Phase III (Closed) ExtreMed – Extreme Ultrashort Pulses for Advanced Medical Applications and Diagnostics

Summary

In neuroscience, medical imaging and clinical applications, fast non-invasive and non-destructive extraction of detailed cellular and functional behaviour of complex samples are of particular importance.

Multi-photon microscopy has emerged as a powerful research and pre-clinical tool and allows for high quality imaging and deep tissue penetration, rendering it an effective tool for observations of live tissue. For complex sample imaging and functional behaviour mapping, repeated scans are required in standard multi-photon microscopy, increasing the total imaging time and photo-induced damage while fast processes, such as protein-protein interaction, can be missed or only partly imaged due to the narrow wavelength laser excitation per scan.

The scope of ExtreMed is to meet these demands by the use of proprietary and patented technologies to develop the SyncRGB-FLIM multi-color bioimaging technique, where the few-cycle ultra-broadband femtosecond laser promoted single-scan operation, results in advanced imaging with lowered photo-induced damage and extending deep tissue imaging capabilities.

The integrated value proposition of ExtreMed will allow corporate and scientific customers of the microscopy market willing to implement this syncRGB-FLIM technology, based on ultrafast laser systems, within their ecosystem.

Expected Outcomes

  • A fully operational and characterized few cycle laser prototype;
  • A broadband passive pulse shaper;
  • A stand-alone SyncRGB-FLIM system;
  • An in vitro study using SyncRGB-FLIM on commercially available nanodrug delivery system;
  • Publication of scientific papers, PhD and MSc thesis;
  • Participation in technological fairs, national and international conferences, forums and seminars
Start Date – End Date:April 1, 2020 – April 1, 2023
Scientific Area:Nanotechnologies
Keywords:Few-cycle ultra-broadband femtosecond lasers, advanced multiphoton microscopy,
deep tissue bioimaging, lowered photo-induced damage
Lead Beneficiary (PT):
Sphere Ultrafast Photonics, S.A.
Co-beneficiaries:
International Iberian Nanotechnologies Laboratory (INL)


Universidade do Porto
PIs at UT Austin:
Andrew Dunn

(College of Natural Sciences, Department of Biomedical Engineering, UT Austin)

Adela Ben-Yakar

(Cockrell School of Engineering, Walker Department of Mechanical Engineering, UT Austin)
Total Eligible Investment (PT):1 281 911,16 EUR
Total Eligible Investment (US):800 000,00 USD
Funding Sources Distribution: 

Papers and Communications

  • Roy, A., & Ben-Yakar, A. (2023). Numerical studies for exploring the effect of cold surface thermal conditions on two-photon brain imaging. In H. W. Kang, R. Sroka, B. L. Ibey, & N. Linz (Eds.), Optical Interactions with Tissue and Cells XXXIII; and Advanced Photonics in Urology. SPIE. https://doi.org/10.1117/12.2609232
  • Ben-Yakar, A. (2022). LEAD fluorescence microscopy performing at 0.8 million frames per second for 3D imaging flow cytometry. In M. P. Georges, G. Popescu, & N. Verrier (Eds.), Unconventional Optical Imaging III. SPIE. https://doi.org/10.1117/12.2628699
  • Herman, P. R., Osellame, R., & Ben-Yakar, A. (Eds.). (2022). Front Matter: Volume 11991. In Frontiers in Ultrafast Optics: Biomedical, Scientific, and Industrial Applications XXII. SPIE. https://doi.org/10.1117/12.2635766
  • Yazgi, S. G., Camli, B., Andrus, L. P., & Ben-Yakar, A. (2022). An improved fluorescence collection method for two-photon imaging endoscopy. In M. J. Suter, G. J. Tearney, & T. D. Wang (Eds.), Endoscopic Microscopy XVII. SPIE. https://doi.org/10.1117/12.2610023
  • Zhou, A., Engelmann, S. A., Mihelic, S. A., Tomar, A., Hassan, A. M., & Dunn, A. K. (2022). Evaluation of resonant scanning as a high-speed imaging technique for two-photon imaging of cortical vasculature. In Biomedical Optics Express (Vol. 13, Issue 3, p. 1374). Optica Publishing Group. https://doi.org/10.1364/boe.448473
  • Maibohm, C., Ferreira, R., Silvestre, O. F., Romero, R., Crespo, H., & Nieder, J. B. (2021). Ultra-broadband few-cycle laser pulses for simultaneous multi-color fluorescence microscopy applications via the SyncRGB-FLIM method. In E. Beaurepaire, A. Ben-Yakar, & Y. Park (Eds.), Advances in Microscopic Imaging III. SPIE. https://doi.org/10.1117/12.2615698
  • Sytcevich, I., Guo, C., Mikaelsson, S., Vogelsang, J., Viotti, A.-L., Alonso, B., Romero, R., Guerreiro, P. T., Sola, Í. J., L’Huillier, A., Crespo, H., Miranda, M., & Arnold, C. L. (2021). Characterizing ultrashort laser pulses with second harmonic dispersion scans. In Journal of the Optical Society of America B (Vol. 38, Issue 5, p. 1546). Optica Publishing Group. https://doi.org/10.1364/josab.412535
  • Almagro-Ruiz, A., Torres-Peiró, S., Muñoz-Marco, H., Dauliat, R., Jamier, R., Romero, R., Guerreiro, P. T., Cunquero, M., Castro, G., Loza, P., Crespo, H., Roy, P., & Pérez-Millán, P. (2021). Few-cycle all-fiber temporally coherent supercontinuum sources. In P. R. Herman, M. Meunier, & R. Osellame (Eds.), Frontiers in Ultrafast Optics: Biomedical, Scientific, and Industrial Applications XXI. SPIE. https://doi.org/10.1117/12.2577641
  • Maibohm, C., Ferreira, R., Silvestre, O. F., Romero, R., Crespo, H., & Nieder, J. B. (2021). Ultra-broadband few-cycle laser pulses for advanced multi-color FLIM- microscopy. In 2021 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC). 2021 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC). IEEE. https://doi.org/10.1109/cleo/europe-eqec52157.2021.9542513
  • Salgado-Remacha, F. J., Alonso, B., Crespo, H., Cojocaru, C., Trull, J., Romero, R., López-Ripa, M., Guerreiro, P. T., Silva, F., Miranda, M., L’Huillier, A., Arnold, C. L., & Sola, Í. J. (2020). Single-shot d-scan technique for ultrashort laser pulse characterization using transverse second-harmonic generation in random nonlinear crystals. In Optics Letters (Vol. 45, Issue 14, p. 3925). Optica Publishing Group. https://doi.org/10.1364/ol.397033
  • Alonso, B., Torres-Peiró, S., Romero, R., Guerreiro, P. T., Almagro-Ruiz, A., Muñoz-Marco, H., Pérez-Millán, P., & Crespo, H. (2020). Detection and elimination of pulse train instabilities in broadband fibre lasers using dispersion scan. In Scientific Reports (Vol. 10, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41598-020-64109-x

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