Editorial Feature

Revolutionizing Disease Studies with Next-Generation Bio-Photonics

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Accurate and rapid medical diagnoses rely heavily on medical imaging technologies that allow us to peer inside the body or identify the presence of unwanted or abnormal cells. There is a large demand for robust and easy-to-use technologies in medical imaging, providing more rapid and accurate screening. This is part of what the CRIMSON project aims to deliver.1

What is the CRIMSON Project?

The CRIMSON project is a highly interdisciplinary research project that has been funded as part of the HORIZON 2020 program.

The project coordinator is Professor Dario Polli at the Politecnico di Milano, Italy and, by bringing together the research expertise of the six research centers, four small-to-medium enterprises (SMEs) and a biomedical manufacturer, the consortium will deliver novel technology for label-free coherent Raman technology for tumor detection and diagnosis.

To develop this next-generation bio-photonics imaging device for biomedical research will require many technological and software developments.

The device is a microscopy-endoscopy tool that uses broadband coherent Raman scattering (CRS) to obtain diagnostic information on cells and tumors by recording data on the molecules' vibrational spectrum.

CRS microscopy is a powerful technique for observing how cells metabolize small molecules and the overall cell structures.2

CRS Microscopy

At present, imaging some cell structures with CRS microscopy relies on ‘tags’, which are chemical compounds that selectively bind to the substrate of interest to enhance the Raman signals from the sample or improve the contrast between specific structures interest and the cell background.3

However, label-free imaging methods are highly desirable. There are concerns that labeling can affect the processes being monitored, and it can be challenging to make tags small enough to pass through some cell structures.

By combining the world-leading spectroscopic expertise of three of the research partners (Politecnico di Milano, Italy, Leibniz Institute of Photonic Technology e.V, Germany and Centre National de la Recherche Scientifique, France) with extensive expertise in biomedical research from the other partners (Istituto Nazionale Tumori, Italy, Institut National de la Santé et de la Recherche Médicale, France and Jena University Hospital, Germany), the team will exploit the potential of spectroscopy for medical applications. This will enable them to perform label-free experiments on various cell types and address open biological questions on cancer and cell diseases.

The development of broadband CRS microscopy and endoscopy will make it possible to investigate disease pathophysiology and understand how normal physiological processes in the body malfunction either as a consequence of, or a cause of, diseases.

Present screening processes, particularly for tumors, often require months to determine whether a treatment has been effective.

The rapid alternative offered by the CRIMSON project will reduce this time and be a huge step forward in the development of personalized medicine. Treatments would be optimized based on the response of a patient’s tumor and would track how the individual’s immune system reacts and interacts with the treatment method.

Innovation in Photonics

Part of the challenge for creating the medical imaging device at the heart of the CRIMSON project will be developing a novel fiber laser source.

As CRS is a non-linear optical process, very high laser powers must obtain an adequate signal level, making it a ‘photon hungry’ technique.

Ideally, these high powers would be combined with high repetition rates to maximize the information obtained from these advanced laser techniques.

Another critical aspect of the fiber laser source design will be robustness and ease-of-use. This will bring new, compact ultrafast laser designs to market, designed to be sufficiently straightforward to operate so that they can be used by medical personnel.

In combination with the novel source design, the team will be exploring new detection schemes for the broadband CRS signals to maximize the spectral and diagnostic information that can be extracted from the experiments.4

To fully exploit the large and complex datasets obtained from the CRS microscopy experiments, part of the consortium will be developing advanced spectral analysis routines. The large volumes of data will require efficient advanced image processing methods, including machine learning-based methods. It will potentially open routes to the automated differential diagnosis of conditions with characteristic abnormal cell histologies, such as many cancers.    

The CRIMSON project started on 1 December 2020 with over 5 million Euros of funding to carry out their ambitious work.

By working in close collaboration with the SMEs involved, the CRIMSON team will be uniquely poised to commercialize the new methodologies and technologies created during the 42-month project.

The CRIMSON project’s outcomes will lead to a substantial competitive advantage in the European biophotonics-related market for microscopes and R&D tools.

By creating a microscopy and endoscopy device with very high acquisition speeds, CRIMSON will make it possible to make in vivo movies of intra and inter-cellular changes and capture 3D maps of the sub-cellular compartments within cells, allowing us to see biology as never before. This project will represent a significant milestone in microscopy and endoscopy developments.

References and Further Reading

  1. CRIMSON EU, CRIMSON Project. (2020) https://www.crimson-project.eu/, accessed 10 December 2020.
  2. Zhang, C., Zhang, D., & Cheng, J. X. (2015) Coherent Raman Scattering Microscopy in Biology and Medicine. Annual Review of Biomedical Engineering (Vol. 17). https://doi.org/10.1146/annurev-bioeng-071114-040554
  3. Zhao, Z., Shen, Y., Hu, F., & Min, W. (2017). Applications of vibrational tags in biological imaging by Raman microscopy. Analyst, 142(21), 4018–4029. https://doi.org/10.1039/c7an01001j
  4. Polli, D., Kumar, V., Valensise, C. M., Marangoni, M., & Cerullo, G. (2018). Broadband Coherent Raman Scattering Microscopy. Laser and Photonics Reviews, 12(9). https://doi.org/10.1002/lpor.201800020

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Rebecca Ingle, Ph.D

Written by

Rebecca Ingle, Ph.D

Dr. Rebecca Ingle is a researcher in the field of ultrafast spectroscopy, where she specializes in using X-ray and optical spectroscopies to track precisely what happens during light-triggered chemical reactions.

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