3DSynth: Design and fabrication of cartridges for digital chemical synthesis

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


This project proposes developing a new approach to chemical synthesis by constructing and demonstrating a software-based toolkit aimed specifically at synthetic chemists, allowing them to easily digitise and democratise their synthetic procedures in the form of code used to create multistage reactor systems and proto-type them using 3D printing.

We aim to explore and validate this concept for a range of targets, from organic to inorganic and nano-scale materials. In preliminary studies published in Science (Science 2018, 359, 314-319) earlier this year we have shown that the digitisation of chemical synthesis is possible. In this grant we propose to expand this methodology that is currently allowing individual reaction steps to be be embodied in parametrically defined reactor 'modules'. The modules are then combined into extended, multi-step sequences, enabling us to turn the complex processes of batch chemical synthesis into small scale, on demand, synthesis cartridges. These cartridges can then be accompanied by a validated set of operating instructions which can be carried out either manually or via an automated interface, minimising the time and skill required to effect the synthesis whilst simultaneously maximising the reproducibility.

Using 3D printed reactionware, developed by us in a £10 K 'creativity at home EPSRC project', in conjunction with robotic interfaces for liquid handling, this project will explore how to chemicals can be made in low-resource / limited skill environment after digitisation, aiming at lower costs, greater reproducibility, and vastly expanding the variety of materials available to the end user. Further, we aim that this toolkit can be used to enable mechanistic and material discovery studies by allowing the manipulation of the physical structure of the reactors to constrain the synthetic and reaction parameters vastly decreasing the timescales for customisation and further development.

Planned Impact

The digitization of chemical synthesis promises to increase both efficiency and reproducibility of chemical synthesis by translating syntheses into digital blueprints in which the entire synthesis, including reactor architectures and process operations are defined and validated. This proposal describes a new concept in the digitization of synthesis by developing the concept of 3D printed reactionware previously developed with EPSRC support (Creativity@home). We will explore the methodology of design, fabrication and use of 3D printed reactionware as a modular system for effecting complete end-to-end syntheses of high value target molecules. The UK is currently a major global center of the pharmaceutical industry with major companies either based in the UK (GSK, AstraZeneca, etc.) or with a major presence in the UK (Pfizer, Novartis, etc.). In order to maintain this position, the UK will need to demonstrate that it is at the forefront of developing new, high value approaches to the core competencies of these industries. This includes working at the forefront of innovative automated approaches to traditional fine chemical synthesis and original methods to streamline and cut costs in API manufacture. In 2016 the government announced the industrial strategy challenge fund and in 2017 the business secretary announced the six key areas. The research funded by this grant has the potential to lead to new patterns of API manufacture and distribution, opening up new markets. We will lead developments in an area where the UK is a potential world leader; and will deliver real applications to cement this, making the UK the port of call for potential investment in basic R&D. As with our previous grant, we will engage with investors like the IP Group and look to establish further new companies.

As part of this grant we will collaborate with large pharmaceutical companies like GSK who are very interested in developing a stand-alone, modular system for the synthesis of APIs which are currently out-of-production, but which maintain a residual commercial value if they can be manufactured with significant capital investment into either the development or re-purposing of industrial scale chemical manufacturing plants. Similar collaborations will be sought with fine chemical manufacturing companies and retailers and manufacturers such as Sigma Millipore, where the focus will be on the production of high-value, small scale production of products. These systems are also of interest, once developed, the synthetic procedure for the small scale manufacture of target fine chemicals need only be stored digitally as the digital model of the reactionware cartridge developed for a particular synthesis. This drastically simplifies the materials and systems.
The society benefits will be realised within a 10-20 year time-frame through the activities described, and we will engage the public through our schools and public engagement work. Funding has been requested to train PDRAs and investigators to inspire others and to show how science, engineering and IT can affect people's lives. The various societies i.e. Royal Society of Chemistry, Royal Academy of Engineering, and Institute of Physics, will be engaged to ensure widespread use of the materials. The investigators and the entire research team has been active in engagement through the media, TED talks, TV documentaries, articles in newspapers, online videos, website news. We will continue to explore new ways to interact with wider society and help explain the opportunities and risks associated with the project.
Description In the course of this award we have developed a software package for the digital design of 3D-printable rection cartridges which is based on the relation between relevant reaction parameters such as reaction volume, scale, solvent identity, temperature, and chemical process. This software is designed specifically for the synthetic chemist to enable the design of these cartridges without specialist experience in 3D CAD modelling.

Reaction cartridges designed by this software have been used to explore the synthesis of various chemical products using the 3D printed cartridges and study the relations between traditional approaches to synthetic chemistry experimental design and the more digitised approach originally proposed in this project.
Exploitation Route The use of 3D printed Reactionware can provide a convenient route to distributed manufacture of fine chemical products which exhibit short shelf-lives or are subject to potential supply chain disruption. Other potential uses for this research is in widening the accessibility of complex chemical products, and libraries of related chemical analogues to researchers withour the necessary synthetic chemical skills, facilities or resources, by providing reactionware synthesis 'kits'.
Sectors Chemicals

Description RSC Digital Futures 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact In September 2019 the Royal Society of Chemistry set out to gain a more in-depth understanding of the long-term promise of and concerns about the use of data and digital technologies for scientific discovery by inviting 14 experts from different scientific fields and sectors to its first Strategic Advisory Forum. This forum brought together leaders from the natural sciences and digital fields to set out a vision for how digital technologies - from computational chemistry and multiscale modelling to machine learning and robotics - will enable and accelerate scientific discovery and solutions to global challenges.

I provided advice and insight on the topic to this forum.
Year(s) Of Engagement Activity 2019
URL https://www.rsc.org/new-perspectives/discovery/digital-futures/