Complex Matrix Systems Research Articles

Persistent Luminescence Lifetime-Based Near-Infrared Nanoplatform via Deep Learning for High-Fidelity Biosensing of Hypochlorite.

In light of deep tissue penetration and ultralow background, near-infrared (NIR) persistent luminescence (PersL) bioprobes have become powerful tools for bioapplications. However, the inhomogeneous signal attenuation may significantly limit its application for precise biosensing owing to tissue absorption and scattering. In this work, a PersL lifetime-based nanoplatform via deep learning was proposed for high-fidelity bioimaging and biosensing in vivo. The persistent luminescence imaging network (PLI-Net), which consisted of a 3D-deep convolutional neural network (3D-CNN) and the PersL imaging system, was logically constructed to accurately extract the lifetime feature from the profile of PersL intensity-based decay images. Significantly, the NIR PersL nanomaterials represented by Zn1+xGa2-2xSnxO4: 0.4 % Cr (ZGSO) were precisely adjusted over their lifetime, enabling the PersL lifetime-based imaging with high-contrast signals. Inspired by the adjustable and reliable PersL lifetime imaging of ZGSO NPs, a proof-of-concept PersL nanoplatform was further developed and showed exceptional analytical performance for hypochlorite detection via a luminescence resonance energy transfer process. Remarkably, on the merits of the dependable and anti-interference PersL lifetimes, this PersL lifetime-based nanoprobe provided highly sensitive and accurate imaging of both endogenous and exogenous hypochlorite. This breakthrough opened up a new way for the development of high-fidelity biosensing in complex matrix systems.

Simple, Visual, Point-of-Care SARS-CoV-2 Detection Incorporating Recombinase Polymerase Amplification and Target DNA-Protein Crosslinking Enhanced Chemiluminescence.

The ongoing COVID-19 pandemic, driven by persistent SARS-CoV-2 transmission, threatens human health worldwide, underscoring the urgent need for an efficient, low-cost, rapid SARS-CoV-2 detection method. Herein, we developed a point-of-care SARS-CoV-2 detection method incorporating recombinase polymerase amplification (RPA) and DNA-protein crosslinking chemiluminescence (DPCL) (RPADPCL). RPADPCL involves the crosslinking of biotinylated double-stranded RPA DNA products with horseradish peroxidase (HRP)-labeled streptavidin (SA-HRP). Modified products are captured using SA-labeled magnetic beads, and then analyzed using a chemiluminescence detector and smartphone after the addition of a chemiluminescent substrate. Under optimal conditions, the RPADPCL limit of detection (LOD) was observed to be 6 copies (within the linear detection range of 1-300 copies) for a plasmid containing the SARS-CoV-2 N gene and 15 copies (within the linear range of 10-500 copies) for in vitro transcribed (IVT) SARS-CoV-2 RNA. The proposed method is convenient, specific, visually intuitive, easy to use, and does not require external excitation. The effective RPADPCL detection of SARS-CoV-2 in complex matrix systems was verified by testing simulated clinical samples containing 10% human saliva or a virus transfer medium (VTM) spiked with a plasmid containing a SARS-CoV-2 N gene sequence or SARS-CoV-2 IVT RNA. Consequently, this method has great potential for detecting targets in clinical samples.

Influence of Pseudopotential Well Depth on the Performance of Hybrid Linear Ion Trap/Time-of-Flight Mass Spectrometry Driven by Square and Sinusoidal Waveform.

Quadrupole devices are widely used as ion analyzers and ion guides, which are usually driven by a sinusoidal waveform. Recently, these devices driven by a digital waveform have attracted much attention. Driven by different rf waveforms, the pseudopotential well depth of quadrupole devices is significantly different, which will affect their performance. However, there is a lack of comprehensive view on the performance differences of quadrupole devices or hybrid instrument driven by different rf waveforms. In this paper, the differences in mass range, resolution, sensitivity, and ion fragmentation of LIT/TOFMS driven by square and sinusoidal waveforms were investigated. Compared with the sinusoidal mode, the square mode had a wider mass range and better mass resolution. Toluene was used to study the difference in sensitivity and ion fragmentation between the two modes. The results showed that the sensitivity of the square mode was 1.7-2.5 times that of the sinusoidal mode at different ion densities. According to the sensitivity differences, it was inferred that the ion-trapping efficiency and ion capacity of LIT in the square mode were 2.0 times and 1.7 times those in sinusoidal mode. It was found that the square mode behaved "softer" and presented less fragmentation, and the proportion of fragment ions in the sinusoidal mode can reach 3.2 times that in the square mode at high ion density. Therefore, LIT/TOFMS driven by a square waveform shows greater potential in the application of the complex matrix system with a wide mass range.

DIFFERENT ULTRAVIOLET SPECTROSCOPIC METHODS: A RETROSPECTIVE STUDY ON ITS APPLICATION FROM THE VIEWPOINT OF ANALYTICAL CHEMISTRY

In routine practice, some simple and rapid analytical methods are needed for the assessment of formulations containing multiple elements, complex matrix system and for biotherapeutic products. There are several methods available for ultraviolet (UV) spectrophotometry that rely on the concept of absorbance difference, absorbance spectra, and additivity, also included in the list are simultaneous equation method, Q-absorbance ratio method, derivative spectrophotometry, ratio derivative spectra, successive ratio-derivative spectra, absorption and absorptivity factor method, and difference spectrophotometry along with multivariate chemometric methods. In this review, emphasis has been given to the theories, mathematical context, advantages, and disadvantages along with the vast applications of UV spectrophotometry. The findings further highlighted that for the analysis of drugs, UV spectrophotometry remains as one of the most simple, cheap, and promising option for routine practice in the field of pharmaceuticals.

Magnetic particle imaging of particle dynamics in complex matrix systems

Abstract Magnetic particle imaging (MPI) is a young imaging modality for biomedical applications. It uses magnetic nanoparticles as a tracer material to produce three-dimensional images of the spatial tracer distribution in the field-of-view. Since the tracer magnetization dynamics are tied to the hydrodynamic mobility via the Brownian relaxation mechanism, MPI is also capable of mapping the local environment during the imaging process. Since the influence of viscosity or temperature on the harmonic spectrum is very complicated, we used magnetic particle spectroscopy (MPS) as an integral measurement technique to investigate the relationships. We studied MPS spectra as function of both viscosity and temperature on model particle systems. With multispectral MPS, we also developed an empirical tool for treating more complex scenarios via a calibration approach. We demonstrate that MPS/MPI are powerful methods for studying particle-matrix interactions in complex media.

On-line Identification of chiral ofloxacin in milk with an extraction/ionization device coupled to Electrospray Mass Spectrometry

The direct separation and analysis of chiral drugs in the complex matrix systems are meaningful and challenging. As the most common broad-spectrum antibiotic, levofloxacin has a strong antibacterial ability, but its enantiomer, dextrofloxacin can cause serious harm to human health. In this work, we reported a rapid on-line extraction/ionization device coupled with Electrospray Mass Spectrometry (ESI-MS) for chiral analysis of ofloxacin enantiomers in complex matrix of milk. Since ofloxacin is difficult to dissolve in water and most organic solvents, the procedure of separating ofloxacin in complex system is often complicated. Using the homemade apparatus, the sample pretreatment process was greatly simplified. Milk sample was directly injected and chiral ofloxacin in the sample was extracted at PTFE membrane for further ionization. It took less than 10s to finish all the procedures including sampling, extraction, reagents mixing, ionization and mass analysis. Utilizing reaction thermodynamics method, trimeric cluster ion [NiΙΙ(ref)2Ofloxacin-H]+ was formed and collisionally dissociated to get chiral resolution of levofloxacin and dextrofloxacin due to the different relative stabilities of the two diastereomeric clusters produced through the dissociation of NiΙΙ bound trimeric clusters. With the proposed method, qualitative and quantitative chiral analysis of ofloxacin in milk was successfully achieved in a simple and fast way.

TRAX: An approach for the time rational analysis of complex dynamic systems

SummaryThis paper introduces a theoretical and algorithmic reduced model approach to efficiently evaluate time responses of complex dynamic systems. The proposed approach combines four main components: analytical expressions of the average of the system's transfer functions in the frequency domain, precise and convergent rational approximations of these exact expressions, exact evaluation of these approximations through model reduction in rational Krylov subspaces and semi‐analytical interpolation at just a few frequency points. The resulting algorithmic principles to evaluate the time response of a particular system are relatively straightforward: one first evaluates the response of the system with slight additional damping at a few frequencies and one then projects or reduces the system in the subspace spanned by these responses. The time response of the reduced model implicitly provides a precise evaluation of that of the original system. The properties of the reduced models and the precision of the proposed approach are studied, and applications on complex matrix systems are presented and discussed. While the theory and numerical algorithms are presented in a matrix context, they are also transposable in a continuous functional context. Copyright © 2015 John Wiley & Sons, Ltd.

An oral controlled release system for amroxol hydrochloride containing a wax and a water insoluble polymer

This study was carried out to develop and optimize oral sustained-release formulations for Ambroxol hydrochloride matrix pellets using a combination of wax and water-insoluble polymer, glyceryl behenate (Compritol 888 ATO) and Ethylcellulose (EC7 FP). It involved three factors: the content of Compritol 888 ATO (X1), EC7 FP (X2), and the matrix formation methods (X3), as independent variables. The drug release percentages at 1, 2 and 4 h were the target responses and were restricted to 15–45% (Y1), 45–80% (Y2) and 80–100% (Y3), respectively. The final blend formulation prepared by extrusion spheronization, was achieved with 27.00% (w/w) Ambroxol hydrochloride, 48.70% (w/w) Compritol 888 ATO, and 24.30% (w/w) EC7 Fp with 40°C for 12 h. Comparing the single matrix materials consisting of just the wax or water-insoluble in the complex matrix system containing wax and water-insoluble polymer, the release of the drug can be far more retarded, when the formulations have undergone the process of heat treatment. Furthermore, the combination of the two polymers, with flexible matrix formation methods, will offer a very promising way of producing matrix pellets instead of coated controlled-release pellets to meet various demands of drug release.

NIR spectroscopy—a non-destructive analytical tool for protein quantification within lipid implants

Lipid implants have been proposed as promising sustained release devices for the parenteral application of pharmaceutical proteins. Near infrared spectroscopy (NIRS) has been reported in the literature to be a non-destructive tool for drug quantification within controlled release matrix systems based on poly-(lactic-co-glycolic) acid (PLGA). The objective of this study was to evaluate the potential application of NIRS for protein content determination within lipid matrices containing stabilizing and release modifying additives. Bovine serum albumin (BSA) and rh-interferon α-2a (IFN α-2a) were initially lyophilized with trehalose and then blended with tristearin (matrix material) and optionally with polyethylene glygol 6000 (PEG, release modifier). Implants were prepared by compression. NIR transmittance spectra were measured on a NIRTab® spectrometer. Partial least squares regression (PLSR) calibration models were developed to predict protein content in implants from the NIRS results. Additional samples were measured after performing release studies. It could be shown that NIRS allowed protein quantification in complex matrix systems with good accuracy after implant manufacture and during release studies [e.g., standard error of prediction (SEP) between 57 μg–176 μg]. In addition, small protein amounts down to 70 μg of incorporated protein per implant could be determined, thus demonstrating the low detection limit of NIRS.

Diffusion Transport Properties of Polymeric Complex Matrix Systems Based on Eudragit E and Sodium Alginate

The search for new polymeric carriers intended for the development of controlled-release drugs is of considerable importance for the pharmaceutical science and technology. A promising basis for solving this task is offered by so-called interpolyelectrolyte complexes (IPCs). The unique properties of these compounds established as a result of extensive physicochemical investigations allowed them to be considered as a special class of polymeric carriers. IPCs are synthesized via interaction of two oppositely charged polyelectrolytes: polycations and polyanions [1]. According to published data, IPCs used as drug carriers possess unique diffusion transport characteristics. This is related to the advantageous structure of IPCs, which can be modified in a controlled manner through modification of the macromolecular parameters of the polymeric components of IPCs [2 – 4]. Taking into account these advantages of IPCs (which provide for the possibility of solving almost any problem encountered in the creation of peroral drugs), we have studied the most frequently applied polymers produced by Roehm Pharma (Germany) on the basis of copolymers of acrylic acid (AA) and poly(methyl methacrylate) (PMMA) under the trade name Eudragit. Taking into account that these copolymers are polyelectrolytes, we attempted to modify the Eudragit structure by including it into an ICP with an oppositely charged polymer. As a result, we obtained new IPCs based on the gastrosoluble component Eudragit E (polycation) and the natural polysaccharide sodium alginate (Na-AL) (polyanion). Preliminarily, we have studied the conditions of formation of polymeric complexes based on the selected pair of polyelectrolytes. We used the methods of turbidimetric titration, viscometry, elemental analyses (for determining the composition of IPCs), and IR and differential scanning calorimetry (for determining the structure of complexes). This paper reports on the results of investigation of the diffusion transport properties of Eudragit E100sodium

Condensing structural finite-element meshes into coarser acoustic element meshes

One method for computing the sound power radiated by a structure is to perform a finite-element analysis of the structural vibrations and a boundary element analysis of the radiated acoustic field. Both analyses are valid in the low- to mid-frequency range and standard implementations require six elements per wavelength. In many cases of practical interest, the structural wavelengths are much smaller than the acoustic, and, thus, using the same mesh for both analyses results in an overly refined acoustic mesh. The extra refinement results in considerable computational expense in the acoustic analysis because the time required to solve the fully populated, complex matrix system depends on the number of unknowns cubed. Here, it is shown that the efficiency of the acoustic analysis can be significantly increased by constructing the acoustic element mesh from conglomerations of structural elements. Two methods are suggested for deriving the basis functions for the acoustic field, and the accuracies of both methods are assessed. A simple analysis of the computation times is given, and the predicted reductions in the times are verified through several example problems. Overall, the results demonstrate that the condensation can dramatically reduce the computation times without significantly altering the solution accuracies.

Finite element analysis of diffusional drug release from complex matrix systems.: II. Factors influencing release kinetics

This work concentrated on the analysis of several factors influencing the kinetics of diffusional drug release from complex matrix devices, such as convex tablets and rings, into a finite volume. These factors include initial drug concentration distribution, anisotropic matrix, and time- and concentration-dependent diffusion coefficients. The individual and comprehensive effects of these factors on the release kinetics were investigated by the finite element method. Errors introduced by neglecting drug diffusion through the ends or edges of cylindrical devices were estimated by comparison of the 1-D models with the 2-D cylinder model. The influence of side-wall coating on the accuracy of the prediction of release profiles by the 1-D slab model for cylindrical devices was studied using various coating materials of different permeabilities. The analyses carried out in this work could assist the design of the complex matrix systems required for controlled drug release.

Finite element analysis of diffusional drug release from complex matrix systems. I.: Complex geometries and composite structures

The finite element method (FEM) was applied to the problems of diffusion-controlled drug release from complex matrix systems. These systems consisted of complex geometries and composite structures with various boundary conditions. The finite element procedures were first verified using analytical solutions for simple geometries, i.e., spherical, planar, and cylindrical geometries, under the perfect sink condition and in a well-stirred finite volume. The finite element solutions agreed very well with the exact solutions. The procedures were then used to analyze drug release into a finite volume from matrix devices of complex geometries including a convex tablet, a hollow cylinder, a doughnut-shaped ring, and an inward-release hemisphere. The effect of mixing on the release kinetics was studied by comparison of release profiles in a well-stirred finite volume with those in a poorly-stirred finite volume. Variation of drug concentration distribution with time within the matrix devices and in the dissolution medium was illustrated. The effect of composite structure on the release kinetics was also investigated using the devices made of two or more materials, such as composite pessaries, coated elastomer rings, and multi-layered tablets.

Acoustic scattering of a plane wave by two spherical elastic shells above the coincidence frequency

The acoustic scattering by two fluid-filled spherical elastic shells in close proximity to each other and insonified by plane waves at arbitrary angles of incidence is analyzed exactly in the frequency range that includes the midfrequency or coincidence enhancement region of the backscattered echoes. The incident and scattered wave fields are expanded in terms of the classical modal series and the addition theorem for the spherical wave functions is used to determine the exact expression for the sound fields scattered by each spherical elastic shell in the presence of the other, referred to coordinate systems at the centers of either spherical shell. The solution to the scattering problem is found by simultaneously solving the Helmholtz equations governing the wave motion in the fluid medium in which the two shells are submerged as well as in the fluid media contained in the shells, together with the two sets of equations of motion of the two elastic shells obtained from the complete three-dimensional elasticity theory after satisfying the boundary conditions at all fluid-shell interfaces as well as the far-field radiation condition. Again, the numerical computation of the scattered pressure wave involves the solution of a truncated ill-conditioned complex matrix system the size of which depends on how many terms of the modal series are required for convergence. This in turn depends on the value of the frequency, and on the proximity of the two spherical elastic shells. The ill-conditioned matrix equation is solved using the Gauss–Seidel iteration method. Backscattered and bistatic echoes from two identical spherical elastic shells are extensively calculated. The result also exhibits the large enhancement present in the backscattered echoes for the endfire situation after the midfrequency or coincidence enhancement has taken place. This can be attributed to the effects of focusing by the front elastic shell and to the reflection and refocusing by the back elastic shell of the a0 Lamb wave reradiation in the observer’s direction.

Scattering of a plane acoustic wave by a spherical elastic shell near a free surface

The acoustic scattering by a submerged spherical elastic shell near a free surface, which is insonified by plane waves at arbitrary angles of incidence is analyzed in an exact fashion using the classical separation of variables technique. To satisfy the boundary conditions at the free surface as well as on the surface of the spherical elastic shell, the mathematical problem is formulated using the image method. The scattered wave fields are expanded in terms of the classical modal series of spherical wave functions utilizing the translational addition theorem. Quite similar to the problem of scattering by multiple spheres, numerical computation of the scattered wave pressure involves the solution of an ill-conditioned complex matrix system the size of which depends on how many terms of the modal series are required for convergence. This in turn depends on the value of the frequency, and on the proximity of the spherical elastic shell to the free surface. The ill-conditioned matrix equation is solved using the Gauss-Seidel iteration method and Twersky's method of successive iteration cross checking each other. Backscattered echoes from the spherical elastic shell are extensively calculated and displayed. The result also demonstrates that the large amplitude low frequency resonances of the echoes of the submerged elastic shell shift upward with proximity to the free surface. This can be attributed to the decrease of added mass for the shell vibration. The present benchmark solution could eventually be used to validate those found by numerical schemes.

Acoustic scattering of a plane wave by two spherical elastic shells

The acoustic scattering by two spherical elastic shells in close proximity insonified by plane waves at arbitrary angles of incidence is analyzed exactly in the low- and intermediate-frequency ranges. The incident and scattering wave fields are expanded in terms of the classical modal series and the addition theorem for the spherical wave functions facilitates the exact expression of the sound fields scattered by each spherical elastic shell in the presence of the other, referred to coordinate systems at the centers of either spherical shell. The solution to the scattering problem is obtained by simultaneously solving the Helmholtz equation governing the wave motion in the fluid medium in which the two shells are submerged and the two sets of equations of motion of the two elastic shells satisfying the boundary conditions at all fluid–shell interfaces and the far-field radiation condition. Numerical computation of the scattered wave pressure involves the solution of the truncation of an ill-conditioned complex matrix system the size of which depends on how many terms of the modal series are required for convergence. This in turn depends on the value of the frequency, and on the proximity of the two spherical elastic shells. The ill-conditioned matrix equation is solved using the Gauss–Seidel iteration method and Twersky’s method of successive iteration double checking each other. Backscattered echoes from two identical spherical elastic shells are extensively calculated. The result also demonstrates that the large amplitude low-frequency resonances of the echoes of the neighboring elastic shells shift downward with proximity to each other. This can be attributed to the increase of added mass for the vibration of the shells.

The exact sonar cross section of an elastic spherical shell near the sea surface

The acoustic scattering by a submerged spherical elastic shell near a free surface and insonified by plane waves at arbitrary angles of incidence is analyzed in an exact fashion by the classical separation of variables method. To satisfy the boundary conditions at the free sea surface, as well as on the surfaces of the elastic shell, the mathematical problem is formulated using the method of images. The scattered wave fields are expanded in terms of spherical wave functions using the addition theorems. The final results come out in terms of Wigner 3‐j symbols or Clebsch–Gordan coefficients. Quite similar to the problem of scattering by multiple spheres, the computation of the scattered pressure field involves the solution of an ill‐conditioned complex matrix system, of size that depends on the number of terms in the modal series required for convergence. This, in turn, depends on the value of the frequency and on the proximity of the steel shell to the free surface. The matrix equation is solved by the Ga...

Exact analysis of the acoustic scattering by an arbitrarily insonified spherical body near a flat boundary

The acoustic scattering by spherical bodies (hard, soft, or elastic) near flat boundaries (hard or soft) insonified by plane waves at arbitrary incident angles is analyzed exactly in the low and intermediate frequency ranges. To satisfy the boundary conditions at the flat boundary as well as on the surface of the sphere, the mathematical problem is formulated using the image technique. The scattering wave fields are expanded in terms of the classical modal series of spherical wave functions utilizing the translational addition theorem. Quite similar to the problem of multiple scattering by spheres, numerical computation of the scattered wave pressure involves the solution of an ill-conditioned complex matrix system the size of which depends on how many terms of the modal series are required for convergence. This in turn depends on the value of the frequency, the proximity of the spherical body relative to the flat boundary and the incident angle. The ill-conditioned matrix equation can be solved using the Gauss–Seidel iteration method and back scattered echoes from the spherical bodies are extensively calculated. [Work supported by the NSWC Independent Research Program.]

Finite Element Analysis of Lossy Waveguides-Application to Microstrip Lines on Semiconductor Substrate

The development of Maxwell's equations is made considering the electromagnetic fields as vector distributions. With the aid of the finite element method, an analysis of lossy shielded inhomogenous waveguides of arbitrary shape is described. To solve the complex matrix system an iterative procedure is presented. The method is applied to study the propagation on MIS or Schottky contact microstrip lines.

Prospective applications of calorimetry in the clinical laboratory.

Calorimetric analysis depends on the direct proportionality between the heat changes that occur during chemical reactions and the amount of reacting substances. Potential uses of calorimetry in the clinical laboratory are discussed, with examples. The calorimetric technique does not require optically clear specimens, and if the specificity of the measured reaction is assured, calorimetry can be used for quantitative determinations of components that are present in a complex matrix system such as body fluids. Specific enzymic reactions have been used to measure substrates and enzyme activities in biological specimens calorimetrically, with precision, sensitivity, and accuracy comparable to routine photometric techniques. The application of calorimetry in the clinical laboratory is limited now by its slowness, but development of automated instruments may enable the technique to become competitive with conventional analytical techniques in the clinical laboratory.