Here we present our latest fiber-optic techniques in spectral range from UV to mid-infrared for research and industrial applications. Depending on the chemical process or materials to be analyzed, fiber probes can be based on 4 different fiber types selected for the required spectral range and used for Transmission, Reflection, ATR-absorption, Raman & Fluorescence spectroscopies. Advanced fiber optic combi probes are capable to utilize two and more spectroscopic methods at the same time assembled in the same probe shaft - such as Mid-FTIR+Fluorescence, Raman+Near IR, Raman+Mid-FTIR, Raman+mid-FTIR-Near IR and others. It improves selectivity and precision of the analysis for media content in process control.
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.
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.
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.
One of the streams in advanced diagnostic technologies is non-invasive spectroscopic investigation or “spectral histopathology” as a novel alternative for rapid cancer diagnostics and label-free cancer specification. Fiber optics enable faster and more convenient way to study different biological tissues than standard techniques which require destructive sample preparation (e.g. histopathology, chemical analysis). Moving on this direction, we developed and applied various fiber optic probes for key spectroscopy methods such as Raman scattering, Mid IR-absorption, Diffuse NIR-reflection, and auto-fluorescence – to compare them and select the best combination for a real-time detection of malignant tissue in pre-clinical and clinical environment. All four spectroscopic methods have been tested for cancer diagnostics on biopsies of normal and cancer tissues (abdominal, oral and brain), ex-vivo samples and bioliquids. Obtained spectral data were evaluated by multivariate discrimination analysis to enable clear separation of malignant and normal tissues. Benefits of combination of several spectroscopic modalities and data fusion is presented for the better sensitivity, specificity and accuracy. The best synergetic effect was observed of combining Mid IR-absorption and fluorescence spectroscopy, (98% Sensitivity vs 63% or 88% for fluorescence or Mid IR-absorption correspondingly). Based on obtained results, several fiber optic probes combining several spectroscopic modalities implemented within the same single probe were designed, assembled and evaluated.
Combination of FTIR spectroscopy with fiber optics provides a powerful diagnostic tool for diagnosing of human diseases, including osteoarthritis. To detect cartilage degradation, an arthroscopic probe based on polycrystalline fibers was developed and evaluated on equine cartilage specimen. The hook shape allows reaching a significant portion of the articular surface; the flat tip ensures avoidance of tissue destruction. Efficient QCL-coupling and stable transmission of PIR fibers under bending allows the assembling of effective thin arthroscopy probes and customized multispectral systems for medical diagnostic applications. The presented work was performed within the MIRACLE project (Grant Agreement No 780598, Horizon 2020).
In oral cavity cancer only 15% of operations succeed in removing the whole tumor with the required margin of more than 5 mm of surrounding healthy tissue. This negatively affects prognosis. Clearly the hands and eyes of the surgeon do not suffice.
We use a fiber optic needle probe for high-wavenumber Raman spectroscopic analysis of the freshly resected tissue to determine if the distance between the resection surface and the tumor is sufficient.
A system is under development to inspect the resected tissue in under 15 minutes, while the patient is still in the OR.
Medical fiber optics as a part of laboratory and clinical diagnostic tools, surgical instrumentation and endoscopy should satisfy modern biomedical requirements. The flexibility, small size, bio-compatibility and feasibility to use sterilisable or disposable parts allow to apply fiber optic probes in clinical environment both ex-vivo and in-vivo.
To enable spectroscopic differentiation cancer and normal tissue, we developed and applied various single and combined fiber optic probes using key spectroscopy methods such as Raman scattering, Mid IR-absorption, Diffuse NIR-reflection, and fluorescence in order to compare them and select the best combination for malignant detection of tissue in clinical environment.
All four spectroscopic methods have been tested on biopsies of health and malignant tissues (colon and kidney) and bioliquids (serum, plasma and urine) of patients before and after surgery. The tiny Raman probe with 1.5 mm diameter has been developed for experimental ex-vivo tests. Further multivariate data analysis of spectroscopic data, both individual techniques and their combinations has provided a reliable cancer recognition for colon and kidney biopsies. The best synergic gain was observed of combining Mid IR-absorption and fluorescence spectroscopy (98% Sensitivity vs 63% or 88% for fluorescence or Mid IR-absorption correspondingly). Based on obtained results, both techniques were implemented within the same fiber probe to provide a simultaneous measurement of exactly the same spot at the sample surface. An innovative combi Fluo-ATR probe was designed, fabricated and tested.
Diffuse NIR-reflection and fluorescence spectroscopy as the fastest measurement techniques were used for investigation of surgically removed colorectal tissue samples in a few minutes after resection. Taking into account the necessity of rapid measurement process, we developed multispectral NIR-UV probe that enables efficient excitation and collection of NIR diffuse reflectance and fluorescence spectra of the same point. Needle probe design with diameter 0.7 mm allows to penetrate in some depth of tissue and obtain most reliable spectra avoiding artefacts related to surface drying. Multivariate data analysis proved the increased sensitivity of methods combination in one dataset (94% Sensitivity vs 85% or 85% for fluorescence or NIR reflection correspondingly).
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