CONTRAST facility: clinical coherent Raman scattering facility

Lead Research Organisation: UNIVERSITY OF EXETER
Department Name: Physics and Astronomy


The UK has a rich and vibrant Raman spectroscopy community, which is at the forefront of developments showing that the technique holds the key to the next generation of enabling healthcare technologies. Raman spectroscopy is an established analytical technique that derives information regarding chemical composition based on the vibrational frequency of the chemical bonds within a sample. Due to its unique 'optical fingerprinting' capability, Raman spectroscopy has the potential to play a significant role in healthcare including: histopathology, cytology, biopsy targeting, surgical targets, treatment monitoring and drug studies. However, for many healthcare applications Raman scattering when compared with optical techniques that rely on labelling, has the drawback of being too weak for real-time imaging. Coherent Raman scattering (CRS), is an alternative approach that uses extremely short (approximately one thousandth of one billionth of a second in duration) pulses of lasers to exploit to boost the weak molecular vibrational signals to a level that is compatible with real-time imaging of tissues; a capability that holds the key to the next generation of diagnostic technologies and the development of targeted therapies. We propose to establish a CRS user facility at Exeter that will allow leading UK researchers to develop novel Healthcare Technologies based on this emerging technology.

Planned Impact

The CONTRAST facility will enable leading researchers to explore the rapid label-free chemical imaging capability of an exciting emerging technology for a wide range of novel healthcare related applications. Specifically, new knowledge will be created that will enable the development of future diagnostic and analytical tools for the development of future therapeutic technologies. Beyond the healthcare community the facility will benefit the wider analytical science communities leading to technologies that will underpin many scientific and applied research fields.

Capitalizing on the existing skill base of individuals, highly trained in cutting-edge spectroscopy techniques, is vital to the continued sustainability and growth of the UK's position on the global research stage. Expertise in coherent Raman in the UK is largely confined to a handful of research groups with niche expertise in nonlinear optics and access to ultrafast laser systems. Our facility would enable the translation of this cutting-edge technique into the wider spectroscopy and healthcare technologies community. Users will gain experience in cutting-edge nonlinear optical spectroscopy techniques with expert guidance and support.

The UK industry has a strong share of the global spectroscopy market, both in terms of instrument development and as a reliance as an R&D tools for product development. However, UK industry has yet to exploit CRS. The proposed facility would significantly enhance the UK's instrumentation and knowledge base in this emerging technique and significantly increase the translation of cutting-edge spectroscopy into industry applications.

In the short-term term, the analytical capability afforded by the facility will have a significant impact on the development of future chemical, biotech, and pharmaceutical technologies. Many drugs, active ingredients and formulation compounds are smaller than the tags used to image them with conventional techniques, which significantly modifies their behaviour under observation in biological systems. The high-resolution label-free chemically specific contrast of CRS is a step change for monitoring the uptake and distribution of these compounds at the cellular level, leading to new understanding and ultimately rational engineering of compounds that perform better with fewer side effects.

In the longer-term, future analytical and diagnostic technologies based on CRS will open new market opportunities for the UK technology industry. In addition to commercialisation of the next generation of instruments, there will also be new opportunities for companies involved in the supply chain for instruments in this sector. By engaging with the CONTRAST user community, companies will be able to gain an understanding for the future market opportunities associated with this emerging technology and identify how they can best be exploited.

The facility has great potential deliver economic impact beyond the Healthcare sector. The ability to monitor the distribution of chemical species without reliance on extrinsic labels is extremely appealing to other high-tech industry sectors such as the consumer chemical and agrichemical industries. Access to cutting-edge analytical tools plays a vital role in maintaining the UK's competitiveness and the proposed facility would significantly enhance the R&D capability.

Research enabled by the facility will deliver better quality of life and higher standards of affordable care for patients and will drive UK growth through new products and services. Novel technologies developed by the facility users will improve our ability to predict, diagnose and treat disease. Moreover, the facility will support the development of novel therapies with technologies to enhance efficacy, minimise costs and reduce risk to patients.
Description CONTRAST is a user access facility that provides real-time label-free chemical imaging based on vibrational spectroscopy and during RaNT enhancements were made to improve the selective detection of biomolecules. Following this, a collaboration with BASF (spanning October 2022 to March 2023) set out to explore whether it could visualise agrochemical uptake into plants. A PDRA at Exeter made a significant breakthrough in data processing software to allow the detection of low molecular weight agrochemicals against the strong autofluorescence of plant tissues. We then demonstrated that this enables us to visualise the uptake and cellular fate of field-rate agrochemicals in live plants. This is a world first that could transform the development of agrochemicals, and we are currently exploring how BASF can implement the technology into their analytical pathway. The ability to monitor agrochemicals at the cellular level in plants represents a paradigm shift in R&D capability and Exeter is ideally placed to deliver significant impact in this area. Thanks to EPSRC funding [EP/S009957/1], our custom-built CONTRAST facility is currently the only of its type in the UK. Once we have performed standardisation measurements with BASF, CONTRAST would become a European analytical hub for the development of agrochemical formulations and play a key role in rationally engineering future agrochemical formulations with enhanced efficiency and lower environmental impact. The global agrochemical market is currently estimated to be $230 billion and set to grow to $280 billion by 2029. Improving the performance and reducing the environmental impact of agrochemicals are key drivers for the industry and any advances in formulation that increase their market share are extremely beneficial. Furthermore, contributing to an overall reduction in the environmental side effects of agrochemicals would have enormous implications.
First Year Of Impact 2023
Sector Agriculture, Food and Drink,Chemicals,Healthcare
Impact Types Societal,Economic

Description 21ENGBIO: Engineering targeted activation of fungicides at the plant-pathogen interface
Amount £83,471 (GBP)
Funding ID BB/W012936/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 01/2023
Description Application of CRS to track chocolate bloom development over time: shelf life study 
Organisation Mendeley Ltd
Country United Kingdom 
Sector Private 
PI Contribution Identifying and characterising changes in surface morphology, chemical composition and polymorphic forms of chocolate bloom. A longitudinal spectroscopic study of chocolate bloom will be performed with the aim to track the evolution of bloom through surface compositional changes. Hyperspectral CRS images using methodologies developed in WP1 & WP2 will be used to acquire data in a timed study. Analysis will be performed to determine the morpho-chemical properties of the sample at each timepoint.
Collaborator Contribution Provided all chocolate samples
Impact none yet. project still running
Start Year 2021
Description Biological imaging of Zymoseptoria tritici wheat infection by stimulated Raman scattering microscopy 
Organisation Syngenta International AG
Country Switzerland 
Sector Private 
PI Contribution This is an industry funded project exploring the feasibility of using the CONTRAST facility to better understand how anti-fungal agrochemicals can be engineered with enhanced efficacy. My team are providing expertise in SRS imaging and undertaking all experiments carried out in the CONTRAST facility.
Collaborator Contribution Syngenta are providing funding (£25,000) for this project and expertise in the development of novel anti-fungal agrochemical agents.
Impact New understanding of the host-pathogen interaction during fungal infection of wheat
Start Year 2021
Description Chemical imaging by Coherent Raman Scattering (CRS) methods for com-pounds visualization in pesticidal target systems 
Organisation BASF
Country Germany 
Sector Private 
PI Contribution The evaluation of Coherent anti-Stokes Raman Scattering (CARS) and Stimulated Raman Scattering (SRS) to investigate uptake and distribution of pesticides in plant leaves after foliar application including co-localization of compounds with inner leaf structure (subcellular level), in roots, in seeds, in in-sects and microorganisms.
Collaborator Contribution Funding a post-Doctoral research for 12 months. Providing agrochemicals and agrochemical knowhow.
Impact None as yet. Project still running
Start Year 2021