A multifunctional biomimetic lab-on-a-chip assault course for agrochemical bioavailability screening

A current challenge with the delivery of agrochemicals is their non-specific distribution throughout the plant. This is compounded by the lack of a systematic fundamental physicochemical based set of rules to effectively predict agrochemical bioavailability. This proposal aims to address this challenge by designing and establishing a modular on-chip model transport system that can mimic the various compartments and layers an agrochemical needs to traverse to gain access to its active-site within the plant. We propose to do this using automated droplet-based microfluidics that will enable the user to "dial up" in-vitro biologically relevant mimics of plant compartments and barriers. The resulting biomimicry toolkit will capture the key features of the molecular environments (molecular interactions, degree/length scale of compartmentalization, sequencing of barriers, types of barriers (e.g waxy cuticle vs biomembrane) at each phase of the bioavailability pathway. This will involve plugging together novel motifs including vesicles, multisomes, droplet interface bilayers, phase-separated domains and vesicle interface bilayers. Control of the end-to-end connectivity of motifs and being able to embed one motif within another motif will be features engineered into the resulting device. The fully integrated system will have added functionalities of dynamic and real-time molecule tracking across key stages of the assault course with read outs facilitated by fibre-optic based UV Vis, Raman Imaging, Mass Spec and HPLC depending on the assault course element under study. The device will enable us to screen a library of Syngenta's existing agrochemicals with defined physicochemical properties and to identify those molecules that can successfully cross key barriers in plants. Knowledge gained will facilitate the design of more effective agrochemicals that can cross plant structures beyond simple diffusion or ion trapping mechanisms and allow sitetargeted distribution of agrochemicals, leading to a more sustainable, economical and environmentally green approach to agrochemical use in agriculture.

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.