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Femtosecond Temporally Coherent Supercontinuum Fiber Laser for Multi-Photon Microscopy

Periodic Reporting for period 1 - FEMTOCOLORS (Femtosecond Temporally Coherent Supercontinuum Fiber Laser for Multi-Photon Microscopy)

Reporting period: 2017-09-29 to 2018-09-28

In recent years, photonics is playing a vital role in the well-being of people. Today there are many initiatives, such as HUMAN BRAIN PROJECT, that reinforce the use of fiber optic lasers in fields such as Medical Diagnostics, specifically in Diagnostic Imaging (IMG) or Bio-image. Within the Diagnostic Imaging (IMG) sector, the Microscopy of Life Sciences will be the main niche of the FEMTOCOLORS project. To penetrate this market, FEMTOCOLORS will offer an advanced tool for MPE technology (known as multiphoton or two-photon excitation microscopy).

MPE microscopy is particularly useful in medical diagnostics and in live imaging because it reduces phototoxicity, increases the depth of tissue images and allows localized photochemistry. Therefore, it is a fundamental tool for research and diagnosis in such important fields as brain diseases, neurobiology, cardiovascular research, gynecology or oncology.

However, and despite its many benefits in many fields of science, there are still some technical and market problems that are hindering the progress of the sector and its massive implementation in hospitals, research centers or universities. The three main problems to solve are:
1.High cost and availability. Its high price limits its massive implantation in research institutions (hospitals, universities or research institutes).
2. Low usability and versatility. Currently, the components needed for an MPE system are large and heavy, which makes it impossible to directly include them to the microscope. On the other hand, the implementation of these systems requires a complex installation process and high maintenance costs. Finally, microscopists (not experts in lasers) require training in technical aspects related to coupling, alignment and use.
3. Technical limitations. The current MPE systems offer low temporal coherence of the pulses; they are not monolithic systems, which reduces their efficiency, increases their cost and complexity and does not allow the reproducibility of measurements.

In this sense, the FEMTOCOLORS project proposes an innovative approach based on the integration of the subsystems that make up the MPE systems in a compact and universal product, easy to attach and use with any microscope, reducing the purchase price, its maintenance and the expensive handling and installation procedures. All this, at the same time as it improves the technical features provided by the MPE system laser.
The mail goal of this project is the recruitment of a postdoctoral researcher from other countries (not Spain) to explore an innovation business idea: the development of a Femtosecond (Fs) Temporally Coherent Supercontinuum (SC) Fiber Laser for Multi-Photon Microscopy (MPM). FYLA LASER S.L. has recruit a highly qualified specialist in photonics, that is not available in the Spanish job market, but whose knowledge has been crucial to open up opportunities for innovation and significant growth for the enterprise.

Apart from the technical objectives, training objectives have been defined and accomplished:
-To train the innovation associate with valuable transferable skills
-To train the innovation associate in several cutting-edge disciplines in photonics including; laser engineering, optical fiber sensing, materials science, nanotechnologies, programmable optoelectronics, laser microscopy and nanoscopy.
-To provide hands-on managerial and entrepreneurial training to the innovation associate.
The innovation associate carried out different activities related with the development and execution of the following technical tasks:
- Development of photonic crystal fibers
- Integration of Coherent SC laser
- Pulse management
In addition, in order to transform the innovation idea in an innovation programme, a business exploitation plan has been developed.

The activities developed were:
- Project plan elaboration and supervision
- Experimental design
- Lab tasks
- Analysis of results
- Elaboration of deliverables, reports…
- Internal presentation of the research
To FYLA, this INNOSUP program has been the formal frame within which developing this new product. As a result of this project, FEMTOCOLORS has implied a big leap forward to FYLA. Today FYLA has a fiber laser prototype that did not have before FEMTOCOLORS. It is a Femtosecond Temporally Coherent Supercontinuum Fiber Laser, close to a pre-commercial version to be introduced in the Multiphoton Microscopy market.
The main goal of the training activities carried out by the innovation associate during the contract period has been the following:
- Providing the overview for innovation
- Focus on Innovaton Strategy
- Approaches for industrial innovation management
- Marketing of Innovation
In addition, the innovate associate was trained by several workers of the company during the contract period, with the aim to maximise the potential of the recruitment and multiply its effects while assuring a smooth integration of the research structure and cultural environmental of the company. The different skills achieved by the innovation associate during the training are:
- Analytical/Theoretical skills: Mathematical and numerical modelling of light propagation in ultrafast fiber lasers and photonic crystal fibers
- Experimental skills: Manufacturing of photonic crystal fibers, photoinscription of FBGs, use of fiber fused components workstation for fiber laser manufacturing. Characterization of ultrafast fiber lasers in the optical and temporal domain
- Soft (business) skills: Embrace the “Start-up spirit” motivational environment of FYLA, acquisition of conceptual and practical tools to develop Deeply-Focused-to-Market Research. Market analysis, product oriented technology-watch, team managing, factory production processes, IP rights production and management, field training on B2C (Scientific) and B2B (Industry) business models.
The results of this project will mean an improvement in health and in the quality of life since an integrated laser lighting equipment will be obtained for biological-clinical super-resolution microscopy equipment.
Superresolution microscopy exceeds the diffraction limit of light and allows researchers to study subcellular structures in greater detail than is possible with a confocal microscope. Resolutions of up to 20 nm can be achieved; in biology, this represents the end-to-end length of 10 proteins of average size or 60 base pairs of DNA. With the introduction of the first superresolution microscope in 2004 and, with current models, it has been a revolution for opportunities for research in biological sciences, which allows new discoveries to be made in the fields of virology, neuroscience and cancer.

Thanks to this project, it has been possible to obtaine the prototype of an innovative new laser that reduces the dimensions of fiber optic-based microscopy equipment and reduces the complexity of the system by improving its operation. In turn it gives greater freedom of selection of the wavelength and spectral line width of the pulses thrown on the biological samples as well as decreases the complexity of the lighting equipment and increases the robustness and half-life (up to more than 10,000 hours), and all at a lower cost. What will allow in addition to obtaining more precise results, reach a greater number of laboratories and research teams, increasing the possibility of obtaining new discoveries that will improve our health.