP) |
| Funding ID | EP/V048139/1 |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 05/2021 |
| End | 04/2023 |
| Description | UK Catalysis Hub funding 'Science' 3: Sustaining pharma-relevant metal -catalysed cross-couplings: interrogation of metal catalysts using automated optimisation routines, rich data analytics and mechanistic studies |
| Amount | £225,454 (GBP) |
| Funding ID | EP/R027129/1 |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 05/2021 |
| End | 04/2023 |
| Description | Uncovering competing catalytic cycles in cross-couplings through rich data analysis of reaction outcomes gained by high-throughput experimental screening |
| Amount | £120,862 (GBP) |
| Funding ID | EP/X525042/1 |
| Organisation | University of York |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2022 |
| End | 09/2027 |
| Description | Johnson-Matthey - High Throughput Experiments, Screening and Mechanistic Insight into New Palladium Precatalysts |
| Organisation | Johnson Matthey |
| Department | Johnson Matthey Technology Centre |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | This is a new project that started in January 2023, as a follow on from the research grant award, supporting a post-doctoral research assistant (PDRA). The PDRA is working in catalysis, mechanistic studies and high throughput reaction screening and data analysis. The work is protected by a contractual agreement with the company. We will report on the outcomes from this new project in due course. This project benefits from the expertise of our robotic research technician, Dr. Chris Horbaczewskyj, who was originally appointed through the grant being reported upon here. The PI, Prof Ian Fairlamb, is leading on the project design and execution in York, which links to a Royal Society Industry Fellowship with Johnson-Matthey. |
| Collaborator Contribution | The company are providing expertise on in house palladium catalysts. The work is protected by a contractual agreement with the company. |
| Impact | No outputs to report at this time (March 2023). |
| Start Year | 2023 |
| Description | Reaction Screening in Heck alkenylation chemistry |
| Organisation | Lancaster University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are currently collaborating with Professor Joseph Sweeney (Department of Chemistry, University of Lancaster). Prof. Sweeney was one of the named collaborators on the funded grant, who provided us with an interesting Heck alkenylation reaction which required further mechanistic examination, with a view to expanding the scope of a promising synthetic methodology published by his team (in Journal of Catalysis; http://www.research.lancs.ac.uk/portal/en/publications/-(4d36ed61-dd87-4c61-8d37-47aac69ba0c3).html). We are currently screening a wide variety of reaction variables to understand more holistically the complexity of the reaction systems, including products of interest and side-products. Rich data analysis and statistical methods are being employed to provide a more generalised understanding of a promising Heck alkenylation reaction. |
| Collaborator Contribution | Our partners at Lancaster University have engaged in several discussions with us about the Heck alkenylation chemistry being investigated. They have also supplied us with chemical materials, so that the reactions of interest could be screened efficiently, particularly in a timely manner. |
| Impact | No outputs have yet resulted. We plan for any promising results to reported by the end of the next reporting period (March 2021). |
| Start Year | 2019 |
| Description | Robotic synthesis of 15N and 2H-isolopically labelled nitro compounds for biochemical studies |
| Organisation | University of York |
| Department | Department of Biology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We prepared a series of isotopically labelled nitrated compounds for biochemical studies. |
| Collaborator Contribution | Our collaborators provided guidance on the types of compounds that were needed for the biochemical studies. |
| Impact | No direct outputs or outcomes (yet). |
| Start Year | 2017 |
| Description | Synthesis of potential inhibitors of the SARS-CoV-2 main protease (MPro) using an automated robotic system |
| Organisation | Newcastle University |
| Department | School of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The project took advantage of a promising breakthrough in the identification of hit drug compounds that inhibit SARS-CoV-2 main protease (MPro), which is essential for viral replication, and a potential therapeutic target for COVID-19 (work conducted at the University of Newcastle. We worked on the chemical synthesis of new potential inhibitor compounds in collaboration with the Newcastle research team lead by Professor Mike Waring. |
| Collaborator Contribution | We were provided with background information about the SARS-CoV-2 main protease target, and guidance on the types of chemical structures that could be targeted using our synthetic approaches and methodologies. |
| Impact | The collaboration involves medicinal chemistry, catalysis and synthetic chemistry. There are no formal outputs or outcomes to report at this stage. |
| Start Year | 2020 |
| Description | Chemistry at Work coordinated by NYBEP: Lego Robotics in Chemistry |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Event report: Four classes of students (83 students, 49 males and 34 females, in total) used Lego robotic serial dillution equipment to prepare 6 different concentrations of a green dye solution. UV data was collected on these solutions. Their data was compared with manually-prepared solutions. The idea for the event was to showcase how Lego EV3 robotic systems can be used in experiments conducted in a typical chemical synthesis laboratory. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.york.ac.uk/research/graduate-school/updates/2019/discovery-zone/ |
| Description | Discovery Zone at the York Festival of Ideas 2019: Lego Robotics in Chemistry |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Event abstract: We showcased the use of Lego Mindstorms EV3 robotics with Chemistry experiments. There were demonstrations and the opportunity to get involved with experiments using dyes and also the chemical reactions of purple cabbage juice. The event saw a footfall of ca. 6000 people, over the two day event. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.york.ac.uk/research/graduate-school/updates/2019/discovery-zone/ |
| Description | School Visit (York) - four indivudual sessions linking light, chemistry, analytical chemistry and Lego robotics |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | We engaged with four groups of 15 pupils each (delivering four 45 minute teaching sessions). The activity sparked many interesting questions and discussion, which was part of the British Science Week 2023 that took place in Schools across the UK. Copmanthorpe Primary School mentioned that the pupils very much enjoyed the activity. We also received positive feedback separately from some parents. The activity involved understanding how we use light in our chemistry experiments, linked to high throughput experiments and using robotic systems (demonstrated with programmable Lego robotic systems, EV3 LEGO). We have built and programmed the Lego robotic systems, which are taken into the School for this activity. The activity involved the PI, Prof Ian Fairlamb, and two other researchers, Dr. Chris Horbaczewskyj and Dr. Abigail Frith (visiting PDRA from University of Cork, Ireland). |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://twitter.com/Ian_Fairlamb/status/1635730078339407872 |
| Description | YorNight 2020: Lego Mindstorm robotics for chemistry |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | The event abstract: Find out about some of the inventive Lego Mindstorm devices that have been developed, including automated syringe pumps, solution dispensers, sample collectors and reaction stations. Using Lego Mindstorm EV3 systems, researchers from the University of York's Department of Chemistry demonstrate how you can conduct chemistry experiments in a safe, controlled and reliable way. This was an incredibly successful event. There were nearly 4000 people from the general public in attendance. For over 4 hours we had ca. 50 people interested in the Lego Robotics for Chemistry demonstrations. Children between the age of 6 to 9 arguably benefited the most, but also some very interested adults too. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.york.ac.uk/news-and-events/events/yornight/2020/activities/robotics-chemistry/ |
| Description | YorRobots Exhibition: Molecules made by robots |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | The YorRobots Exhibition was held in the Department of Computer Science at the University of York on Friday 28 February 2020. Academics from Chemistry, Computer Science, Electronic Engineering, Environment & Geography, Philosophy, Psychology, and Sociology within the University of York shared their current research and challenges in the area of robotics, along with industry representatives from D-RisQ, Dyson, RACE, Rolls-Royce, Shadow Robots, and Thales. The event abstract (Prof. Fairlamb presenting): Scientists are dependent on lead chemical compounds with precise 'drugable' properties. Chemical synthesis of a new drug target often requires many reaction steps. A key problem is in optimising each chemical reaction, which is a labour-intensive and time-consuming process. It is common to dedicate six months to one reaction step, creating a drug development bottleneck, arising from the way that chemical reactions are optimised. This inefficient work pattern operates in chemical synthesis laboratories the world over. Using a combination of robotics, statistical analysis and machine learning it is possible to greatly improve the chemical synthesis of drug targets. I will introduce new approaches used in our research programmes in my talk. Improving reaction efficiency, sustainability and safety are key drivers for the use of robotic systems in chemical synthesis. There were a variety of questions from academics and industrial participants. Many of the demonstrations and posters were presented by those who have either had funding from YorRobots (three Computer Science students who are entering the Pi Wars competition in Cambridge in March 2020), or attended one of the YorRobots Sandpits in 2019. The event was well attended, with energy and enthusiasm from all participants. Presentation slides are available below. This activity was funded by The University of York's EPSRC Impact Acceleration Account, the Department of Computer Science, and the RoboStar group. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.york.ac.uk/yorrobots/news-events/yorrobots-events/2020/exhibition-2020/ |