Raman Probe Research Articles

Tracking Conical Intersections with Nonlinear X-ray Raman Spectroscopy

Conical intersections are formed when 2 or more electronic states become degenerate and give rise to ultrafast nonadiabatic processes such as radiation-less decay channels and geometric phase effects. The branching of nuclear wave packets near a conical intersection creates a coherent superposition of electronic states, which carries information about the energy difference of the involved states. X-ray Raman techniques have been proposed to observe the coherent superposition of the electronic states and to monitor the evolving electronic state separation. However, these techniques rely on the coherence generated as the wave packet passes through the conical intersection, and the electronic energy gap before the wave packet passes through the conical intersection is not tracked. In this paper, we theoretically demonstrate how a nonlinear Raman detection scheme can be used to gain further insight into the nonadiabatic dynamics in the vicinity of the conical intersection. We employ a combination of a resonant visible/infrared pulse and an off-resonant x-ray Raman probe to map the electronic state separation around the conical intersection. We demonstrate that this technique can achieve high contrast and is able to selectively probe the narrow electronic state separation around the conical intersection.

Quantitative analysis of blend uniformity within a Three-Chamber feed frame using simultaneously Raman and Near-Infrared spectroscopy

This study reports the use of Raman and Near-infrared (NIR) spectroscopy to simultaneously monitor the drug concentration in flowing powder blends within a three-chamber feed frame. The Raman probe was located at the top of the dosing chamber, while the NIR probe was located at the top of the filling chamber. The Raman and NIR spectra were continuously acquired while the powder blends flowed through the feed frame. Calibration models were developed with spectra from a total of five calibration blends ranging in caffeine concentration among 3.50 and 6.50% w/w. These models were optimized to predict three test set blends of 4.00, 5.00, and 6.00% w/w caffeine. The results showed a high predictive ability of the models based on root mean square error of predictions of 0.174 and 0.235% w/w for NIR and Raman spectroscopic models, respectively. Concentration profiles with higher variability were observed for the Raman spectroscopy predictions. An estimate of the mass analyzed by each spectrum showed that a NIR spectrum analyzes approximately 4.5 times the mass analyzed by a Raman spectrum; despite these differences in the mass analyzed, blend uniformity results are equivalent between techniques. Variographic analysis demonstrated that both techniques have significantly low sampling errors for the real-time monitoring process of drug concentration within the feed frame.

3D arrangement of epitaxial graphene conformally grown on porousified crystalline SiC

Nanoporous materials represent a versatile solution for a number of applications ranging from sensing, energy applications, catalysis, drug delivery, and many others. The synergy between the outstanding properties of graphene with a three-dimensional porous structure, circumventing the limits of its 2D nature, constitutes therefore a breakthrough for many fields. We report the first three-dimensional growth of epitaxial graphene on a porousified crystalline 4H–SiC(0001). The wafer porosification is performed via a sequence of metal-assisted photochemical and photoelectrochemical etching in hydrofluoric acid based electrolytes. Pore dimensions of the matrix have been evaluated by electron tomography resulting in an average diameter of 180 nm. Graphene growth is performed in an ultra high vacuum environment at a base pressure of 10−11 mbar. The graphene growth inside the pores is uniform as confirmed by Transmission Electron Microscopy (TEM) analysis. Raman spectroscopy confirms the high quality of the graphene with a 2D/G intensity ratio >1 and an average graphene crystal size of ≈ 100 nm. Furthermore, it demonstrates a uniform coverage of graphene across the whole sample area accessible to the Raman probe. The surface-to-volume ratio of this novel material, its properties, the tunability of the pore size and the scalability of the surface porosification process offer a game changing perspective for a large number of applications.

Multicolor Photoactivatable Raman Probes for Subcellular Imaging and Tracking by Cyclopropenone Caging.

Photoactivatable probes, with high-precision spatial and temporal control, have largely advanced bioimaging applications, particularly for fluorescence microscopy. While emerging Raman probes have recently pushed the frontiers of Raman microscopy for noninvasive small-molecule imaging and supermultiplex optical imaging with superb sensitivity and specificity, photoactivatable Raman probes remain less explored. Here, we report the first general design of multicolor photoactivatable alkyne Raman probes based on cyclopropenone caging for live-cell imaging and tracking. The fast photochemically generated alkynes from cyclopropenones enable background-free Raman imaging with desired photocontrollable features. We first synthesized and spectroscopically characterized a series of model cyclopropenones and identified the suitable light-activating scaffold. We further engineered the scaffold for enhanced chemical stability in a live-cell environment and improved Raman sensitivity. Organelle-targeting probes were then generated to achieve targeted imaging of mitochondria, lipid droplets, endoplasmic reticulum, and lysosomes. Multiplexed photoactivated imaging and tracking at both subcellular and single-cell levels was next demonstrated to monitor the dynamic migration and interactions of the cellular contents. We envision that this general design of multicolor photoactivatable Raman probes would open up new ways for spatial-temporal controlled profiling and interrogations in complex biological systems with high information throughput.

Redox state changes of mitochondrial cytochromes in brain and breast cancers by Raman spectroscopy and imaging

This paper presents a non-invasive approach to study redox status of cytochromes in vitro human brain cells of normal astrocytes (NHA), astrocytoma (CRL-1718), glioblastoma (U87-MG) and medulloblastoma (Daoy), and human breast cells of normal cells (MCF10A), slightly malignant cells (MCF7) and highly aggressive cells (MDA-MB-231), in vivo animal models, and ex vivo brain and breast tissues surgically resected human specimens by means of Raman microspectroscopy at 355 nm, 532 nm, 785 nm and endospectroscopic Raman probe at 785 nm. Here we show that the amount of reduced cytochrome becomes abnormally high in human brain tumors and breast cancers. In contrast, the amount of reduced cytochrome c is lower in cancer cells when compared to the normal one at in vitro conditions when the effect of microenvironment is eliminated. Mitochondrial dysfunction and alterations in the chemical composition of the nucleus, mitochondria, lipid droplets, cytoplasm in single cells have been detected by Raman imaging. Incubation in vitro with retinoic acid increases the amount of reduced cytochrome c.

Plasmonics on a Neural Implant: Engineering Light–Matter Interactions on the Nonplanar Surface of Tapered Optical Fibers

AbstractOptical methods are driving a revolution in neuroscience. Ignited by optogenetic techniques, a set of strategies has emerged to control and monitor neural activity in deep brain regions using implantable photonic probes. A yet unexplored technological leap is exploiting nanoscale light‐matter interactions for enhanced bio‐sensing, beam‐manipulation and opto‐thermal heat delivery in the brain. To bridge this gap, we got inspired by the brain cells’ scale to propose a nano‐patterned tapered‐fiber neural implant featuring highly‐curved plasmonic structures (30 μm radius of curvature, sub‐50 nm gaps). We describe the nanofabrication process of the probes and characterize their optical properties. We suggest a theoretical framework using the interaction between the guided modes and plasmonic structures to engineer the electric field enhancement at arbitrary depths along the implant, in the visible/near‐infrared range. We show that our probes can control the spectral and angular patterns of optical transmission, enhancing the angular emission and collection range beyond the reach of existing optical neural interfaces. Finally, we evaluate the application as fluorescence and Raman probes, with wave‐vector selectivity, for multimodal neural applications. We believe our work represents a first step towards a new class of versatile nano‐optical neural implants for brain research in health and disease.

Simultaneous and multiplex detection of exosomal microRNAs based on the asymmetric Au@Au@Ag probes with enhanced Raman signal

Simultaneous and quantitative detection of multiple exosomal microRNAs (miRNAs) was successfully performed by a surface-enhanced Raman scattering (SERS) assay consisting of Raman probes and capture probes. In this design, the asymmetric core-shell structured Au@Au@Ag nanoparticles were first synthesized by layer-by-layer self-assembly method and modified with different Raman molecules and recognition sequences (polyA-DNA) to prepare the surface-enhanced Raman probes. Then, the streptavidin-modified magnetic beads were used to immobilize the biotinylated DNA capture sequences (biotin-DNA) to obtain capture probes. In the presence of target exosomal miRNAs, the Raman probes and capture probes could bind to the target exosomal miRNAs in the partial hybridization manner. Thus, the developed SERS sensor could indicate the target miRNAs levels in the buffer solution. Using breast cancer-related miRNAs as model targets, the limits of detection of this sensor were determined to be 1.076 fmol/L for synthetic miR-21, 0.068 fmol/L for synthetic miR-126, and 4.57 fmol/L for synthetic miR-1246, respectively. Such SERS sensors were further employed to detect the miR-21 in 20% human serum and the extraction solution of exosomes, respectively. Therefore, simultaneous and multiplex detection of cancer-related exosomal miRNAs by this assay could provide new opportunities for further biomedical applications.

Lateral Size Effect of Graphene Oxide on Its Surface-Enhanced Raman Scattering Property.

The lateral size effect of graphene oxide (GO) on surfaced-enhanced Raman scattering (SERS) property is systematically investigated by using size-fractionalized GO. For the size fractionalization without changes of chemical structure, large-sized GO (LGO) and small-sized GO (SGO) are separated from the as-synthesized GO (AGO) by centrifugation and membrane filtration, respectively. The size-fractionalized GO sheets are immobilized on a solid substrate for the parallel comparison of their SERS property. As a result, we find that LGO shows considerably higher SERS property than SGO for typical Raman probes such as rhodamine 6G and crystal violet. Furthermore, the lateral size effect of GO derivatives is consistently observed when they are hybridized with plasmonic silver nanoparticles. These results indicate that LGO is superior to AGO and SGO as a SERS platform, and it is also quantitatively confirmed by calculating their enhancement factor.

Enriching surface-enhanced Raman spectral signatures in combined static and plasmonic electrical fields in self-powered substrates

Promoting the quality of surface-enhanced Raman spectra (SERS) holds immense significance in various research fields, such as high-sensitive detection or real-time in situ monitoring. However, obtaining rich molecular information from the vibration modes in SERS remains difficult due to the surface selection rules. Herein, we develop an electrically enhanced, composite SERS substrate by combining flower-like Ag nanostructures with a piezoelectric-dielectric polymeric film. The piezoelectricity generated in the polymeric film transforms into combined quasi-static electrical fields with multi-directional distributions and intensified plasmonic hotspots in the Ag nanoflowers. Molecules adsorbed on the Ag nanoflowers are propelled by the quasi-static electrical fields and deviate from the absorption equilibrium states, a key criterion to present additional SERS peaks. In addition, the intensified hotpots generate SERS peaks with higher intensities (> ~ 2 times). Dual-enhanced SERS in both the intensity and the number of vibration peaks e.g., 3 peaks more for 4-Mpy, are obtained from a variety of widely used molecular Raman probes as well as pesticide contaminants. The universality of the dual enhancement effects from our SERS design with increasing detection sensitivity demonstrates high applicability in the rapid and on-site detection of real samples. The changes to SERS spectra, and thus the molecular vibrational fingerprints, in the combined static and plasmonic electrical fields may also inspire scientific understanding in photoelectrical catalytic processes.

Developing Macro-Raman Mapping as a Tool for Studying the Pigment Distribution of Art Objects.

Raman spectroscopy is a well-appreciated technique in cultural heritage research for its ability to obtain molecular information nondestructively. During Raman mapping experiments, advantage is taken of the excellent spatial resolution of the approach, allowing to visualize the spatial distribution of the molecules. In the current research, macro-Raman mapping is proposed, allowing us to map large areas of an artwork (typically tens or hundreds of square centimeters). Therefore, a new setup is made, using a commercially available mobile Raman spectrometer and fast translation stages. Moreover, the probe is equipped with a triangulator to measure the distance to the surface of the artwork and thus achieving accurate focusing of the Raman probe. Finally, the correct setup is guaranteed by using a calibration module that is designed to allow for spectral calibration and aligning all components of the probe. The use of the method is demonstrated by three cases, where different data processing techniques are illustrated.

Cancer Cell-Specific Enhanced Raman Imaging and Photothermal Therapeutic Effect Based on Reversibly pH-Responsive Gold Nanoparticles.

Stimuli-responsive nanoparticles are favorable for improving the selective delivery and rational vocation that easily avoids the undesirable barriers or side effects, leading to a further improved therapeutic efficiency. Furthermore, multifunctional nanomaterials have been extensively developed as attractive candidates for theranostic reagents for cancer treatment. In this article, we developed reversibly pH-responsive gold nanoparticles (AuNPs) with an enhanced Raman scattering signal as well as an efficient photothermal effect and demonstrated their applications as a theranostic reagent for cancer treatment. Surfaces of these AuNPs were modified with mixed layers of Cy3-modified single-stranded DNA (ssDNA-Cy3) for Raman probing and a negative charge supply and cytochrome C (Cyt C) for pH-responsive charge inversion. This combination of pH-responsive ligands and Raman probes played an important role in inducing the assembly or disassembly of AuNPs corresponding to the neighboring pH, accompanied by an additional highly distinguished Raman signal intensity. An operative reversible response of the AuNPs to pH is endowed with the characteristic behavior of AuNPs with the cancerous cell's acidic microenvironment of low pH. The responsive aggregation of AuNPs in a lower pH medium provides highly amplified signals attributed to well-formed hot spots between the particle surfaces that deliver better Raman scattering signals. The acidic pH-responsive aggregation of the particles also provided efficient photothermal treatments using a long-wavelength laser light with the benefit of deeper penetration for cancer cells. In vitro experiments employing cancer cells and control normal cells well-demonstrated the specificity of the particles to cancer cells in terms of highly enhanced Raman imaging and therapeutic efficiency.

Ex Vivo Vibration Spectroscopic Analysis of Colorectal Polyps for the Early Diagnosis of Colorectal Carcinoma.

Colorectal cancer is one of the most common and often fatal cancers in humans, but it has the highest chance of a cure if detected at an early precancerous stage. Carcinogenesis in the colon begins as an uncontrolled growth forming polyps. Some of these polyps can finally be converted to colon cancer. Early diagnosis of adenomatous polyps is the main approach for screening and preventing colorectal cancer, and vibration spectroscopy can be used for this purpose. This work is focused on evaluating FTIR and Raman spectroscopy as a tool in the ex vivo analysis of colorectal polyps, which could be important for the early diagnosis of colorectal carcinoma. Multivariate analyses (PCA and LDA) were used to assist the spectroscopic discrimination of normal colon tissue, as well as benign and malignant colon polyps. The spectra demonstrated evident differences in the characteristic bands of the main tissue constituents, i.e., proteins, nucleic acids, lipids, polysaccharides, etc. Suitable models for discriminating the three mentioned diagnostic groups were proposed based on multivariate analyses of the spectroscopic data. LDA classification was especially successful in the case of a combined set of 55 variables from the FTIR, FT Raman and dispersion Raman spectra. This model can be proposed for ex vivo colorectal cancer diagnostics in combination with the colonoscopic extraction of colon polyps for further testing. This pilot study is a precursor for the further evaluation of the diagnostic potential for the simultaneous in vivo application of colonoscopic Raman probes.

Shape-diversified silver nanostructures on Al foil fabricated in micellar template for high performance surface enhanced Raman scattering applications

Highly effective surface-enhanced Raman substrates with shape-diversified silver nanostructures on Al foil (AlF) were fabricated by galvanic replacement reaction in micellar template which is easy to control, simple and cost-effective. Due to the localized surface plasmon resonance (LSPR) of silver nanostructures, the substrates were used as surface enhanced Raman substrates. The shape-diversified silver nanostructures on AlF exhibited stronger surface enhanced Raman scattering (SERS) effects compared with flowerlike Ag nanostructures on ITO glass substrate fabricated by electrodeposition in micellar template. The maximum Raman enhancement factor of 109 fold was obtained, which is 236 times larger than the flowerlike silver nanostructures on ITO glass substrate. The scanning electron microscope (SEM) images show that the size and shape of the nanostructures and surface morphology make a valuable contribution to SERS. Raman enhancement experiments of three Raman probes were studied, which shows that different vibrational modes of Raman probe affect SERS effect. The fabricated shape-diversified silver nanostructures on AlF fabricated by galvanic replacement reaction in micellar template are cheap, controllable and simple. It could be potentially useful in SERS field such as imaging applications and highly sensitive molecule detecting.

Bimetallic Ag-Cu Alloy Microflowers as SERS Substrates with Single-Molecule Detection Limit.

Bimetallic Ag-Cu alloy microflowers with tunable surface compositions were fabricated as surface-enhanced Raman spectroscopy (SERS) substrates with a limit of detection in the zeptomolar range for the analyte molecule rhodamine 6G (R6G). The substrates were prepared on a glass coverslip through a bottom-up strategy by simple thermolysis of metal-alkyl ammonium halide precursors. The reaction temperature and composition of the alloy were varied sequentially to find out the maximum SERS efficiency from the substrates. While UV-vis spectroscopy was employed to characterize the optical properties of the substrates, the bulk and surface compositions of the microflowers were determined using energy-dispersive X-ray fluorescence (ED-XRF) and X-ray photoelectron spectroscopy (XPS) techniques, respectively. Also, the structural and morphological characterizations of the substrates were performed by X-ray diffraction and scanning electron microscope (SEM), respectively. For alloys, the ED-XRF studies confirmed that the bulk compositions matched with the feed ratio, while the surface compositions were found to be rich in copper in the form of both elementary copper and copper oxide, as revealed by XPS studies. From the efficiency studies for different compositions prepared, it was found that 10% Ag-Cu alloy microflowers produced the maximum SERS intensity for resonant R6G molecules as probes. In fact, R6G evidences a 50-fold enhancement in SERS spectra with 10% alloy microflowers as against pure Ag microflowers. Using 1, 2, 3-benzotriazole as a nonresonant Raman probe, uniform enhancement factors on the order of ≈108 were achieved from different parts of the 10% Ag-Cu alloy microflower. The same substrate showed excellent Raman response for detecting R6G at very low concentrations such as 10 zM, leading to detection and analysis of SERS spectra from a single R6G molecule.

Development and characterization of a disposable submillimeter fiber optic Raman needle probe for enhancing real-time in vivo deep tissue and biofluids Raman measurements.

We report on the development and characterization of disposable submillimeter fiber optic Raman needle probe for enhancing real-time in vivo tissue and biofluids Raman measurements. The submillimeter Raman probe is designed and fabricated using an aluminum-coated multimode fiber tapered with a semispherical lens, resulting in the coaxial laser excitation/Raman collection configuration for maximizing tissue and biofluid Raman measurements. We demonstrate that, with the use of the Raman needle probe associated with the structured background subtraction algorithms developed, high quality tissue Raman spectra covering both the fingerprint (FP) (800-1800cm-1) and high-wavenumber (HW) (2800-3300cm-1) regions can be acquired within subseconds from different tissue types (e.g., skin, muscle, fat, cartilage, liver, and brain) and biofluids (e.g., blood, urine). By advancing the Raman needle probe into the murine brain tissue model, high quality depth-resolved deep tissue Raman spectra can also be acquired rapidly. This work shows that the submillimeter fiberoptic Raman needle probe is capable of achieving real-time collection of deep tissue and biofluids FP/HW Raman spectra with high signal to noise ratios. This opens a new avenue with dual functioning of Raman optical biopsy and fine needle aspiration biopsy for enhancing in vivo deep tissue and biofluids diagnosis and characterization in different organs.

Raman spectroscopy as a process analytical technology to investigate biopharmaceutical freeze concentration processes.

Freezing processes are a well-established unit operation in the biopharmaceutical industry to increase the shelf-life of protein-based drugs. While freezing reduces degradation reaction rates, it may also exert stresses such as freeze concentration. Macroscopic freeze concentration in large-scale freezing processes has been described thoroughly by examination of frozen bulk material, but the transient process leading to such freeze concentration profiles has not been monitored yet for biopharmaceutical solutions. In this study, Raman spectroscopy as a process analytical technology is demonstrated for model formulations containing monoclonal antibodies (mAbs) or bovine serum albumin (BSA) in varying concentrations of sucrose and buffer salts. Therefore, a Raman probe was immersed into a bulk volume at different heights, monitoring the freeze concentration in the liquid phase during the freezing processes. Partial least square regression models were used to quantitatively discriminate between the protein and excipients simultaneously. The freeze concentration profiles were dependend on freezing temperature and formulation with freeze concentrations up to 2.4-fold. Convection currents at the bottom of the freezing container were observed with a maximum height of 1 mm. Furthermore, freeze concentration was correlated with the sucrose concentration in a formulation. Analysis of the freeze concentration slope indicated diffusion from the bottom to the top of the container. In summary, Raman spectroscopy is a valuable tool for process validation of freeze concentration simulations and to overcome scale-dependent challenges.

A ‘sandwich’ structure for highly sensitive detection of TNT based on surface-enhanced Raman scattering

Ultra-sensitive detection of 2,4,6-trinitrotoluene (TNT) plays an important role in society security and human health. The Raman probe molecule p-aminothiophenol (PATP) can interact with TNT in three ways to form a TNT-PATP complex. In this paper, a ‘sandwich’ structure was developed to detect TNT with high sensitivity. Au nano-pillar arrays (AuNPAs) substrates modified by low-concentration PATP through Au–S bonds were acted as capture probe for TNT. Meanwhile, Ag nano-particles (AgNPs) modified by PATP at higher concentration were employed as tags for surface-enhanced Raman scattering (SERS). The formation of the TNT-PATP complex is not only the means by which AuNPAs substrates recognize and capture TNT, but also links the SERS tags to TNT, forming an AuNPAs-TNT-AgNPs ‘sandwich’ structure. The Raman signal of PATP was greatly enhanced mainly because novel ‘hot spots’ formed between the AuNPAs and AgNPs of the ‘sandwich’ structure. The Raman signal of PATP was further amplified by the chemical enhancement effect induced by the TNT-PATP complex formation. Based on this mechanism, the limit of detection (LOD) of TNT was determined from the Raman signal of PATP. The LOD reached 10−9 mg/mL (4.4 × 10−12 M), much lower than that suggested by the US Environmental Protection Agency (88 nM). Moreover, TNT was selectively detected over several TNT analogues 2,4-dinitrotoluene (DNT), p-nitrotoluene (NT) and hexogen (RDX). Finally, the ‘sandwich’ structure was successfully applied to TNT detection in environmental water and sand.

Raman needle arthroscopy for in vivo molecular assessment of cartilage.

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can “optically biopsy” cartilage and quantify key extracellular matrix (ECM) biomarkers for determining cartilage composition, structure, and material properties in health and disease. Technological and analytical innovations to optimize Raman analysis include (1) multivariate decomposition of cartilage Raman spectra into ECM‐constituent‐specific biomarkers (glycosaminoglycan [GAG], collagen [COL], water [H2O] scores), and (2) multiplexed polarized Raman spectroscopy to quantify superficial zone (SZ) COL anisotropy via a partial least squares–discriminant analysis‐derived Raman collagen alignment factor (RCAF). Raman measurements were performed on a series of ex vivo cartilage models: (1) chemically GAG‐depleted bovine cartilage explants (n = 40), (2) mechanically abraded bovine cartilage explants (n = 30), (3) aging human cartilage explants (n = 14), and (4) anatomical‐site‐varied ovine osteochondral explants (n = 6). Derived Raman GAG score biomarkers predicted 95%, 66%, and 96% of the variation in GAG content of GAG‐depleted bovine explants, human explants, and ovine explants, respectively (p < 0.001). RCAF values were significantly different for explants with abrasion‐induced SZ COL loss (p < 0.001). The multivariate linear regression of Raman‐derived ECM biomarkers (GAG and H2O scores) predicted 94% of the variation in elastic modulus of ovine explants (p < 0.001). Finally, we demonstrated the first in vivo Raman arthroscopy assessment of an ovine femoral condyle through intraarticular entry into the synovial capsule. This study advances Raman arthroscopy toward a transformative low‐cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.

New perspective for probe development assessing salivary biomarkers in periodontal affected diabetic patients

The study was performed to have chairside identification of specific biomarkers for diagnosing periodontal disease in diabetic patients at a very early stage using spectroscopic probe design and parameters. Patients were divided into groups: Group (A) - healthy patients, Group (B) - patients with type 2 Diabetes Mellitus (DM) without chronic periodontitis, Group (C) - mild chronic periodontitis patients without type 2 DM, Group (D) - moderate chronic periodontitis patients without type 2 DM, Group (E) - mild chronic periodontitis patients with type 2 DM, and Group (F) - moderate chronic periodontitis patients with type 2 DM. Conceptual and practical design for achieving chairside Raman probe has specific tips and optics applied based on temperature of the mouth. Activation of Matrix metalloproteinase-8 (MMP-8) within salivary specimens were analysed. For molecular docking studies, binding pocket was selected with larger SiteScore. MMP-8 and C-terminal cross-linked telopeptide (CTX) of type I collagen levels in saliva were analysed using MMP-8 Immunoassay. Raman measurements were carried out of salivary specimens. Continuous variables were compared by one‑way analysis of variance. Rate of MMP-8/CTX release was significantly higher in diabetes chronic moderate periodontitis group (p < 0.05). Heat map colour scheme of green indicates increase while the yellow track lines indicate a decrease. Striking difference is seen in Amide regions amongst different groups with lowest intensities seen in diabetic chronic moderate groups and the highest amongst healthy patients (p < 0.05). Major peak at 1447 cm−1 differed in intensities between all groups. Chairside identification of specific biomarkers to diagnosing periodontal disease at a very early stage using spectroscopic probe design and parameters has shown potential.

A Highly Stable Two-Photon Ratiometric Fluorescence Probe for Real-Time Biosensing and Imaging of Nitric Oxide in Brain Tissues and Larval Zebrafish

A Highly Stable Two-Photon Ratiometric Fluorescence Probe for Real-Time Biosensing and Imaging of Nitric Oxide in Brain Tissues and Larval Zebrafish