Periodic Reporting for period 1 - CRIMSON (Coherent Raman Imaging for the Molecular Study of the OrigiN of diseases)
Berichtszeitraum: 2020-12-01 bis 2022-05-31
CRIMSON aims to provide a next-generation bio-photonics imaging device based on vibrational spectroscopy, with the potential to revolutionise the study of the cellular origin of diseases allowing for novel approaches
towards personalised therapy. CRIMSON 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. The project consortium 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. Partners 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. CRIMSON relies on the development of new compact ultrafast lasers, innovative broadband CRS detection schemes and advanced spectral analysis routines.
To validate the CRS platform, CRIMSON will investigate three open biological questions related to cancer, as paradigmatic 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 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 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.
towards personalised therapy. CRIMSON 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. The project consortium 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. Partners 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. CRIMSON relies on the development of new compact ultrafast lasers, innovative broadband CRS detection schemes and advanced spectral analysis routines.
To validate the CRS platform, CRIMSON will investigate three open biological questions related to cancer, as paradigmatic 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 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 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.
During the first Reporting Period (M1-M18) the consortium has performed all planned tasks in line with the foreseen Description of Action (DoA), along different lines, from the technology (WP1) to the prototyping (WP2), from the data analysis (see WP3) to the biological applications (see WP4). Overall, the results are very positive, and represent a considerable advancement in the state of the art of coherent Raman Spectroscopy (CRS) and microscopy. Some of them have already been published and others have recently been submitted or are going to be submitted soon in international peer-reviewed Journals. In particular, in WP1 project partners have demonstrated various approaches to high-speed CRS microscopy in the fingerprint region based either on coherent anti-Stokes Raman scattering (CARS) or stimulated Raman scattering (SRS). In WP2, partners have designed and are developing new devices such as a fiber-based ultrashort pulsed laser, a multimodal microscope and a scanning endoscope for future commercialisation of CRS technology for mainstream biological labs. In WP3, CRIMSON consortium has developed numerical algorithms for data analysis, including artificial-intelligence approaches, to reduce the noise, improve the signal-to-noise ratio (SNR) and remove spurious signals such as the non-resonant background (NRB) to extract the most relevant information from the measured three- dimensional hypercubes. In WP4, the partners are studying three biological case studies related to cancer and applying vibrational spectroscopy to understand the origin of subtle mechanisms such as autophagy, immuno-oncology and senescence in cells and tissues. The CRIMSON consortium has studied cell damage induced by focused ultrashort infrared laser pulses, to understand this mechanism and provide a safety rule to extract the maximum amount of signal before the onset of sample damage.
The goal of the CRIMSON project is the development of an innovative bio-photonic system for cell/tissue imaging which will be used as a research tool to understand the cellular origin of diseases. The selected imaging technique is broadband coherent Raman scattering (CRS) extended to the fingerprint region. Broadband CRS brings about several advantages, such as:
1. Label-free imaging, avoiding the use of exogenous or endogenous labels.
2. Living cell imaging capability.
3. High acquisition speed, enabling the observation of dynamic cellular processes by time-lapse imaging.
4. High biochemical sensitivity, thanks to the capability to acquire quantitative hyperspectral images allowing the identification of molecules by their unique vibrational spectrum.
5. The possibility to couple these advantages with endoscopy-based in vivo imaging.
Despite the potential of broadband CRS as a disruptive cell/tissue imaging method, several limitations have hindered the adoption of CRS microscopy by biologists as a standard research tool and the technology remains confined to low Technology Readiness Level (TRL) laboratory applications. Limitations comprise the costs and the need of regular alignment or maintenance, which make the technology not suitable for biomedical research laboratories and the lack of capability to provide rich chemical information and spectroscopic information in the fingerprint region.
With the aim of overcoming the limitations and contributing to making broadband CRS a mature technology used by biology laboratories in cellular diseases’ research, The CRIMSON project will deliver:
1. A compact and turnkey laser system specifically optimised for broadband CRS.
2. A high-speed broadband CRS acquisition system.
3. Optimised microscopy and endoscopy platforms, combining the laser and the detection system.
4. Advanced AI analysis tools, including chemometrics, machine- and deep-learning, provide a classification of cells and tissues, enabling the rich data sets obtained with CRS to be interpreted with high sensitivity and specificity.
We are validating the technology through the application to three case studies related to cancer, focusing on inter- and intra-cellular processes occurring in liver, head & neck and thyroid tumours.
1. Label-free imaging, avoiding the use of exogenous or endogenous labels.
2. Living cell imaging capability.
3. High acquisition speed, enabling the observation of dynamic cellular processes by time-lapse imaging.
4. High biochemical sensitivity, thanks to the capability to acquire quantitative hyperspectral images allowing the identification of molecules by their unique vibrational spectrum.
5. The possibility to couple these advantages with endoscopy-based in vivo imaging.
Despite the potential of broadband CRS as a disruptive cell/tissue imaging method, several limitations have hindered the adoption of CRS microscopy by biologists as a standard research tool and the technology remains confined to low Technology Readiness Level (TRL) laboratory applications. Limitations comprise the costs and the need of regular alignment or maintenance, which make the technology not suitable for biomedical research laboratories and the lack of capability to provide rich chemical information and spectroscopic information in the fingerprint region.
With the aim of overcoming the limitations and contributing to making broadband CRS a mature technology used by biology laboratories in cellular diseases’ research, The CRIMSON project will deliver:
1. A compact and turnkey laser system specifically optimised for broadband CRS.
2. A high-speed broadband CRS acquisition system.
3. Optimised microscopy and endoscopy platforms, combining the laser and the detection system.
4. Advanced AI analysis tools, including chemometrics, machine- and deep-learning, provide a classification of cells and tissues, enabling the rich data sets obtained with CRS to be interpreted with high sensitivity and specificity.
We are validating the technology through the application to three case studies related to cancer, focusing on inter- and intra-cellular processes occurring in liver, head & neck and thyroid tumours.