Femtosecond laser micromachining can be used either to remove materials or to change a material's properties, and can be applied to both absorptive and transparent substances. Over the past decade, this technique has been used in a broad range of applications, from waveguide fabrication to cell ablation. This review describes the physical mechanisms and the main experimental parameters involved in the femtosecond laser micromachining of transparent materials, and important emerging applications of the technology. Interactions between laser and matter are fascinating and have found a wide range of applications. This article gives an overview of the fundamental physical mechanisms in the processing of transparent materials using ultrafast lasers, as well as important emerging applications of the technology.

Femtosecond laser micromachining in transparent materials

We review recent advances in laser cell surgery, and investigate the working mechanisms of femtosecond laser nanoprocessing in biomaterials with oscillator pulses of 80-MHz repetition rate and with amplified pulses of 1-kHz repetition rate. Plasma formation in water, the evolution of the temperature distribution, thermoelastic stress generation, and stress-induced bubble formation are numerically simulated for NA=1.3, and the outcome is compared to experimental results. Mechanisms and the spatial resolution of femtosecond laser surgery are then compared to the features of continuous-wave (cw) microbeams. We find that free electrons are produced in a fairly large irradiance range below the optical breakdown threshold, with a deterministic relationship between free-electron density and irradiance. This provides a large ‘tuning range’ for the creation of spatially extremely confined chemical, thermal, and mechanical effects via free-electron generation. Dissection at 80-MHz repetition rate is performed in the low-density plasma regime at pulse energies well below the optical breakdown threshold and only slightly higher than used for nonlinear imaging. It is mediated by free-electron-induced chemical decomposition (bond breaking) in conjunction with multiphoton-induced chemistry, and hardly related to heating or thermoelastic stresses. When the energy is raised, accumulative heating occurs and long-lasting bubbles are produced by tissue dissociation into volatile fragments, which is usually unwanted. By contrast, dissection at 1-kHz repetition rate is performed using more than 10-fold larger pulse energies and relies on thermoelastically induced formation of minute transient cavities with lifetimes <100 ns. Both modes of femtosecond laser nanoprocessing can achieve a 2–3 fold better precision than cell surgery using cw irradiation, and enable manipulation at arbitrary locations.

Mechanisms of femtosecond laser nanosurgery of cells and tissues

Recent years have seen a growing interest in using metal nanostructures to control temperature on the nanoscale. Under illumination at its plasmonic resonance, a metal nanoparticle features enhanced light absorption, turning it into an ideal nano-source of heat, remotely controllable using light. Such a powerful and flexible photothermal scheme is the basis of thermo-plasmonics. Here, the recent progress of this emerging and fast-growing field is reviewed. First, the physics of heat generation in metal nanoparticles is described, under both continuous and pulsed illumination. The second part is dedicated to numerical and experimental methods that have been developed to further understand and engineer plasmonic-assisted heating processes on the nanoscale. Finally, some of the most recent applications based on the heat generated by gold nanoparticles are surveyed, namely photothermal cancer therapy, nano-surgery, drug delivery, photothermal imaging, protein tracking, photoacoustic imaging, nano-chemistry and optofluidics.

http://www.guillaume.baffou.com/publications/020-Baffou-LPR.pdf

Thermo‐plasmonics: using metallic nanostructures as nano‐sources of heat

The unique characteristics of ultrafast lasers, such as picosecond and femtosecond lasers, have opened up new avenues in materials processing that employ ultrashort pulse widths and extremely high peak intensities. Thus, ultrafast lasers are currently used widely for both fundamental research and practical applications. This review describes the characteristics of ultrafast laser processing and the recent advancements and applications of both surface and volume processing. Surface processing includes micromachining, micro- and nanostructuring, and nanoablation, while volume processing includes two-photon polymerization and three-dimensional (3D) processing within transparent materials. Commercial and industrial applications of ultrafast laser processing are also introduced, and a summary of the technology with future outlooks are also given. Scientists in Asia have reviewed the role of ultrafast lasers in materials processing. Koji Sugioka from RIKEN in Japan and Ya Cheng from the Shanghai Institute of Optics and Fine Mechanics in China describe how femtosecond and picosecond lasers can be used to perform useful tasks in both surface and volume processing. Such lasers can cut, drill and ablate a variety of materials with high precision, including metals, semiconductors, ceramics and glasses. They can also polymerize organic materials that contain a suitable photosensitizer and can three-dimensionally process inside transparent materials such as glass, and are already being used to fabricate medical stents, repair photomasks, drill ink-jet nozzles and pattern solar cells. The researchers also explain the characteristics of such lasers and the interaction of ultrashort, intense pulses of light with matter.

/pdf/ultrafast-lasers-reliable-tools-for-advanced-materials-vf0u8o1rkp.pdf

Ultrafast lasers—reliable tools for advanced materials processing

http://www.dmphotonics.com/Femtosecond_Imaging/143.pdf

Principles of Two-Photon Excitation Microscopy and Its Applications to Neuroscience

Understanding how nerves regenerate is an important step towards developing treatments for human neurological disease, but investigation has so far been limited to complex organisms (mouse and zebrafish) in the absence of precision techniques for severing axons (axotomy). Here we use femtosecond laser surgery for axotomy in the roundworm Caenorhabditis elegans and show that these axons functionally regenerate after the operation. Application of this precise surgical technique should enable nerve regeneration to be studied in vivo in its most evolutionarily simple form.

Neurosurgery: Functional regeneration after laser axotomy

http://worms.zoology.wisc.edu/pdfs/kal-1_DB.pdf

C. elegans Kallmann syndrome protein KAL-1 interacts with syndecan and glypican to regulate neuronal cell migrations.

We perform submicrometer-scale surgery with femtosecond lasers to study nerve regeneration in the tiny nematode Caenorhabditis elegans, an invertebrate model organism with only 302 neurons. By cutting nanoscale nerve connections inside the nematode C. elegans , the feedback loops that control backward motion of the worm can be disconnected. This operation stops the whole worm from moving backward while leaving its forward motion intact. The femtosecond laser-based axotomy creates little peripheral damage so that the cut axons can regrow, and the worms recover and move backward again within one day. We conduct several assays to assess target specificity, damage threshold, and the extent of femtosecond laser axotomy. We also study nerve regeneration in touch neurons, and report an interesting type of nerve regeneration that salvages the severed parts of neurons from degeneration. The use of femtosecond laser pulses as a precise surgical tool allowed, for the first time, observation and study of nerve regeneration in C. elegans with a simple nervous system. The ability to perform precise axotomy on such organisms provides tremendous research potential for the rapid screening of drugs and for the discovery of new biomolecules affecting regeneration and development

/pdf/nerve-regeneration-in-caenorhabditis-elegans-after-nb4lfchbt2.pdf

Nerve Regeneration in Caenorhabditis elegans After Femtosecond Laser Axotomy

We isolated egl-13 mutants in which the pi cells of the Caenorhabditis elegans uterus initially appeared to develop normally but then underwent an extra round of cell division. The data suggest that egl-13 is required for maintenance of the pi cell fate.

https://www.genetics.org/content/genetics/165/3/1623.full.pdf

The EGL-13 SOX domain transcription factor affects the uterine π cell lineages in Caenorhabditis elegans

PAX-6 proteins are involved in eye and brain development in many animals. In the nematode Caenorhabditis elegans the pax-6 locus encodes multiple PAX-6 isoforms both with and without a paired domain. Mutations in the C. elegans pax-6 locus can be grouped into three classes. Mutations that affect paired domain-containing isoforms cause defects in epidermal morphogenesis, epidermal cell fates, and gonad cell migration and define the class I (vab-3) complementation group. The class II mutation mab-18(bx23) affects nonpaired domain-containing isoforms and transforms the fate of a sensory organ in the male tail. Class III mutations affect both paired domain and nonpaired domain isoforms; the most severe class III mutations are candidate null mutations in pax-6. Class III mutant phenotypes do not resemble a simple sum of class I and class II phenotypes. A comparison of class I and class III phenotypes indicates that PAX-6 isoforms can interact additively, synergistically, or antagonistically, depending on the cellular context.

https://www.genetics.org/content/genetics/168/3/1307.full.pdf

Hediye Nese Cinar

Papers

Neurosurgery: Functional regeneration after laser axotomy

C. elegans Kallmann syndrome protein KAL-1 interacts with syndecan and glypican to regulate neuronal cell migrations.

Nerve Regeneration in Caenorhabditis elegans After Femtosecond Laser Axotomy

The EGL-13 SOX domain transcription factor affects the uterine π cell lineages in Caenorhabditis elegans

Genetic Analysis of the Caenorhabditis elegans pax-6 Locus: Roles of Paired Domain-Containing and Nonpaired Domain-Containing Isoforms