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Ex vivo nonlinear microscopy imaging of Ehlers-Danlos syndrome-affected skin
by Norbert Kiss, Dóra Haluszka, Kende Lőrincz, Enikő Kuroli, Judit Hársing, Balázs Mayer, Sarolta Kárpáti, György Fekete, Róbert Szipőcs, Norbert Wikonkál, Márta Medvecz || 2018
Abstract:
Ehlers–Danlos syndrome (EDS) is the name for a heterogenous group of rare genetic connective tissue disorders with an
overall incidence of 1 in 5000. The histological characteristics of EDS have been previously described in detail in the late
1970s and early 1980s. Since that time, the classification of EDS has undergone significant changes, yet the description of
the histological features of collagen morphology in different EDS subtypes has endured the test of time. Nonlinear microscopy
techniques can be utilized for non-invasive in vivo label-free imaging of the skin. Among these techniques, two-photon
absorption fluorescence (TPF) microscopy can visualize endogenous fluorophores, such as elastin, while the morphology
of collagen fibers can be assessed by second-harmonic generation (SHG) microscopy. In our present work, we performed
TPF and SHG microscopy imaging on ex vivo skin samples of one patient with classical EDS and two patients with vascular
EDS and two healthy controls. We detected irregular, loosely dispersed collagen fibers in a non-parallel arrangement in the
dermis of the EDS patients, while as expected, there was no noticeable impairment in the elastin content. Based on further
studies on a larger number of patients, in vivo nonlinear microscopic imaging could be utilized for the assessment of the
skin status of EDS patients in the future.
Quantitative Analysis on Ex Vivo Nonlinear Microscopy Images of Basal Cell Carcinoma Samples in Comparison to Healthy Skin
by Norbert Kiss, Dóra Haluszka, Kende Lőrincz, Nóra Gyöngyösi, Szabolcs Bozsányi, András Bánvölgyi, Róbert Szipőcs, Norbert Wikonkál || 2018
Abstract:
Basal cell carcinoma (BCC) is the most frequent malignant neoplasm in the Caucasian population. There are several therapeutic
options for BCC, but surgical excision is considered gold standard treatment. As BCCs often have poorly defined borders, the
clinical assessment of the tumor margins can be challenging. Therefore, there is an increasing demand for efficient in vivo
imaging techniques for the evaluation of tumor borders prior to and during surgeries. In the near future, nonlinear microscopy
techniques might meet this demand.We measured the two-photon excitation fluorescence (TPEF) signal of nicotinamide adenine
dinucleotide hydride (NADH) and elastin and second harmonic generation (SHG) signal of collagen on 10 ex vivo healthy control
and BCC skin samples and compared the images by different quantitative image analysis methods. These included integrated
optical density (IOD) measurements on TPEF and SHG images and application of fast Fourier transform (FFT), CT-FIRE and
CurveAlign algorithms on SHG images to evaluate the collagen structure. In the BCC samples, we found significantly lower IOD
of both the TPEF and SHG signals and higher collagen orientation index utilizing FFT. CT-FIRE algorithm revealed increased
collagen fiber length and decreased fiber angle while CurveAlign detected higher fiber alignment of collagen fibers in BCC.
These results are in line with previous findings which describe pronounced changes in the collagen structure of BCC. In the
future, these novel image analysis methods could be integrated in handheld nonlinear microscope systems, for sensitive and
specific identification of BCC.
Quantitative analysis of lipid debris accumulation caused by cuprizone induced myelin degradation in different CNS areas
by Attila Ozsvár, Róbert Szipőcs, Zoltán Ozsvár, Judith Baka, Pál Barzó, Gábor Tamás, Gábor Molnár || 2018
Abstract:
Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis
(MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation
of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte
degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone
and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free
method to image lipid structures in living tissue. We confirmed earlier results showing a brain region dependent
myelin destructive effect of cuprizone. In addition, high resolution in situ CARS imaging revealed myelin debris
forming lipid droplets alongwith myelinated axon fibers. Quantification of lipid debris with custom-made
software for segmentation and three dimensional reconstruction revealed brain region dependent accumulation
of lipid drops inversely correlated with the thickness of myelin sheaths. Finally, we confirmed that in situ CARS
imaging is applicable to living human brain tissue in brain slices derived from a patient. Thus, CARS microscopy
is potent tool for quantitative monitoring of myelin degradation in unprecedented spatiotemporal resolution
during oligodendrocyte damage. We think that the accumulation of lipid drops around degrading myelin might
be instrumental in triggering subsequent inflammatory processes.
Stain-free Histopathology of Basal Cell Carcinoma by Dual Vibration Resonance Frequency CARS Microscopy
by Norbert Kiss, Ádám Krolopp, Kende Lőrincz, András Bánvölgyi, Róbert Szipőcs, Norbert Wikonkál || 2017
Abstract:
Basal cell carcinoma (BCC) is the most common
malignancy in Caucasians. Nonlinear microscopy has been
previously utilized for the imaging of BCC, but the captured
images do not correlate with H&E staining. Recently,
Freudiger et al. introduced a novel method to visualize tissue
morphology analogous to H&E staining, using coherent anti-
Stokes Raman scattering (CARS) technique. In our present
work, we introduce a novel algorithm to post-process images
obtained from dual vibration resonance frequency (DVRF)
CARS measurements to acquire high-quality pseudo H&E
images of BCC samples. We adapted our CARS setup to
utilize the distinct vibrational properties of CH3 (mainly in
proteins) and CH2 bonds (primarily in lipids). In a narrowband
setup, the central wavelength of the pump laser is set to
791 nm and 796 nm to obtain optimal excitation. Due to the
partial overlap of the excitation spectra and the 5–10 nm
FWHM spectral bandwidth of our lasers, we set the wavelengths
to 790 nm (proteins) and 800 nm (lipids).
Nonresonant background from water molecules also reduces
the chemical selectivity which can be significantly improved
if we subtract the DVRF images from each other. As a result,
we acquired two images: one for Blipids^ and one for^ proteins^
when we properly set a multiplication factor to minimize
the non-specific background. By merging these images,
we obtained high contrast H&E Bstained^ images of BBC’s.
Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity
by Kende Lőrincz, Dóra Haluszka, Norbert Kiss, Nóra Gyöngyösi, András Bánvölgyi, Róbert Szipőcs, Norbert M. Wikonkál || 2017
Abstract:
Obesity is a risk factor for several cardiovascular
and metabolic diseases. Its influence on the skin is
less obvious, yet certain negative effects of adipose tissue
inflammation on the dermis have been suggested. Excess
weight is closely associated with sedentary behavior, so any
increase in physical activity is considered beneficial against
obesity. To investigate the effects of obesity and physical
exercise on the skin, we established a mouse model in
which mice were kept either on a high-fat diet or received
standard chow. After the two groups achieved a significant
weight difference, physical exercise was introduced to both.
Animals were given the opportunity to perform voluntary
exercise for 40 min daily in a hamster wheel for a period
of 8 weeks. We evaluated the status of the dermis at the
beginning and at the end of the exercise period by in vivo
nonlinear microscopy. Obese mice kept on high-fat diet lost
weight steadily after they started to exercise. In the high-fat
diet group, we could detect significantly larger adipocytes
and a thicker layer of subcutaneous tissue; both changes
started to normalize after exercise. Nonlinear microscopy
revealed an impaired collagen structure in obese mice that
improved considerably after physical activity was introduced.
With the ability to detect damage on collagen structure,
we set out to address the question whether this process
is reversible. With the use of a novel imaging method, we
were able to show the reversibility of connective tissue
deterioration as a benefit of physical exercise.
Diet-induced obesity skin changes monitored by in vivo SHG and ex vivo CARS microscopy
by Dóra Haluszka, Kende Lőrincz, Norbert Kiss, Róbert Szipőcs, Enikő Kuroli, Nóra Gyöngyösi, and Norbert M.
Wikonkál || 2016
Abstract:
Obesity related metabolic syndrome and type 2 diabetes have severe consequences
on our skin. Latest developments in nonlinear microscopy allow the use of noninvasive, label
free imaging methods, such as second harmonic generation (SHG) and coherent anti-Stokes
Raman scattering (CARS), for early diagnosis of metabolic syndrome-related skin
complications by 3D imaging of the skin and the connective tissue. Our aim was to study
effects of various types of diet-induced obesity in mice using these methods. We examined
mice on different diets for 32 weeks. The collagen morphology was evaluated four times in
vivo by SHG microscopy, and adipocytes were examined once at the end of experiment by ex
vivo CARS method. A strong correlation was found between the body weight and the
adipocyte size, while we found that the SHG intensity of dermal collagen reduces
considerably with increasing body weight. Obese mice on high-fat diet showed worse results
than those on high-fat - high-fructose diet. Animals on high-fructose diet did not gain more
weight than those on ordinary diet despite of the increased calorie intake, but their collagen
damage was nonetheless significant. Obesity and high sugar intake damages the skin, mainly
the dermal connective tissue and subcutaneous adipose tissue, which efficiently can be
monitored by in vivo SHG and ex vivo CARS microscopy.
Handheld nonlinear microscope system comprising a 2 MHz repetition rate, modelocked Yb-fiber laser for in vivo biomedical imaging
by Ádám Krolopp, Attila Csákányi, Dóra Haluszka, Dániel Csáti, Lajos Vass, Attila Kolonics, Norbert Wikonkál, Róbert Szipőcs || 2016
Abstract:
A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is
introduced. It is suitable for in vivo imaging of murine skin at an average power level as low
as 5 mW at 200 kHz sampling rate. Amplified and compressed laser pulses having a spectral
bandwidth of 8 to 12 nm at around 1030 nm excite the biological samples at a ~1.89 MHz
repetition rate, which explains how the high quality two-photon excitation fluorescence
(2PEF) and second harmonic generation (SHG) images are obtained at the average power
level of a laser pointer. The scanning, imaging and detection head, which comprises a
conventional microscope objective for beam focusing, has a physical length of ~180 mm
owing to the custom designed imaging telescope system between the laser scanner mirrors
and the entrance aperture of the microscope objective. Operation of the all-fiber, all-normal
dispersion Yb-fiber ring laser oscillator is electronically controlled by a two-channel
polarization controller for Q-switching free mode-locked operation. The whole nonlinear
microscope imaging system has the main advantages of the low price of the fs laser applied,
fiber optics flexibility, a relatively small, light-weight scanning and detection head, and a very
low risk of thermal or photochemical damage of the skin samples.
In vivo second-harmonic generation and ex vivo coherent
anti-Stokes Raman scattering microscopy to study the effect
of obesity to fibroplast cell function using an Yb-fiber laser
based CARS extension unit
by Haluszka Dóra, Lőrincz Kende, Molnár Gábor, Tamás Gábor,
Kolonics Attila, Szipőcs Róbert, Kárpáti Sarolta, Wikonkál Norbert || 2015
Abstract:
Nonlinear microscopy techniques are being increasingly used to perform in vivo studies in
dermatology. These methods enable us to investigate the morphology and monitor the
physiological process in the skin by the use of femtosecond lasers operating in the red, nearinfrared
spectral range (680-1300 nm). In this work we used two different techniques that
require no labeling: second harmonic generation (SHG) for collagen detection and coherent
anti-Stokes Raman scattering (CARS) to assess lipid distribution in genetically obese murine
skin. Obesity is one of the most serious public health problems due to its high and increasing
prevalence and the associated risk of type 2 diabetes and cardiovascular diseases. Other than
these diseases, nearly half of patients with diabetes mellitus suffer from dermatological
complications such as delayed wound healing, foot ulcers and several other skin changes. In
our experiment we investigated and followed the effects of obesity on dermal collagen
alterations and adipocyte enlargement using a technique not reported in the literature so far.
Our results indicate that the in vivo SHG and ex vivo CARS imaging technique might be an
important tool for diagnosis of diabetes-related skin disorders in the near future.
Hosszú távú PUVA kezelés bôröregítô hatásának vizsgálata egereken
(Analysis of skin aging during long term PUVA treatment on mice)
by Lőrincz Kende Dr, Bánvölgyi András Dr, Haluszka Dóra,
Keszeg András, Márton Dalma, Kuroli Enikő Dr, Szipőcs Róbert Dr,
Karin Scharfetter-Kohsanek Dr, Meinhard Wlaschek Dr,
Kárpáti Sarolta Dr, Wikonkál Norbert Dr. || 2015
Abstract:
PUVA therapy is a frequently used treatment option in a
variety of dermatological diseases for decades. However
there is no comprehensive consensus in its short and longterm
risks, according to the literature. Many animal
experiments proved the carcinogenic and photoaging
potential of narrow band UVB radiation. Such effects of
PUVA therapy are not well documented in similar
experimental settings. Epidemiological studies, on the
other hand indicate the formerly mentioned long-term
adverse effects of PUVA therapy. For this reason we set
out to investigate and demonstrate the effects of chronic
PUVA therapy with using a mouse model.
Nemlineáris mikroszkópia alapjai és alkalmazási lehetôségei a dermatológiában
(Principles of nonlinear microscopy and application possibilities in dermatology)
by Haluszka Dóra, Lőrincz Kende Dr, Csákányi Attila, Vass Lajos,
Krolopp Ádám, Kolonics Attila Dr, Szipőcs Róbert Dr,
Kárpáti Sarolta Dr, Wikonkál Norbert Dr. || 2015
Abstract:
Nonlinear optical imaging techniques have become
increasingly popular over the past decade both in the field
of basic research and clinical practice. The excitation of
skin chromophores in the near infrared spectral range
(700-1300 nm) allows safe, label-free imaging with high
spatial and temporal resolution. In the first part of our
article we discuss the main principles of various nonlinear
optical techniques, then we show the application
possibilities of them in dermatology. In the second part of
our review we report the main investigations and results of
our group.
Monitoring the dominance of higher-order chromatic dispersion with
spectral interferometry using the stationary phase point method
by Tímea Grósz, Attila P.Kovács, Katalin Mecseki, Lénárd Gulyás, Róbert Szipőcs || 2015
Abstract:
Simulations were performed in order to investigate whether the stationary phase point method can be
used to estimate the dominance of higher-order dispersion of the optical element under study. It was
shown that different higher-order dispersion terms may result in the appearance of more than one
stationary phase point on the interferogram in contrast to common glasses having group-delay dispersion
as the highest decisive term in their spectral phase. The results obtained by simulations were demonstrated
experimentally with spectral interferometric measurements conducted on a photonic
bandgap ?ber sample and a prism pair. We concluded that from the shape, movement and number of the
stationary phase points it is generally possible to predict which dispersion terms are the most signi?cant,
however, in some cases the retrieval of the coef?cients is also necessary in order to rule out any ambiguity.
The method can offer a dispersion monitoring possibility which is useful in quality testing of
specialty ?bers and when adjusting stretcher-compressor systems, for example.
Stored Energy, Transmission Group Delay and Mode
Field Distorsion in Optical Fibers
by Zoltán Várallyay and Róbert Szipőcs || 2014
Abstract:
The relationship between transmission group delay
and stored energy in optical fibers is discussed. We show by
numerical computations that the group delay of an optical pulse of
finite bandwidth transmitted through a piece of a low loss optical
fiber of unit length is proportional to the energy stored by
the standing wave electromagnetic field. The stored energy-group
delay ratio typically approaches unity as the confinement loss
converges to zero. In case of a dispersion tailored Bragg fiber, we found
that the stored energy-group delay ratio decreased while the
confinement loss increased compared to those of the standard quarter-wave
Bragg fiber configuration. Furthermore, a rapid variation in
the group delay versus wavelength function due to mode-crossing
events (in hollow core photonic bandgap fibers for instance) or
resonances originating from slightly coupled cavities, surface or
leaking modes in index guiding, photonic bandgap, or photonic
crystal fibers always results in a rapid change in the mode-field
distribution, which seriously affects splicing losses and focusability
of the transmitted laser beam. All of these factors must be taken
into consideration during the design of dispersion tailored fibers
for different applications.
In vivo study of targeted nanomedicine delivery into
Langerhans cells by multiphoton laser scanning microscopy
by Attila Kolonics, Zsolt Csiszovszki, Enikő R.Tőke
Orsolya Lőrincz, Dóra Haluszka and Szipőcs Róbert || 2014
Abstract:
333 Epidermal Langerhans cells (LCs) function as
professional antigen-presenting cells of the skin. We investigated
the LC-targeting properties of a special mannose–moiety-coated
pathogen-like synthetic nanomedicine DermaVir (DV), which is
capable to express antigens to induce immune responses and kill
HIV-infected cells. Our aim was to use multiphoton laser
microscopy (MLM) in vivo in order to visualize the uptake of
Alexa-labelled DV (AF546-DV) by LCs. Knock-in mice expressing
enhanced green fluorescent protein (eGFP) under the control of
the langerin gene (CD207) were used to visualize LCs. After 1 h,
AF546-DV penetrated the epidermis and entered the eGFP-LCs.
The AF546-DV signal was equally distributed inside the LCs.
After 9 h, we observed AF546-DV signal accumulation that
occurred mainly at the cell body. We demonstrated in live
animals that LCs picked up and accumulated the nanoparticles in
the cell body.
Exploitition of Langerhans cells for in vivo DNA
vaccine delivery into the lymph nodes
by ER Tőke, O Lőrincz, Z Csiszovszki, E Somogyi, G Felföldi,
L Molnár, R Szipőcs, A Kolonics, B Malisson, F Lori, J Trocio, N Bakare,
F Horkay, N Romani, CH Tripp P Stoizner and J Lisziewicz. || 2014
Abstract:
There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic
cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic
‘pathogen-like’nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a
patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination
strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the
native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment
was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the
lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an
effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph
nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin
treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting
vaccines to generate therapeutic immunity against cancer.
Measurement of higher order chromatic dispersion in a photonic
bandgap filter: comparative study of spectral interferometric methods
by T.Grósz, A.P.Kovács, M.Kiss and R.Szipőcs || 2014
Abstract:
Chromatic dispersion of a 37 cm long, solid-core photonic bandgap (PBG) fiber was studied in the
wavelength range of 740–840 nm with spectral interferometry employing a Mach–Zehnder interferometer and
a high resolution spectrometer. The interferometer was illuminated by a Ti:sapphire laser providing 20 fs
pulses. A comparative study has been carried out to find the most accurate spectral phase retrieval
method that is suitable for measuring higher order chromatic dispersion. The stationary phase point,
the minima–maxima, the cosine function fit, the Fourier transform, and the windowed Fourier transform
methods were tested. It was shown that out of these five techniques, the Fourier-transform method
provided the dispersion coefficients with the highest accuracy, and it could also detect rapid phase changes in
the vicinity of leaking mode frequencies within the transmission band of the PBG fiber. © 2014 Optical
Society of America
Pre-excitation studies for rubidium-plasma generation
by Márk Aladi, József Bakos, I.F. Barna, Aladár Czitrovszky, Gagik Djotyan,
Péter Dombi, David Dzsotjan, István Földes, Gergő Hamar, Péter Ignácz,
Miklós Kedves, Attila Kerekes, Péter Lévai, István Márton, Attila Nagy,
Dániel Oszetzky, Mihály Pocsai, Péter Rácz, Béla Ráczkevi, János Szigeti,
Zsuzsa Sörlei, Róbert Szipöcs, Dezső Varga, Károly Varga-Umbrich, Sándor Varró,
Lénárd Vámos, György Vesztergombi || 2014
Abstract:
The key element in the Proton-Driven-Plasma-Wake-Field-Accelerator (PWFA) project is the generation
of highly uniform plasma from Rubidium vapor. A scientifically straightforward, yet highly challenging
way to achieve full ionization is to use high power laser which can assure the barrier suppression
ionization (BSI) along the 10 m long active region. The Wigner-team in Budapest is investigating an
alternative way of uniform plasma generation. The proposed Resonance Enhanced Multi-Photon
Ionization (REMPI) scheme can be probably realized by much less laser power. In the following we plan
to investigate the resonant pre-excitations of the Rb atoms, both theoretically and experimentally. In the
following our theoretical framework is presented together with the status report about the preparatory
work of the planned experiments.
Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice
by Peter Bognár, Ilona Nemeth, Dora Haluszka, Norbert Wikonkál, Eszter Ostorhazi,
Susan John, Mats Paulsson, Neil Smyth, Maria Pasztoi, Edit Buzas, Robert Szipocs,
Attila Kolonics, Erzsebet Temesvari and Sarolta Karpati || 2013
Abstract:
Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development,
but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes
was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to
FITC in TGM3/KO (n = 64) and C57BL/6 wild-type (WT) mice (n = 36). Cutaneous inflammation was evaluated by
mouse ear swelling test (MEST), histology, serum IgE levels, and by flow cytometry from draining lymph
nodes. Inflammation-induced significant MEST difference (P < 0.0001) was detected between KO and WT mice
and was supported also by histopathology. A significant increase of CD4+ CD25+ -activated T cells (P < 0.01) and
elevated serum IgE levels (P < 0.05) in KO mice indicated more the development of FITC sensitization
than an irritative reaction. Propionibacter acnes–induced intracutaneous inflammation showed no difference
(P = 0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration
from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration
in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher
susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact
cutaneous barrier.
Relation among group delay, energy storage and loss in dispersive dielectric mirrors
by P.G. Antal, R. Szipocs || 2012
Abstract:
We show that absorbed and stored electromagnetic energy are proportional to the reflection group delay in
highly reflective dispersive dielectric mirrors over the high-reflectivity band. Our theoretical considerations
are verified by numerical simulations performed on different dielectric mirror structures. The revealed proportionality
between group delay and absorbed energy sets constraint on the application of ultrabroadband
and/or dispersive dielectric mirrors in broadband or widely tunable, high power laser systems.
Tunable, low-repetition-rate, cost efficient femtosecond Ti:sapphire laser for nonlinear microscopy
by P.G. Antal, R. Szipocs || 2011
Abstract:
We report on a broadly tunable, long-cavity
Ti:sapphire laser oscillator being mode-locked in the net
negative intracavity dispersion regime by Kerr-lens mode-locking,
delivering τFWHM < 300 fs pulses at 22 MHz repetion
rate. The wavelength of the laser can be tuned over
a 170 nm wide range between 712 nm and 882 nm. Having
a typical pump power of 2.6 W, the maximum pulse
peak power is 60 kW. Comparison of the reported laser
with a standard, 76 MHz Ti:sapphire oscillator regarding
two-photon excitation efficiency in a laser scanning microscope
shows that the 22 MHz laser generates the same fluorescence
signal at considerably, 1.82 times lower average
power, which is expected to result in a reduced photothermal
damage probability of biological samples. This fact along
with the broad tunabiéity and a low pump power requirement
makes this cost-effective laser and ideal light source for
nonlinear microscopy.
Photonic bandgap fibers with resonant
structures for tailoring the dispersion
by Z. Varallyay, K. Saitoh, A. Szabo, and R. Szipocs || 2009
Abstract:
Numerical simulations on different kinds of realistic photonic bandgap
fibers exhibiting reversed dispersion slope for the propagating fundamental
mode are reported. We show that reversed or flat dispersion functions in a wide
wavelength range using hollow-core, air-silica photonic bandgap fibers and
solid core Bragg fibers with step-index profile can be obtained by introducing
resonant structures in the fiber cladding. We evaluate the dispersion and
confinement loss profiles of these fibers from the Helmholtz eigenvalue
equation and the calculated fiber properties are used to investigate the
propagation of chirped femtosecond pulses through serially connected
hollow core fiber compressors
All-fiber, all-normal dispersion ytterbium ring oscillator
by J. Fekete, A. Cserteg, and R. Szipocs || 2008
Abstract:
Experimental results on an all-fiber, all-normal dispersion ytterbium ring laser
are reported. It produces stable mode-locking of ~10 ps pulses that can be externally
compressed to as short as ~200 fs.
Reversed dispersion slope photonic bandgap fibers for broadband dispersion control
in femtosecond fiber lasers
by Z. Varallyay, K. Saitoh, J. Fekete, K. Kakihara, M. Koshiba, and R. Szipocs || 2008
Abstract:
Higher-order-mode solid and hollow core photonic bandgap
fibers exhibiting reversed or zero dispersion slope over tens or hundreds of
nanometer bandwidths within the bandgap are presented. This attractive
feature makes them well suited for broadband dispersion control in femtosecond
pulse fiber lasers, amplifiers and optical parametric oscillators.
The canonical form of the dispersion profile in photonic bandgap fibers
is modified by a partial reflector layer/interface placed around the core
forming a 2D cylindrical Gires-Tournois type interferometer. This small
perturbation in the index profile induces a frequency dependent electric
field distribution of the preferred propagating higher-order-mode resulting
in a zero or reversed dispersion slope.
Design of high-bandwidth one- and two-dimensional photonic
bandgap dielectric structures at grazing incidence of light
by J. Fekete, Z. Varallyay, and R. Szipocs || 2008
Abstract:
We propose one-dimensional photonic bandgap (PB) dielectric structures to be used at grazing incidence
in order to obtain an extended bandgap exhibiting considerably reduced reflection loss and dispersion
compared to similar structures used at a normal incidence of light. The well-known quarter-wave
condition is applied for the design in this specific case, resulting in resonance-free reflection bands without
drops in reflection versus wavelength function and a monotonous variation of the group delay dispersion
versus wavelength function, which are important issues in femtosecond pulse laser applications. Based
on these results we extend our studies to two-dimensional PB structures and provide guidelines to the
design of leaking mode-free hollow-core Bragg PB fibers providing anomalous dispersion over most of the
bandgap.
Chirped-pulse supercontinuum generation with a long-cavity Ti:sapphire oscillator
by P. Dombi, P. Antal, J. Fekete, R. Szipőcs, Z. Várallyay || 2007
Abstract:
We demonstrate chirped-pulse supercontinuum generation
in a conventional fibre with a relatively narrowband,
long-cavity, chirped-pulse Ti:sapphire oscillator delivering
200 nJ pulses. The inherent chirp of the outcoupled pulses
were overcompensated by a 4-prism compressor to overcome
damage threshold problems at the fibre entrance. The resulting
fibre output spectrum corresponds to a pulse length of 7 fs in the
transform-limit. The experimentally observed highly efficient
spectral broadening process of negatively chirped pulses in the
fibre is supported by simulation data.
Optimizing input and output chirps up to the third-order for sub-nanojoule,
ultra-short pulse compression in small core area PCF
by Z. Várallyay, J. Fekete, Á. Bányász, R. Szipőcs || 2006
Abstract:
Compression of sub-nanojoule laser pulses using a commercially available
photonic crystal fiber (PCF)with zero dispersion wavelength of 860 nm
is discussed. A twofold pulse
compression starting from 24 fs transform limited seed pulses
around 800 nm is experimentally demonstrated as a verification
of our simulations. Theory shows that by the optimization of
input and output chirp parameters up to the third order, high
quality, 5.7 fs pulses can be generated from a cost efficient
experimental setup. Further calculations show that 1 ps pulses
with central wavelength of 800 nm can be compressed down to 50 fs
in the normal dispersion regime of the fiber with proper dispersion
compensation. Calculations also show that dispersion
flattened fibers can improve both the quality and the duration of
compressed pulses.
Random access three-dimensional two-photon microscopy
by Balázs Rózsa, Gergely Katona, E. Sylvester Vizi, Zoltán Várallyay,
Attila Sághy, László Valenta, Pál Maák, Júlia Fekete, Ákos Bányász,
and Róbert Szipőcs || 2006
Abstract:
We propose a two-photon microscope scheme capable of real-time,
three-dimensional investigation of the electric activity pattern of
neural networks or signal summation rules of individual neurons
in a 0.6 mm x 0.6 mm x 0.2 mm volume of the sample.
The points of measurement are chosen according to a conventional
scanning two-photon image, and they are addressed by separately
adjustable optical fibers. This allows scanning at kilohertz
repetition rates of as many as 100 data points. Submicrometer
spatial resolution is maintained during the measurement similarly
to conventional two-photon microscopy.
Trends in Optics and Photonics Series || TOPS Vol 98, Series
editor Alexander A. Sawchuck || 2005, Optical Society of America
Sub-nanojoulepulse compression in small core area photonic crystal
fibers below the zero dispersion wavelength
by Z. Várallyay, J. Fekete, Á.Bányász, R. Szipőcs || p. 571-576
Low reflection loss ion-beam sputtered negative dispersion mirrors with MCGTl
structure for low pump threshold, compact femtosecond pulse lasers
by B. Császár, A. Koházi- Kis, F. Szipőcs & R. Szipőcs || p 674-679
Cubic phase distortion of single attosecond pulses being reflected
on narrowband Mo/Si filtering mirrors
by András Lukács, Zoltán Várallyay, Róbert Szipőcs || p. 806-810
Real time 3D nonlinear microscopy
by B. Rozsa, E. S. Vizi, G.Katona, A. Lukács, Z. Várallyay, A. Sághy,
L. Valenta, P. Maák, J. Fekete, Á. Bányász, R. Szipőcs || p. 858-863
Broad tunability from a compact, low-threshold
Cr:LiSAF laser incorporating an improved birefringent filter and
multiple-cavity Gires-Tournois interferometer mirrors
by Barry Stormont, Alan J. Kemp, Iain G. Cormack, Ben Agate,
C. Tom A. Brown, and Wilson Sibbett and Róbert Szipőcs || 2005
Abstract:
We demonstrate prismless tuning of a compact femtosecond Cr:LiSAF laser. The employed technique, which
uses a specially designed birefringent filter in combination with dispersion compensation from a pair of
multiple-cavity Gires-Tournois interferometer mirrors, provides tuning over 20 nm. We give the results of theoretical
modeling of the tuning velocity and the spectral width of the central passband. We show, both experimentally
and theoretically, that a single birefringent plate can be used to control the oscillating bandwidth of
the laser. The effect this has on the output-pulse duration has also been investigated.
2005 Conference on Lasers and Electro-Optics, Quantum Electronics and
Laser Science, May22-27, Baltimore, MD, USA ||
The four articles presented at the CLEO 2005 conference are now available online.
Nonlinear refraction and absorption of Mg doped stoichiometric and congruent LiNbO3
by L. Pálfalvi, G. Almási, Á. Péter, K. Polgár,
K. Lengyel, and R. Szipőcs || February 2004
Abstract:
The light induced change of refraction
is studied in pure and Mg doped LiNbO3 with congruent and stoichiometric
compositions by the Z-scan method using all-lines visible argonion laser,
up to MW/cm intensity
level. In Mg-doped congruent and stoichiometric crystals with Mg concentrations
above threshold a positive change in the refractive index was found,
in contrast to all other cases where beam fanning and negative change
of the refractive index were observed.
Pulse compression of nanojoule pulses in the visible using
microstructure optical fiber and dispersion compensation
by S. Lakó, J. Seres, P. Apai, J. Balázs, R.S. Windeler, and R. Szipőcs
|| June 2002
Abstract: Experimental results on the pulse
compression of 1-nJ, 150-fs pulses from a tunable, 76-MHz Ti:sapphire
laser oscillator operating at around 750 nm are reported. The length
of the pulses can be compressed to nearly one tenth by applying a high-delta,
single-mode microstructured optical fiber exhibiting zero group-delay
dispersion at 767 nm, and by a prismpair/ chirped-mirror compressor.
The experimental results are verified by theoretical investigations
modeling the pulse propagation taking into account non-linear self-phase
modulation and fiber dispersion. PACS 42.65; 42.81
Spectral filtering of femtosecond laser pulses by interference filters
by R. Szipőcs, A.Köházi-Kis, P. Apai, E. Finger, A. Euteneuer M.Hofmann
|| October 1999
Abstract: Phase properties of optical thin film
interference filters are discussed from the aspect of their usage for
phaseerror free wavelength separation of broadband femtosecond laser
pulses. It is shown that both transmissive or reflective interference
filters with high contrast ratios exhibit high cubic phase shifts on
transmission or reflection, respectively, causing intolerable distortion
in the temporal pulse shape. We show, however, that high efficiency
wavelength separation of broadband femtosecond laser pulses can be achieved
by using low contrast, properly designed reflective optical interference
filters directly built into the cavity of the broad spectrum, femtosecond
pulse lasers or parametric oscillators. For demonstrative purposes,
we implemented the idea for a Kerrlens mode-locked Ti:sapphire laser,
and obtained two-color, inherently synchronized, unchirped, femtosecond
pulse outputs from a single laser oscillator.
Negative
dispersion mirrors for dispersion control in femtosecond lasers: chirped
dielectric mirrors and multi-cavity Gires-Tournois interferometers by
R. Szipőcs, A.Köházi-Kis, S. Lakó, P. Apai, A.P.Kovács,
G. DeBell, L.Mott, A.W. Louderback, A.V. Tikhonravov, M.K. Trubetskov
|| October 1999
Abstract. Chirped dielectric laser mirrors
have been known for years as useful devices for broadband feedback and
dispersion control in femtosecond pulse lasers. First we present a novel
design technique referred to as frequency domain synthesis of chirped
mirrors. These mirrors exhibit high reflectivity and nearly constant
group delay over 150 THz supporting generation of sub-5-fs pulses in
the visible...
Measurement
of dispersive properties of optical materials and mirrors using spectrally
resolved white- light interferometry by Zsolt Bor, Attila P Kovács,
Károly Osvary and Róbert Szipőcs || April 1998
Abstract: We present a simple, accurate and
inexpensive interferometric technique based on spectrally resolved white-light
iterferometry to determine the group-delay dispersion of optical elements,
such as layer crystals and multilayer mirrors. Due to the different
dispersion of these elements, different evaluation methis of interference
fringes are used for the mirrors and crystals.
A
Compact All-Solid-State Sub-5fsec Laser by Andrius Baltu ka,
Maxim S Pschenichnikov, Róbert Szipőcs, Douwe A. Wiersma || December
1997
Abstract: n/a
Sub-20 fs pulse generation from the mirror dispersion controlled Cr:LiSGaFandCr:LiSAFlasers
by I.T. Sorokina, E. Sorokin, E.Wintner, A. Cassanho, H.P. Jenssen and
R. Szipőcs || May 1997
Abstract: We describe the state of the art of
mirror-dispersioncontrolled (MDC) Kerr-lens mode-locked (KLM) Cr:LiSGaF
and Cr:LiSAF lasers. Such lasers, in comparison to their prism-controlled
forerunners, are distinguished by high reproducibility, stability, and
quality of the pulses, as well as compactness of the cavity. The shortest
pulses of ~18 fs duration and nearly bandwidth-limited quality
(delta = 0.33)
have been produced in Cr:LiSGaF lasers, which have an average
output power of 100mW. In both lasers, krypton-laser was used as an
ideal pump source. The effect of a red-shift of the operating wavelength
(from 850 to 880 nm) when shortening of the pulse width (from ~ 50 fs
to ~ 20 fs) has been observed and discussed.
Theory
and design of chirped dielectric laser mirrors by A.Kõházi-Kis
and R. Szipőcs || April 1997
Abstract: Chirped dielectric laser mirrors offer
a general solution for broadband feedback and dispersion control in
femtosecond laser systems. Chirped mirrors developed for modelocked
solid-state lasers, femtosecond parametric oscillators, chirped pulse
amplification systems and pulse compressors are introduced. Basic theoretical
and design considerations are also presented.
All-solid-state
cavity-dumped sub-5-fs laser by A. Baltu ka1,
Z.Wei, M.S. Pshenichnikov, D.A. Wiersma, Róbert Szipőcs || March 1997
Abstract. We discuss in detail a compact all-solid-state
laser delivering sub-5-fs, 2-MW pulses at repetition rates up to 1MHz.
The shortest pulse generated thus far measures only 4:6 fs. The laser
system employed is based on a cavitydumped Ti:sapphire oscillator whose
output is chirped in a single-mode fiber. The resulting white-light
continuum is compressed in a novel high-throughput prism chirped-mirror
Gires-Tournois interferometer pulse compressor. The temporal and spectral
phase of the sub-5-fs pulses are deduced from the collinear fringe-resolved
autocorrelation and optical spectrum. The derived pulse shape agrees
well with the one retrieved from the measured group delay of the continuum
and calculated characteristics of the pulse compressor.
Ultrabroadband chirped mirrors for femtosecond lasers
by E. J. Mayer, J. Möbius, A. Euteneuer, and W. W. Rühle and R. Szipőcs
|| November 1996
Abstract: We report on the performance of widely
tunable femtosecond and continuous-wave Ti:sapphire lasers that use
a newly developed ultrabroadband mirror set. The mirrors exhibit high
ref lectivity (R > 99%) and smooth variation of group delay versus
frequency over a wavelength range from 660 to 1060 nm. Mode-locked operation
with pulse durations of 85 fs was achieved from 693 to 978 nm with only
one set of ultrabroadband mirrors.
Compression of high-energy laser pulses below 5 fs
by M. Nisoli, S. De Silvestri and O. Svelto;
R. Szipőcs and K. Ferencz;
Ch. Spielmann, S. Sartania, and F. Krausz;
|| February 1996
Abstract:
High-energy 20-fs pulses generated by a Ti:sapphire laser system were spectrally broadened to more than
250 nm by self-phase modulation in a hollow fiber filled with noble gases and subsequently compressed in
a broadband high-throughput dispersive system. Pulses as short as 4.5 fs with energy up to 20-mJ were
obtained with krypton, while pulses as short as 5 fs with energy up to 70 mJ were obtained with argon.
These pulses are, to our knowledge, the shortest generated to date at multigigawatt peak powers.
Prismless passively mode-locked femtosecond Cr:LiSGaF laser
by I. T. Sorokina, E. Sorokin, and E. Wintner, A. Cassanho, H. P. Jenssen and R. Szipőcs
|| February 1996
Abstract: A Kerr-lens mode-locked Cr:LiSrGaF
laser containing no intracavity prisms has been demonstrated for the
first time to the authors' knowledge. The laser produced stable near-transform-limited
44-fs pulses with an output power of 200 mW, tunable between 833 and
857 nm. Low-loss Gires-Tournois structured dielectric mirrors were used
for dispersion control. The measured group-delay dispersion of the active
medium as well as of the mirrors permitted to minimize the number of
ref lections, permitting higher output power.
Ultrabroadband ring oscillator for sub-10-fs pulse generation
by Lin Xu, Christian Spielmann, Ferenc Krausz and R. Szipőcs || January 1996
Abstract:
A four-mirror ring cavity formed by
chirped dielectric mirrors is proposed for self-mode-locked solid-state
lasers. It offers, for the first time to our knowledge, the potential
for approaching the gain-bandwidth limit in Ti:sapphire and related
broadband lasers. Using this concept, we produced nearly bandwidth-limited
7.5-fs pulses from a feedback-initiated, self-mode-locked Ti:sapphire
ring oscillator. Our experiments provide new insight into the physics
and limitations of sub-10-fs oscillators.
Chirped dielectric mirrors improve Ti:sapphire lasers
by Ch. Spielmann, M. Lenzner, R. Szipőcs and F. Krausz || December 1995
Abstract:
High quality seed pulses from mirror
dispersion-controlled Ti:sapphire system allow chirped pulse amplification
without a pulse strectcher.
Compact, high-throughput expansion-compression scheme for chirped pulse amplification
in the 10 fs range
by Ch. Spielmanna, M. Lenzner, F. Krausz, R.Szipőcs || July 1995
Abstract:
A novel pulse stretching-compression
system suitable for kHz-rate chirped-pulse amplification of ~10 fs pulses
in Ti:sapphire systems is demonstrated. The material dispersion of the
system components used for pulse selection and isolation broadens the
wide-band seed pulses by a factor of -300, allowing amplification up
to the submillijoule energy range. The compressor consists of a pair
of prisms and newly-developed chirped multilayer dielectric mirrors
for compensating high order dispersion. Using this simple scheme a recompression
of unamplified pulses down to 15 fs with a throughput as high as 80%
is demonstrated.
Pushing the limits of Femtosecond Technology: Chirped Dielectric Mirrors
by Róbert Szipőcs, Andreas Sitingl, Christian Spielmann and Ferenc Krausz || June 1995
Abstract:
The authors explain the theory behind
the ultrashort pulses and offer a new method - chirped dielectric mirrors - for achieving.
Measurement of the group delay of laser mirrors by a Fabry-Perot interferometer
by K. Osvay, G. Kurdi, J. Hebling, A. P. Kovács, Z. Bor and R.Szipőcs || June 1995
Abstract:
The group delay of multilayer laser
mirrors was measured by determining the spectral position of transmission
maxima of a Fabry–Perot interferometer formed by the mirrors to be characterized.
By optimizing the spacer thickness, we obtained an accuracy of the group-delay
measurement of better than 0.23 fs. To our knowledge, this is the most
precise direct measuring method reported.
Chirped-mirror dispersion-compensated femtosecond optical parametric oscillator
by J. Hebling, E. J. Mayer, J. Kuhl, R. Szipőcs || January 1995
Abstract: We describe the operating characteristics
of a femtosecond optical parametric oscillator employing chirped mirrors
for intracavity group-velocity dispersion compensation. Pumped by 760
mW of power from a self-mode-locked Ti:sapphire laser, this device provides
100-fs near-transform-limited pulses continuously tunable from 1.18
to 1.32 mm with an average power of 100-180 mW. The limitations of the
present setup and strategies for further pulse shortening are discussed.
Group-delay easurement on laser mirrors by spectrally resolved white-light interferometry
by A. P. Kovács, K. Osvay, Zs. Bor and R. Szipőcs || October 1994
Abstract:
The frequency-dependent group delay
of dielectric mirrors was measured by spectrally resolved white-light
interferometry. Chirped mirrors and thin-film Gires-Tournois interferometers
designed for dispersion control in a femtosecond Ti:sapphire laser oscillator-amplifier
system were tested with a group-delay resolution of 60.2 fs and a spectral
resolution of ,1 nm over the spectral range of 670-870 nm.
Sub-10-fs
mirror-dispersion-controlled Ti:sapphire laser by A. Stingl, M.
Lenzner, Ch. Spielmann, and F. Krausz and R. Szipőcs || October 1994
Abstract:
We demonstrate the generation of nearly
bandwidth-limited 8-fs optical pulses near 0.8 mm from a self-modelocked
Ti:sapphire laser oscillator, using chirped dielectric mirrors for dispersion
control. The mode-locking performance is described, and limitations
are discussed.
Design
of dielectric high reflectors for dispersion in femtosecond lasers
by Róbert Szipőcs, Ambrus Kõházi-Kis || June 1994
Abstract:
Chirped dielectric rugate mirrors
were constructed for broadband dispersion control in femtosecond laser
oscillators by Fouries transform. Dispersive properties of the mirrors
are tailored and explained on the basis of the time shifting theorem
of Fourier analysis. Depending on their construction parameters, these
chirped gradientüindex structures exhibit high reflectivity amd
neary constamt negative, i.e. anomalous, group delay dispersion over
frequency ranges well beyond the currently available fluorescence bandwidth
of broadbanc laser-active materials. As a consequence, practical implementation
of these novel dispersive devices would permit the full utilisation
of the bandwidth offered by these broadband gain media, and allow the
construction of small, compat femtosecond solid state laser oscillators
generating optical pulses shorter than those achieved so far, directly
from the laser oscillator.
Tunneling
of Optical Pulses through Photonic Band Gaps by and Ch. Spielmann,
F. Krausz, A. Stingl and R. Szipőcs || April 1994
Abstract:
Propagation of electromagnetic wave
packed through ID photonic band gap materials has been studies using
12 fs optical pulses. The measured transit time is found to be paradoxically
short (implying superluminal tunneling) and independent of the barriers
thickness for opaque barriers, in analogy to the behavior of electrons
tunneling through potential barriers. Shortening of Fourier-limited
incident wave packets is observed upon transmission through these linear
systems. Although in apparent conflict with causality and the uncertainty
principle, neither of these general principles is violated because of
the strong attenuation suffered by the transmitted signals.
Generation
of 11-fs pulses from a Ti:sapphire laser without the use of prisms
by Andreas Stingl, Christian Spielmann, Ferenc Krausz and Róbert
Szipőcs || September 1993
Abstract:
The generation of highly stable optical
pulses as short as 11 fs from a Kerr-lens mode-locked Ti:sapphire laser
containing no intracavity prisms is demonstrated. In the femtosecond
oscillator design reported, novel dielectric mirrors provide broadband
dispersion control for solitonlike pulse formation.
Chirped multilayer coatings for broadband dispersion control in femtosecond lasers
by Robert Szipőcs, Kárpát Ferencz, Christian Spielmann and
Ferenc Krausz || August 1993
Abstract:
Optical thin-film structures exhibiting
high reflectivity and a nearly constant negative group-delay dispersion
over frequency ranges as broad as 80 THz are presented. This attractive
combination makes these coatings well suited for intracavity dispersion
control in broadband femtosecond solid-state lasers. We address design
issues and the principle of operation of these novel devices...
Recent Developements of Laser Optical Coatings in Hungary
by Kárpát Ferencz and Robert Szipőcs || October 1993
Abstract:
Optical coating suppliers specialized to meet pecial
needs of laser developers often have to face challenges to help them
in building high-performance, high-efficiency lasers. Some aspects of
laser optical coating design and manufacturing are discussed.
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