Surface optical sensitivity enhanced by a single dielectric microsphere.

Single dielectric microspheres can manipulate light focusing and collection to enhance optical interaction with surfaces. To demonstrate this principle, we experimentally investigate the enhancement of the Raman signal collected by a single dielectric microsphere, with a radius much larger than the exciting laser spot size, residing on the sample surface. The absolute microsphere-assisted Raman signal from a single graphene layer measured in air is more than a factor of two higher than that obtained with a high numerical aperture objective. Results from Mie's theory are used to benchmark numerical simulations and an analytical model to describe the isolated microsphere focusing properties. The analytical model and the numerical simulations justify the Raman signal enhancement measured in the microsphere-assisted Raman spectroscopy experiments.

Two-Dimensional Phononic Crystal Based Sensor for Characterization of Mixtures and Heterogeneous Liquids.

We show new approaches to developing acoustic liquid sensors based on phononic crystals. The proposed phononic crystal integrates fluidic elements. A solid block with periodic cylindrical holes contains a defect-a liquid-filled cylindrical cavity. We pay attention to acoustic excitation and the readout of the axisymmetric cylindrical resonator eigenmode of the liquid-filled defect in the middle of the phononic crystal structure. This mode solves the challenge of mechanical energy losses due to liquid viscosity. We also analyze the coupling effects between oscillations of liquid and solid systems and consider coupling issues between piezoelectric transducers and the liquid-filled cavity resonator. The numerical simulation of the propagation of acoustic waves through the phononic crystal sensor was carried out in COMSOL Multiphysics Software. The phononic crystal was made of stainless steel with mechanically drilled holes and was fabricated for experimental verification. We show that a tuning of the solid-liquid vibrational modes coupling is the key to an enhanced level of sensitivity to liquid properties. Besides (homogeneous) water-propanol mixtures, experimental studies were carried out on (disperse) water-fuel emulsions.

Label-Free Physical Techniques and Methodologies for Proteins Detection in Microfluidic Biosensor Structures.

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices for point-of-care (POC) analysis based on microfluidic technology as an alternative to conventional laboratory protein assays. In contrast to universally accepted analytical methods involving protein labeling, label-free approaches often allow the development of biosensors with minimal requirements for sample preparation by omitting expensive labelling reagents. The aim of the present work is to review the variety of physical label-free techniques of protein detection and characterization which are suitable for application in micro-fluidic structures and analyze the technological and material aspects of label-free biosensors that implement these methods. The most widely used optical and impedance spectroscopy techniques: absorption, fluorescence, surface plasmon resonance, Raman scattering, and interferometry, as well as new trends in photonics are reviewed. The challenges of materials selection, surfaces tailoring in microfluidic structures, and enhancement of the sensitivity and miniaturization of biosensor systems are discussed. The review provides an overview for current advances and future trends in microfluidics integrated technologies for label-free protein biomarkers detection and discusses existing challenges and a way towards novel solutions.

Periodic Tubular Structures and Phononic Crystals towards High-Q Liquid Ultrasonic Inline Sensors for Pipes.

The article focuses on a high-resolution ultrasound sensor for real-time monitoring of liquid analytes in cylindrical pipes, tubes, or capillaries. The development of such a sensor faces the challenges of acoustic energy losses, including dissipation at liquid/solid interface and acoustic wave radiation along the pipe. Furthermore, we consider acoustic resonant mode coupling and mode conversion. We show how the concept of phononic crystals can be applied to solve these problems and achieve the maximum theoretically possible Q-factor for resonant ultrasonic sensors. We propose an approach for excitation and measurement of an isolated radial resonant mode with minimal internal losses. The acoustic energy is effectively localized in a narrow probing area due to the introduction of periodically arranged sectioned rings around the tube. We present a sensor design concept, which optimizes the coupling between the tubular resonator and external piezoelectric transducers. We introduce a 2D-phononic crystal in the probing region for this purpose. The Q-factor of the proposed structures show the high prospects for phononic crystal pipe sensors.

Label-Free Protein Detection by Micro-Acoustic Biosensor Coupled with Electrical Field Sorting. Theoretical Study in Urine Models.

Diagnostic devices for point-of-care (POC) urine analysis (urinalysis) based on microfluidic technology have been actively developing for several decades as an alternative to laboratory based biochemical assays. Urine proteins (albumin, immunoglobulins, uromodulin, haemoglobin etc.) are important biomarkers of various pathological conditions and should be selectively detected by urinalysis sensors. The challenge is a determination of different oligomeric forms of the same protein, e.g., uromodulin, which have similar bio-chemical affinity but different physical properties. For the selective detection of different types of proteins, we propose to use a shear bulk acoustic resonator sensor with an additional electrode on the upper part of the bioliquid-filled channel for protein electric field manipulation. It causes modulation of the protein concentration over time in the near-surface region of the acoustic sensor, that allows to distinguish proteins based on their differences in diffusion coefficients (or sizes) and zeta-potentials. Moreover, in order to improve the sensitivity to density, we propose to use structured sensor interface. A numerical study of this approach for the detection of proteins was carried out using the example of albumin, immunoglobulin, and oligomeric forms of uromodulin in model urine solutions. In this contribution we prove the proposed concept with numerical studies for the detection of albumin, immunoglobulin, and oligomeric forms of uromodulin in urine models.

Barium-Strontium Titanate/Porous Glass Structures for Microwave Applications.

Based on porous silicate glasses obtained by ion exchange, glass-ceramic materials containing a solid solution of barium-strontium titanate with a dielectric constant of more than 100 at microwaves, were synthesized for the first time. Glass-ceramic structures were studied using X-ray diffraction, secondary electron microscopy, Mössbauer spectroscopy and porometry methods. Electrical characteristics such as permittivity and losses of as-prepared and annealed in oxygen medium samples were also investigated at microwaves. It was shown that the method of obtaining porous glasses, due to ion exchange between KFeSi glass and LiNO3 and NaNO3 melts, allows for controlling a wide range of pore sizes and makes it possible to form glass porous structures with pores of the required size. The efficiency of the process of filling a porous matrix with a ferroelectric filler was investigated and the average depth of its penetration was estimated. It was shown that annealing glass-ceramic structures in an oxygen environment had a positive effect on their structural and electrical characteristics. Glass-ceramic structures demonstrate a significant increase in permittivity and a decrease in losses after high-temperature treatment in oxygen.

Structural Dependent Eu3+ Luminescence, Photoelectric and Hysteresis Effects in Porous Strontium Titanate.

Eu3+ doped porous nanostructured SrTiO3 films and powder fabricated by sol-gel route without using any precursor template are characterized by different morphology and phase composition. The films show red and yellow luminescence with the most intensive photoluminescence (PL) bands at 612 nm and 588 nm, respectively. Raman, secondary ion mass spectrometry (SIMS), and X-ray diffraction (XRD) analysis of undoped nanostructured porous SrTiO3 films showed the presence of TiO2, SrO, and SrTiO3 phases and their components. The undoped porous SrTiO3 films are photosensitive and demonstrate resistive switching. The capacitance-voltage hysteresis loops with the width of about 6 V in the frequency range of 2 kHz-2 MHz were observed.

Topology Challenge for the Assessment of Living Cell Deposits with Shear Bulk Acoustic Biosensor.

Shear bulk acoustic type of resonant biosensors, such as the quartz crystal microbalance (QCM), give access to label-free in-liquid analysis of surface interactions. The general understanding of the sensing principles was inherited from past developments in biofilms measurements and applied to cells while keeping the same basic assumptions. Thus, the biosensor readouts are still quite often described using 'mass' related terminology. This contribution aims to show that assessment of cell deposits with acoustic biosensors requires a deep understanding of the sensor transduction mechanism. More specifically, the cell deposits should be considered as a structured viscoelastic load and the sensor response depends on both material and topological parameters of the deposits. This shifts the paradigm of acoustic biosensor away from the classical mass loading perspective. As a proof of the concept, we recorded QCM frequency shifts caused by blood platelet deposits on a collagen surface under different rheological conditions and observed the final deposit shape with atomic force microscopy (AFM). The results vividly demonstrate that the frequency shift is highly impacted by the platelet topology on the bio-interface. We support our findings with numerical simulations of viscoelastic unstructured and structured loads in liquid. Both experimental and theoretical studies underline the complexity behind the frequency shift interpretation when acoustic biosensing is used with cell deposits.

Microstructure and Properties of PZT Films with Different PbO Content-Ionic Mechanism of Built-In Fields Formation.

Experimental studies were conducted on the effects of lead oxide on the microstructure and the ferroelectric properties of lead zirconate-titanate (PZT) films obtained by the method of radio frequency (RF) magnetron sputtering of a ceramic PZT target and PbO2 powder with subsequent heat treatment. It is shown that the change in ferroelectric properties of polycrystalline PZT films is attributable to their heterophase structure with impurities of lead oxide. It is also shown that, even in the original stoichiometric PZT film, under certain conditions (temperature above 580 °C, duration greater than 70 min), impurities of lead oxide may be formed. The presence of a sublayer of lead oxide leads to a denser formation of crystallization centers of the perovskite phase, resulting in a reduction of the grain size as well as the emergence of a charge on the lower interface. The formation of the perovskite structure under high-temperature annealing is accompanied by the diffusion of lead into the surface of the film. Also shown is the effect of the lead ions segregation on the formation of the self-polarized state of thin PZT films.

Narrow Band Solid-Liquid Composite Arrangements: Alternative Solutions for Phononic Crystal-Based Liquid Sensors.

Periodic elastic composite structures attract great attention. They offer the ability to design artificial properties to advance the control over the propagation of elastic/acoustic waves. In previous work, we drew attention to composite periodic structures comprising liquids. It was shown that the transmission spectrum of the structure, specifically a well-isolated peak, follows the material properties of liquid constituent in a distinct manner. This idea was realized in several liquid sensor concepts that launched the field of phononic crystal liquid sensors. In this work we introduce a novel concept-narrow band solid-liquid composite arrangements. We demonstrate two different concepts to design narrow band structures, and show the results of theoretical studies and results of experimental investigations that confirm the theoretical predictions. This work extends prior studies in the field of phononic crystal liquid sensors with novel concepts and results that have a high potential in a field of volumetric liquid properties evaluation.

Heat-Resistant Ferroelectric-Polymer Nanocomposite with High Dielectric Constant.

The high dielectric constant ferroelectric-polymer nanocomposite was developed for producing the heat-resistant and chemical stable planar layers. According to the composite coatings formation conditions, the following value ranges of dielectric constant and loss factor were received: 30⁻400 for dielectric constant and 0.04⁻0.1 for loss tangent, accordingly. Unlike of composite components, the obtained composite material is characterized by thermo-stability of electrical parameters up to 250 °C. The dielectric frequency spectra of the composite exhibit two clearly visible peaks in contrast to the spectra of the polymer and ferroelectric ceramics. The developed composite material can be used as a built-in film capacitors material in microelectronic devices.

SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept.

End-stage renal disease in ANCA-associated vasculitis.

The outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved significantly over the past decades, although a significant proportion of them still reach end-stage renal disease (ESRD). Renal replacement therapy (RRT) is associated with a relatively low risk of relapsing vasculitis as a result of anti-rejection treatment after kidney transplantation or quiescence of the autoimmune process in haemodialysis patients, but a flare of vasculitis in the latter setting presents a challenge because the treatment is poorly tolerated. There are benefits of rituximab in haemodialysed patients, as it is more steroid sparing in the treatment of extrarenal disease. More favourable outcomes of kidney transplantation compared with haemodialysis support its use as a preferable method of RRT in patients with vasculitis remission or low disease activity.

Predictors of AA amyloidosis in familial Mediterranean fever.

The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI 1.17-4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.

Changing patterns of clinical severity and risk of mortality in granulomatosis with polyangiitis over four decades: the Russian experience.

The aim of our study was to study the changes in the clinical picture and outcomes of granulomatosis with polyangiitis (Wegener's) (GPA) over 40 years. Two hundred and forty-two consecutive patients with GPA were distributed into retrospective (1970-2003) and prospective (2004-2012) cohorts. Anti-neutrophil cytoplasmic antibodies were present in 82.6 % of patients. In 78.0 % of patients, diagnosis was confirmed histologically. We compared the clinical features of GPA and the incidence of the major and minor relapses and mortality in the two cohorts. The majority of patients in both cohorts had generalized GPA that involved upper respiratory tract (retrospective 89.5 % vs prospective 82.85 %), kidneys (60.5 vs 50.8 %) and lungs (64.0 vs 52.3 %). The total duration of follow-up in the retrospective and prospective cohorts was 468 and 397 patients-years, respectively. In the prospective cohort, we found trend to lower incidence of relapses (54.2 vs 66.2 per 100 patient-year; p = ns; odds ratio 0.82; 95 % CI 0.53-1.21) and significantly lower mortality (4.3 vs 7.9 per 100 patient-year; p = 0.04; odds ratio 0.54; 95 % CI 0.31-0.94). The leading causes of death in the retrospective cohort were lung disease (37.8 %), complications of immunosuppressive treatment (35.1 %) and kidney failure (13.5 %). In the prospective cohort, patients rarely died from terminal uraemia and pulmonary complications (0.0 and 17.6 %) while the proportion of cardiovascular events and complications of the immunosuppression as the causes of death increased (29.4 and 47.1 %). Modern treatment apparently reduced the incidence of relapses and mortality and modified the causes of death in the GPA patients.