A High Throughput Experimentation Platform for Next Generation Chemical Synthesis

Lead Research Organisation: University of Cambridge
Department Name: Chemistry


The overarching goal of this PhD is to create an integrated system that can reduce the timeframe needed for the 'small molecule design to biological assay' process to just 60 minutes. Central to the project will be a new automated high throughput synthesis platform that directly links the preparation of 'assay ready' small molecules to biological evaluation. The development of a streamlined system for the automated optimization of biological activity will require input from many different areas of science. Key aspects of this project will include (a) the evolution of an automation platform for multi-step chemical synthesis of 'assay ready' small molecules; (b) the design of a robotic system that links the synthesis platform directly to biological evaluation; (c) the creation of a feedback process to connect the acquired synthesis data optimization to enable machine-assisted secondary design; (d) the development of in-line work-up, analytical and purification methods that can accommodate high throughput experimentation; and (e) informatics systems to handle the vast amount of synthesis and biological data, upon which predictable synthesis models can be founded. Key deliverables include an integrated platform for automated high throughput synthesis and a predictive model for individual reaction optimization.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509620/1 01/10/2016 30/09/2022
1985251 Studentship EP/N509620/1 01/01/2018 30/06/2021 Antonio Pedrina McCarthy
Description The main goals of this research grant were to develop methods & techniques to accelerate the drug discovery process (specifically reaction optimisation - a significant bottleneck in chemical R&D).

Towards this goal significant progress has been made:

1. The workflow has been streamlined significantly, methods which were not beneficial for data quality were circumvented, and new analysis protocols were developed utilising tandem mass spectrometry technology. Significant effort has been put into verifying data reliability with the new MS instruments.

2. Development of new methods for visualisation & processing of the data has been undertaken - enabling more facile handling of large volumes of data & easier analysis of reaction outcome.

3. Original limitations were overcome. Originally work was conducted at room temperature with high boiling solvents only (DMSO predominantly). Since then, we have developed two custom reactor mounts which are able to reliably seal 384- and 1536- well plates. Allowing less volatile solvents (MeCN / H2O), and heating (up to approx. 100 C). In addition, these same plates have been modified to facilitate light mediated chemistry (of which testing is still underway).
Exploitation Route These methods & techniques can be applied to significantly reduce the time / material consumption of chemical R&D both in academia and industry. The miniaturisation of light-mediated chemistry is a significant advance. These techniques can directly be applied to reaction optimisation for complex pharmaceuticals, reaction discovery, generation of data sets for machine learning and many more areas.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology