Femtosecond and picosecond pulses can find many applications if they can be produced with laser sources that are not only powerful and efficient but also compact and reliable. In continuous wave operation, diode pumping of solid-state lasers has allowed for a rapid progress towards powerful, compact and reliable sources, while the often used technique of Kerr lens modelocking for pulsed operation tends to be in conflict with requirements for diode-pumpable high power designs. Passive modelocking with semiconductor saturable absorber mirrors solves this problem as it relaxes the restrictions on the cavity design. We report on our recent achievements in this field. In particular we present a novel semiconductor device for dispersion compensation and various improved diode-pumped passively modelocked lasers. Also we show which laser parameters determine the stability of a passively modelocked lasers against Q-switching instabilities.
The current status of ultrafast fiber lasers is discussed. Recent advances in optical fiber designs as well as improved saturable absorbers have greatly improved the performance and the reliability of ultrafast fiber oscillators. Equally significant have been improvements in ultrafast fiber amplifier designs and compact chirped pulse amplification systems in conjunction with chirped periodically-poled LiNbO3, which now allow the manufacture of compact ultrafast fiber laser systems that can exceed the performance of conventional ultrafast lasers based on bulk optics. The unique size advantage of fiber lasers opens up the field of ultrafast optics to novel OEM-type applications. For example ultrafast fiber lasers have been successfully employed as subsystems in all-optical time delay scanning, for two-photon microscopy as well as for THz pulse generation.
We describe a pulse shaping technique which uses second harmonic generation with Fourier synthetic quasi-phase- matching gratings. We demonstrate both amplitude and phase tailoring by generating a picosecond square-like pulse as well as trains of femtosecond pulses with a terahertz-range repetition rate from either a transform-limited or chirped pump pulse.
We review the progress made in determining the trends in retinal damage from laser pulse from one nanosecond to one hundred femtoseconds in the visible and near-infrared wavelength regimes. These trends have suggested a maximum permissible exposure limit for laser pulses in the retinal hazard regime between one nanosecond and one hundred femtoseconds. We discuss the likely mechanisms for retinal damage and the implications to using ultrashort laser systems safely. We will summarize the challenges in appropriately addressing safety when using ultrashort laser systems in advanced applications.
The medical applications for ultra short pulse lasers (USPLs) and their associated commercial potential are reviewed. Short pulse lasers offer the surgeon the possibility of precision cutting or disruption of tissue with virtually no thermal or mechanical damage to the surrounding areas. Therefore the USPL offers potential improvement to numerous existing medical procedures. Secondly, when USPLs are combined with advanced tissue diagnostics, there are possibilities for tissue-selective precision ablation that may allow for new surgeries that cannot at present be performed. Here we briefly review the advantages of short pulse lasers, examine the potential markets both from an investment community perspective, and from the view of the technology provider. Finally nominal performance and cost requirements for the lasers, delivery systems and diagnostics and the present state of development will be addressed.
We investigated three potential femtosecond laser ophthalmic procedures: intrastromal refractive surgery, transcleral photodisruptive glaucoma surgery and photodisruptive ultrasonic lens surgery. A highly reliable, all-solid-state system was used to investigate tissue effects and demonstrate clinical practicality. Compared with longer duration pulses, femtosecond laser-tissue interactions are characterized by smaller and more deterministic photodisruptive energy thresholds, smaller shock wave and cavitation bubble sizes. Scanning a 5 (mu) spot below the target tissue surface produced contiguous tissue effects. Various scanning patterns were used to evaluate the efficacy, safety, and stability of three intrastromal refractive procedures in animal eyes: corneal flap cutting, keratomileusis, and intrastromal vision correction (IVC). Superior dissection and surface quality results were obtained for the lamellar procedures. IVC in rabbits revealed consistent, stable pachymetric changes, without significant inflammation or corneal transparency degradation. Transcleral photodisruption was evaluated as a noninvasive method for creating partial thickness scleral channels to reduce elevated intraocular pressure associated with glaucoma. Photodisruption at the internal scleral surface was demonstrated by focusing through tissue in vitro without collateral damage. Femtosecond photodisruptions nucleated ultrasonically driven cavitation to demonstrate non-invasive destruction of in vitro lens tissue. We conclude that femtosecond lasers may enable practical novel ophthalmic procedures, offering advantages over current techniques.
The photodynamic properties of several photosensitive compounds have been evaluated in vivo using simultaneous two-photon excitation (TPE) and multi-photon excitation (MPE). TPE and MPE are effected using a mode-locked laser, such as the mode-locked titanium:sapphire or Nd:YLF laser, the near infrared output of which allows direct promotion of various non-resonant transitions. Such lasers are exceptionally well suited for non-linear activation of exogenous or endogenous PDT agents in biological systems due to their extremely short pulse width, modest pulse energy, and high repetition rate; these features combine to effect efficient PDT activation with minimal potential for non- specific biological damage, improved spatial localization of activation, and enhanced depth of penetration. Results in several murine models are presented.
Proc. SPIE 3616, Spatial and temporal characterization of the focusing of ultrashort pulses by high-NA objectives for ultrafast multiphoton microscopy, 0000 (4 June 1999); https://doi.org/10.1117/12.351823
As ultrafast multiphoton microscopes become more useful for biological imaging, a major challenge for researchers is to determine the exposure conditions that provide the best combination of image resolution, contrast and specimen viability. To do this requires an accurate understanding of the spatial and temporal evolution of ultrashort pulses at the focus produced by a microscope objective. The objective itself, however, can significantly alter the pulses. Some effects, such as the broadening of pulses due to group delay dispersion in materials along the path, are understood and partial compensation for them can be made. Other effects, such as radial variations in the propagation time and variations in the pulse width, are less well understood. In this work, we investigate the radially dependent propagation and focusing of ultrashort pulses through a Zeiss CP- Achromat 100X, 1.25 NA, infinity-corrected, oil immersion microscope objective. We also extend to this high numerical aperture case the technique of collinear type II second harmonic generation frequency-resolved optical grating which has previously been used to measure the temporal intensity and phase of ultrashort pulses at the focus of air objectives with lower numerical aperture.
We present potential biomedical applications for a diode- pumped ultrafast Cr:LiSGAF oscillator-amplifier system. A whole-field fluorescence lifetime imaging system has been demonstrated for the first time using such a laser system. Fluorescence lifetime imaging of unstained biological tissue in vitro using this instrument has shown contrast between different tissue constituents. Initial results of applying this laser system to the ablation of glass are also presented.
We report on the development of practical and user friendly lasers for multiphoton imaging of biological material. The laser developed for the work is a laser diode pumped Cr:LiSAF source modelocked using a saturable Bragg reflector as the passive modelocking element. For this system we routinely obtain 100 fs pulses at a repetition rate 200 MHz with an average output power of 20 mW. The laser has a single operator control and is particularly suitable for use by non-laser specialists. We have used the source developed to image a range of biologically significant samples. The initial work has centered on the imaging of intact human dental tissue. The first two-photon images of dental tissue are reported showing the development of early dental disease from depths up to 500 micrometers into the tooth. These results demonstrate the detection of carious lesions before the more conventional techniques currently used by dental practitioners. Work on other living intact biological tissue is also reported, in particular plants containing a genetically bred fluorescent marker to enable the examination of complete and intact living plant tissue.
We tightly focus femtosecond laser pulses in the bulk of a transparent material. The high intensity at the focus causes nonlinear absorption of the laser energy, producing a microscopic plasma and damaging the material. The tight external focusing allows high intensity to be achieved with low energy, minimizing the effects of self-focusing. We report the thresholds for breakdown and critical self- focusing in fused silica using 110-fs pulses at both 400-nm and 800-nm wavelength. We find that permanent damage can be produced with only 10 nJ (25 nJ) for 400-m (800-nm) pulses, and that the threshold for critical self-focusing is 140 nJ for the 400-nm pulses and 580 nJ for the 800-nm pulses. The critical self-focusing thresholds are more than an order of magnitude above the breakdown thresholds, confirming that self-focusing does not play a dominant role in the damage formation. This lack of self-focusing allows a straightforward interpretation of the wavelength and bandgap dependence of bulk breakdown thresholds. The energies necessary for material damage are well within the range of a cavity-dumped oscillator, allowing for precision microstructuring of dielectrics with a high repetition-rate laser that is roughly one-third the cost of an amplified system.
Ablation rates and etched-surface morphology of fused silica has been studied with 1-ps Nd:glass laser pulses in a regime of near-diffraction-limited spot size. Shallow holes of 1.7- micrometers diameter were too small for the formation of laser- induced periodic-surface structures. Atomic-force and scanning-electron microscopy showed that reproducible etch depth and moderately smooth surfaces are attainable for low fluences of 5.5 - 45 J/cm2--the `gentle' ablation regime. Etch depth progressed linearly with the number of laser pulses until the onset of surface swelling and shock- induced microcracks after a critical number Nc of laser pulses, scaling as Nc equals 1.7 + 80/F (fluence F in J/cm2). Below this limit--for accumulated etch depths less than approximately 2 micrometers --3D surface structuring with sub-micron precision is possible with picosecond-laser pulses. In the strong ablation regime (F > 45 J/cm2), surface morphology was poor and microcracking developed within 2 - 4 pulses. These shock-induced microcracking effects were eliminated when a mode-locked train of approximately 400 identical 1-ps pulses, each separated by 7.5 ns, was applied. Very smooth and deep (approximately 30- micrometers ) holes of 7 - 10-micrometers diameter were excised at a total fluence of approximately 100 kJ/cm2, establishing a new means for rapid and precise micromachining of fused silica and other brittle materials.
We utilize a novel hybrid wavelength division multiplexed, optical time division multiplexed (WDM-OTDM) modelocked semiconductor laser for applications in ultrahigh data rate communication links, computer interconnects, and optical sampling applications. The key philosophy behind using a hybrid approach is that state-of-the-art system performance can be achieve without the necessity of operating at the limits of either a pure WDM or OTDM technology platform.
Industrial applications of THz techniques require compact and reliable systems. We have designed and constructed two portable THz systems integrated with femtosecond, erbium- doped fiber lasers. Terahertz emitters based on photoelectron-transport and optically-rectification were tested in the system. With the use of a 10-mW laser pump beam, the signal-to-noise ratio of the system is greater than 5,000. We studied THz beam generation and detection with two different laser wavelengths. Under the consideration of group velocity matching, the frequency response of the THz system is calibrated. Our portable systems have been applied for the coherent measurement of the refractive index and dielectric constant of polymer thin films, which will play an important role in the ongoing quest for higher speeds in integrated circuits. The measurement is based on a comparison of THz phases with and without the film. The refractive index of thin film can be derived according to the phase difference. The system has sufficient sensitivity to perform these measurements on films as thin as 10 microns. We have also used one of these systems for THz measurements of molecular rotation spectra in air/vapor mixtures.
The two counter-propagating waves in a mode-locked ring laser--as opposed to a cw ring laser--can be totally uncoupled in phase. As a result, these lasers can be used as ultra-sensitive detectors of phase shifts, and in particular, laser gyros. Some of the implementations of these laser gyros are reviewed.
Timing stabilization of mode-locked femtosecond laser is reported. Timing fluctuations of mode-locked laser come from the change in gain medium, and the change in cavity length via mechanical vibrations and environmental disturbances. To suppress the gain change, a low noise all-solid-state pump source was used. And the cavity optical length was controlled to be stable with a PZT and a motor driven translation stage. The timing jitter was reduced to be 77 fs.
The timing jitter measurement scheme for low repetition rate pulse train is proposed. Measuring a spectrum of upconverted light generated from frequency mixing with a transform limited reference pulse and a linear-chirped amplified pulse, a relative time lag between two pulses can be obtained. The measurable range and resolution with this method are discussed.
The influence of the peak power, laser wavelength and the pulse duration of near infrared ultrashort laser pulses on the reproduction behavior of Chinese hamster ovary (CHO) cells has been studied. In particular, we determined the cloning efficiency of single cell pairs after exposure to ultrashort laser pulses with an intensity in the range of GW/cm2 and TW/cm2. A total of more than 3500 non- labeled cells were exposed to a highly focused scanning beam of a multiphoton laser microscope with 60 microsecond(s) pixel dwell time per scan. The beam was provided by a tunable argon ion laser pumped mode-locked 76 MHz Titanium:Sapphire laser as well as by a compact solid-state laser based system (Vitesse) at a fixed wavelength of 800 nm. Pulse duration (tau) was varied in the range of 100 fs to 4 ps by out-of- cavity pulse-stretching units consisting of SF14 prisms and blazed gratings. Within an optical (laser power) window CHO cells could be scanned for hours without severe impact on reproduction behavior, morphology and vitality. Ultrastructural studies reveal that mitochondria are the major targets of intense destructive laser pulses. Above certain laser power P thresholds, CHO cells started to delay or failed to undergo cell division and, in part, to develop uncontrolled cell growth (giant cell formation). The damage followed a P2/(tau) relation which is typical for a two- photon excitation process. Therefore, cell damage was found to be more pronounced at shorter pulses. Due to the same P2/(tau) relation for the efficiency of fluorescence excitation, two-photon microscopy of living cells does not require extremely short femtosecond laser pulses nor pulse compression units. Picosecond as well as femtosecond lasers can be used as efficient light sources in safe two photon fluorescence microscopy. Only in three photon fluorescence microscopy, femtosecond laser pulses are advantageous over picosecond pulses.
Fluorescence microscopy is an invaluable technique for investigating structural and biochemical changes in cells and tissues. While it is preferable to study these changes in living specimens, such studies are often compromised by the destructive properties of light which can cause cellular damage either directly (photoablation) or indirectly by generating toxic by-products (phototoxicity). To minimize these problems, new methods of illuminating cells are being developed. In particular, ultrafast infrared lasers have been employed to excite fluorophores at one-half and one- third the wavelength of the laser by a process called multiphoton excitation. This process limits excitation to a small volume of indicator which, together with fast scanning of the sample, may reduce photodamage. One source of photodamage is light-induced stimulation of H2O2 in cells. In this report, we tested whether scanning with an ultrafast Ti:sapphire laser could stimulate H2O2 production in cultured human and monkey cells measured with the fluorescent indicator dichlorodihydrofluorescein. We demonstrate that illumination at 800 - 900 nm induced H2O2 production in cells when laser power was increased above 10 mW (at the specimen plane). The frequency of scanning (duty cycle) also influenced H2O2 production indicating that a trade-off between power and exposure time may be an appropriate way to control this type of toxicity. Alternatively, high power and increased exposure time could provide an effective means for controlling H2O2 production and subsequent damage to cellular structures.