We have successfully developed a highly-stable commercial femtosecond laser. We achieved continuous operation of femtosecond laser over 4,000 hours.

We show that a simple plane wave analysis can be used even under tight focusing conditions to predict the dependence of third-harmonic generation on the polarization state of the incident beam. Exploiting this fact, we then show that circularly polarized beams may be used to spatially characterize the beam focus and temporally characterize ultrashort pulses in high numerical aperture systems by experimentally demonstrating, for the first time, novel collinear, background-free, third-harmonic intensity autocorrelations in time and space in a high numerical aperture microscope.

Fiber optics provide a convenient way to deliver light to remote locations otherwise optically inaccessible. Arguably, optical fibers represent the most effective means of delivering optical radiation through nearly arbitrary paths. The delivery of ultrashort pulses through fibers is a topic of interest for a variety of applications yet constitutes a challenge due to the physical interaction between the intense light fields and the bulk constituents of the fiber. The nonlinear optical effects that take place induce a variety of distortion on the pulses which alter the features of the optical field at the output of the fiber. The ability to control these nonlinearities and use them as means to passively control the pulse characteristics at the output end of the fiber would be of extreme practical use. Phase sensitive pulse measurement techniques are a crucial element needed for the characterization of the pulses and to control their shape so that fibers and femtosecond phenomena may coexist effectively and advantageously.

Biomedical applications of low-energy (< 2nJ) near infrared (NIR) femtosecond laser pulses provided by compact, turn-key Ti:sapphire lasers are presented in this review. Applications include (i) ultrahigh resolution optical diagnostics ("optical biopsies"), (ii) gene therapy by optical targeted transfection of cells, and (iii) ultraprecise laser therapy ("nanosurgery"). The novel femtosecond laser system DermaInspec (JenLab GmbH) enables for the first time in vivo deep tissue imaging of intracellular compartments with submicron spatial and picosecond temporal resolution in patients with dermatological disorders. Using the system FemtOcut, intracellular surgery, optical gene transfer, and intraocular refractive surgery can be performed. The major process behind the diagnostical and therapeutical laser effects is non-resonant multiphoton absorption which results in two-photon autofluorescence and second harmonic generation at transient intensities of GW/cm² as well as multiphoton ionization and plasma formation at TW/cm² intensities, respectively.

When ultrashort laser pulses are focused inside transparent materials, extremely high field intensities can easily be achieved in the focal volume leading to nonlinear interaction with the material. In corneal tissue this nonlinear interaction results in an optical breakdown that may serve as a cutting mechanism in ophthalmology. As a side effect of optical breakdown in corneal tissue, streak-like structures have been observed as discoloration in histological sections under a light microscope. To investigate the streak formation, a numerical model including nonlinear pulse propagation due to self-focusing, group velocity dispersion, and plasma defocusing due to generated free electrons is presented. The model consists of a (3+1)-dimensional nonlinear Schroedinger equation, describing the pulse propagation coupled to an evolution equation covering the generation of free electrons. The rate equation contains multi photon ionization as well as avalanche ionization. The model is applicable to any transparent Kerr-medium.

Nd:glass femtosecond laser is promising as next generation mini-invasive eye surgical laser, with the advantages of excellent beam quality, high surgical precision and minimized side effects. However, there are still many open questions concerning the precision, efficiency and collateral effects of femtosecond laser refractive surgery. By non-invasive microscopic imaging methods including confocal, multiphoton, second harmonic and atomic force microscopy, we successfully characterized the three dimensional corneal ultrastructure without applying fixation and slicing. Based on the intrinsic properties of collagen, second harmonic cornea imaging proved to be outstanding to analyze the outcome of femtosecond laser intrastromal ablations. Strong contrast and large sensing depth second harmonic image was obtained without fixation, sectioning or labelling. The three dimensional ultrastructure of porcine cornea after Nd:glass femtosecond laser intrastromal surgery was examined to evaluate the concepts of minimum-invasive all-optical refractive eye surgery. No thermal damages were recognized and the surgical outcome appeared highly predictable. Due to the similarities between the physical principals of nonlinear laser scanning microscopy and femtosecond laser ablations, a setup of the Nd:glass femtosecond laser system integrating both the surgery and probing functions was proposed.

We report the use of sub-picosecond near-IR and ps UV pulsed lasers for precision ablation of freshly extracted human teeth. The sub-picosecond laser wavelength was ~800nm, with pulsewidth 150 fs and pulse repetition rate of 1kHz; the UV laser produced 10 ps pulses at 266 nm with pulse rate of ~1.2x10⁵ pulses/s; both lasers produced ~1 W of output energy, and the laser fluence was kept at the same level of 10-25 J/cm². Laser radiation from both laser were effectively absorbed in the teeth enamel, but the mechanisms of absorption were radically different: the near-IR laser energy was absorbed in a plasma layer formed through the optical breakdown mechanism initiated by multiphoton absorption, while the UV-radiation was absorbed due to molecular photodissociation of the enamel and conventional thermal deposition. The rise in the intrapulpal temperature was monitored by embedded thermocouples, and was shown to remain low with subpicosecond laser pulses, but risen up to 30°C, well above the 5°C pain level with the UV-laser. This study demonstrates the potential for ultra-short-pulsed lasers to precision and painless ablation of dental enamel, and indicated the optimal combination of laser parameters in terms of pulse energy, duration, intensity, and repetition rate, required for the laser ablation rates comparable to that of mechanical drill.

Ultrashort laser pulses can be used to create high precision incision in transparent and translucent tissue with minimal damage to adjacent tissue. These performance characteristics meet important surgical requirements in ophthalmology, where femtosecond laser flap creation is becoming a widely used refractive surgery procedure. We summarize clinical findings with femtosecond laser flaps as well as early experiments with other corneal surgical procedures such as corneal transplants. We also review laser-tissue interaction studies in the human sclera and their consequences for the treatment of glaucoma.

The pulse train from a Mark III FEL tuned to a wavelength of 6.45 microns has been shown to be efficient at ablating soft tissue with minimal collateral damage. This laser has a unique pulse structure consisting of a train of 1ps micropulses spaced 350ps apart, which is maintained for 4-5 microseconds (the macropulse) and is repeated at 1-30Hz. We are investigating the role of the pulse structure in the ablation mechanism. In order to determine the importance of non-linear effects potentially induced by the high peak power of the micropulses, we are using a grating pulse stretcher optimized for 6.45 microns to vary the micropulse duration while maintaining the macropulse duration and micropulse frequency. The technique allows use of the same pulse energy and average power with widely variable peak power. Ablation thresholds were measured using PROB-IT analysis and crater depths were measured using OCT imaging. In water, gelatin, and mouse dermis, we have found no statistically significant difference in the ablation threshold of pulses having widths of 1, 30, 60, and 100ps. The measured ablation efficiency of mouse dermis also showed no significant difference over the same range of pulse widths. This data suggests that the ablation characteristics obtained with the FEL at 6.45 microns are independent of the micropulse duration and do not rely on the high peak power of the FEL pulse train.

Simultaneous detection of second harmonic generation (SHG), third harmonic generation (THG) and multiphoton excitation fluorescence with ultrafast laser pulses from a Nd:Glass laser was used to image isolated adult rat cardiomyocytes. The simultaneous detection enabled visualization of different organelles of cardiomyocytes, based on the different contrast mechanisms. It was found that SHG signal depicted characteristic patterns of sarcomeres in a myofilament lattice. The regular pattern of the THG signal, which was anticorrelated with the SHG signal, suggested that the third harmonic is generated within mitochondria. By labeling the cardiomyocytes with the mitochondrial dye tetramethylrhodamine methyl ester (TMRM), comparisons could be made between the TMRM fluorescence, THG, and SHG images. The TMRM fluorescence had significant correlation with THG signal confirming that part of the THG signal originates from mitochondria.

Time-correlated single photon counting (TCSPC) is based on the detection of single photons of a periodic light signal, measurement of the detection time of the photons, and the build-up of the photon distribution versus the time in the signal period. TCSPC achieves a near ideal counting efficiency and transit-time-spread-limited time resolution for a given detector. The drawback of traditional TCSPC is the low count rate, long acquisition time, and the fact that the technique is one-dimensional, i.e. limited to the recording of the pulse shape of light signals. We present an advanced TCSPC technique featuring multi-dimensional photon acquisition and a count rate close to the capability of currently available detectors. The technique is able to acquire photon distributions versus wavelength, spatial coordinates, and the time on the ps scale, and to record fast changes in the fluorescence lifetime and fluorescence intensity of a sample. Biomedical applications of advanced TCSPC techniques are time-domain optical tomography, recording of transient phenomena in biological systems, spectrally resolved fluorescence lifetime imaging, FRET experiments in living cells, and the investigation of dye-protein complexes by fluorescence correlation spectroscopy. We demonstrate the potential of the technique for selected applications.

A laser driven electron x-ray source (LEXS) emitting tungsten L_α lines has been built based on a high repetition rate, terawatt laser system. The Lα characteristic lines overlap with the absorption edge of Ni near 8333 eV. Using this x-ray source, the x-ray absorption spectra near the absorption edge of different Ni compounds have been measured. We term this new method "ultrafast selected energy x-ray absorption spectroscopy (USEXAS)." It provides an efficient way to study ultrafast reaction dynamics of many metal complexes in solution.

When femtosecond laser pulses are focused inside the bulk of transparent materials, the intensity in the focal volume becomes high enough to produce permanent structural modifications. This technique has been applied to fabricate three-dimensional photonic structures such as optical memory, waveguides, gratings, and couplers inside a wide variety of transparent materials. In this paper, we review fabrication of photonic elements in glasses with femtosecond laser pulses, including fabrication of waveguides, couplers, volume gratings, zone plates, holographic memory, and micro channels.

Conventional manufacturing of individual ceramic dental prosthesis implies a handmade metallic framework, which is then veneered with ceramic layers. In order to manufacture all-ceramic dental prosthesis a CAD/CAM system is necessary due to the three dimensional shaping of high strength ceramics. Most CAD/CAM systems presently grind blocks of ceramic after the construction process in order to create the prosthesis. Using high-strength ceramics, such as Hot Isostatic Pressed (HIP)-zirconia, this is limited to copings. Anatomically shaped fixed dentures have a sculptured surface with small details, which can't be created by existing grinding tools. This procedure is also time consuming and subject to significant loss in mechanical strength and thus reduced survival rate once inserted. Ultra-short laser pulses offer a possibility in machining highly complex sculptured surfaces out of high-strength ceramic with negligible damage to the surface and bulk of the ceramic. In order to determine efficiency, quality and damage, several laser ablation parameters such as pulse duration, pulse energy and ablation strategies were studied. The maximum ablation rate was found using 400 fs at high pulse energies. High pulse energies such as 200μJ were used with low damage in mechanical strength compared to grinding. Due to the limitation of available laser systems in pulse repetition rates and power, the use of special ablation strategies provide a possibility to manufacture fully ceramic dental prosthesis efficiently.

Dielectric oxide and fluoride films used for optical coatings are studied with femtosecond laser pulses with respect to their breakdown and pre-breakdown behavior. A phenomenological model with only three figures of merit is used to explain the measured breakdown thresholds for pulse durations from 25 fs to 1 ps. The temporal evolution of the dielectric constant in the pre-breakdown regime is obtained from transient reflection and transmission measurements after taking into account standing wave effects of pump and probe. In addition to electron-electron and electron-phonon scattering processes, the creation of a new sample state after a few hundred fs is observed. The experimental data are explained with a computer simulation based on the Boltzmann equation.

Femtosecond laser systems offer a good solution for the creation of straight microcuts and grooves on macroscopic workpieces, as they are becoming more established in industrial applications. Although such linear ablation processes have been investigated and improved before, the main obstacle is still the long processing time. Increasing the processing speed by applying high pulse energies usually leads to a significant quality loss. Using high pulse repetition rates at low pulse energies would lead to the best results, but the repetition rate of commercially available laser sources is mostly restricted to one to several kilohertz. However, a systematic investigation of further relevant parameters enables the processing quality and speed to be optimized. To demonstrate these relations, cuts and grooves using different motion parameters and focusing strategies are presented at the example of metal and silicon samples. With regard to the focusing strategy, it is shown that by using linear focus shapes in the direction of the cut, cutting speeds can be increased while maintaining high edge qualities of the cuts and grooves. The presented results prove the potential of femtosecond lasers for high quality cuts in different industrially relevant materials.

In the course of increasing miniaturization of components in minimal access surgery the superelastic properties of nickel titanium shape memory alloys (NiTi-SMA) find more and more attention. However, only a few processes are available for machining of miniaturized NiTi-components. Changes of the mechanical properties due to heat input or mechanical tensions have to be avoided. Especially for complex geometries with dimensions in the submillimeter-range, these requirements are hardly to meet. Finding new methods for manufacturing micro-instruments of NiTi wires with high geometrical resolution and superelastic mechanical properties for applications in endoscopic surgery are the main goals of the investigations presented here. Because of the precise focussing properties and the possibility of an excellent non-tactile energy coupling, material processing by lasers is a suitable alternative to conventional machining-processes. Comparing investigations with laser systems with different wavelengths and pulse duration show the suitability of ultra-short pulse Ti:Sapphire lasers for this machining process. Only by the use of ultra-short laser pulses it is possible to structure micro-components of NiTi almost without thermal influence. Results of mechanical and metallographic examinations show that the special properties of miniaturized SMA-components can be maintained. Experimental results as well as example geometries produced with ultra-short pulse lasers are presented in the paper.

The fabrication of waveguides inside transparent media using ultrashort laser pulses has gained a lot of interest during the past years. When these intense pulses are tightly focused inside the material a refractive index increase in the focal volume can be achieved. Low-loss waveguides and true three-dimensional integrated optical devices have been produced by this direct writing technique in silicate glasses. However, other materials like phosphate glasses or crystalline quartz show a different behavior. In this case stress is induced around the focal volume leading to a refractive index increase in the surrounding areas (inverse profile). As a consequence high quality waveguides with a mode profile matched to conventional fibers cannot be fabricated. In this presentation we demonstrate a new approach to overcome this problem. The laser beam is split by a transmission grating and simultaneously focused at two different areas. When the distance between the two foci is appropriate the desired refractive index profile is obtained. We will demonstrate high quality waveguides in crystalline quartz and in phosphate glasses produced by this technique. The influence of the processing parameters is discussed in detail.

We report on the generation of sub-30fs pulses from a mirror-dispersion-controlled (MDC) Ti:sapphire oscillator, containing a multiple-pass Herriott-cell for increasing the cavity length. Using that scheme, repetition rates down to some few MHz could be achieved. To avoid multiple pulsing instabilities, we operate the laser in a regime of slight positive group-delay dispersion (GDD) over a very broad wavelength range. This results in the formation of strongly chirped light pulses, reducing the otherwise very high peak-intensity inside the laser crystal, which would limit the maximum output energy. We have investigated the spectral phase associated with these pulses with the help of the well known SPIDER-technique, and, based on the results, have constructed an optimized compressor. When pumped with the full 10 W of a frequency-doubled Nd:YVO₄ laser (Coherent Verdi V10), output energies well above 200 nJ could be obtained. As no signs of instabilities were observed, we believe, that our approach is scaleable to even higher energies if more powerful pump lasers are used. Thanks to the excellent beam profile, high-resolution micromachining of various materials, including transparent dielectrica could be demonstrated. Results on sub-micrometer surface modification of transparent materials will be presented.

We have comparatively studied waveguide fabrication characteristics in various transparent materials by use of temporally shaped femtosecond laser pulses. The materials which we studied here are fused quartz, K-PG375 glass whose melting point is as low as 648 K, and polymethylmethacrylate (PMMA). We have measured amount of refractive index change, writing speed, and laser fluence threshold for waveguide writing in the above mentioned materials. To optimize the optical quality of internal modification of transparent materials by femtosecond laser pulses, we controlled the free electron density induced in the materials by tailoring energy injection as a function of time.

The study of neurovascular diseases such as vascular dementia and stroke require novel models of targeted vascular disruption in the brain. We describe a model of microvascular disruption in rat neocortex that uses ultrashort laser pulses to induce localized injury to specific targeted microvessels and uses two-photon microscopy to monitor and guide the photodisruption process. In our method, a train of high-intensity, 100-fs laser pulses is tightly focused into the lumen of a blood vessel within the upper 500 μm of cortex. Photodisruption induced by these laser pulses creates injury to a single vessel located at the focus of the laser, leaving the surrounding tissue intact. This photodisruption results in three modalities of localized vascular injury. At low power, blood plasma extravasation can be induced. The vessel itself remains intact, while serum is extravasated into the intercellular space. Localized ischemia caused by an intravascular clot results when the photodisruption leads to a brief disturbance of the vascular walls that initiates an endogenous clotting cascade. The formation of a localized thrombus stops the blood flow at the location of the photodisruption. A hemorrhage, defined as a large extravasation of blood including plasma and red blood cells, results when higher laser power is used. The targeted vessel does not remain intact.