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This PDF file contains the front matter associated with SPIE Proceedings Volume 11920, including the Title Page, Copyright information, and Table of Contents.
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Diffuse correlations spectroscopy (DCS) is a non-invasive optical technique that, studying the speckle intensity fluctuations of light diffused through a biological tissue, measures its microvascular blood flow. Typically, a long coherence length continuous wave source is used, which limits the possibility to resolve the photon path lengths. Recently, time-domain (TD) DCS was proposed, where a pulsed yet coherent light source is used to resolve the speckle fluctuations at different time-of-flights. Due to the constraint of single-speckle detection and time-resolved acquisition, the technique has a limited throughput which limits depth sensitivity. Here, we demonstrate TD DCS with a superconducting nanowire single-photon detector (SNSPD). The SNSPD has a high quantum efficiency and temporal resolution, while maintaining a very low background and no after-pulsing.We report results on phantom and in vivo experiments, which show the potentiality of the proposed detection system for highly accurate TD DCS experiments.
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A multimodal instrument for breast imaging was developed, combining ultrasound (morphology), shear wave elastography (stiffness), and time domain multiwavelength diffuse optical tomography (blood, water, lipid, collagen) to improve the non-invasive diagnosis of breast cancer.
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We show both on phantoms and in-vivo the full potential of fast time-gated acquisitions exploiting an innovative custom-developed digital silicon photomultiplier, overcoming consolidated limitations showed by single-photon avalanche diodes linked to their small sensitive area.
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We present the largest detectors for time-domain diffuse optics, showing superior performances in depth penetration and light-harvesting capability. In-vivo measurements demonstrate their potentialities for futuristic disruptive applications such as optical radiography.
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Large-area detectors for time-domain diffuse optics are increasingly available, with enormous gain in collected light intensity. Pile-up distortion is nowadays the main limit, here studied to anticipate the possibility of a new working modality.
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A multi-distance Diffuse Correlation Spectroscopy system combined with a compact state-of-the-art Time Domain Near-Infrared Spectroscopy device is presented. The device was used to validate the protocol of VASCOVID project on healthy subject.
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Hybrid device for the study of blood flow index and hemoglobins concentrations changes was developed. Diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy were applied to study brain hemodynamics of healthy adults human during the Valsalva maneuver.
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Hypoxia assessment needs tools beyond the oxygen measurement. With both transmission and on-the-surface measurements in liquid phantoms, animal, and human samples we show ability of LW-NIR spectroscopy as a continuous monitoring and diagnostic tool.
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We present a real-time frequency-domain near-infrared spectroscopy imager capable of displaying 2D chromophore images. The system addresses many of the challenges for fdNIRS clinical use including system size, speed, ease of use, and real-time feedback.
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We present a spatial frequency domain imaging (SFDI) system based on single-pixel imaging (SPI) techniques with a single digital micromirror device (DMD) modulating simultaneously the sinusoidal pattern and the spatial sampling masks.
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Frequency domain functional near infrared spectroscopy and tomography (FD-fNIRS-DOT) utilizes information about attenuation and pathlength of measurements. The improved quantitative accuracy of FD-fNIRS-DOT is shown as applied in brain imaging.
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Based on theoretical investigations of integrating sphere measurements, we developed an novel approach for precise determination of optical properties. The setup was used to obtain the optical properties of various porcine tissue types between 400 nm and1400 nm.
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Absorption coefficient of oxygenated human lysed blood is evaluated with collimated transmission (SCT) to predict blood oxygen saturation using tabulated hemoglobin absorption spectra. We report on discrepancies in expected and observed oxygen levels.
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The effect of hemoglobin spectra on quantification of concentrations of oxy-, deoxyhemoglobin, and oxygen saturation were studied using multi-wavelength time-domain NIRS measurements performed on a series of blood-lipid phantoms.
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In this TD-fNIRS study on 98 subjects, primary open angle glaucoma patients have an involvement of the occipital (visual) cortical region; we assess the best fNIRS parameters for discriminating between glaucoma patients and healthy subjects.
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We show the hemodynamic response of a visual cortex on healthy volunteers under, hypoxia as registered with fNIRS system. Results show that amplitude of hemodynamic response to a visual stimulation correlates with the arterial oxygen saturation.
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We present a new optical platform that combines broadband near-infrared spectroscopy and diffuse correlation spectroscopy for identification of brain injury severity in a preclinical model of hypoxic-ischemic encephalopathy of the neonatal brain.
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We present a study investigating the effect of non-medical face masks (FFP2 and surgical) on cerebral hemodynamics measured by transcranial hybrid diffuse optics, and on systemic physiology in 13 healthy adults (age: 23-33 years).
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Neural and cerebral hemodynamic activities of 16 programmers were monitored during programming tasks by simultaneous EEG and Time-Domain fNIRS measurements aiming at identifying cognitive and emotional states during code programming.
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Subject specific atlas based tomography was achieved using a 3D camera scan for surface registration. The registered atlas was then used for diffuse optical tomography from frequency domain measurements.
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We present the methodology for the intraoperative pixel-wise identification of activated cortical areas using RGB imaging. The results indicate that RGB imaging could be a useful complement to the electrical brain stimulation.
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Clinical and Preclinical Applications of Diffuse Optics
Breastfeeding plays a crucial role in public health, but relatively few imaging and sensing technologies are employed to study human lactation physiology. As a consequence, many breastfeeding problems are not well understood. We hypothesize that diffuse optical spectroscopic
imaging (DOSI) can potentially reveal important physiological parameters that help to define milk synthesis and secretion: glandular tissue content, hemodynamics and milk ejection. The aim of this study is to investigate the sensitivity of DOSI to these physiological parameters in (i) a case study (1 subject) on mammary involution of the lactating breast to its pre-pregnant state and (ii) a pilot study during milk extraction with a breast pump (4 lactating subjects, 5 non-lactating subjects). For the case study, the measured changes in the DOSI parameters (water, lipid, hemoglobin concentration) were consistent with the gradual replacement of fibro-glandular tissue by adipose tissue and vascular regression during mammary involution. For the pilot study, the measured changes in the DOSI parameters correlated with the extracted milk volume and occurrence of the milk ejection reflex. In conclusion, DOSI is sensitive to human lactation physiology, which can potentially aid to obtaining an in-depth understanding on the origin and treatment of breastfeeding problems.
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We present in vivo tests on healthy women through our optical mammograph in preparation for a clinical validation on neoadjuvant chemotherapy monitoring, and we report preliminary data on the first patient enrolled in the study.
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LUCA platform combines clinical ultrasound with near-infrared time-domain and correlation spectroscopies to improve thyroid cancer screening. We characterized its precision and classified thyroid nodules in a clinical campaign on 45 subjects.
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We have previously developed a non-invasive intracranial pressure sensor based on cerebral blood flow cardiac pulse shape changes. Here, we present steps towards clinical translation in pediatric patients in critical care.
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HEMOCOVID-19 project spans four countries and eight hospitals to evaluate the microvascular and endothelial health of severe COVID-19 patients using near-infrared spectroscopy (NIRS) of the forearm muscle. In order to implement the project, we have developed protocols and
tested ten commercial continuous-wave NIRS devices of the same model (PortaMon, Artinis, NL). They were characterized and compared for intra- and inter-device, inter- and intra-operator and temporal variability in solid phantoms and in vivo.
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We present a feasibility study on the use of a time domain NIRS instrument, named MAESTROS, to explore the cerebral optical parameters and physiology of people with multiple sclerosis.
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We present simulation and in-vivo Time Domain NIRS studies to investigate differential pathlength factor in skeletal muscles at rest and its dependence on the subcutaneous adipose tissue thickness, tissue absorption and reduced scattering coefficients.
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Diffuse optical tomography relies on anatomical models to simulate light transport. We investigate which cotside measures are best to choose an individual-level head model when subject-specific data is unavailable for neonatal infants.
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We present a calibration-free instrument to measure absolute broadband absorption spectra of biological tissue. Initial measurements in skeletal muscle show that the fit to the data improves by introducing a spectrally flat absorption background.
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A numerical simulation tool for spatial frequency domain imaging (SFDI) has been developed. Validation against current methods for parameter recovery is presented including heterogenic models demonstrating a complex light propagation tool for SFDI.
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A comprehensive phantom study on spatially resolved reflectance shows noisy or systematic deviations from the true optical properties for relative data analysis depending on the applied spatial interval. Absolute data analysis yields correct results.
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We present the design of an endoscopic imaging system based on Deep Learning-optimized 3D profile corrected “Single Snapshot imaging of Optical Properties” (3D-SSOP), for real-time, wide-field quantitative oxygenation imaging of biological tissues.
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The Fourier transform was compared to conventional temporal moments for time-domain diffuse optical tomography. Both approaches provided similar accuracies. The Fourier transform enabled a computationally cheaper implementation of the inverse solver.
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We present a Monte-Carlo study for the identification of the hyperspectral camera’ spectral bands for intraoperative hemodynamic and metabolic brain mapping. We also show that a RGB camera is suitable for hemodynamic brain mapping.
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We assessed the sensitivity of 1D and 2D homogeneous photon diffusion models for Time Domain NIRS in estimating preterm and term neonates’ cerebral hemodynamic parameters simulated by Monte Carlo methods on realistic 3D anatomical meshes.
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We present a multi-layered and voxel-based Monte Carlo methods with auxiliary utilities implemented in Python for user-friendly, open-source and multi-purpose modeling of light propagation in turbid media based on PyOpenCL computational platform.
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Finger pulse oximetry traditionally assumes a semi-infinite, homogenous media where the wavelength dependent differential pathlength is assumed or calibrated for. We developed an algorithm which does not require this assumption.
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High-frequency modulation has been shown to provide superior image quality over continuous wave high density diffuse optical tomography (HD-DOT). Herein, we evaluated a range of modulation frequencies on the image quality for frequency domain HD-DOT.
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We developed and applied tomosynthesis algorithms to obtain 3D maps of the absorption properties of slab-like diffuse media. Spatial resolution was found to be superior to conventional 3D reconstruction by a finite element method.
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A novel algorithm to simultaneously recover bioluminescence source location and optical parameters is developed. In-vivo studies show 30% improvement in localization error while also providing local total hemoglobin concentration.
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We present a method for simulating speckle contrast signal, noise, and signal offset in speckle contrast optical spectroscopy and tomography. The simulations provide a realistic model by simulating custom system and tissue properties.
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Wearable and Portable Diffuse Optics Instrumentation and Applications
We report on motor cortex hemodynamic responses to different motor tasks on humans in ecological environment. The portable, time-domain near-infrared spectroscopy (TD-NIRS) device we present enables cerebral hemodynamic measurements on freely moving subjects.
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We investigated the performance of a novel HD-DOT system by replicating a series of classic visual stimulation paradigms. Haemodynamic response functions and cortical activation maps replicated the results obtained with larger fibre-based systems.
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We have developed a series of wearable high-density diffuse optical tomography (HD-DOT) technologies specifically for neonatal applications. These systems provide an ultra-lightweight form factor, a low profile and high mechanical flexibility. This new technology is validated using a novel, anatomically accurate dynamic phantom.
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We applied a wearable 24-module high-density diffuse optical tomography (HD-DOT) system in a resting state (RS) paradigm repeatedly in one subject. Seed-based correlation maps show large field-of-view RS functional connectivity.
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We are translating wearable HD-DOT to the neonatal clinic to investigate healthy and brain-injured infants and establish a model of the developmental trajectory of the infant sensorimotor system.
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Near-infrared spectroscopy was used to observe the cerebral hemodynamic response of freedivers during single breath-hold training dives. We observed variability in hemodynamic progression, and heartbeat shape changes with diving depth.
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Functional near-infrared spectroscopy is successfully used to measure brain activation to visual, auditory, and tactile stimuli in non-domesticated grey seals. The results encourage further investigation of cognition in free-ranging animals.
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We have applied a CNN to preprocess Raman spectra from fresh tissue samples from brain tumors. The neural network can handle the variations that occur naturally, which enables explorative data analysis methods such as PCA.
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Here we implemented a Monte Carlo photon migration model to simulate optical tissue interaction during external jugular vein distension, supporting the potential of non-contact hemodynamic imaging techniques.
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We compare flat and spherical models of the human head using Bayesian inference. Monte Carlo simulations are used to obtain the photons times of flight. Results suggest that the spherical model better represents the data.
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We present a computationally fast algorithm for estimating the optical property distribution of turbid media using diffuse optics principles without the inversion of Jacobian matrix. The algorithm is validated by simulations and experimental studies.
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A smartphone-based prototype has been demonstrated and calibrated as a tool to identify the spectral differences from fluorophores during disease progression. Polarized fluorescence is captured through smartphone camera using a 405nm laser source.
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We explore various source configurations (such as point source, line sources and its variants, uniform illumination) for laser speckle-based imaging of blood flow and validate by simulation studies and in-vivo imaging of mice brain.
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By simulating measurements from a HD-DOT system on a head atlas, we show that combining multiple modulation frequencies improves image quality over the standard continuous wave method and performs comparably to the single frequency counterpart.
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We propose a 3D δ-SP3 model based reconstruction scheme for fluorescence optical tomography with directed sources. Numerical validations in reflectance-mode demonstrate improvements over existing approaches justifying the use of the proposed scheme.
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Dermal thickness variation is observed with laser illuminated skin-mimicking phantoms. From the acquired laser speckle images, the contrast ratio and percentage change in intensity autocorrelation of static and dynamic components are estimated.
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Monitoring of cell culture growth is of interest for many industrial and scientific areas. We present a device that non-invasively evaluates the cell concentration in a culture flask based on the light scattering measurements.
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A new fast biochemical analyzer for biological liquids analyses has been described. The advanced light source involving the set of LEDs and diffraction grating together with consequently installed acousto-optic tunable filter provide high operation rate and information productivity.
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We propose a standardized approach for performance assessment and quality-control of the novel VASCOVID system based on optical phantoms. This approach is tailored to meet the requirements of the Medical Device Regulation, and is extendable to other biophotonics devices.
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Visualization of the spatial distribution of nanoparticles in organs and tumors is a rapidly developing field in terms of diagnostics and therapy of oncological diseases. The method of imaging up-conversion nanoparticles in tissues and organs using a scanning system has become widespread. In this case, the exciting radiation is focused on the surface of the object, the luminescence is collected by a wide-aperture optical system and is recorded by a photodetector. The aim of this study was to register the spatial distribution of upconversion nanoparticles in sections of organs and tumors of laboratory animals in health and disease (liver cancer) using a fluorescent microscope. It was shown that upconversion nanoparticles accumulate mainly in the spleen, which is confirmed by the data of histopathological analysis. With a three-fold intravenous injection of particles, their maximum accumulation in the tumor tissue occurs. In general, the particles accumulated in the tumor and did not damage organs, tissues, or erythrocytes.
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This work is devoted to the development and manufacture of the collection channel for the Raman probe using 3D printing technologies. Possibilities of FFF and SLA technologies were investigated for the manufacture of optical elements holders and alignment relative to each other. The design provides for a modular approach allowing for replacing one element with another or installation additional optical elements. The Raman spectrum of aspirin was recorded by the
developed probe and the results were compared with the commercial StellarNet Raman probe.
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The lasers used for the telecom industry associated with the focal plane embedded in LIDAR for automotive could pave the way to robust yet low cost Spatially Resolved Diffuse Reflectance Spectroscopy in the SWIR range.
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We propose neural network-based regression model for efficient Monte Carlo simulations of subdiffusive reflectance for spatial frequency domain imaging with low NA and validate the methodology with inverse models for estimation of optical properties.
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In this work, we use a statistical skin model to compare the measured distribution of optical path lengths to time-resolved Monte Carlo simulated reflectance and validate the simulations by the use of optical phantoms.
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Shifted position-diffuse reflectance imaging is a technique for the non-invasive assessment of microcirculation. In this study, its lateral resolution and imaging depth were determined to be 95 μm and 295 μm, respectively, by Monte-Carlo simulations.
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Four different Beer-Lambert law expanded models for skin chromophore mapping are discussed. Each model is analyzed in a diffuse reflectance case, when reference is white reference or healthy skin. Advantages and limitations will be presented.
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This work proposes a finite element based human skin tissue model for generating a diffuse reflectance spectrum and were trained with an artificial neural network. Tissue chromophore concentration was estimated accurately after inverse modelling.
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Novel deep-learning algorithm is utilized to detect simulated tumors embedded inside 3D turbid media using a small set of sources and detectors. Thus, proving the utility of deep-learning methods for solving diffuse imaging 3D inverse problems.
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PLA and ABS filaments, 3D printed as thin sheets were optically characterized in UV/VIS/NIR. The applicability of these materials, used as optical probes, in diffused optics applications was tested through TD-NIRS and DCS measurements.
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We introduce method of lock-in amplifying optical signals originating within brain. It requires 90-degree rotated source-detector pairs. In-vivo results suggest the proposed hardware and algorithm are brain-sensitive and real-time.
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We have compared multiple exposure speckle imaging using two approaches: (i) duration modulation of laser diode pulses with fixed exposure time and (ii) synthetic exposure created from the sum of frames obtained at 1ms exposure time. Both methods have been applied to evaluate controlled flows in micro-channels. The results demonstrate that the synthetic exposure method provides accurate speckle contrast data over a wide range of exposures, channel diameters and flows.
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In this work, experimental setups and software algorithms were written, and implemented on medical imaging modalities to illustrate the importance of using the computer generated holography to create holograms and spatial light modulators to reconstruct them.
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The laser speckle subpixel correlation method was proposed to investigate bacterial activity moving from center to the colony edges. Results could facilitate epidemiological analysis and improve mathematical models of colony growth.
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We introduce an efficacious machine learning classification plus chemostructural characterization of proteins by a mixed data processing based on Principal Component Analysis applied to multipeak fitting on Surface-enhanced Raman Scattering spectra.
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