Application of femtosecond‐pulsed lasers for direct optical manipulation of biological functions

Abstract

Absorption of photon energy by cells or tissue can evoke photothermal, photomechanical, and photochemical effects, depending on the density of the deposited energy. Photochemical effects require a low energy density and can be used for reversible modulation of biological functions. Ultrashort-pulsed lasers have a high intensity due to the short pulse duration, despite its low average energy. Through nonlinear absorption, these lasers can deliver very high peak energy into the submicrometer focus area without causing collateral damage. Absorbed energy delivered by ultrashort-pulsed laser irradiation induces free electrons, which can be readily converted to reactive oxygen species (ROS) and related free radicals in the localized region. Free radicals are best known to induce irreversible biological effects via oxidative modification; however, they have also been proposed to modulate biological functions by releasing calcium ions from intracellular organelles. Calcium can evoke variable biological effects in both excitable and nonexcitable cell types. Controlled stimulation by ultrashort laser pulses generate intracellular calcium waves that can modulate many biological functions, such as cardiomyocyte beat rate, muscle contractility, and blood-brain barrier (BBB) permeability. This article presents optical methods that are useful therapeutic and research tools in the biomedical field and discuss the possible mechanisms responsible for biological modulation by ultrashort-pulsed lasers, especially femtosecond-pulsed lasers.

Ultrasmall Chitosan–Genipin Nanocarriers Fabricated from Reverse Microemulsion Process for Tumor Photothermal Therapy in Mice

“…Temperature of all samples increased rapidly at the first 5 min then gradually in accordance with the results in vitro (Fig. 8B) reported that even below the plasma formation threshold energy, laser pulses can also induce irreversible damage to the biological sample by reduction of enzyme activity, protein denaturation and increase in cell membrane stress 38 . In this case, CG-PEG-ICG nanoparticles with ICG concentration of 100, 200 and 500 μg·mL -1 induced irreversible tissue damage which was confirmed in Fig.…”

Cytosolic Irradiation of Femtosecond Laser Induces Mitochondria-dependent Apoptosis-like Cell Death via Intrinsic Reactive Oxygen Cascades

“…Our group has recently been engaged in the development of new optical methods that can be used for reversible modulation of biological functions by utilizing femtosecond-pulsed lasers. We have demonstrated that laser-induced photobiomodulation can be mediated by laser-induced intracellular ROS 1 3 . We reported previously that femtosecond laser stimulation induces two distinctive responses in primary cultured smooth muscle cells, i.e., reversible and irreversible responses, depending on the energy delivered 3 .…”

“…Focused irradiation of high-intensity femtosecond laser can induce non-linear optical effects, such as multiphoton absorption and frequency doubling. As these non-linear phenomena can only occur in the tightly focused area, this reduces out-of-focus signals and has been applied in the field of biomedical imaging as multiphoton microscopy 1 . Recently, it has been reported that femtosecond laser pulses can be used to regulate biological functions, such as muscle contraction 2 3 , blood-brain barrier permeabilization 4 , cellular activation 5 6 , and gene transfection 7 , which is known as reversible biophotomodulation.…”

“…Most intracellular ROS are generated as byproducts of oxidative phosphorylation in the mitochondria, which play a vital role in activation of intrinsic cell death process by releasing proapoptotic proteins 11 . Although laser-induced ROS regulate biological function in a reversible manner 1 3 , they are also related to the laser-induced cytotoxicity 9 12 . The exact molecular mechanisms by which optical stimulation may induce cytotoxicity remain unclear, although membrane disruption has been proposed as one possibility.…”

Phase and polarization changes of pulsed Gaussian beams during focusing and propagation

“…In areas that are closer to everyday life or direct applications, femtosecond lasers have shown their beneficial properties in material processing [50]. In addition, medical utilization is manifold as well, people just have to think about the therapeutic [51], surgical [52] or imaging methods they are used for [53].…”