Coherent Raman Imaging for the Molecular Study of the Origin of Diseases
CRIMSON aims to provide a next-generation bio-photonics imaging device based on vibrational spectroscopy, with the potential to revolutionize the study of the cellular origin of diseases allowing for novel approaches towards personalized therapy.
We will employ label-free broadband coherent Raman scattering (CRS) extended to the fingerprint region, in combination with artificial-intelligence spectroscopic data analysis, for fast cell/tissue classification with unprecedented biochemical sensitivity. We will develop a hyperspectral CRS microscope for 3D quantitative imaging of sub-cellular compartments in living cells and organoids. High acquisition speed will enable the observation of intra- and inter-cellular dynamic changes by time-lapse imaging. We will simulate future in-vivo studies and demonstrate the capability to image inside the body, realizing an innovative CRS endoscope and applying it to ex-vivo thick tissue slides.
To validate the CRS platform, we will investigate three open biological questions related to cancer, as typical examples of the complexity and heterogeneity of cellular diseases. The results will have profound societal impacts, improving patients’ quality of life and reducing public healthcare costs. CRIMSON relies on the development of new compact ultrafast lasers, innovative broadband CRS detection schemes and advanced spectral analysis routines.
CRIMSON brings together a multidisciplinary team of world-leading academic organizations, biomedical end users and innovative SMEs, with vertical integration of all required skills. CRIMSON will bridge the gap between research and product development, increasing the Technology Readiness Level (TRL) and making CRS a user-friendly, robust and cost-effective mainstream tool for a vast biological research community. Commercial exploitation by the participating SMEs, including a biomedical equipment manufacturer, will create a competitive advantage in the European biophotonics-related market for microscopes and R&D tools.
The main impact of CRIMSON will be the development of a non-invasive, label-free optical microscopy-endoscopy tool, based on broadband CRS, for fast, quantitative and objective imaging of biological specimens like 2D/3D cells, tissue sections or organs, to determine their morphological and molecular nature (morphochemistry) with an unprecedented precision.
The broadband CRS microscope together with the tailor-made automated data analysis pipelines will allow to unravel new aspects of disease pathophysiology that were not accessible before or which required the combination of multiple sophisticated approaches like e.g. fluorescence staining approaches, OMICS etc. Within the framework of patient care, detailed knowledge of the molecular and pathophysiological background of a disease will help to treat those affected in a targeted personalized manner – without detour via “trial and error” – e.g. with the drug that is most suitable for them. For example, immunotherapy, which has become of great interest to researchers, clinicians and also pharmaceutical companies because of its promise to treat various forms of cancer, is currently only effective in <10% of the patients. Tumour response evaluation after/during immunotherapy takes months before the efficacy can be determined, which means that, in many patients, this expensive therapy is useless, while it can have important side effects. The novel broadband CRS imaging tool developed within CRIMSON will allow for a better tumour characterization for personalized immunotherapy on a cellular level. Overall, any improvement in understanding diseases on a molecular and cellular level will lead to more efficient and targeted therapy concepts (personalized precision medicine) and will have a significant benefit not only to patients, but also to the economic sustainability of the healthcare system as a whole.
CRIMSON will push forward CRS microscopy – so far mainly used to image single molecular vibrations in the chemically less sensitive CH-stretch wavenumber region – accessing the fingerprint region by establishing various novel photonic solutions (e.g. fast Fourier transform-CRS, innovative and compact laser sources etc.) in combination with tailor-made AI-aided data analysis platforms to shed new light on the pathogenesis of diseases. To highlight the unique potential of the developed CRS imaging platform for the study of diseases on a cellular and molecular level, CRIMSON addresses three different important biomedical case scenarios: (1) Understanding the pathogenesis of non-alcoholic steatohepatitis. (2) Understanding the interaction between head-and-neck tumor cells and immune cells. (3) Accurate assessment of senescence and tumor heterogeneity. We expect great international interest in the novel CRS imaging platform because the possibility to image cells, tissue and even organs quickly, with subcellular resolution and, most importantly, label-free and with molecular contrast, will lead to new insights in disease pathology, allowing for completely novel approaches towards personalised therapy.
In summary, the broadband CRS technology developed in this project will have an impact on:
Opening new markets for the European photonic industry, both for the partner SMEs and for other companies which will develop new products leveraging on the project innovations.
Building a stepping stone for an improved understanding of diseases by allowing for a more complex analysis of biological specimens in one experimental step and using a single instrument.
Improving the health of the European population, by designing novel personalized treatment strategies with the help of the CRS data.