Search Results (52)

Background/Objectives: Therapeutic drug monitoring (TDM) of immunosuppressants is essential in treating pediatric kidney diseases; however, repeated venipuncture is burdensome in children. We evaluated whether minimally invasive fingerstick capillary sampling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) provides results analytically comparable to those of conventional venous sampling. Methods: Capillary whole blood (2.8 µL) was collected via fingersticks from pediatric patients receiving mycophenolate mofetil, with or without tacrolimus (TAC) or cyclosporine A (CsA). Drug concentrations were quantified using a previously validated simultaneous LC-MS/MS method and compared with conventional venous sampling using linear regression and Bland–Altman analyses. Results: Seventy-four paired samples from 21 patients were analyzed. Strong correlations were observed between capillary and venous samples for mycophenolic acid (MPA), TAC, and CsA (R² > 0.90). Hematocrit correction improved agreement for MPA. Bland–Altman analyses demonstrated acceptable bias across analytes. Conclusions: Fingerstick-based microvolume sampling combined with LC-MS/MS provides analytically reliable immunosuppressant quantification in pediatric patients. Although larger clinical validation is required, this minimally invasive approach may reduce procedural burden and may support future outpatient or home-based TDM strategies. Full article

Blood glutathione (GSH), its oxidized form glutathione disulfide (GSSG), and especially the ratio of reduced to oxidized glutathione (GSH/GSSG) are recognized as robust biomarkers of oxidative stress. However, the broader application of these biomarkers has been limited by two major challenges: (1) the high risk of artifact formation during sample handling, which can artificially increase GSSG levels and bias redox balance measurements, and (2) the reliance on complex, instrument-intensive analytical procedures and the requirement for venous blood. We present an adaptation of the highly sensitive and easy-to-perform Tietze recycling method for microvolumes of blood. The challenge is to achieve accurate and precise measurements while avoiding artifacts, taking advantage of the high sensitivity of this enzymatic recycling analytical procedure. The method uses a simplified sample preparation protocol compatible with small blood volumes (up to 10 μL) and requires only basic laboratory equipment, such as a standard spectrophotometer or microplate reader. As this is an enzyme-based assay, we also carefully evaluate the main factors that can affect the measurements. This novel procedure provides a practical tool for monitoring GSH/GSSG as a biomarker of oxidative stress in various experimental settings by eliminating the need for trained personnel for blood sampling (it is suitable for capillary blood), minimizing discomfort for subjects, and avoiding complex procedures or instruments for analyte detection. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) is essential for optimizing immunosuppressive therapy in solid-organ transplant recipients by maintaining efficacy, while minimizing adverse effects. However, conventional TDM relies on venous sampling and separate assays for tacrolimus (TAC) in whole blood and mycophenolic acid (MPA) in plasma, thereby increasing patient burden and procedural complexity. To address these limitations, we investigated the clinical utility of a microvolume, liquid-phase microsampling device (MSW2™) in combination with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Methods: We established and applied an LC-MS/MS method for simultaneous quantification of TAC, MPA, and mycophenolic acid β-D-glucuronide (MPAG) using only 2.8 µL of whole blood collected with MSW2™, which eliminates drying or extraction steps. Hematocrit-based correction was applied to estimate plasma MPA concentrations from whole-blood measurements. The method was evaluated in 60 renal transplant recipients with paired venous samples for comparison. Analytical performance was assessed using regression, Bland–Altman analyses, predictive metrics, and stability testing under different storage conditions. Results: Microsampled and venous concentrations were strongly correlated (R² > 0.95). Estimated plasma MPA concentrations derived from whole blood closely approximated plasma concentrations (bias < 5%). Reducing the sample volume from 5.6 µL to 2.8 µL improved precision and increased the success rate of blood collection from 72.9% to 94.0%. All analytes remained stable for up to 72 h at ≤25 °C. Conclusions: This approach enables accurate, simultaneous quantification of multiple immunosuppressants from trace blood volumes. By reducing sampling burden and simplifying logistics, it provides a clinically feasible and patient-centered strategy for precision TDM, supporting broader implementation of limited sampling strategies and expanding applicability to pediatric, home-based, and telemedicine settings. Full article

Electropolishing is an essential process for the surface treatment of metallic materials. To determine the appropriate replacement timing of electropolishing solutions for their efficient use and improved productivity, it is important to periodically analyze the amounts of dissolved metals in the solutions. However, these solutions are typically highly corrosive, and on-site analytical techniques that can be easily applied at production sites have not yet been established. In this study, we demonstrated microvolume liquid analysis using low-energy laser-induced breakdown spectroscopy (LIBS) combined with a porous silicon substrate fabricated by metal-assisted etching (metal-assisted chemical etching) and a non-contact gas-blowing pretreatment. In the analysis of electropolishing solutions used for niobium superconducting cavities and stainless steel products, emission lines of niobium and of iron and chromium were successfully detected after blowing the respective microdroplet samples on porous silicon, and linear correlations were observed between the spectral line intensity and the polished amounts. The present results provide a basis for future on-site application of LIBS to highly corrosive electropolishing solutions in the metal finishing industry. Full article

The experimental study has been carried out using advanced computer vision methods in order to visualize the moment of excitation and further propagation of a non stationary isotropic domain in a hybrid aligned nematic (HAN) microsized volume under the effect of a laser beam focused on a bounding liquid crystal surface. It has been shown that, when the laser power exceeds a certain threshold value, in bulk of the HAN microvolume, an isotropic circular domain is formed. We also observed a structure of alternating concentric rings around the isotropic circular region, which increases with distance from the center of the isotropic domain. The formation of a sequence of rings in a polarizing microscopic image indicates the formation of a complex topology of the director field in the HAN cell under study. The following evolution of the texture can be represented by two modes. Firstly, the “fast” heating mode, which is responsible for the formation and explosive expansion of an isotropic zone in bulk of the HAN microvolume with characteristic time ${\tau }_1$ due to a laser spot heating on the upper indium tin oxide (ITO) layer. Secondly, the “slow” heating mode, when an isotropic zone and concentric rings slowly expand with characteristic time ${\tau }_2$ mainly due to the finite thermoconductivity of ITO layer. When the laser power significantly exceeds the threshold value, damped oscillations of the isotropic domain are observed. We also introduced the metrics that allows quantitatively estimate the behavior of texture observed. The results obtained form an experimental basis for further investigation of thermomechanical force appearing in the LC system with coupled gradients of temperature and director fields. Full article

This paper deals with an important issue, which is the influence of failure caused by the quality of matrix post-curing on the strength of complex and difficult materials of the “new generation” such as fibre composites, particularly with a polymer matrix. In recent years, significant advances in the field of adhesive materials chemistry have led to the constant development of bonding technology. The effectiveness of bonding depends, to a large extent, on the suitable selection of the adhesive and the use of appropriate surface treatment technology. It is difficult to imagine virtually any modern industry without adhesive joints, be it the aircraft, aerospace or automotive industries, which simultaneously highlights the great importance of adhesives and adhesive materials for the present-day economy. In modern technology, it is extremely important to obtain the right combination of modern construction materials. The statistical analysis of the components showed the complexity of the layered composite structure. The proposed model of the weakest micro-volume developed in this study indirectly reflects the experimentally based curing variables that affect the stresses of the components in the composite (laminate) structure. The strength of fibrous composite structures based on the Markov chain theory considers technological aspects during hardening. The model proposed in the paper was validated on the basis of examples from the literature and experimental data obtained in the research project. The numerical results are in good agreement with the literature database and measurement data. The presented model could be a novel method, which allows better insight into the curing process of epoxy resins. Full article

Immunosuppressants are essential for preventing allograft rejection; however, they require therapeutic drug monitoring to maintain efficacy and to prevent severe complications such as opportunistic infections. Calcineurin inhibitors (CIs) are primarily distributed in red blood cells, whereas mycophenolic acid (MPA) and its metabolites are found in plasma. These differences necessitate separate analyses for each drug, increasing laboratory workload, analytical complexity, and patient burden. We developed a liquid chromatography–tandem mass spectrometry method for simultaneous quantification of CIs such as tacrolimus (Tac), everolimus (Eve), sirolimus (Sir), cyclosporine A (CycA) and MPA in 2.8-µL whole-blood samples, with a hematocrit-based correction to estimate plasma-equivalent MPA concentrations. Performance of this method was assessed by comparison with conventional immunoassay results using linear regression and Bland–Altman analyses, demonstrating excellent agreement, with strong linearity (R² > 0.995) at <2 to 35 ng/mL for three CIs, 26.0 to 1866 ng/mL for CycA, and 0.1 to 50 μg/mL for MPA. Furthermore, MPA and tacrolimus concentrations closely aligned with routine clinical results (R² > 0.900), indicating high accuracy and reproducibility. This new approach may be particularly beneficial for hospitalized patients with limited venous access, pediatric populations, and in remote care settings where frequent blood sampling is challenging because of simultaneous quantification and fewer sample volume requirements. Full article

Currently, research on the modification mechanisms of activated rubber/SBS (styrene–butadiene–styrene) composites and the microscopic processes involved remains limited. To investigate the impact of the rubber activation treatment combined with SBS modifier on asphalt modification, this study employs composite-modified asphalt formulations using either a conventional mix or activated rubber in conjunction with SBS. Infrared spectroscopy (IR) and scanning electron microscopy (SEM) were utilized to analyze the chemical components and microscopic morphology of the composite-modified asphalt following activation treatment. Microscopic analysis revealed that the asphalt stirred for 20 min has a characteristic peak with a wave number of 966 cm⁻¹, while the characteristic peak with a wave number of 700 cm⁻¹ is not obvious. That is, the asphalt sample contains the polybutadiene component and a reduced amount of the polystyrene component. Therefore, it can be inferred that the asphalt sample only contains activated rubber, along with less SBS modifier content. Traditional rubber undergoes significant expansion reactions during the mixing stage, but there are difficulties in degradation, which leave large particles and reduce the proportions of the lightweight asphalt components. However, active rubber and SBS mainly expand and degrade more completely during the shear stage, forming many micro-volume particles in asphalt. Additionally, frequency scanning and multiple creep recovery tests were conducted to evaluate the high-temperature rheological properties of the asphalt. The results indicate that activated rubber, doped at 20%, and SBS, doped at 2%, significantly enhance the high-temperature rheological properties of the composite-modified asphalt compared to base asphalt, exhibiting a 417.16% increase in the complex modulus at 64 °C and 1 Hz. Furthermore, these modifiers interact synergistically to improve modification efficiency. Full article

Intra-tissue endoscopy, providing real-time images at all scales, from macroscopic to microscopic, from inside living tissue during surgical procedures, has revealed the existence of a body-wide fibrillar architecture that extends from the surface of the skin to the cell. Different types of cells are housed within this fibrillar architecture and gather together to carry out specific functions. This challenges the commonly accepted notion of the organization of living matter that associates separate organs with connective tissue packaging. We are thus confronted with the global nature of the living human body and its vital processes. This paper sets out to describe the architecture of this fibrillar network which could be assimilated with the fascial tissue and which attributes a more constitutive role to connective tissue. It also demonstrates how movements within this fibrillar network can occur with minimal local distortion while maintaining tissue continuity. The authors propose that the gliding of tissues can be explained by the existence of a highly adaptable fibrillar network that enables the gliding of distinct anatomical structures such as tendons and muscles, without any dynamic influence on the surrounding tissues. The authors propose a new model of tissue movement based on the observation of a ubiquitous dynamic polyhedric fibrillar network with an apparently dispersed and complex pattern of organization, that forms fluid-filled microvolumes, and is found everywhere in the human body. Furthermore, this fibrillar network appears to act as a force absorption system, in addition to providing a framework or scaffolding for cells throughout the body. Observation during intra-tissue endoscopy suggests that this fundamental architectural organization extends into the extracellular matrix that is the natural environment of all cells in the living body, regardless of their size, location or specific function. Full article

A theoretical analysis of the influence of the distribution of the local specific energy dissipation rate on the specific interfacial area, the surface and volumetric mass transfer coefficients in apparatuses with heterophase processes and a liquid continuous phase, as well as the quality of mixing in apparatuses with homophase reactions in the liquid phase, is performed. It is shown that the average value of the specific energy dissipation rate over the volume of the device is not a full-fledged criterion for assessing the useful effect since it does not take into account, on the one hand, the local level of energy dissipation in the active zones and, on the other hand, the features of the flow structure and the local residence time in the active zones, depending on the geometry of the device and the method of energy input into it. Limiting cases are discussed: (1) uneven energy distribution in the presence of a small volume with a high specific dissipation rate and (2) ideally uniform energy distribution throughout the entire volume of the device. In the first case, a significant part of the volume is used inefficiently; in the second case, an excessive amount of energy is spent. In this regard, the concepts of dosed distributed energy input for long-term processes and maximum energy concentration in a microvolume for fast-flowing processes are considered. Full article

We have carried out a numerical study of hydrodynamic processes in the hybrid-aligned channel of a compressible liquid crystal (HACLC) under the effect of a temperature gradient $\nabla T$ applied across a liquid crystal film. Calculations based on the classical Leslie–Ericksen theory showed that under the effect of $\nabla T$, the HACLC sample settles down to a stationary flow regime with both horizontal u and vertical w components of velocity $\mathbf{v}$, and the direction and magnitude of $\mathbf{v}$ are strongly effected by the direction of $\nabla T$. Calculations also showed that the relaxation of the stress tensor components ${\sigma }_{\mathrm{ij}}(z,t)(\mathrm{i},\mathrm{j}=\mathrm{x},\mathrm{z})$ in the hybrid-aligned compressible nematic microvolume is determined by the direction and magnitude of the thermomechanical force. Full article

Microvolume ELISA platforms have become vital in diagnostics for their high-throughput capabilities and minimal sample requirements. High-quality substrates with advanced surface properties are essential for these applications. They enable both efficient biomolecule immobilization and antifouling properties, which are critical for assay sensitivity and specificity. This study presents PET-based microvolume ELISA spot arrays coated with amine- and DBCO-reactive copolymers MCP-2 and Copoly Azide. The platforms were designed for the sensitive and specific detection of specific antibodies such as COVID-19 biomarkers. Supporting robust attachment of the SARS-CoV-2 nucleoprotein (NP), these arrays outperform traditional approaches. It was demonstrated that covalent attachment methods proved more efficient than passive adsorption, together with the reduction of non-specific binding. Analytical performance was verified with classical ELISA and real-time Surface Plasmon Resonance (SPR) analysis. It enables sensitive detection of IgG and IgA antibodies, including IgG subclasses, in human serum. Clinically, the platform achieved 100.0% sensitivity and 92.9% specificity for anti-NP antibody detection in COVID-19-positive and negative samples. Additionally, DNA-directed immobilization extended the platform’s utility to multiplex serological measurements. These findings underscore the potential of PET-based microvolume ELISA arrays as scalable, high-throughput diagnostic tools suitable for detecting multiple biomarkers in a single assay and easily integrated into microfluidic devices. Full article

Mercury, a toxic heavy metal produced through both natural and anthropogenic processes, is found in all of Earth’s major systems. Mercury’s bioaccumulation characteristics in the human body have a significant impact on the liver, kidneys, brain, and muscles. In order to detect Hg²⁺ ions, a highly sensitive and specific fluorescent biosensor has been developed using a novel, modified seven amino acid peptide, FY7. The tyrosine ring in the FY7 peptide sequence forms a 2:1 complex with Hg²⁺ ions that are present in the water-based sample. As a result, the peptide’s fluorescence emission decreases with higher concentrations of Hg²⁺. The FY7 peptide’s performance was tested in the presence of Hg²⁺ ions and other metal ions, revealing its sensitivity and stability despite high concentrations. Conformational changes to the FY7 structure were confirmed by FTIR studies. Simultaneously, we designed a miniaturized setup to support an in-house-developed micro-volume capillary container for volume fluorometry measurements. We compared and verified the results from the micro-volume system with those from the commercial setup. The micro-volume capillary system accommodated only 2.9 µL of sample volume, allowing for rapid, sensitive, and selective detection of toxic mercury (II) ions as low as 0.02 µM. Full article

A rapid and online microvolume flow-through dialysis probe designed for sample preparation in the analysis of veterinary drug residues is introduced. This study addresses the need for efficient and green sample preparation methods that reduce chemical waste and reagent use. The dialysis probe integrates with liquid chromatography and mass spectrometry (LC-MS) systems, facilitating automated, high-throughput analysis. The dialysis method utilizes minimal reagent volumes per sample, significantly reducing the generation of solvent waste compared to traditional sample preparation techniques. Several veterinary drugs were spiked into tissue homogenates and analyzed to validate the probe’s efficacy. A diagnostic sensitivity of >97% and specificity of >95% were obtained for this performance evaluation. The results demonstrated the effective removal of cellular debris and particulates, ensuring sample integrity and preventing instrument clogging. The automated dialysis probe yielded recovery rates between 27 and 77% for multiple analytes, confirming its potential to streamline veterinary drug residue analysis, while adhering to green chemistry principles. The approach highlights substantial improvements in both environmental impact and operational efficiency, presenting a viable alternative to conventional sample preparation methods in regulatory and research applications. Full article

In this study, to improve the efficiency of the pipetting workstation and reduce the impact of the pipetting device on the stability performance of the workstation, a novel fully automatic pipetting method is proposed. Based on this method, a lightweight, multifunctional, and quantitative twelve-channel pipetting device was designed. This device can achieve simultaneous quantitative liquid absorption for twelve channels and sequential interval liquid discharge for each channel. Initially, the overall functional requirements were determined, and with the aim of a lightweight design, the total weight of the device was controlled to be within 580 g through a reasonable structural design, material selection, and choice of driving source. The device’s overall dimensions are 170 mm × 70 mm × 180 mm (length × width × height), with a micropipetting volume ranging between 1.3 $\mathrm{\mu }$L and 1.4 $\mathrm{\mu }$L. Subsequently, factors affecting liquid suction stability were experimentally analyzed, and appropriate pipetting parameters were selected. The stability performance of this pipetting method during prolonged operation was investigated. Finally, the twelve-channel pipetting device was validated through experiments, demonstrating results that meet the national standards for the stability of a pipetting device. In summary, the device designed in this study exhibits novel design features, low cost, and modularity, thus demonstrating promising potential for applications in high-speed micro-volume pipetting. Full article