Active Cells, Biochemistry & Physiology Chemistry

Label-Free Chemical Imaging with High Temporal Resolution for Application in Advanced Materials

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AI plain-English summary

A new microscope at the University of Leeds will let researchers watch drugs move through living tissue in real time, without needing to dye or label the molecules first. The problem is that standard microscopy often requires researchers to stain samples with fluorescent dyes to see specific components. This is slow, expensive, and assumes the researcher already knows what to look for. It also struggles to image deep inside dense tissues. The Stellaris 8 CRS microscope bypasses these limits by detecting each molecule's unique vibrational fingerprint—its natural signature—allowing label-free, high-resolution, 3D imaging of living cells and tissues. If successful, the system could transform how scientists study chemoresistance in hard-to-treat cancers, track how new drugs distribute in model tissues, and detect early biochemical changes at the single-cell level before disease develops. Beyond medicine, it will help map molecular distributions in food products, hydrogels, and biomaterials. The work is primarily fundamental science—building a deeper understanding of molecular behaviour across length scales—but past advances in label-free imaging have directly accelerated drug discovery and reduced healthcare costs.

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The ability to visualise molecules, cells, tissues and other materials using optical microscopy is often limited by the researcher's ability to successfully label different components with a suitable dye, which can be inefficient and expensive, and also requires the researcher to know what they are looking for in advance of the experiment. In addition, imaging can be limited by how deep light can penetrate into dense samples such as tissues, reducing a researcher's ability to image complex structures such as tissues in 3D. Yet, single-molecule and live-cell imaging are recognised as invaluable tools in biophysics and bioengineering for many applications such as drug discovery, disease pathology and mechanistic biology. In addition, understanding the molecular distribution and structure of materials is critical for applications in drug delivery, food science, and regenerative medicine and needs to be studied across multiple length scales, from molecular to millimetres. The Stellaris 8 CRS Microscope will enable researchers to map how different molecular species are distributed in their samples by observing their unique molecular fingerprints. This type of imaging allows imaging without requiring the 'labelling' or 'tagging' of components with dye molecules, providing real-time, high-resolution imaging of complex systems. It is beneficial for studying the distribution of different molecular components in food products, polymeric materials, and cellular components of tissue length. The system uses methods capable of penetrating deep into multicellular systems, providing unrivalled 3D resolution in tissue imaging. Since every molecule has a unique vibrational signature, the Stellaris 8 will allow the monitoring of drug distribution and accumulation in real-time, helping develop better models for studying disease and new methods for treating disease. At the University of Leeds and beyond, a Stellaris 8 microscope will enable new science in areas of disease modelling and drug delivery; for example, understanding the biophysical and biochemical mechanisms of chemoresistance in cancer is critical to designing new therapeutics and understanding how new drugs interact with and distribute in model tissues facilitate drug discovery and improve patient outcomes in hard to treat cancers. In soft matter and biophysics, recent developments in hydrogel materials, lipid membranes and biomaterials in food science. In early detection and diagnosis, the advent of disease at the single-cell level is often accompanied by subtle changes in biochemistry and the spectral fingerprint. Detecting these early changes before advanced disease develops would ultimately save lives and reduce the health care costs to the nation. The Stellaris 8 microscope will enable multimodal imaging and measurements across various biophysical research areas in a manner that is not currently possible, enhancing existing research and leading to new research and collaborations across multiple institutions.

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Researchers

Aleks Ponjavic (Co-Investigator)Christoph Walti (Co-Investigator)Michelle Peckham (Co-Investigator)Sally Peyman (Co-Investigator)Stephen Evans (Principal Investigator)

Related Research

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Original classification

Research Grant

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