A new microscope in southern England will let researchers watch living cells and tissues in action without needing to dye or label them first. Standard fluorescence microscopy can only track a handful of targets at a time, and the dyes themselves can disturb the biology. This instrument uses stimulated Raman scattering—a laser technique that reads the natural chemical vibrations of molecules—to map everything from drug molecules inside tissues to the fatty layers of a biofilm. The microscope will be the first of its kind in the region, and the team plans to push its limits across five research areas: designing synthetic Raman tags for bioanalysis, monitoring organoids without interference, building new biosensors, imaging drug-tissue interactions at high speed, and studying biofilms that drive antimicrobial resistance. If successful, the work could speed up drug screening, improve how researchers grow and test lab-grown tissues, and reveal new ways to break down stubborn biofilms on medical implants. The project is fundamentally curiosity-driven, but the applicants’ track record of patents and spin-out companies suggests practical applications are likely to follow.
View original technical description
Our understanding of how biological systems interact and behave is always limited by what we can measure, and observe. The predominant technique to visualize biological systems is fluorescence microscopy, which excels at spatial resolution but is challenged by the number, type and choice of targets that can be visualized. Raman spectroscopy is a complementary, label-free technique which allows for the measurement of vibrational spectra that are related to the chemical composition of a sample. Stimulated Raman scattering (SRS), a type of Raman spectroscopy, has exquisite sensitivity and spatial resolution via use of a second photon to enhance a specific vibrational transition in (bio)chemical structures. We propose to procure Leica’s Stellaris Coherent Raman Scattering microscope (CRS) (Table 1), an SRS instrument, with support from the MRC to overcome fundamental limitations facing biological research. The CRS will be the first in southern England, helping to drive the UK’s position at the forefront of biomedical research. We will utilise and push the boundaries of the CRS to engineer Raman tags for transformative bioanalysis, perform minimally invasive monitoring of advanced biological models, develop next generation biosensing approaches, image in high throughput drug-tissue interactions, and pursue innovative strategies to combat biofilm formation. PL Stevens is an international leader in Raman spectroscopy and its application to fundamental issues in biomedical research, ranging from label free monitoring of organoid development to understanding heterogeneity in drug loaded nanoparticles, priming her to host the CRS and lead the proposed scientific vision. She will be supported by PcLs and collaborators from a range of key Universities across the medical, physical and life sciences, who bring a wealth of expertise in designing, characterising, analysing, and applying biomedical systems across a range of relevant scales from molecules to cells and tissues. Guided by the applicants’ collective experience co-founding >10 companies, holding >40 patents, and linking to many large industrial partners the discoveries will be primed for translation. Altogether, the CRS will enable us to drive a step change in fundamental physico-chemical interrogation for biomedical discovery and translation application toward unmet needs in the clinic. We will pursue five research themes enabled by the CRS: 1) Raman tags for transformative bioanalysis, 2) Minimally invasive monitoring of advanced biological models, 3) Next generation biosensing approaches, 4) High-throughput imaging of drug-tissue interactions, and 5) Innovative strategies to interrogate and combat biofilms underlying antimicrobial resistance. This proposal aligns with the overall vision of the MRC to ‘accelerate improvements in human health by supporting world-class biomedical research and innovation.’ The CRS is a game-changing technology, and as such directly allows the MRC to ‘harness the opportunities from transformative technologies’, which underpins its overall vision. Careful consideration of technical support and management will potentiate the CRS, as detailed in the Approach section. Interrogation with the CRS will be complemented by a suite of in-house techniques including Single Particle Automated Raman Trapping Analysis (SPARTA®), Atom Probe Tomography, focussed ultrasound, advanced light and electron microscopy, and machine learning. The CRS therefore represents outstanding value for money for the MRC.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know