Plug and play microfluidics for frontier Agri-Tech assays

Lead Research Organisation: Imperial College London
Department Name: Chemistry

Abstract

Development of plug and play lab-on-chip technologies for high-throughput profiling of pesticide metabolic degradation: One of the greatest bottlenecks in the agrichemical industry is the lack of a quantitative and predictive understanding of how pesticides are metabolised by a given species (both desired and undesired). This goes to the heart of many unresolved challenges the industry faces, which centre around the following questions: How can we use fewer pesticides, thus minimising environmental exposure? How can we design pesticides that are more specific to the target pest, avoiding non-target species? How can we reduce the cost of getting an agrichemical to market using predictive tools to make decisions upstream of the development pipeline? Understanding how a pesticide is metabolised by a species of interest therefore of central importance for compound development, and determination of its bioavailability. Current methods to probe pesticide metabolism are slow, laborious, and low-throughput: compounds are essentially tested one-by-one, considerably reducing possibilities to test new molecules. This project will bring together our expertise in microfluidics, analytical chemistry, metabolomics, and agri-science to develop new state-of-the-art platforms, allowing us to tackle this challenge head-on. Our technologies will fuse robotic sampling, continuous flow microfluidics, and microdroplet production to generate a library of active ingredients (AIs) that will be incubated with a model pathogen. Metabolic degradation of the AIs within each droplet will be measured online using coupled rapid sub-30-second analytical separation and/or mass spectrometry directly, to yield thousands of data points within a single run. When coupled to big-data analysis, rapid screening will allow us to build a suite of predictive models to correlate chemical structure with metabolic degradation characteristics. Our lab-on-chip setup will be a step-change from current methods, which rely on manual handling of well plates. Importantly, our technologies will be enabling ones: once established, they can be repurposed to assay multiple cell types, and extended to transcriptomic, proteomic & lipidomic analysis in future iterations.

Planned Impact

Addressing UK skills demand: The most important impact of the CDT will be to train a new generation of Chemical Biology PhD graduates (~80) to be future leaders of enterprise, molecular technology innovation and translation for academia and industry. They will be able to embrace the life science's industrialisation thereby filling a vital skills gap in UK industry. These students will be able to bridge the divide between academia/industry and development/application across the physical/mathematical sciences and life sciences, as well as the human-machine interfaces. The technology programme of the CDT will empower our students as serial inventors, not reliant on commercial solutions.
CDT Network-Communication & Engagement: The CDT will shape the landscape by bringing together >160 research groups with leading players from industry, government, tech accelerators, SMEs and CDT affiliates. The CDT is pioneering new collaboration models, from co-located prototyping warehouses through to hackathons-these will redefine industry-academic collaborations and drive technology transfer.
UK plc: The technologies generated by the CDT will produce IP with potential for direct commercial exploitation and will also provide valuable information for healthcare and industry. They will redefine the state of the art with respect to the ability to make, measure, model and manipulate molecular interactions in biological systems across multiple length scales. Coupled with industry 4.0 approaches this will reduce the massive, spiralling cost of product development pipelines. These advances will help establish the molecular engineering rules underlying challenging scientific problems in the life sciences that are currently intractable. The technology advances and the corresponding insight in biology generated will be exploitable in industrial and medical applications, resulting in enhanced capabilities for end-users in biological research, biomarker discovery, diagnostics and drug discovery.
These advances will make a significant contribution to innovation in UK industry, with a 5-10 year timeframe for commercial realisation. e.g. These tools will facilitate the identification of illness in its early stages, minimising permanent damage (10 yrs) and reducing associated healthcare costs. In the context of drug discovery, the ability to fuse the power of AI with molecular technologies that provide insight into the molecular mechanisms of disease, target and biomarker validation and testing for side effects of candidates will radically transform productivity (5-10 yrs). Developments in automation and rapid prototyping will reduce the barrier to entry for new start-ups and turn biology into an information technology driven by data, computation and high-throughput robotics. Technologies such as integrated single cell analysis and label free molecular tracking will be exploitable for clinical diagnostics and drug discovery on shorter time scales (ca.3-5 yrs).
Entrepreneurship & Exploitation: Embedded within the CDT, the DISRUPT tech-accelerator programme will drive and support the creation of a new wave of student-led spin-out vehicles based on student-owned IP.
Wider Community: The outreach, responsible research and communication skill-set of our graduates will strengthen end-user engagement outside their PhD research fields and with the general public. Many technologies developed in the CDT will address societal challenges, and thus will generate significant public interest. Through new initiatives such as the Makerspace the CDT will spearhead new citizen science approaches where the public engage directly in CDT led research by taking part in e.g hackathons. Students will also engage with a wide spectrum of stakeholders, including policy makers, regulatory bodies and end-users. e.g. the Molecular Quarter will ensure the CDT can promote new regulatory frameworks that will promote quick customer and patient access to CDT led breakthroughs.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023518/1 01/10/2019 31/03/2028
2596489 Studentship EP/S023518/1 02/10/2021 30/09/2025 Shameem GOLESTANEH