Currently, the majority of methods to monitor cancer treatment through the analysis of body fluids are based on a highly selective detection of single molecules or cells. In this study, we are considering the analysis of the aqueous medium of liquid samples, that is, water, itself, using aquaphotomics and near-infrared spectroscopy (NIR) for spectral data acquisition and processing, within cancer research. Water, as a molecular system, is a rich source of information about the current state of a patient, which can be extracted from near-infrared spectra of liquid samples via simple algorithms based on multivariate data analysis. The reported results, obtained ex vivo of body fluids, demonstrate the potential of aquaphotomics in cancer research.
A fiber probe has been developed that enables simultaneous acquisition of mid-infrared (MIR) and Raman spectra in the region of 3100–2600 cm−1. Multimodal measurement is based on a proposed ZrO2 crystal design at the tip of an attenuated total reflection (ATR) probe. Mid-infrared ATR spectra are obtained through a pair of chalcogenide infrared (CIR) fibers mounted at the base of the crystal. The probe enables both excitation and acquisition of a weak Raman signal from a portion of the sample in front of the crystal using an additional pair of silica fibers located in a plane perpendicular to the CIR fibers. The advantages of combining MIR and Raman spectra in a single probe have been discussed.
A compact fiber-optic probe for combinational vibrational spectroscopy was developed and evaluated. The probe is capable of simultaneous acquisition of mid-infrared ATR and Raman spectra from the same spot in the region 3100-2600 cm-1 which contains predominantly the responses of C-H stretching vibrations of hydrocarbon residues that has been widely employed in organic, analytic, biological, and polymer chemistry.
We report on the development of a dedicated Raman spectroscopic system employing a thin fiber optic needle for rapid determination of tumor resection margins on fresh intact specimens. This information will enable the surgeon to excise additional tissue if and where needed for complete tumor removal with adequate margins.
Maxillary sinus pathologies remain among the most common ENT diseases requiring timely diagnosis for successful treatment. Standard ENT inspection approaches indicate low sensitivity in detecting maxillary sinus pathologies. In this paper, we report on capabilities of digital diaphanoscopy combined with machine learning tools in the detection of such pathologies. We provide a comparative analysis of two machine learning approaches applied to digital diapahnoscopy data, namely, convolutional neural networks and linear discriminant analysis. The sensitivity and specificity values obtained for both employed approaches exceed the reported accuracy indicators for traditional screening diagnosis methods (such as nasal endoscopy or ultrasound), suggesting the prospects of their usage for screening maxillary sinuses alterations. The analysis of the obtained values showed that the linear discriminant analysis, being a simpler approach as compared to neural networks, allows one to detect the maxillary sinus pathologies with the sensitivity and specificity of 0.88 and 0.98, respectively.
The latest fiber solutions to be described for innovative applications in chemical process control, remote environment monitoring and biomedical diagnostics. Advanced fiber probes based on 4 different fiber types will be presented for their applications in very broad range of spectra 0.3-16µm – designed for all key spectroscopy methods: Transmission, ATR-absorption, Raman and fluorescence, - plus for their various combinations. The great synergy effect in fusion of spectral data from 2 (or more) spectral methods is available now when the advanced combi-fiber probes collect spectra from the same spot: Raman+DRS (Diffuse Reflection Scattering), Raman+Fluorescence, Near+Mid IR-absorption, Fluorescence + Mid ATR-absorption. The new generation of multiwavelength spectral sensors will be shown where the bundle of thin Mid IR-fibers combines radiation from the set of selected QCL into the innovative arthroscopy probe with side ATR-distal tip – for in-vivo diagnostics of osteoarthritis in car
In dairy, there is a growing request for laboratory analysis of the main nutrients in milk. High throughput of analysis, low cost, and portability are becoming critical factors to provide the necessary level of control in milk collection, processing, and sale. A portable desktop analyzer, including three light-emitting diodes (LEDs) in the visible light region, has been constructed and tested for the determination of fat content in homogenized and raw cow's milk. The method is based on the concentration dependencies of light scattering by milk fat globules at three different wavelengths. Univariate and multivariate models were built and compared. The red channel has shown the best performance in prediction. However, the joint use of all three LED signals led to an improvement in the calibration model. The obtained preliminary results have shown that the developed LED-based technique can be sufficiently accurate for the analysis of milk fat content. The ways of its further development and improvement have been discussed.
Biological tissue is complex substance which characterization demands combination of several spectroscopic techniques. Spectroscopy enables real-time label-free chemical and structural evaluation of samples for medical diagnostics in situ and in vivo. Fiber-optic probes provide flexible, sterilizable, and compact solutions for simultaneously analyzing tissue samples with several spectroscopic modalities. Modern fiber spectroscopy seamlessly covers entire wavelength range from 0.3µm with silica fibers to 20µm with chalcogenide, silver halide PIR fibers, and hollow glass waveguides. Here we present our latest achievements in developing multispectral compact fiber-optic probes for biomedical applications. We focused on combining all four key spectroscopic modalities (NIR, MIR, Raman, and Fluorescence) in single fiber probe tip. In preliminary studies of clinical bio-samples, combination of NIR diffuse reflection or MIR absorption spectroscopy with fluorescence spectroscopy gives synergy effect in differentiation of diseased and normal tissues. In our Raman experiments, we evaluate primary signals together with fluorescence background, which helps enhance analysis accuracy. Combined with advanced chemometrics data analysis, this concept enables the development of customized spectral fiber sensors based only on several wavelengths, hence their simple design, small size, high speed, and cost savings. It is possible to make rapid measurements directly in the operation theater by using tiny (<200 µm OD) but robust monofiber disposable Raman needle probes. Our recent experiments have shown the possibility of combining mid-IR ATR absorption and Raman spectroscopy in one compact fiber-optic probe. These advances turn fiber-optic multispectral probes into universal tools for any biomedical application requiring analysis of complex tissue.
Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.
Spectroscopy has become a popular method in research devoted to cancer diagnostics, therapy, and surgery - anywhere we need to detect tumor cells surrounded by non-cancerous ones. Usually, chemometrics methods are applied to classify cancerous and non-cancerous sites, so proper validation of classification models is required to ensure the reliability of the obtained results. In this study, we suggest using real data for simulation of spectral sets with varying characteristics (size, distribution of classes) - an analog of "sandbox" used in software development - and to validate the models in different conditions. Near-infrared spectra (939-1796 nm) measured from breast tumors and healthy tissues of laboratory mice (152 spectra) were used for simulation of spectral data sets of different sizes (50, 100, 150 spectra). We proposed a simple simulation method based on a singular value decomposition of the real spectral dataset and rearrangement of the calculated residuals. Several algorithms of training and test set selection have been applied to the simulated data (Kennard-Stone, DUPLEX, random, MonteCarlo cross-validation), and corresponding Support Vector Machines classification models have been trained, optimized, and validated by using a series of test sets with varying "healthy: tumor" classes distribution (1:1,3:1,1:3) and size (10%, 30%, and 50% of the training data set). Performance of the classification models, expressed in values of accuracy, sensitivity, and selectivity, has been compared, and a validation strategy has been proposed.
Silver halide polycrystalline infrared fibers (PIR) have unique properties such as excellent transmittance in the spectral range from 3 to 17 µm, while also being highly flexible, non-toxic, and non-hygroscopic. They are used in industry and medicine for CO 2 -laser power delivery, flexible infrared imaging, and remote process spectroscopy. While PIR fibers possess a quite low attenuation (0.1-0.5 dB/m) in the 8-12 µm range, their total transmittance is limited by significant Fresnel reflections at the fiber end faces due to the high refractive index of silver halide (>2.1). Functionalization of these surfaces with specially designed Anti-Reflective Microstructures (ARMs) enables a striking enhancement of fiber transmittance. In this work, direct imprinting (or embossing) of microstructures to fiber ends and their profiling with a microstructured knife was applied to fabricate such ARMs. The resulting two-dimensional Moth-eye microstructures and one-dimensional microgrooves at the PIR-fiber ends enable to an increase of fiber transmittance in a broadband range of (5-17 µm) as well as to reach up to 20% improvement for PIR-fiber laser cables used for power delivery of CO 2 -lasers at 10.6 µm.
Fiber optic spectroscopy label-free composition analysis makes it the best tool for reaction monitoring in Process Analytical Technologies (PAT) and chemical analysis of bio tissues for medical diagnostics in-citu and in-vivo. Biological samples and modern chemicals are complex substances, which composition analysis requires combining several spectroscopic techniques. Fiber optics probes provide compact, flexible, robust, and cost-effective solutions to merge different optical modalities in one tool for sample analysis at the same point. This spatial synchronization of the analysis is critical for heterogeneous samples. Recent advances in optical fiber manufacturing significantly expand the wavelength range of the analysis from 0,3-2µm range with Silica fibers towards middle IR (with chalcogenide, AgCl:AgBr Polycrystalline PIR fibers, and Ag/AgI hollow glass waveguides covering together 1-20 µm range). We were able to fuse all 4 key spectroscopic methods (Fluorescence, NIR, MIR, and Raman) in compact fiber probes. In preliminary studies of tissue samples we showed that a combination of fluorescence with NIR or ATR-IR spectroscopy results in much better accuracy of the tumor margin detection than each of the individual methods separately. This synergy is explained by the capability of different light modalities to deliver complementary chemical information. We are using information from fluorescence background subtracted from Raman spectra to enhance the accuracy of the analysis. This concept, combined with advanced chemometrics data analysis, enables the development of customized spectral fiber sensors based only on several wavelengths or wavelength regions. Our recent experiments have shown the possibility of combining mid-IR ATR absorption and Raman spectroscopy in one compact fiber-optic probe. Thus it is possible to obtain an extended optical spectrum of molecular vibrations from the same point of a complex sample. These advances turn fiber-optic multispectral probes into the universal tool for applications that require in vivo analysis or real-time process monitoring.
Silver halide polycrystalline infrared (PIR) fibers and hollow waveguides (HWGs) have high transmission at midinfrared wavelengths from 3 to 18 μm. Their applications include a flexible delivery of CO2 and CO laser power. We investigated transmission of PIR fibers and HWGs at different bending radii using CO2 laser radiation and studied the intensity distribution after the distal fiber. The PIR fibers show only a relatively weak decrease in transmission with increasing curvature 1/R or decreasing bending radius R. This is an advantage over hollow waveguides, where transmission decreases sharply with curvature. Disadvantages are high reflection losses at the PIR fiber end faces due to the high refractive index of 2.15 for wavelengths in the mid-infrared region. To reduce these losses, the surface of the fiber end faces must be treated with several special methods including microstructuring or coupling with an antireflective window. The measured near-field and far-field intensity distributions or beam profiles are highly inhomogeneous for both fiber types. For large core diameters of 0.9 or 1 mm, the beam profiles appear to be more homogeneous for the PIR fibers.
Pyrometry is widely used in science, medicine, and industry to measure the surface temperature of objects in a non-contact way. IR fibers are an ideal solution for the flexible delivery of thermal radiation emitted from objects inside a complex structure like internal organs inside the human body. Silver halide polycrystalline infrared fibers (PIR) are transparent in a spectral range of 3 - 18 µm, matching perfectly with the spectra of black body radiation for temperatures ranging from 20°C to 200°C. These fibers are non-toxic and allow small bending radii. They could become critical components in pyrometric systems for temperature-controlled laser surgeries. Here we discuss the ability of the PIR fibers for simultaneous laser power delivery and real-time temperature monitoring in laser surgery applications and demonstrate two different setups for this purpose.
The paper presents the results of a study of conditionally healthy volunteers and patients with various maxillary sinuses diseases by digital diaphanoscopy with a comparison of the results obtained with CT studies. The results of the classification of pathological changes based on a quantitative assessment of the registered scattering patterns of light are also presented.
Review of the latest progress of special optical fiber applications in laser optics, IR-Imaging and spectrometry. The advanced fiber solutions will be presented for Quantum Cascade Lasers in Mid-IR range. A high coupling efficiency of optical fiber and Hollow Waveguides to QCL is demonstrated. A novel combined fiber optic multispectral probe for tissue diagnostics is demonstrated and discussed. Flexible solutions for thermal imaging in mid-IR range are proposed on the base of high quality optical fibers.
AgClBr polycrystalline fibers with refractive index above 2 are used to transmit radiation of the infrared range. To improve the efficiency of AgClBr fiber based devices, it is beneficial to increase the fiber end faces transmittance. The conventional method for increasing the surface transmittance is to use antireflection coatings (ARCs). However, in the case of AgClBr ARCs cannot be applied to a fiber end face due to its unevenness. The plasticity and softness of the material prevent chipping, cleavage, and polishing. Thus a slicing technique should be used to cut the fiber, but even with the most precise technique perfect flatness cannot be achieved. An alternative approach is to fabricate antireflection microstructures (ARMs) [1] on the surface of a fiber end face. In this work a single-pulse direct femtosecond laser ablation for ARM fabrication was used. This technique provides good quality of ARM [2] and has already been tested on A 2 B 6 group semiconductors [3] which are promising gain media matrices [4] , chalcogenide glasses used for optical fiber production [5] , and infrared nonlinear crystals [6] .
A multispectral fiber optic probe has been developed that enables simultaneous analysis of various liquid and solid samples using attenuated total reflection mid-infrared spectroscopy and fluorimetry. The probe design was optimized using ray-tracing simulation of the light propagation. Technical evaluation of the probe has confirmed its output signal quality that was comparable to that of respective probes for single methods. The capability of the probe to deliver complementary chemical information from the same measurement point has been illustrated using model samples of biological tissue. Qualitative analysis of the biological tissue is one of the most important applications of the developed multispectral probe.
The work is devoted to the development of a scientific and technical basis for instrument implementation of a digital diaphanoscopy technology for the diagnosis of maxillary sinus inflammatory diseases taking into account the anatomical features of patients (differences in skin structure, skull bone thickness, and sinus size), the optical properties of exercised tissues, and the age and gender characteristics of patients. The technology is based on visualization and analysis of scattering patterns of low-intensity radiation as it passes through the maxillary sinuses. The article presents the experimental data obtained using the digital diaphanoscopy method and the results of numerical simulation of the optical radiation passage through the study area. The experimental setup has been modernized through the installation of a a device for controlling the LED applicator brightness. The approach proposed may have considerable promise for creating diagnostic criteria for various pathological changes and can be used to assess the differences in the optical and anatomical features of males and females.