Surface-Enhanced Raman Scattering from Dye Molecules in Silicon Nanowire Structures Decorated by Gold Nanoparticles.

Silicon nanowires (SiNWs) prepared by metal-assisted chemical etching of crystalline silicon wafers followed by deposition of plasmonic gold (Au) nanoparticles (NPs) were explored as templates for surface-enhanced Raman scattering (SERS) from probe molecules of Methylene blue and Rhodamine B. The filling factor by pores (porosity) of SiNW arrays was found to control the SERS efficiency, and the maximal enhancement was observed for the samples with porosity of 55%, which corresponded to dense arrays of SiNWs. The obtained results are discussed in terms of the electromagnetic enhancement of SERS related to the localized surface plasmon resonances in Au-NPs on SiNW's surfaces accompanied with light scattering in the SiNW arrays. The observed SERS effect combined with the high stability of Au-NPs, scalability, and relatively simple preparation method are promising for the application of SiNW:Au-NP hybrid nanostructures as templates in molecular sensorics.

Development and validation of hybrid Brillouin-Raman spectroscopy for non-contact assessment of mechano-chemical properties of urine proteins as biomarkers of kidney diseases.

BACKGROUND: Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria however, some patients may have slow decline of renal function despite lower level of urinary protein excretion. The different mechanical (visco-elastic) and chemical properties, as well as the proteome profiles of urinary proteins might explain their tubular toxicity mechanism. Brillouin light scattering (BLS) and surface enhanced Raman scattering (SERS) spectroscopies are non-contact, laser optical-based techniques providing visco-elastic and chemical property information of probed human biofluids. We proposed to study and compare these properties of urinary proteins using BLS and SERS spectroscopies in nephrotic patient and validate hybrid BLS-SERS spectroscopy in diagnostic of urinary proteins as well as their profiling. The project ultimately aims for the development of an optical spectroscopic sensor for rapid, non-contact monitoring of urine samples from patients in clinical settings. METHODS: BLS and SERS spectroscopies will be used for non-contact assessment of urinary proteins in proteinuric patients and healthy subjects and will be cross-validated by Liquid Chromatography-Mass Spectrometry (LC-MS). Participants will be followed-up during the 1 year and all adverse events such as exacerbation of proteinuria, progression of CKD, complications of nephrotic syndrome, disease relapse rate and inefficacy of treatment regimen will be registered referencing incident dates. Associations between urinary protein profiles (obtained from BLS and SERS as well as LC-MS) and adverse outcomes will be evaluated to identify most unfavored protein profiles. DISCUSSION: This prospective study is focused on the development of non-contact hybrid BLS - SERS sensing tool and its clinical deployment for diagnosis and prognosis of proteinuria. We will identify the most important types of urine proteins based on their visco-elasticity, amino-acid profile and molecular weight responsible for the most severe cases of proteinuria and progressive renal function decline. We will aim for the developed hybrid BLS - SERS sensor, as a new diagnostic & prognostic tool, to be transferred to other biomedical applications. TRIAL REGISTRATION: The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT04311684). The date of registration was March 17, 2020.

Assessing performance of modern Brillouin spectrometers.

Brillouin spectroscopy and imaging has experienced a renaissance in recent years seeing vast improvements in methodology and increasing number of applications. With this resurgence has come the development of new spontaneous Brillouin instruments that often tout superior performance compared to established conventional systems such as tandem Fabry-Perot interferometers (TFPI). The performance of these new systems cannot always be thoroughly examined beyond the scope of the intended application, as applications often take precedence in reports. We therefore present evaluation of three modern Brillouin spectrometers: two VIPA-based spectrometers with wavelength-specific notch filters, and one scanning 6-pass TFPI. Performance analysis is presented along with a discussion about the dependence of measurements on excitation laser source and the various susceptibilities of each system.

Brillouin Biosensing of Viscoelasticity across Phase Transitions in Ovine Cornea.

Noninvasive in situ monitoring of viscoelastic characteristics of corneal tissue at elevated temperatures is pivotal for mechanical property-informed refractive surgery techniques, including thermokeratoplasty and photorefractive keratectomy, requiring precise thermal modifications of the corneal structure during these surgical procedures. This study harnesses Brillouin light scattering spectroscopy as a biosensing platform to noninvasively probe the viscoelastic properties of ovine corneas across a temperature range of 25-64 °C. By submerging the tissue samples in silicone oil, consistent hydration and immiscibility are maintained, allowing for their accurate sensing of temperature-dependent mechanical behaviors. We identify significant phase transitions in the corneal tissue, particularly beyond 40 °C, likely due to collagen unfolding, marking the beginning of thermal destabilization. A subsequent transition, observed beyond 60 °C, correlates with collagen denaturation. These phase transformations highlight the cornea's sensitivity to both physiologically reversible and irreversible viscoelastic changes induced by mild to high temperatures. Our findings underscore the potential of the Brillouin biosensing technique for real-time diagnostics of corneal biomechanics during refractive surgeries to attain optimized therapeutic outcomes.

Mechano-Chemistry across Phase Transitions in Heated Albumin Protein Solutions.

The presence of certain proteins in biofluids such as synovial fluid, blood plasma, and saliva gives these fluids non-Newtonian viscoelastic properties. The amount of these protein macromolecules in biofluids is an important biomarker for the diagnosis of various health conditions, including Alzheimer's disease, cardiovascular disorders, and joint quality. However, existing technologies for measuring the behavior of macromolecules in biofluids have limitations, such as long turnaround times, complex protocols, and insufficient sensitivity. To address these issues, we propose non-contact, optical Brillouin and Raman spectroscopy to assess the viscoelasticity and chemistry of non-Newtonian solutions, respectively, at different temperatures in several minutes. In this work, bovine and human serum albumin solution-based biopolymers were studied to obtain both their collective dynamics and molecular chemical evolution across heat-driven phase transitions at various protein concentrations. The observed phase transitions at elevated temperatures could be fully delayed in heated biopolymers by appropriately raising the level of protein concentration. The non-contact optical monitoring of viscoelastic and chemical property evolution could represent novel potential mechano-chemical biomarkers for disease diagnosis and subsequent treatment applications, including hyperthermia.

Raman, Infrared and Brillouin Spectroscopies of Biofluids for Medical Diagnostics and for Detection of Biomarkers.

This review surveys Infrared, Raman/SERS and Brillouin spectroscopies for medical diagnostics and detection of biomarkers in biofluids, that include urine, blood, saliva and other biofluids. These optical sensing techniques are non-contact, noninvasive and relatively rapid, accurate, label-free and affordable. However, those techniques still have to overcome some challenges to be widely adopted in routine clinical diagnostics. This review summarizes and provides insights on recent advancements in research within the field of vibrational spectroscopy for medical diagnostics and its use in detection of many health conditions such as kidney injury, cancers, cardiovascular and infectious diseases. The six comprehensive tables in the review and four tables in supplementary information summarize a few dozen experimental papers in terms of such analytical parameters as limit of detection, range, diagnostic sensitivity and specificity, and other figures of merits. Critical comparison between SERS and FTIR methods of analysis reveals that on average the reported sensitivity for biomarkers in biofluids for SERS vs FTIR is about 103 to 105 times higher, since LOD SERS are lower than LOD FTIR by about this factor. High sensitivity gives SERS an edge in detection of many biomarkers present in biofluids at low concentration (nM and sub nM), which can be particularly advantageous for example in early diagnostics of cancer or viral infections.HighlightsRaman, Infrared spectroscopies use low volume of biofluidic samples, little sample preparation, fast time of analysis and relatively inexpensive instrumentation.Applications of SERS may be a bit more complicated than applications of FTIR (e.g., limited shelf life for nanoparticles and substrates, etc.), but this can be generously compensated by much higher (by several order of magnitude) sensitivity in comparison to FTIR.High sensitivity makes SERS a noninvasive analytical method of choice for detection, quantification and diagnostics of many health conditions, metabolites, and drugs, particularly in diagnostics of cancer, including diagnostics of its early stages.FTIR, particularly ATR-FTIR can be a method of choice for efficient sensing of many biomarkers, present in urine, blood and other biofluids at sufficiently high concentrations (mM and even a few µM)Brillouin scattering spectroscopy detecting visco-elastic properties of probed liquid medium, may also find application in clinical analysis of some biofluids, such as cerebrospinal fluid and urine.

Thermo-Visco-Elastometry of RF-Wave-Heated and Ablated Flesh Tissues Containing Au Nanoparticles.

We report non-contact laser-based Brillouin light-scattering (BLS) spectroscopy measurements of the viscoelastic properties of hyperthermally radiofrequency (RF)-heated and ablated bovine liver and chicken flesh tissues with embedded gold nanoparticles (AuNPs). The spatial lateral profile of the local surface temperature in the flesh samples during their hyperthermia was measured through optical backscattering reflectometry (OBR) using Mg−silica-NP-doped sensing fibers distributed with an RF applicator and correlated with viscoelastic variations in heat-affected and ablated tissues. Substantial changes in the tissue stiffness after heating and ablation were directly related to their heat-induced structural modifications. The main proteins responsible for muscle elasticity were denatured and irreversibly aggregated during the RF ablation. At T > 100 °C, the proteins constituting the flesh further shrank and became disorganized, leading to substantial plastic deformation of biotissues. Their uniform destruction with larger thermal lesions and a more viscoelastic network was attained via AuNP-mediated RF hyperthermal ablation. The results demonstrated here pave the way for simultaneous real-time hybrid optical sensing of viscoelasticity and local temperature in biotissues during their denaturation and gelation during hyperthermia for future applications that involve mechanical- and thermal-property-controlled theranostics.

Mechano-Chemical Properties of Electron Beam Irradiated Polyetheretherketone.

In this study, the mechano-chemical properties of aromatic polymer polyetheretherketone (PEEK) samples, irradiated by high energy electrons at 200 and 400 kGy doses, were investigated by Nanoindentation, Brillouin light scattering spectroscopy and Fourier-transform infrared spectroscopy (FTIR). Irradiating electrons penetrated down to a 5 mm depth inside the polymer, as shown numerically by the monte CArlo SImulation of electroN trajectory in sOlids (CASINO) method. The irradiation of PEEK samples at 200 kGy caused the enhancement of surface roughness by almost threefold. However, an increase in the irradiation dose to 400 kGy led to a decrease in the surface roughness of the sample. Most likely, this was due to the processes of erosion and melting of the sample surface induced by high dosage irradiation. It was found that electron irradiation led to a decrease of the elastic constant C11, as well as a slight decrease in the sample's hardness, while the Young's elastic modulus decrease was more noticeable. An intrinsic bulk property of PEEK is less radiation resistance than at its surface. The proportionality constant of Young's modulus to indentation hardness for the pristine and irradiated samples were 0.039 and 0.038, respectively. In addition, a quasi-linear relationship between hardness and Young's modulus was observed. The degradation of the polymer's mechanical properties was attributed to electron irradiation-induced processes involving scission of macromolecular chains.

Size-Dependent Phonon-Assisted Anti-Stokes Photoluminescence in Nanocrystals of Organometal Perovskites.

Anti-Stokes photoluminescence (ASPL), which is an up-conversion phonon-assisted process of the radiative recombination of photoexcited charge carriers, was investigated in methylammonium lead bromide (MALB) perovskite nanocrystals (NCs) with mean sizes that varied from about 6 to 120 nm. The structure properties of the MALB NCs were investigated by means of the scanning and transmission electron microscopy, X-ray diffraction and Raman spectroscopy. ASPL spectra of MALB NCs were measured under near-resonant laser excitation with a photon energy of 2.33 eV and they were compared with the results of the photoluminescence (PL) measurements under non-resonant excitation at 3.06 eV to reveal a contribution of phonon-assisted processes in ASPL. MALB NCs with a mean size of about 6 nm were found to demonstrate the most efficient ASPL, which is explained by an enhanced contribution of the phonon absorption process during the photoexcitation of small NCs. The obtained results can be useful for the application of nanocrystalline organometal perovskites in optoelectronic and all-optical solid-state cooling devices.

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19−53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49−117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.

Photothermal Effects and Heat Conduction in Nanogranular Silicon Films.

We present results on the photothermal (PT) and heat conductive properties of nanogranular silicon (Si) films synthesized by evaporation of colloidal droplets (drop-casting) of 100 ± 50 nm-sized crystalline Si nanoparticles (NP) deposited on glass substrates. Simulations of the absorbed light intensity and photo-induced temperature distribution across the Si NP films were carried out by using the Finite difference time domain (FDTD) and finite element mesh (FEM) modeling and the obtained data were compared with the local temperatures measured by micro-Raman spectroscopy and then was used for determining the heat conductivities k in the films of various thicknesses. The cubic-to-hexagonal phase transition in Si NP films caused by laser-induced heating was found to be heavily influenced by the film thickness and heat-conductive properties of glass substrate, on which the films were deposited. The k values in drop-casted Si nanogranular films were found to be in the range of lowest k of other types of nanostructurely voided Si films due to enhanced phonon scattering across inherently voided topology, weak NP-NP and NP-substrate interface bonding within nanogranular Si films.

Brillouin spectroscopy and radiography for assessment of viscoelastic and regenerative properties of mammalian bones.

Biomechanical properties of mammalian bones, such as strength, toughness, and plasticity, are essential for understanding how microscopic-scale mechanical features can link to macroscale bones' strength and fracture resistance. We employ Brillouin light scattering (BLS) microspectroscopy for local assessment of elastic properties of bones under compression and the efficacy of the tissue engineering approach based on heparin-conjugated fibrin (HCF) hydrogels, bone morphogenic proteins, and osteogenic stem cells in the regeneration of the bone tissues. BLS is noninvasive and label-free modality for probing viscoelastic properties of tissues that can give information on structure-function properties of normal and pathological tissues. Results showed that MCS and BPMs are critically important for regeneration of elastic and viscous properties, respectively, HCF gels containing combination of all factors had the best effect with complete defect regeneration at week nine after the implantation of bone grafts and that the bones with fully consolidated fractures have higher values of elastic moduli compared with defective bones.