BACKGROUND: Congenital giant pigmented nevi (CGPN) occur in 1:20 000 to 1:500 000 newborns. They are small (1.5 to 5 sq. cm), medium (5 to 50 sq. cm) and a truly gigantic (more than 50 sq. cm) types of pigmented nevi. CGPN create a psychological problem in children, due to aesthetic discomfort. Various techniques for their removal are not always effective and may cause complications: relapse (6–41%), skin scarring (6%), malignancy is possible in adults (10%). The question of CGPN effective removal remains open. This stimulates search for the optimization of applied curative options; and one of the ways is to use laser light for CGPN removal in children. Previously, individual researchers used infrared radiation (λ 10.6 microns) generated by pulsed periodic CO2 laser for this purpose; some experimental work on "blue" (λ 0.45) light generated by diode laser was done too. Experimental studies on the skin of laboratory animals could define features of exposure and promising modes of these types of laser radiation for surgical application in CGPN removal. AIM: To improve outcomes of treatment of various CGPN forms in children with optimized laser techniques. METHODS: The CGPN removal was done with "blue" laser light (λ 0.45 micron) using Lasermed 10-03 device manufactured by Russian Engineering Club LLC (Tula) and laser light (λ 10.6 microns) generated by pulsed periodic CO2 laser device ALDAN (manufacturer IOF RAS, Moscow, Russia). 35 children with various CGPN forms were treated in the Clinical and Research Institute of Emergency Pediatric Surgery and Trauma. Among them: 18 patients with a small form, 11 children with an average form, and 6 with a true gigantic form. Children’s age ranged from 6 to 18 years. In 13 children, CGPN located on the face, in 6 — on the anterior surface of the chest, in 8 — on the lower and upper extremities, in 4 — on the abdominal wall and in 4 — on the back. RESULTS: The final good clinical and aesthetic outcome was registered in 29 children with small and medium CGPN forms. In 6 patients with true gigantic forms, good clinical and satisfactory aesthetic results were registered preliminary, at the treatment stage. No unsatisfactory results were seen. CONCLUSION: Our experience with optimized techniques using mentioned types of laser light for the removal of various CGPN forms in children has confirmed their clinical and aesthetic effectiveness and outlined the prospect of their application in pediatric surgery.

Background. Currently, the problem of radical removal of pigmented skin formations with good clinical and aesthetic results remains open. These formations, including congenital giant pigmented nevi (CGPN), are found at birth in 2 % of newborns; acquired nevi are registered in 75 % of children. They can be large in size and quite often are located on visible parts of the body, creating psychological problems in children and leading to aesthetic discomfort. In adulthood, various complications may develop including malignancy which may develop in 10% of patients. Management of pigmented skin formations causes both medical and psychological problems. So, it is reasonable to solve them in childhood. Modern various techniques for the removal of pigmented nevi are not always effective; besides, they are often followed by various complications, like relapses (in 6–41 %) and skin scarring (in 6 %). Such a situation requires development of new highly effective techniques for removing various pigmented nevi, including laser light. Recently, separate works on the application of “blue” (λ = 450 nm) laser light and infrared (λ = 10.6 μm) laser light generated by periodic CO2 laser for the discussed pathology have appeared.Purpose. To conduct a comparative experimental study on the effects of “blue” (λ = 450 nm) laser light and infrared (λ = 10.6 μm) laser light generated by pulsed periodic CO2 laser at the skin of laboratory rats in order to find out promising parameters for surgical removal of pigmented skin formations.Material and methods. Laser devices “Lasermed 10-03” (LLC RIK, Russia) generating in “blue” (λ = 450 nm) and pulsed periodic CO2 laser “ALDAN” (IOF RAS, Russia) generating in infrared (λ = 10.6 μm) laser light were used. In present in vivo experiment, pigmented skin of laboratory rats was exposed to laser light. Exposure zones were compared; features and regeneration terms were analyzed too.Results. The researchers registered specific effects in skin irradiation with laser light as well as in terms of wound regeneration. They also identified optimal parameters of “blue” (λ = 450 nm) and infrared (λ = 10.6 μm) laser light for the removal of CGPN and pigmented skin formations.Conclusion. The obtained results of the present comparative experimental trial have outlined prospects for the application of “blue” (λ = 450 nm) laser light and infrared laser light (λ = 10.6 μm) generated by pulsed periodic CO2 laser for surgical removal of pigmented skin formations.

The process of $\text{Au}+$ and $\text{Au}$ -ions formation on a surface of nanostructured gold plate under pulsed laser irradiation with energy density below plasma threshold is studied. The role of nanoscale objects produced on the surface under laser irradiation higher than the plasma threshold in the ion formation process is discussed.

Background: Primary vesicoureteral reflux (VUR) is the most common congenital uropathy (CU) in children, leading to the development of reflux nephropathy and chronic kidney disease, reaching the terminal stage in 25-60% of patients. The insufficient sensitivity of modern methods of instrumental and laboratory diagnostics of the initial stages of renal parenchyma damage dictates the need to develop new non-invasive technologies for screening and monitoring kidney conditions in patients with CU. Aims: To evaluate the possibility of separating groups of healthy children and children with kidney damage with CU using the analysis of the mass spectra of volatile organic compounds (VOCs) in urine samples. Materials and methods: This study involved 42 patients (average age 5.4 + 2.3 years), divided into 2 groups: group 1 24 children with congenital uropathies (grade II-V PMR) and comparison group 2 - 18 patients with minor surgical pathology without pathology of the urinary system. Urine samples were collected before the start of treatment. Composition analysis of VOCs samples was carried out through express-analysis method for biological objects at atmospheric pressure without preliminary preparation using a mass spectrometer with ionization by laser plasma radiation. Urinary levels of markers of inflammation (MCP-1, IL-8, IL-18), angiogenesis (VEGF) and fibrosis (TGF-1) were measured by solid-phase ELISA. Results: Composition changes in urine VOCs were detected in group 1 patients with congenital uropathies (VUR). These changes made it possible to distinguish group 1 samples from the comparison group 2. Creatinine level and glomerular filtration rate (GFR) in both groups had no statistical difference. An increase in concentration of inflammatory markers MCP-1, IL-18, IL-8, VEGF angiogenesis and TGF-1 fibrosis was observed in the urine of children with congenital uropathies (VUR) (p0.001). In group 1 patients the concentration of markers did not correlate with the reflux level. Conclusions: The performed research allowed to find a set of peaks in the recorded mass spectra, according to which it is possible to divide groups into healthy and sick. It also demonstrated the potential of volatolom analysis to detect kidney damage in children with congenital uropathies. The use of standard methods: creatinine and GFR did not allow us to find a threshold value to divide patient into healthy and sick groups. The increase of biomarkers of inflammation, angiogenesis and fibrosis in the urine of children with congenital uropathies confirmed the presence of persistent kidney damage, parenchymal hypoxia, activation of fibrosis and inflammation in children with CU kidneys.

Trained detection dogs distinguish between urine samples from healthy organisms and organisms with malignant tumors, suggesting that the volatile urine metabolome contains information about tumor progression. The aim of this study was to determine whether the stage of tumor growth affects the chemical differences in the urine of mice and to what extent the "olfactory image of disease" perceived by dogs coincides with the "image of disease" recorded by the mass spectrometer. We used a novel laser ionization mass spectrometry method and propose a mass spectrometric analysis without detailed interpretation of the spectrum of volatile metabolomes in urine. The mass spectrometer we use works without sample preparation and registers volatile organic compounds in air at room temperature without changing the pH of the sample, i.e. under conditions similar to those in which dogs solve the same problem. The experimental cancer models were male BDF-f1 hybrid mice transplanted with hepatocarcinoma tissue, and similar mice transplanted with healthy liver tissue were used as controls. Our data show that both dogs and our proposed laser mass spectrometry method are able to detect both the entire spectrum of volatile organic compounds associated with the disease and minor changes in this spectrum during its course.

Surface layers of molybdenum oxide MoO3 and tungsten oxide WO3 produced by thermal oxidation of molybdenum and tungsten plates in the air were studied for the first time as a platform for laser-induced electron transfer desorption/ionization. High analytical performance of such layers for the determination of metal complexes with dithiocarbamates, such as tetramethylthiuram disulfide, tetraethylthiuram disulfide, and diethyldithiocarbamate, has been demonstrated. All studied complexes are detected as radical cations, with no fragment ions. The ion yields from MoO3 and WO3 surfaces were found to be more than two orders of magnitude higher than those from nanocrystalline silicon surfaces. A novel method has been developed for the determination of trace amounts of dithiocarbamates based on the complexation of analytes with gold ions, followed by laser-induced electron transfer desorption/ionization. The limits of detection of dithiocarbamates were estimated to be about 1 ng/mL. The proposed method was successfully applied to the rapid screening of tetramethylthiuram disulfide residues in juice.

A laser plasma ion source was used to ionize volatile organic compounds in a gas sample. The plasma was generated on a metal target in the intermediate vacuum region of ~0.3 Torr using a pulsed Nd:YAG laser with a wavelength of 1 μm. The resulting ions mass spectra were acquired using orthogonal time-of-flight mass spectrometer (O-TOF MS). When using a copper target, the ions formed are simple complexes (CuM+ ) of copper ions with organic molecules. The possibility of online identification of trace amounts of alkanes in nitrogen and air, with a detection limit of ~10 ppb, was demonstrated. The ionization efficiency of volatile organic compounds through the formation of clusters with metal ions is 10-4 in terms of the quasimolecular complex ions. The rate constants of ion-molecular reactions of copper ions with octane and water molecules in nitrogen and air are estimated.

Laser-induced plasma generated by exposing a metal target to pulsed laser radiation with a power density of similar to 70 GW cm(-2) is used to ionize organic compounds in gases at atmospheric pressure. The estimation of the plasma temperature based on the analysis of the plasma emission spectra has shown that in the first few nanoseconds the temperature exceeds 5.5 x 10(4) K. The vacuum ultraviolet radiation of that plasma provides ionization of any organic compounds and water molecules. The main ionization channels of the studied compounds are proton transfer reactions, addition reactions with the formation of [M + NH4](+) and [M + H3O](+) ions and photoionization. Hydrocarbons are ionized by pre-oxidation and subsequent ionization of oxygenated molecules. The optimal surrounding gas for the analysis is pure argon, since the ionization efficiency of organic compounds in argon is up to a hundred times higher than that in atmospheric air and pure nitrogen. (C) 2020 Elsevier B.V. All rights reserved.

УД-VII-4МАСС-СПЕКТРОМЕТРИЯ ОРГАНИЧЕСКИХ СОЕДИНЕНИЙ С

Vacuum UV radiation from laser-induced plasma is used to ionise volatile organic compounds (VOCs) released by living organisms during their mass spectrometric analysis at atmospheric pressure without sample preparation. It is shown that the probability of ionisation of organic compounds with different ionisation potentials and proton affinity at atmospheric pressure in the argon flow weakly depends on the compound parameters and can be 3.6 × 10−5 – 1.4 × 10−4. The VOC spectra of mouse and human biological fluids are obtained without sample preparation at room temperature of the sample. The possibility of using the proposed method for the diagnosis of pathological changes is demonstrated.

The approach to quantitative analysis by silicon Surface Assisted Laser Desorption Ionization Mass Spectrometry (Si-SALDI) is proposed. The approach is based on the new method for forming an active surface layer on a silicon substrate by exposing to laser radiation directly in the ion source of a mass spectrometer. The method can be used repeatedly on the same substrate, providing high reproducibility of its surface ionization properties and high ionization efficiency of organic compounds. Within the proposed approach, the methods of improvement of signal reproducibility are also considered, including continuous monitoring of the silicon surface ionization properties using a Knudsen effusion cell; scanning the surface of a silicon substrate with a laser beam; selecting the optimal value of laser fluence and using a reproducible sample introduction technique. It is demonstrated that this approach can be successfully applied to quantify clinically relevant concentrations of pharmaceutical drugs in extracts of blood.

Представлены результаты математического моделирования импульсного источника ионов при атмосферном давлении с ионизацией анализируемого вещества УФ излучением лазерной плазмы. Расчеты проводились на основе разработанной авторами математической модели, описывающей эволюцию ансамбля ионов под действием скрещенных газодинамических и электрических полей с учетом эффектов кулоновского взаимодействия. Модель включает в себя систему уравнений Навье-Стокса для описания формирования газодинамических течений в исследуемом объеме, уравнение Пуассона для определения результирующего распределения электрического поля в этом объеме и уравнение Лоренца для построения ионных траекторий ионов от места их рождения до собирающей диафрагмы. Показана сходимость метода релаксации при численном решении основных уравнений модели. Исследована зависимость ионного тока от приложенного напряжения и показано, что учет конечности времени жизни ионов за счет эффекта рекомбинации позволяет получить хорошее согласие между расчетными и экспериментальными данными. Ключевые слова: лазерная плазма, математическое моделирование, ионный источник, газодинамические и электростатические поля, масс-спектрометрия.

A method of rapid mass spectrometric analysis of volatile organic compounds (VOC) of biological samples at atmospheric pressure has been developed. The method uses laser plasma radiation for ionization of VOC molecules. Multivariate statistics was used for the mass spectra analysis. The possibility of identification of progressing oncological process in mice with analyzing the composition of VOCs of the urine samples was showcased.

A pulsed source of ions with ionization of the substance under study at atmospheric pressure by the UV radiation of laser plasma is numerically simulated. The calculations are based on an original mathematical model that describes evolution of an ensemble of ions in the presence of superimposed gas-dynamic and electric fields with allowance for the Coulomb interaction. The model contains a system of the Navier–Stokes equations for gas-dynamic flows in the volume under study, the Poisson equation for the resulting distribution of electric field in such a volume, and the Lorentz equation for construction of ion trajectories from the ionization place to collecting diaphragm. Convergence of the relaxation method is demonstrated for the numerical solution of the main model equations. The dependence of ion current on applied voltage is studied. It is shown that the calculated results are in good agreement with the experimental data when finiteness of the ion lifetime due to recombination effect is taken into account.

A single-particle mass spectrometer (SPMS) can provide a wealth of valuable information on chemical and physical parameters of individual particles in real time. One of the main performance criteria of the instrument is efficiency of particle detection (hit rate). Most SPMS instruments use constant electrical field (DC) extraction, where stationary high voltage is applied to the extraction electrodes. As the aerosol particles initially carry a certain charge, those with a high amount to charge can be deflected by this electric field and lost, thus decreasing the hit rate. We realized that the delayed extraction technique can eliminate the stochastic dispersion of the particle beam caused by their deflection in the stationary electric field. As the result, the hit rate of the instrument can be significantly improved. Also, as the effect of the deflection in the electric field is mass dependent, it can cause distortion of the measured size distribution of the particles. Hence, the delayed extraction technique can bring the recorded distribution closer to the actual one. We found that the delayed extraction technique provides a mass resolution improvement as well as increases the hit rate. The gain in the hit rate depends on the type of particles. It can be 2 orders of magnitude for model particles and up to 2–4 times for ambient particles. In the present work we report experiments and results showing the effect of the delayed extraction on the beam divergence caused by particle charge, the hit rate improvement, and the effect of the delayed extraction on the measured particle size distribution.

Laser desorption of organic compound ions from specially prepared surfaces is known as surface-assisted laser desorption/ionization (SALDI). In this work the properties of a SALDI ion emitter obtained by two-stage laser treatment of crystalline silicon surface have been investigated. The laser surface treatment leads to the formation of a layer with nanoscale objects—quantum dots (QDs) less than 10 nm in size, providing laser desorption of organic compound ions. A change in the desorbing laser wavelength from 351 to 263 nm at comparable laser-exposed spot sizes and fluences results in a sharp decrease in the formation efficiency for MH+ ions and appearance of ions M+ for the same analytes. The effect is apparently determined by the spectral properties of the quantum dots formed on the silicon surface under laser irradiation.

A method for the chemical modification (derivatization) of ions obtained by surface assisted laser desorption/ionization (SALDI) is proposed. Derivatization is based on the interaction of desorbed ions with alcohol molecules. The method is simple, does not affect the duration of analysis and ensures the improvement of the analytical characteristics of the SALDI method, when analysis is carried out under the conditions of peak interference and strong fragmentation of analyte ions. The efficiency of the method is demonstrated in the determination of caffeine, pyrrolidine, and diphenhydramine under the conditions of atmospheric pressure sample application.

Delay Extraction (DE) in Single Particle Mass Spectrometry (SPMS) provides substantial resolution enhancement. However, DE has two main drawbacks which are discussed in our article. First, ion peak position in this case becomes very sensitive to initial ion coordinate. Therefore, substantial peak jitter is observed when switching between mass spectra of individual particles. This peak jitter obstructs correct mass spectra accumulation resulting in wide peaks with irregular shapes in the accumulated mass spectrum, which leads to the fact that isotopic pattern identification becomes difficult. In the present article two ways of the peak jitter compensation, Dynamic Calibration and Mass Spectra correction based on Spectra Correlation, are proposed. It was shown that both proposed techniques provide substantial resolution improvement in the summed mass spectrum especially for small peaks with complex isotopic patterns. Second, time delay distorts regular quadratic dependence between time-of-flight and m/z. In our paper we also propose calibration equation with variable exponent for SPMS modified with DE. It is shown that usage of an exponent as a fitting parameter allows to achieve mass accuracy comparable with 4th degree equation proposed earlier. (C) 2018 Elsevier B.V. All rights reserved.