Multimodal label-free optical microscopy for in vivo and in situ imaging of human tissue represents a challenge especially when nonlinear optical techniques are used. One possible solution to address this challenge is the use of specific hand-held and endomicroscopy probes, based on optical fibers, capable to image at the same time the chemical composition and the morphological structure of the tissues. Nonlinear optical imaging techniques, including TPEF, SHG, spectral focusing CARS, combined with spectral domain OCT are capable to give functional, molecular and morphological information. Since nonlinear optical microscopy and SD-OCT require ultrashort pulses to efficiently image the targeted sample, the development of such probes requires specific attention to high peak power and ultrashort pulse delivery at the focal plane. Different optical fiber technologies for femtosecond pulse delivery are experimentally investigated in order to suggest an optical fiber that fulfill at the same time the requirements for above mentioned imaging modalities. We investigated three different approaches that are normally considered for ultrashort pulse delivery: large-mode area (LMA) fiber, hollow-core photonic bandgap fiber and kagome hollow-core fiber from GLOphotonics. We tested this three fibers on our label-free multimodal imaging platform which is capable to simultaneously acquire TPEF, SHG, spectral focusing CARS and SD-OCT. From our investigation, we identify the fiber which better satisfy the requirements of all the above mentioned imaging modalities in terms of dispersion profile and transmission of high energy pulses. Imaging capabilities are shown on a biological tissue of interest.
We have developed an epi-detected multimodal nonlinear optical microscopy platform based on a compact and cost-effective laser source featuring simultaneous acquisition of signals arising from hyperspectral coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence, and second harmonic generation. The laser source is based on an approach using a frequency-doubled distributed Bragg reflector-tapered diode laser to pump a femtosecond Ti:sapphire laser. The operational parameters of the laser source are set to the optimum trade-off between the spectral and temporal requirements for these three modalities, achieving sufficient spectral resolution for CARS in the lipid region. The experimental results on a biological tissue reveal that the combination of the epi-detection scheme and the use of a compact diode-pumped femtosecond solid-state laser in the nonlinear optical microscope is promising for biomedical applications in a clinical environment.
Femtosecond near infrared laser microscopes are widely used to perform high resolution 3D imaging of biological samples based on second harmonic generation (SHG) and non-resonant simultaneous absorption of two or more photons at GW/cm2 intensities. However, high contrast imaging of living specimens without any destructive effect is limited to certain laser and exposure parameters with respect to the optical properties of the target.
We compared three different femtosecond lasers, including a novel ultra-compact ultrashort fiber laser, in the range of 15-180 fs and repetition rates of 50–300 MHz for optimal non-destructive two-photon autofluorescence imaging. In particular we determined the thresholds for the onset of photodamage effects such as impaired cell reproduction.
Diode-pumping Ti:sapphire lasers promises a new approach to low-cost femtosecond light sources. Thus in recent years much effort has been taken just to overcome the quite low power and low beam qualities of available green diodes to obtain output powers of several hundred milliwatts from a fs-laser. In this work we present an alternative method by deploying frequency-doubled IR diodes with good beam qualities to pump fs-lasers. The revolutionary approach allows choosing any pump wavelengths in the green region and avoids complicated relay optics for the diodes. For the first time we show results of a diode-pumped 10 fs-laser and how a single diode setup can be integrated into a 30 x 30 cm2 fs-laser system generating sub 20 fs laser pulses with output power towards half a Watt. This technology paves the way for a new class of very compact and cost-efficient fs-lasers for life science and industrial applications.
A single-pass frequency doubled high-power tapered diode laser emitting nearly 1.3 W of green light suitable for direct
pumping of Ti:sapphire lasers generating ultrashort pulses is demonstrated. The pump efficiencies reached 75 % of the
values achieved with a commercial solid-state pump laser. However, the superior electro-optical efficiency of the diode
laser improves the overall efficiency of the Ti:sapphire laser by a factor > 2. The optical spectrum emitted by the
Ti:sapphire laser shows a spectral width of 112 nm (FWHM). Based on autocorrelation measurements, pulse widths of
less than 20 fs are measured. These results open the opportunity of establishing diode laser pumped Ti:sapphire lasers for
e.g. biophotonic applications like retinal optical coherence tomography or pumping of photonic crystal fibers for CARS
microscopy.
A simple and robust diode laser system emitting 1.28 W of green light suitable for pumping an ultrafast Ti:sapphire laser
is presented. To classify our results, the diode laser is compared to a standard, commercially available diode pumped
solid-state (DPSS) laser system pumping the same oscillator. When using our diode laser system, the optical conversion
efficiencies from green to near-infrared light reduces to 75 % of the values achieved with the commercial pump laser.
Despite this reduction the overall efficiency of the Ti:sapphire laser is still increased by a factor > 2 due to the superior
electro-optical efficiency of the diode laser. Autocorrelation measurements show that pulse widths of less than 20 fs can
be expected with an average power of 52 mW when using our laser. These results indicate the high potential of direct
diode laser pumped Ti:sapphire lasers to be used in applications like retinal optical coherence tomography (OCT) or
pumping of photonic crystal fibers for CARS (coherent anti-stokes Raman spectroscopy) microscopy.
Ultrashort pulse fiber delivery for Ti:Sapphire lasers is basically restricted to distances below a few meters which is due
to the application of dispersion compensating devices that are not capable of managing third and higher order material
dispersion. By the use of a fiber delivery concept based on higher order mode fibers ultrashort laser pulses in the 800 nm
wavelength range are transmitted over 20 meters without the need for pulse pre-chirping. For the first time a large
distance fiber delivery module is demonstrated, revealing its potential for remote THz imaging or spectroscopy using
ultrashort laser pulses. Application of the fiber delivery is demonstrated by generating and detecting broadband THz
radiation at the fiber output.
Circularly polarized, 25 fs 5 mJ pulses generated at a repetition rate of 1 kHz from a two-stage chirped pulse amplifier
were spectrally broadened by means of nonlinear propagation in a Ne-filled hollow fiber. Subsequent compression with
dispersive mirrors resulted in 5.2 fs, 1.7 mJ pulses. After recompression an all-reflective achromatic phase retarder was
used to obtain linear polarization.
Although fiber delivery of 25 fs laser pulses were recently shown possible reported results are restricted to 1 to 2 m
single-mode optical fiber due to the high amount of group delay dispersion, guiding losses or fiber nonlinearities. On the
other hand conceivable applications of ultrashort laser pulses in inhospitable environment, their use for security or even
telecommunication purposes require optical pulses to be delivered over much longer fiber distances. Here we
demonstrate 160 fs laser pulses from a Ti:Sapphire laser travelling over 45 m optical fiber. In theory even 130 fs can be
sent through 50 m single-mode fiber with the herein described technique.
Latest advances in femtosecond technology have strongly emphasized the control of ultra-short pulses in many
applications where the preservation of the pulse duration is most important. Recently, the delivery of ultra-short pulses
through optical fibers has become possible which opens up remarkable chances for simplifying optical setups or reaching
inaccessible regions. In this study we report on fiber delivery of 2 nJ and sub 65 fs pulses from a Ti:Sapphire laser
through 1.5 m LMA photonic crystal fiber. Application of such a fiber in an all-integrated THz imaging system to obtain
contactless information on the doping concentration of semiconductor wafers is shown.
The ability of ultra-high-resolution optical coherence tomography (UHR OCT) to discriminate between healthy and pathological human brain tissue is examined by imaging ex vivo tissue morphology of various brain biopsies. Micrometer-scale OCT resolution (0.9×2 µm, axial×lateral) is achieved in biological tissue by interfacing a state-of-the-art Ti:Al2O3 laser (c=800 nm, =260 nm, and Pout=120 mW exfiber) to a free-space OCT system utilizing dynamic focusing. UHR OCT images are acquired from both healthy brain tissue and various types of brain tumors including fibrous, athypical, and transitional meningioma and ganglioglioma. A comparison of the tomograms with standard hematoxylin and eosin (H&E) stained histological sections of the imaged biopsies demonstrates the ability of UHR OCT to visualize and identify morphological features such as microcalcifications (>20 µm), enlarged nuclei of tumor cells (~8 to 15 µm), small cysts, and blood vessels, which are characteristic of neuropathologies and normally absent in healthy brain tissue.
The feasibility of ultrahigh resolution optical coherence tomography (UHR OCT) to image ex vivo and in vitro brain tissue morphology on a scale from single neuron cells to a whole animal brain was investigated using a number of animal models. Sub-2-µm axial resolution OCT in biological tissue was achieved at different central wavelengths by separately interfacing two state-of-the-art broad bandwidth light sources (titanium:sapphire, Ti:Al2O3 laser, c = 800 nm, = 260 nm, Pout = 50 mW and a fiber laser light source, c = 1350 nm, = 470 nm, Pout = 4 mW) to free-space or fiber-based OCT systems, designed for optimal performance in the appropriate wavelength regions. The ability of sub-2-µm axial resolution OCT to visualize intracellular morphology was demonstrated by imaging living ganglion cells in cultures. The feasibility of UHR OCT to image the globular structure of an entire animal brain as well as to resolve fine morphological features at various depths in it was tested by imaging a fixed honeybee brain. Possible degradation of OCT axial resolution with depth in optically dense brain tissue was examined by depositing microspheres through the blood stream to various depths in the brain of a living rabbit. It was determined that in the 1100 to 1600-nm wavelength range, OCT axial resolution was well preserved, even at depths greater than 500 µm, and permitted distinct visualization of microspheres 15 µm in diameter. In addition, the OCT image penetration depth and the scattering properties of gray and white brain matter were evaluated in tissue samples from the visual cortex of a fixed monkey brain.
A compact, low cost prismless Titanium:sapphire laser with 154nm bandwidth and 20mW output power was developed and ultrahigh resolution OCT ex vivo imaging in an animal model with sub-2μm and in vivo imaging in patients with 3μm axial resolution is demonstrated. This light source not only significantly reduces costs for broadband OCT light sources, but has also great potential for clinical OCT applications due to its small footprint (500x200mm including pump laser), user-friendliness and power stability.
By integration of a semiconductor mirror into a chirped mirror based Ti:Sapphire oscillator a very compact pulsed Terahertz source is demonstrated. Terahertz radiation is generated by a transient photocurrent in a LT-GaAs layer grown on a semiconductor saturable absorber mirror. This technique allows the manufacturing of ultra-stable, small-size (600 x 200 mm) and self-starting THz systems pushing forward the usability and availability for commercial pulsed Terahertz sources. The Terahertz spectrum goes up to 3 THz and average output power of about 7 μW is achieved.
Although the plasma properties of CO2 gas lasers have been extensively investigated there seems to be remaining uncertainties concerning the achievement of an optimized plasma state giving the best possible laser efficiency. Such optimization would be especially for high power lasers where a loss of some percents in efficiency can mean a considerable decrease for the laser output. To investigate the effects of plasma vs. rf interactions in longitudinal fast-flow CO2 lasers a sufficient adequate plasma theory is used, based on the cross-sections of all involved processes. The main interest lies in the determination of all relevant parameters such as the electric field and current density along the electrodes which have pronounced dependencies on gas temperature and pressure. Although these variables change enormously in downstream direction the model reveals plasma coefficients which stay as unchangeable constants. Moreover, as is common for longitudinal fast-flow CO2 lasers the electrodes are slightly inclined to obtain an increased laser performance, independent of the rf matching. By a rather simple consideration of plasma and rf interactions this effect can be basically explained so that an optimization for the best attainable efficiency is possible. The calculations are compared to measurements of different authors and are applied to a 6 kW fast flow coaxial system.
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