Elena G. Domracheva

The use of measurements in several ranges leads to an increase in the reliability of the determination of substances in the compositions of multicomponent gas mixtures of various origins (detection of a substance in several ranges reliably confirms its presence in the studied mixture), which is relevant for various applications, including those actual for the medical diagnosis and control of the treatment of metabolites-markers of diseases and pathologies. In addition, it becomes possible to detect substances in a more convenient range for measurements. The aim of the work is to develop and implement a non-stationary gas spectrometer in the 75-110 GHz range with phase switching of radiation acting on the gas. The spectrometer concept is based on the use of commercially available devices and components. Test measurements were carried out using the example of acetonitrile, which has strong absorption lines in the operating range of the spectrometer. The developed and realized spectrometer complements the spectroscopic complex, which includes high-resolution gas spectrometers based on the effect of fast frequency swiping and phase manipulation of radiation acting on the gas in the frequency ranges 18-26 GHz, 118-175 GHz, as well as near 2 THz and 3.78 THz. In addition, besides developed software for measuring and processing the results obtained, a program has been written that allows the identification of experimentally measured absorption lines using freely available spectroscopic databases.

The work is devoted to applications of terahertz spectroscopic technique and methods for ecological applications and monitoring. Preliminary quantum-chemical calculations of rotational spectra of some chlorine-containing substances studied were carried out. The measurements of the absorption lines of the rotational spectrum for a number of chlorine-containing substances (dichloromethane, chloroform) were carried out in the 2-mm range using spectrometers developed by the authors. The spectroscopic absorption lines of some chlorine-containing substances, revealed during the investigations, can be used for ecological monitoring.

The work is devoted to studying the metabolites composition for human urine of prostate cancer and benign prostatic hyperplasia patients by terahertz (THz) high-resolution gas spectroscopy. The comparison of the composition of metabolites formed during thermal decomposition of urine of prostate cancer patients collected with preliminary prostate massage, without preliminary prostate massage and benign prostatic hyperplasia patients was carried out. The high-resolution THz spectrometer of 118-178 GHz frequency range with fast frequency sweeping developed by the authors was used. Free online spectroscopy databases were used for identification of substances. The sets of metabolites for two types of urine samples are revealed and metabolites which can be considered as potential markers of prostate cancer are determined.

The work is devoted to studying the composition for grain (barley and wheat) by terahertz (THz) high-resolution gas spectroscopy. The comparison of the set of chemical compounds formed during thermal decomposition of grain and cereals produced from grain was carried out with using a high-resolution spectrometer with phase-switching of radiation in the range of 115-175 GHz acting on studied gas developed by the authors. Free online spectroscopy databases were used for identification of substances. The results of comparison of molecular profiles of gas mixtures of thermal decomposition products of two varieties of barley, pearl barley and one variety of wheat are presented. Good agreement of the molecular composition for barley and pearl barley and some difference from the composition of the mixture obtained by heating wheat are shown.

The work is devoted to the study of the chemical composition of tissue metabolites for the organs of the ear, throat and nose and various life support systems by high-resolution THz spectroscopy on the example of samples of relatively healthy mucous membranes and cysts of the paranasal sinuses, as well as the shell of the renal cyst and median cyst of the neck. A high-resolution THz spectrometer with phase manipulation developed by the authors, operating in the 115-178 GHz range, was used. The chemical compounds were identified by absorption lines using electronic databases. Rotational absorption lines of alcohols, nitriles and organosulfur compounds are detected both in the spectra of samples of relatively healthy mucous membranes and in the spectra of cystic tissues. However, in the spectra of a relatively healthy mucous membrane, the number of absorption lines of some of these chemicals is less than in the spectra of cysts, which indicates their lower concentration. In addition, during thermolysis of cystic tissue samples, substances such as ketones, organic acids, aldehydes, and nitriles are formed, which can be considered as potential biomarkers of the pathological state of the tissue. A comparative analysis of the spectra of the maxillary sinus cyst, the shell of the kidney cyst and the median cyst of the neck showed that they are similar with minor differences. Identification of similar substances in tissues with the same pathology, but in different life support systems of the body, may be the first step towards determining the metabolic profile of this pathology as a whole. Thus, the potential possibility of using high-resolution THz spectroscopy to analyze the metabolic composition of tissues of various life support systems is shown.

The metabolomics‐based approach to diagnostics and therapy monitoring is a fast‐emerging trend in modern medicine. Terahertz nonstationary spectroscopy based on the induction and disintegration of freely decaying polarization in the gas mixture during the interaction of radiation with molecules at resonance frequencies is a high‐sensitivity method for studying multicomponent gas mixtures, which is promising for identifying metabolites in the thermal decomposition products of biological samples. The paper presents the results of the application of high‐resolution terahertz spectroscopy to the study of biological samples taken from patients with certain diseases (pathologically changed tissues of ear‐nose‐throat organs and similar pathologic tissues formed in other life support systems) to search for characteristic sets of metabolites characterizing the pathology. The world's first measurements of the spectra of pathologic samples of cysts, formed in different life support systems, were carried out, which made it possible to identify similar substances in tissues having the same pathology.

The results of using nonstationary high-resolution THz spectroscopy for detecting a characteristic set of metabolites of thermal decomposition products of urine from prostate cancer patients, aimed at identifying specific markers, are presented. Studies of the composition of biological fluid in prostate cancer were carried out using 12 urine samples from cancer patients and 4 samples from conditionally healthy volunteers. Differences in the composition and content of substances in the urine samples of cancer patients compared to the urine of conditionally healthy volunteers were identified, which allows preliminary conclusions to be drawn about substances promising for use as markers of prostate cancer in urine. The presented approach is promising for developing a method for noninvasive study of the composition of biological fluids, which makes it possible to identify metabolite markers of various pathologies and diseases.

Subject of study. The subject of this study was the chemical composition of multicomponent gas mixtures of biological origin. Aim of study. This study aimed to construct the metabolic profiles of diseases by studying biological samples (tissues of ear-nose-throat organs, urine) with high-resolution terahertz (THz) spectroscopy. Method. Spectroscopy based on nonstationary effects, such as inducing and decaying the free dumping polarization in a gas sample during the interaction of radiation and gas molecules, is a highly sensitive method for investigating multicomponent gas mixtures. A spectrometer based on these principles operates in the modes with the phase switching or fast sweeping of the probing radiation. Main results. Some experimental results of using high-resolution THz spectroscopy for medical diagnostics and treatment control are presented in this paper. The multicomponent gas mixtures, such as vapors or thermal decomposition products of various samples [biological liquids (urine) and pathological tissues of living organisms], were studied using THz nonstationary spectrometers for developing diagnostic methods. The results of experimental data analysis reveal the markers for specified diseases of living organisms (diabetes, pathology tissues of ear-nose-throat organs) or substances appearing during therapeutic treatment (nephrotoxical influence of chemotherapy). Practical significance. THz nonstationary high-resolution spectroscopy can be considered a prospective analytical method of spectral analysis for fundamental and applied research.

Nowadays, physicochemical methods of analysis are used in medical diagnostics. One can identify metabolites characteristic of a particular disease. The compilation of a metabolic profile will facilitate the diagnosis of diseases, evaluate their stage and etiology, and predict treatment. The goal of the study is to analyze the metabolite composition of the ear-nose-throat (ENT) tissues by high-resolution THz spectroscopy based on nonstationary effects and compare metabolites formed during the thermal decomposition of relatively healthy mucosa, polyps, and cysts. Studies were performed with the spectrometers operating from 118 to 178 GHz. The chemical compounds were identified using online catalogs. In all samples, there are such substances as methanol, propanediol, acetaldehyde, acetonitrile, butyronitrile, methyl mercaptan, azole, ethylene sulfide, carbon sulfide, and sulfur dioxide. In the spectrum of relatively healthy mucosa, the number of absorption lines of these substances is much less than in the spectrum of the polyps and cysts, which indicates their lower concentration. In the products of the polyps and cysts, acetone, hydroxyacetone, dihydroxyacetone, propionitrile, acrylonitrile, aminopropionitrile, hydroxyacetonitrile, aminoacetonitrile, methylbutironitrile, propanal, glycolaldehyde, lactaldehyde, and malone dialdehyde appear. The products of cysts’ thermal decomposition also contain acetic and acrylic acids. High-resolution THz spectroscopy has been shown to be promising for detecting disease metabolites in ENT tissues.