Multimodal fiber probe for simultaneous mid-infrared and Raman spectroscopy.

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.

LED-Based Desktop Analyzer for Fat Content Determination in Milk.

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.

Intraoperative assessment of resection margins by Raman spectroscopy to guide oral cancer surgery.

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.

Digital diaphanoscopy of maxillary sinus pathologies supported by machine learning.

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.

Pyrometry with flexible infrared fibers for temperature-controlled laser surgery.

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.

Fiber Probe for Simultaneous Mid-Infrared and Fluorescence Spectroscopic Analysis.

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.

Optical Diagnostics of the Maxillary Sinuses by Digital Diaphanoscopy Technology.

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.

Synergy Effect of Combined Near and Mid-Infrared Fibre Spectroscopy for Diagnostics of Abdominal Cancer.

Cancers of the abdominal cavity comprise one of the most prevalent forms of cancers, with the highest contribution from colon and rectal cancers (12% of the human population), followed by stomach cancers (4%). Surgery, as the preferred choice of treatment, includes the selection of adequate resection margins to avoid local recurrences due to minimal residual disease. The presence of functionally vital structures can complicate the choice of resection margins. Spectral analysis of tissue samples in combination with chemometric models constitutes a promising approach for more efficient and precise tumour margin identification. Additionally, this technique provides a real-time tumour identification approach not only for intraoperative application but also during endoscopic diagnosis of tumours in hollow organs. The combination of near-infrared and mid-infrared spectroscopy has advantages compared to individual methods for the clinical implementation of this technique as a diagnostic tool.

Light guidance up to 6.5†µm in borosilicate soft glass hollow-core microstructured optical waveguides.

Limited operating bandwidth originated from strong absorption of glass materials in the infrared (IR) spectral region has hindered the potential applications of microstructured optical waveguide (MOW)-based sensors. Here, we demonstrate multimode waveguide regime up to 6.5 µm for the hollow-core (HC) MOWs drawn from borosilicate soft glass. Effective light guidance in central HC (diameter ∼240 µm) was observed from 0.4 to 6.5 µm despite high waveguide losses (0.4 and 1 dB/cm in near- and mid-IR, respectively). Additional optimization of the waveguide structure can potentially extend its operating range and decrease transmission losses, offering an attractive alternative to tellurite and chalcogenide-based fibers. Featuring the transparency in mid-IR, HC MOWs are promising candidates for the creation of MOW-based sensors for chemical and biomedical applications.

Fiber-cap biosensors for SERS analysis of liquid samples.

Optical detection techniques based on surface enhanced Raman spectroscopy (SERS) are a powerful tool for biosensing applications. Meanwhile, due to technological advances, different approaches have been investigated to integrate SERS substrates on the tip of optical fibres for molecular probing in liquids. To further demonstrate the perspectives offered by SERS-on-fiber technology for diagnostic purposes, in this study, novel cap-shaped SERS sensors for reversible coupling with customized multimodal probes were prototyped via low-cost polymer casting of polydimethylsiloxane (PDMS) and further assembly of gold nanoparticles (Au NPs) of varied sizes and shapes. To demonstrate the feasibility of liquid sensing with cap sensors using backside illumination and detection, the spectra of rhodamine were acquired by coupling the caps with the fiber. As expected by UV-vis, the highest SERS efficiency was observed for NP-decorated substrates with plasmonic properties in resonance with the irradiation wavelength. Then, SERS biosensors for the specific detection of amyloid-ß (Aß) neurotoxic biomarkers were realized by covalent grafting of Aß antibodies. As attested by fluorescence images and SERS measurements, the biosensors successfully exhibited enhanced Aß affinity compared to the bare sensors without ligands. Finally, these versatile (bio)sensors are a powerful tool to transform any milli-sized fibers into functional (bio)sensing platforms with plasmonic and biochemical properties tailored for specific applications.

iBEAM: substrate-integrated hollow waveguides for efficient laser beam combining.

Laser light sources are routinely applied building blocks in optical sensor technologies. While lasers are emitting at a precisely defined wavelength within narrow emission bands, chem/bio-sensing applications frequently demand multi-wavelength illumination for addressing a series of species. Instead of using broadband radiation sources, it is a viable strategy to efficiently combine the beams emitted from different lasers to maintain the spectral brightness and yet cover extended wavelength regimes. In this study, substrate-integrated hollow waveguides (iHWGs) are reported as a versatile and efficient alternative compared to conventional beam combining concepts, especially for applications in the mid-infrared spectral regime leading to a highly efficient multi-port beam combiner-the iBEAM.

Synergy of Fluorescence and Near-Infrared Spectroscopy in Detection of Colorectal Cancer.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide. There is an urgent need for simple and fast methods to improve tumor detection in the diagnostic and intraoperative setting to avoid complications and provide objective information in distinguishing malignant and benign colorectal tissue. Optical spectroscopy methods have recently shown a great potential for this discrimination in different organs. MATERIALS AND METHODS: In this pilot study, fluorescence emission spectra (excitation: 473 nm) and diffuse reflectance spectra (DRS) of normal and tumor tissues from resected colorectal cancer specimen were measured using fiber optical probes in an ex vivo setting, and the data were subjected to multivariate analysis. RESULTS: Substantial spectral differences were found in the fluorescence and DRS spectra of colorectal cancer tissue in comparison to benign tissue. The diagnostic potential of a multimode optical system combining both spectroscopic methods was investigated by mathematical combination. Compared with the individual techniques, a higher sensitivity of the joint DRS-fluorescence optical system in the discrimination between malignant and benign colorectal tissue could be observed. CONCLUSIONS: In the pilot study presented herein, a quick and reliable method to differentiate malignant and benign colorectal tissue ex vivo with different spectroscopic techniques using spectral fiber probes could be established. Joint fluorescence and near-infrared spectroscopy had a higher sensitivity in tissue discrimination and showed to be a promising combination of two spectroscopic methods. Further studies using the synergic effect of fluorescence and DRS spectroscopy are needed to transfer these findings into the in vivo situation.

In vivo and in vitro application of near-infrared fiber optic probe for Ehrlich carcinoma distinction: Towards the development of real-time tumor margins assessment tool.

This report describes a full-scale experiment on intradermal Ehrlich carcinoma (EC) differentiation in mouse model using NIR spectroscopy in diffuse reflectance mode and chemometric data processing. EC is widely used as an experimental tumor model due to its resemblance with human undifferentiated epithelial tumors and can be applied as a preclinical testing in order to verify the capability of NIR spectroscopy to distinguish cancer from healthy tissues before a clinical research with an aim of creating a new analytical tool for on-line intraoperative tumor margins assessment. The study consists of five steps of NIR spectra measurements: in vivo on the early stage of carcinoma growth; in vivo on the advanced stage of carcinoma growth; in vivo during the surgery; in vitro study of the post-operative materials stored in formalin; in vitro study of the post-operative materials stored in paraffin. It was shown that reliable tumor differentiation with a compact optic fiber probe was possible in all these cases. The classification models were built on two data sets, obtained during in vivo and in vitro measurements; both of them demonstrated 100% specificity and sensitivity.

Synergy Effect of Combining Fluorescence and Mid Infrared Fiber Spectroscopy for Kidney Tumor Diagnostics.

Matching pairs of tumor and non-tumor kidney tissue samples of four patients were investigated ex vivo using a combination of two methods, attenuated total reflection mid infrared spectroscopy and fluorescence spectroscopy, through respectively prepared and adjusted fiber probes. In order to increase the data information content, the measurements on tissue samples in both methods were performed in the same 31 preselected positions. Multivariate data analysis revealed a synergic effect of combining the two methods for the diagnostics of kidney tumor compared to individual techniques.

Development and Testing of an LED-Based Near-Infrared Sensor for Human Kidney Tumor Diagnostics.

Optical spectroscopy is increasingly used for cancer diagnostics. Tumor detection feasibility in human kidney samples using mid- and near-infrared (NIR) spectroscopy, fluorescence spectroscopy, and Raman spectroscopy has been reported (Artyushenko et al., Spectral fiber sensors for cancer diagnostics in vitro. In Proceedings of the European Conference on Biomedical Optics, Munich, Germany, 21-25 June 2015). In the present work, a simplification of the NIR spectroscopic analysis for cancer diagnostics was studied. The conventional high-resolution NIR spectroscopic method of kidney tumor diagnostics was replaced by a compact optical sensing device constructively represented by a set of four light-emitting diodes (LEDs) at selected wavelengths and one detecting photodiode. Two sensor prototypes were tested using 14 in vitro clinical samples of 7 different patients. Statistical data evaluation using principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) confirmed the general applicability of the LED-based sensing approach to kidney tumor detection. An additional validation of the results was performed by means of sample permutation.

Noninvasive biochemical monitoring of physiological stress by Fourier transform infrared saliva spectroscopy.

Physical stress affects the immune system, activates the sympathetic (SNS) and parasympathetic (PNS) subsystems of autonomic nervous system (ANS), and increases the activity of the hypothalamic-pituitary-adrenal axis (HPA). The specific response of the major regulatory systems depends on the human functional state. Saliva is a unique diagnostic fluid, the composition of which immediately reflects the SNS, PNS, HPA and immune system response to stress. A new method of saliva biomarker determination by Attenuated Total Reflection Fourier-Transform Infrared (ATR FTIR) spectroscopy has been developed to monitor the exercise induced metabolic changes in saliva from male endurance athletes. The method has been tested using a group of professional athletes by analysing saliva samples collected before and after the exercise, and the saliva composition monitoring by ATR FTIR spectroscopy was shown to be suitable for real-time checking of response to stress.