CC BY
14LMI-I-19
Free-electron-mediated effects of single femtosecond pulses and pulse series in the (irradiance/fluence) parameter space
A. Vogel1, X.X. Liang1, S. Freidank1, N. Linz1
1University of Luebeck, Institute of Biomedical Optics, Luebeck, Germany
Laser-induced plasma generation by single and multiple femtosecond laser pulses is used surgically and constitutes also a source of unwanted photodamage in nonlinear microscopy. The irradiance threshold at which transient vapor bubbles in water are produced by single pulses is 20 times higher than the irradiance used for nonlinear microscopy. However, photodamage in multiphoton microscopy already starts, when the irradiance is raised 1.5 times above the value used for autofluorescence imaging. Thus, there is a huge realm of low-density plasma effects between the multi-pulse damage threshold and the single-pulse surgical regime, which has been little explored to date. The talk will provide a systematic overview over laser applications in this regime and the irradiance and radiant exposure dependence of the laser effects.
Single-pulse effects are used for flap-cutting in corneal refractive laser surgery, for cataract surgery, and in cell surgery. The bubble threshold is here determined by a temperature threshold above which a phase transition occurs.
Pulse-series effects, in which a few fs pulses of lower energy overlap, are used for gentle flap-cutting in refractive surgery. Here, dissection relies on molecular disintegration of biomolecules by the interaction with electrons of the low-density plasma, and the bubble produced contains non-condensable gas rather than water vapor. The underlying process is a nonlinear chemical rate process, and the character of the threshold is thus fundamentally different from the single-pulse threshold.
At even lower pulse energies, fs laser irradiation can be employed to create refractive index changes of the corneal tissue for non-ablative treatment of myopia or hyperopia [1]. The n-changes have been attributed to free-electron-induced generation of reactive oxygen species in water, which then create crosslinks in collagen molecules. However, calculations of the free-electron energy spectrum using our model [2] revealed that electrons have sufficient energy to also directly modify collagen molecules.
Photodamage in multiphoton microscopy was explored for various cell types and tissues using physical indicators that enable real-time-monotoring of the photodamage kinetics. We established algorithms that can evaluate the transition from unchanged tissue (emitting 2-photon-excited autofluorescence) to slightly changed tissue (hyperfluorescence), drastically changed tissue (plasma luminescence) and disintegrated biomolecules (gas bubble formation). Series of scans at different irradiance values, I, were evaluated to determine the radiant exposure values, H, for the onset of hyperfluorescence, plasma luminescence, and bubble formation. By plotting these threshold values in (H, I) space, a "safe" region can be identified, in which nonlinear microscopy without photodamage is possible, and the photomodification regime can be delineated.
Altogether, we created a comprehensive picture of photomodification kinetics and mechanisms by fs single- and multipulse irradiation in the realm of low-density plasmas. Exploration of this regime implies many opportunities for novel applications in the future.
References
[1] Wang C., Fomovsky M., Miao G., Zyablitskaya M. and Vukelic, S. Nat. Photon. 12:416-422 (2018).
[2] Liang X.-X., Zhang Z., and Vogel A. Optics Express 27:4672 (2019)
