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Laser Speckle Contrast Analysis (LASCA) has been proven to be a highly useful tool for the full-field determination of the blood perfusion of a variety of tissues. Some of the major advantages of this technique are its relatively high spatial and temporal resolution as well as its good or excellent accordance to Doppler systems. However, traditionally it is only able to report a single characteristic speed regarding to the actual range of interest. This might be misleading if multiple characteristic speeds are present (e. g. tremor and perfusion in skin) or if several kinds of tissues are mixed (e. g. parenchyma and vessels in brain). Here we present two relatively simple extensions of LASCA for these problems. The application of multiple autocorrelation functions (combined with the usage of multiple exposure times) can help in the separation of multiple characteristic speeds. We also present a useful method for the separation of information those originate from a mixture of different tissues. The latter method can be also implemented to single-exposure systems.

Laser Speckle Contrast Analysis (LASCA) was introduced in 1981. Since then, several enhancements were applied to it. Nowadays, the technique can provide relatively high accuracy as well as high temporal and spatial resolution during the examination of ocular or cerebral tissues. However, in the case of skin, the results are highly affected by the intensive scattering on the skin surface, as the scattering on the non-moving parts of the sample lead to the detrimental decrease of the accuracy. We present a LASCA method based on the use of multiple exposure times, combined with the switching-mode control of the light intensity and a special sampling technique to achieve near to real-time measurement of the skin perfusion. The system based on our method is able to automatically handle the destructive effect of the skin surface and re-tune itself according to the changes of the sample, while it provides full-field perfusion maps with high accuracy, without the need of any precalibrations.

An atomic force microscopic method to study the incubation states of UV laser irradiated polymer samples is presented. Targets were illuminated by different number of pulses at 5.8 and 8.9 mJ/cm2 fluences. The induced adhesive and morphological changes were investigated simultaneously by an atomic force microscope equipped with a pulsed force mode extension. Importantly, below 100 pulses morphological changes were not observable while significant changes in the adhesion were found as a result of the incubation at 8.9 mJ/cm2 fluence. This method allows the imaging and detection of the whole laser modified area with nanometer resolution. [ABSTRACT FROM AUTHOR]

We present an investigation on absorbing film assisted laser induced forward transfer (AFA-LIFT) of fungus (Trichoderma) conidia. A KrF excimer laser beam [λ=248 nm,FWHM=30 ns (FWHM, full width at half maximum)] was directed through a quartz plate and focused onto its silver coated surface where conidia of the Trichoderma strain were uniformly spread. The laser fluence was varied in the range of 0–2600 mJ/cm2 and each laser pulse transferred a pixel of target material. The average irradiated area was 8×10-2 mm2. After the transfer procedure, the yeast extract medium covered glass slide and the transferred conidia patterns were incubated for 20 h and then observed using an optical microscope. The transferred conidia pixels were germinated and the areas of the culture medium surfaces covered by the pixels were evaluated as a function of laser fluence. As the laser fluence was increased from 0 to 355 mJ/cm2 the transferred and germinated pixel area increased from 0 to 0.25 mm2. Further increase in fluence resulted in a drastic decrease down to an approximately constant value of 0.06 mm2. The yield of successful transfer by AFA-LIFT and germination was as much as 75% at 355 mJ/cm2. The results prove that AFA-LIFT can successfully be applied for the controlled transfer of biological objects. [ABSTRACT FROM AUTHOR]

ArF excimer laser ablation of micrometer size smoke grains was investigated. It was demonstrated that this procedure is suitable for destruction of these particulates in consequence of very fast heating, oxidation, burning, and evaporation. The time-resolved investigations revealed that the destruction process takes place between 0 and 7 ns after the maximum of the excimer pulse. The efficiency of breaking into small pieces was found to be dependent on the excimer laser fluence. Atomic force microscopic investigations of the sedimented smoke particles proved that the size of the grains significantly decreased by the excimer laser radiation. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In this work various microphysical properties including mass concentration, size distribution and morphology of aerosol particles generated by laser ablation of a high purity graphite sample were investigated in detail. Supplementary chemical analysis of the generated particles including microstructure investigation by high-resolution transmission electron microscopy (HRTEM) and Raman spectroscopy were also made. These measurements proved that the proposed method can be used to model the real atmospheric carbonaceous particulate under various climate relevant conditions regarding its specific properties investigated here. However, to introduce the presented methodology as a novel BC surrogate, further improvement and investigation including simplification in experimental setup, comprehensive analysis of thermochemical refractiveness and optical responses of the generated particles as well as comparative study with the presently available concurrent surrogates are required. The related results of these issues are planned to be demonstrated in other studies. [ABSTRACT FROM AUTHOR]

A possible application of excimer laser irradiation for the preparation of surface enhanced Raman spectroscopy (SERS) substrate is demonstrated. A polyimide foil of 125 μm thickness was irradiated by 240 pulses of focused ArF excimer laser beam (λ = 193 nm, FWHM = 20 ns). The applied fluence was varied between 40 and 80 mJ/cm². After laser processing, the sample was coated with 40 nm silver by PLD in order to create a conducting layer required for the SERS application. The SERS activity of the samples was tested by Raman microscopy. The Raman spectra of Rhodamine 6G aqueous solution (c = 10-3 mol/dm³) were collected from the patterned and metalized areas. For areas prepared at 40-60 mJ/cm² laser fluences, the measured Raman intensities have shown a linear dependence on the applied laser fluence, while above 60 mJ/cm² saturation was observed. The morphology of the SERS active surface areas was investigated by scanning electron microscopy. Finite element modeling was performed in order to simulate the laser-absorption induced heating of the polyimide foil. The simulation resulted in the temporal and spatial distribution of the estimated temperature in the irradiated polyimide sample, which are important for understanding the structure formation process. [ABSTRACT FROM AUTHOR]

Highlights: [•] A method for determining fractal dimension of cauliflower-like layers is presented. [•] An objective thresholding routine for SEM micrographs is introduced. [•] A fractal dimension of 1.83 for TiO x films grown at 5–50Pa pressures was found. [•] The fractal structure of inverse pulsed laser deposited TiO x films was confirmed. [•] The obtained fractal dimension suggests that aggregation of plasma species has only limited contribution to the deposition. [Copyright &y& Elsevier]

The machining process of transparent materials using the laser induced backside wet etching (LIBWE) procedure was studied. In the course of this, experimental investigations and numerical calculations were carried out. Fused silica plates were irradiated by an ArF excimer laser, using a naphthalene–methyl methacrylate solution as an absorbing liquid (concentration 0.85 mol dm-3, absorption coefficient at 193 nm 52 200 cm-1). The etch rate dependence on the applied laser fluence (varied from 110 to 860 mJ cm-2) was derived from the etch depths, measured using an atomic force microscope (AFM). The etch rate was found to be 4.7–49.5 nm/pulse, depending on the laser fluence. The surface morphology of the etched edges was also investigated by AFM. A fast photographic arrangement was used for time resolved observation of bubble development in the liquid absorbent, which is an important phenomenon of LIBWE. The internal pressure of the expanding bubbles was calculated using recorded snapshots. It was found to be 22–120 MPa 17.2 ns after the excimer pulse peak. The one-dimensional heat flow equation, including the melting of the treated fused silica layer and the vaporization of the absorbing solution, was solved using the finite difference method. The surface temperature of the fused silica was found to be a maximal 17.2 ns after the excimer pulse peak. Based on our results, we present a possible interpretation of the LIBWE procedure of fused silica. [ABSTRACT FROM AUTHOR]

Abstract: Matrix assisted pulsed laser evaporation (MAPLE) was used for growing urease thin films designed for bio-sensor applications in clinical diagnostics. The targets exposed to laser radiation were made from a frozen composite manufactured by dissolving biomaterials in distilled water. We used a UV KrF* (λ =248nm, τ FWHM ≅30ns, ν =10Hz) excimer source for multipulse laser irradiation of the frozen targets cooled with Peltier elements. The laser source was operated at an incident fluence of 0.4J/cm2. Urease activity and kinetics were assayed by the Worthington method that monitors urea hydrolysis by coupling ammonia production to a glutamate dehydrogenase reaction. A decrease in absorbance was measured at 340nm and correlated with the enzymatic activity of urease. We show that the urease films obtained by MAPLE techniques remain active up to three months after deposition. [Copyright &y& Elsevier]

Significance: Application of multiexposure speckle contrast imaging (MESI) methods for perfusion measurements can correct for the contribution of static scattering of the skin, at the expense of reduced temporal resolution as compared to classical single-exposure methods. Persistence of tissue scattering properties during the measurements could allow for an initial calibration and enhancement of the temporal resolution of the measurements., Aim: We aim to study the influence of the perfusion on the light scattering of the forearm skin and to use the obtained data for the enhancement of the temporal resolution., Approach: A wide range of skin perfusion states was induced while monitoring the changes in the dynamic range of the exposure-dependent contrast. Different measurement and evaluation methods were tested based on an initial MESI calibration followed by image recording with reduced number of exposure time values., Results: The changes in the skin perfusion can alter not only the contribution of the static scattering to the speckle images but also the short-exposure time contrast limit., Conclusions: The perfusion-dependent scattering of the skin can invalidate the precalibrations (e.g., β calibration) characterizing the combination of the given tissue and the measurement system., (© 2023 The Authors.)

The increasing prevalence of water insoluble or poorly soluble drugs calls for the development of new formulation methods. Common approaches include the reduction of particle size and degree of crystallinity. Pulsed laser ablation is a clean technique for producing sub-micrometre sized drug particles and has the potential to induce amorphization. We studied the effect of femtosecond pulsed laser ablation (ELI ALPS THz pump laser system: λ c  = 781 nm, τ = 135 fs) on meloxicam in distilled water and in air. The ablated particles were characterized chemically, morphologically and in terms of crystallinity. We demonstrated that femtosecond laser ablation can induce partial amorphization of the particles in addition to a reduction in particle size. In the case of femtosecond pulsed laser ablation in air, the formation of pure meloxicam spheres showed that this technique can produce amorphous meloxicam without the use of excipients, which is a unique result. We also aimed to describe the ablation processes in both investigated media., (© 2023. The Author(s).)

Recently, the number of water insoluble and poorly soluble drug compounds has increased significantly. Therefore, growing interest has been witnessed in different particle size reduction techniques to improve the dissolution rates, transport characteristics and bioavailability of drugs. Laser ablation has proven to be an alternative method to the production of nano- and micrometre-sized drug particles without considerable chemical damage. We present the nanosecond laser ablation of drug pastilles in distilled water, targeting meloxicam, a poorly water soluble nonsteroidal anti-inflammatory drug, at different laser wavelengths (248 nm, 532 nm and 1064 nm). Besides chemical characterization, crystallinity, morphology and particle size studies, the mechanism of the particle generation process was examined. The applicability of ablated particles in drug formulation was investigated by solubility, cytotoxicity and anti-inflammatory effect measurements. We showed that laser ablation is a clean, efficient and chemically non-damaging method to reduce the size of meloxicam particles to the sub-micrometre-few micrometre size range, which is optimal for pulmonary drug delivery. Complemented by the excellent solubility (four to nine times higher) and anti-inflammatory (four to five times better) properties of the particles compared to the initial drug, laser ablation is predicted to have wider applications in the development of drug formulations., (© 2022. The Author(s).)

Counterfeiting of the products for healing is as old as trading, and it is difficult to quantify the magnitude of the problem. It is known that substandard and/or falsified (SF) medicines are a growing global threat to health, and they cause serious social and economic damage. The EU has a strong legal framework for medicines, it is mandatory to meet the requirements of Directive 2011/62/EU. Serialisation prevents SF medicinal products from entering the legal distribution chain. The present study is an extension of the original idea and aims to develop a laser technology-based method to mark an individual traceable code on the surface of the tablet, which technology can also be used for marking personalized medicines. The method is based on the ablation of the upper layer of a double-layer, differently coloured coating. The 2D code should be formed without harming the functional layer, and anyone with a smartphone integrated with a camera should be able to authenticate these drugs with a suitable application. The present findings confirmed that KrF excimer laser and Ti:sapphire femtosecond laser are efficient and reliable for marking. These should be promising candidates for pharmaceutical companies that would like to have additional protection against drug counterfeiters., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Static scattering is detrimental to the accuracy of laser speckle contrast analysis (LASCA) measurements on skin when, instead of percentile change monitoring, absolute perfusion values are needed, e.g., for tissue injury examination. Perfusion values were calculated using two evaluation models, while changing the dynamic/static scattering ratio of monitored skin and tissue phantoms. Results were strongly affected by the significant increase of static contribution. Measurements on a modified tissue phantom showed that the changes in the measured perfusion values were mostly caused by the mixed scattering, which was omitted by the tested models. Dynamic ratio values obtained by multi-exposure LASCA could be used for perfusion data correction.

In pharmaceutical development, more and more drugs are classified as poorly water-soluble or insoluble. Particle size reduction is a common way to fight this trend by improving dissolution rate, transport characteristics and bioavailability. Pulsed laser ablation is a ground-breaking technique of drug particle generation in the nano- and micrometer size range. Meloxicam, a commonly used nonsteroidal anti-inflammatory drug with poor water solubility, was chosen as the model drug. The pastille pressed meloxicam targets were irradiated by a Ti:sapphire laser (τ = 135 fs, λ c = 800 nm) in air and in distilled water. Fourier transform infrared and Raman spectroscopies were used for chemical characterization and scanning electron microscopy to determine morphology and size. Additional particle size studies were performed using a scanning mobility particle sizer. Our experiments demonstrated that significant particle size reduction can be achieved with laser ablation both in air and in distilled water without any chemical change of meloxicam. The size of the ablated particles (~50 nm to a few microns) is approximately at least one-tenth of the size (~10-50 micron) of commercially available meloxicam crystals. Furthermore, nanoaggregate formation was described during pulsed laser ablation in air, which was scarcely studied for drug/organic molecules before.

We studied the application of pulsed laser ablation (PLA) for particle size reduction in non-steroidal anti-inflammatory drugs (NSAIDs). Grinding of the poorly water-soluble NSAID crystallites can considerably increase their solubility and bioavailability, thereby the necessary doses can be reduced significantly. We used tablets of ibuprofen, niflumic acid and meloxicam as targets. Nanosecond laser pulses were applied at various wavelengths (KrF excimer laser, λ = 248 nm, FWHM = 18 ns and Nd:YAG laser, λ 1  = 532 nm/λ 2  = 1064 nm, FWHM = 6 ns) and at various fluences. FTIR and Raman spectra showed that the chemical compositions of the drugs had not changed during ablation at 532 nm and 1064 nm laser wavelengths. The size distribution of the ablated products was established using two types of particle size analyzers (SMPS and OPC) having complementary measuring ranges. The mean size of the drug crystallites decreased from the initial 30-80 µm to the submicron to nanometer range. For a better understanding of the ablation mechanism we made several investigations (SEM, Ellipsometry, Fast photography) and some model calculations. We have established that PLA offers a chemical-free and simple method for the size reduction of poorly water-soluble drugs and a possible new way for pharmaceutical drug preformulation for nasal administration.

Substandard and/or falsified medicines are a growing global threat for health and they cause serious social and economic damage. In low- and middle-income countries the failure rate of these medical products is approximately 10.5%. 50% of medicines purchased over the Internet may be fake. According to Directive 2011/62/EU as regards the prevention of falsified medicines from entering into the legal supply chain, a unique identification should be put on each box of drugs in the EU from 9th February 2019. The current project is focusing on the development of a laser technology to mark an individual traceable code on the surface of the tablet. Usually, coatings contain titanium dioxide for sufficient coverage, which makes precision laser coding more difficult. New naturally coloured films do not include those excipients. In this research, we would like to compare the physical-chemical properties of conventionally and naturally coloured coatings after the laser marking procedure by using two types of lasers. This unique identification technology can be used for marking personalized medicine with the doses tailored for each patient, too. To sum up, the present findings may contribute to efficient and reliable laser marking solutions in the unique identification procedure. Based on our measurement results, it can be stated that excimer UV lasers are promising candidates as marking instruments for the polymer film in both conventionally and naturally coloured coatings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The amorphous to crystalline phase transformation of Ge2Sb2Te5 (GST) films by UV nanosecond (ns) and femtosecond (fs) single laser pulse irradiation at the same wavelength is compared. Detailed structural information about the phase transformation is collected by x-ray diffraction and high resolution transmission electron microscopy (TEM). The threshold fluences to induce crystallization are determined for both pulse lengths. A large difference between ns and fs pulse irradiation was found regarding the grain size distribution and morphology of the crystallized films. For fs single pulse irradiated GST thin films, columnar grains with a diameter of 20 to 60 nm were obtained as evidenced by cross-sectional TEM analysis. The local atomic arrangement was investigated by high-resolution Cs-corrected scanning TEM. Neither tetrahedral nor off-octahedral positions of Ge-atoms could be observed in the largely defect-free grains. A high optical reflectivity contrast (~25%) between amorphous and completely crystallized GST films was achieved by fs laser irradiation induced at fluences between 13 and 16 mJ/cm(2) and by ns laser irradiation induced at fluences between 67 and 130 mJ/cm(2). Finally, the fluence dependent increase of the reflectivity is discussed in terms of each photon involved into the crystallization process for ns and fs pulses, respectively.

The newborn pig is a widely accepted large animal model of hypoxic/ischemic (H/I) encephalopathy (HIE) of the term neonate appropriate for translational research. The methodology of the induction of H/I stress shows extensive variability of the literature, and little is known how these affect study outcome. The purpose of the present study was to determine the cerebrocortical microvascular effects of different H/I insults used in current HIE piglet models. For the semiquantitative study of cerebrocortical blood flow, we developed a methodological innovation: an operating microscope was converted into a custom-designed laser-speckle imager. Anesthetized, air-ventilated newborn pigs (n=7) were fitted with a closed cranial window. Speckle image series (2 ms, 1 Hz) were collected during baseline conditions, during transient bilateral carotid artery occlusion (BCAO), hypoxic (FiO(2)=0.1) hypoxia, hypoxia + BCAO, and asphyxia induced by suspending ventilation. Laser-speckle contrast analysis was performed off-line over parenchymal and arteriolar regions of interests, and pial arteriolar diameters were also determined for detailed analysis of cortical perfusion changes. Under normoxic conditions, transient BCAO did not affect parenchymal perfusion or pial arteriolar diameters. Hypoxia induced marked cortical hyperemia in 5 out of 7 piglets, with simultaneous increases in pial arteriolar diameters and arteriolar flow velocity, however, BCAO could not even affect these hypoxia-induced perfusion changes. In contrast to hypoxia or hypoxia + BCAO, asphyxia inevitably led also to severe cerebrocortical ischemia. In summary, acute reversible BCAO does not reduce cerebrocortical blood flow in the piglet, and thus it likely does not exacerbate the effect of hypoxic ventilation. Asphyxia elicits not only severe hypoxia, but also severe brain ischemia. These microcirculatory effects must be taken into consideration when assessing results obtained in the various HIE piglet models.

A new laser speckle-contrast analysis (LASCA) technique based on multi-exposure imaging was employed to simultaneously study pial arteriolar responses with cerebrocortical perfusion changes to various vasodilator (5-10% CO(2) ventilation, bradykinin (1-10 μM), N-methyl-D-aspartate (100 μM)) vasoconstrictor (10-100 μM noradrenaline, 1M KCl), or neutral (2.1% H(2) ventilation) stimuli as well as to asphyxia in the newborn piglet. Anesthetized, ventilated animals (n=20) were fitted with closed cranial windows. Multiple exposure laser-speckle image series (1-100 ms) were obtained using a near infrared diode laser (λ=808 nm). The autocorrelation decay time (τ) of speckle fluctuations was determined over pial arterioles and parenchymal areas to express 1/τ being proportional to blood flow velocity by two different LASCA techniques: our novel multi-exposure or a single exposure (2 and 20 ms) approach. 1/τ values yielded by different LASCA techniques were not significantly different at most points. LASCA easily detected both increases and decreases in cortical blood flow (CoBF). Cortical 1/τ changes to hypercapnia closely matched quantitative CoBF data determined previously, and were also in accordance with increases of pial arteriolar blood flow, calculated from arteriolar flow velocity and cross sectional area changes. In summary, LASCA emerges as an appealing method to simultaneously study microvascular reactivity and cortical perfusion changes in the piglet., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Urease thin films have been immobilized using matrix-assisted pulsed laser evaporation for biosensor applications in clinical diagnostics. The targets exposed to laser radiation were made of frozen composites that had been manufactured by dissolving urease in distilled water. An UV KrF* (lambda = 248 nm, tauFWHM congruent with 30 ns, nu = 10 Hz) excimer source was used for the multipulse laser irradiation of the targets that were cooled down to solidification using Peltier elements. The incident laser fluence was set at 0.4 J/cm2. The surface morphology and chemical bonding states of the laser immobilized urease thin films were investigated by atomic force microscopy and Fourier transform infrared spectroscopy. The enzymatic activity and kinetics of the immobilized urease were assayed by the Worthington method, which monitors urea hydrolysis by coupling ammonia production to a glutamate dehydrogenase reaction. Decreased absorbance was found at 340 nm and correlated with the enzymatic activity of urease., (Copyright 2008 Wiley Periodicals, Inc.)

In laser speckle contrast analysis (LASCA) used for imaging of blood flow, besides the moving blood cells, the speckle pattern is also influenced by the imaging system and scattering properties of the laser-illuminated static surface. A latex microsphere (650 nm size) emulsion was covered with scattering semitransparent materials (Teflon foils, tracing paper). Speckle images were recorded with different exposure times (0.2 ms-500 ms), and correlation times were determined by parameterizing the theoretical contrast-exposure time function. The correlation times obtained for covered and uncovered microsphere emulsions were in good agreement. The possibility of obtaining comparable, setup-independent results in blood perfusion monitoring can contribute to better applicability of LASCA.