Gradient Profile Research Articles

Altered RBC deformability in diabetes: clinical characteristics and RBC pathophysiology

BackgroundReduced red blood cell deformability (RBCD) is associated with diabetic vascular complications, but early pathophysiological RBC changes and predictive demographic and clinical factors in populations with diabetes are unclear. An understanding of early diabetes-specific RBC changes associated with impaired RBCD is essential in investigating mechanisms that predispose to diabetic vascular complications.MethodsWe conducted an outpatient cross-sectional study of participants in a well-controlled diabetes cohort (N81) and nondiabetic controls (N78) at the National Institutes of Health. First, between-group differences in RBCD measures were assessed with shear stress-gradient ektacytometry. Differences in structural RBC parameters were assessed using osmotic gradient ektacytometry and NaCl osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation: p50.ResultsAll shear-stress gradient RBCD measures were significantly altered in the diabetes cohort vs. nondiabetic controls, even after adjustment for confounding covariates (p < 0.001). Adjusted for diabetes-status and demographic factors, significant predictors of reduced RBCD included older age, Black race, male gender, hyperglycemia, and vascular complications (all p < 0.05). Reduced RBCD was also associated with aberrant osmotic-gradient parameters, with a left-shift on osmotic gradient profile indicative of dehydrated RBCs in diabetes. A structure-function relationship was observed with reduced RBCD associated with reduced osmotic fragility (P < 0.001) and increased hemoglobin-oxygen dissociation (P < 0.01).ConclusionsFindings suggest impaired RBCD incurs similar demographic and clinical risk factors as diabetic vascular disease, with early pathophysiological RBC changes indicative of disordered RBC hydration in diabetes. Findings provide strong evidence for disordered oxygen release as a functional consequence of reduced RBCD.Clinical trial number: NCT00071526.

Paper Spray Ionization Mass Spectrometry Coupled with Paper-Based Three-Dimensional Tumor Model for Rapid Metabolic Gradient Profiling.

The tumor microenvironment (TME), especially with its complicated metabolic characteristics, will dynamically affect the proliferation, migration, and drug response of tumor cells. Rapid metabolic analysis brings out a deeper understanding of the TME, while the susceptibility and environmental dependence of metabolites extremely hinder real-time metabolic profiling since the TME is easily disrupted. Here, we directly integrated paper spray ionization mass spectrometry with a paper-based three-dimensional (3D) tumor model, realizing the rapid capture of metabolic gradients. The entire procedure, from sample preparation to mass spectrometry detection, took less than 4 min, which was able to provide metabolic results close to real time and contributed to understanding the real metabolic processes. At present, our method successfully detected 160 metabolites; notably, over 40 significantly gradient metabolites were revealed across the six layers of the paper-based 3D tumor model. At least 22 gradient metabolites were reported to be associated with cell viability. This strategy was powerful enough to rapidly profile metabolic gradients of a paper-based 3D tumor model for revealing cell viability changes from a metabolomics perspective.

Importance estimate of features via analysis of their weight and gradient profile

Understanding what is important and redundant within data can improve the modelling process of neural networks by reducing unnecessary model complexity, training time and memory storage. This information is however not always priorly available nor trivial to obtain from neural networks. There are existing feature selection methods which utilise the internal working of a neural network for selection, however further analysis and interpretation of the input features’ significance is often limiting. We propose an approach that offers an extension that estimates the significance of features by analysing the gradient descent of a pairwise layer within a model. The changes that occur with the weights and gradients throughout training provide a profile that can be used to better understand the importance hierarchy between the features for ranking and feature selection. Additionally, this method is transferable to existing fully or partially trained models, which is beneficial for understanding existing or active models. The proposed approach is demonstrated empirically with a study which uses benchmark datasets from libraries such as MNIST and scikit-feat, as well as a simulated dataset and an applied real world dataset. This is verified with the ground truth where available, and if not, via a comparison of fundamental feature selection methods, which includes existing statistical based and embedded neural network based feature selection methods through the methodology of Reduce and Retrain.

Impact of Brownian motion and thermophoresis in magnetohydrodynamic dissipative: Radiative flow of chemically reactive nanoliquid thin films on an unsteady expandable sheet in a composite media

AbstractThis study comprehensively examines magnetohydrodynamic heat transport characteristics within a thin nanofluid film on a stretchable sheet embedded in a composite medium. By considering factors such as the unsteady nature of sheet velocity, Brownian motion, thermophoresis, thermally radiative heat, irregular heat generation/sink, chemical reactions, and dissipation due to viscous fluid, the research provides valuable insights into the variations in fluid velocity, temperature, and nanoparticles concentration. The computational solution utilizes the efficient numerical method that enables accurate predictions of system behavior under varying conditions. Notable findings include the influence of Schmidt numbers on nanoparticle concentration distribution, the opposing impact of thermophoresis parameter values, and the influence of Brownian motion and heat source/sink on temperature profiles in thin nanofluid film. Also, nanoliquid film thickness is reduced by enhancing the porous parameter values and Hartmann number values. The nanoliquid film becomes thinner when the space‐dependent heat source/sink parameter is considered compared to the temperature‐dependent heat source/sink coefficient. In space‐dependent and temperature‐dependent cases, the increase in these parameters leads to a decrease in the temperature gradient. Furthermore, it is observed that higher thermophoresis values correspond to reduced nanoparticle concentration gradient profiles. Also, enhancement in the chemical reaction values leads to an expansion in the solutal boundary region surrounding nanoparticles, and as a consequence, the concentration gradient of nanoparticles is enhanced. This research has significant potential for optimizing heat performance and advancing innovation in industrial and engineering processes.

B-155 Analysis of Monoclonal Antibodies Using a Quantification LC-MS/MS Kit - Spotlight on Infliximab

Abstract Background The use of immunoassays for measuring mAbs is well established but has some limitations, including poor performance, lack of standardization, a high cost when processing a limited number of samples, limited dynamic range, and the potential for cross-reactivity. Using LC-MS/MS associated with the ready-to-use commercial mAbXmise Kit is a simple way to implement mAbs measurement for infliximab, providing high analytical performance, ease of use, and flexibility. Methods The Promise Proteomics Inflammation mAbXmise Kit contains all the calibrators, QCs, internal standard and sample preparation consumables to run the LC-MS/MS method for infliximab. Briefly, 20µL samples are dispensed into the mAbXmise plates containing lyophilized stable labelled infliximab. Samples are transferred to the PuriXmise plate to perform the immunocapture of infliximab and allow washing of the samples. Samples are eluted into a collection plate, evaporated to dryness, resuspended, and the protease (CutXmise) is added to the sample to digest infliximab overnight. The digestion is quenched, with the samples immediately ready for analysis. Using an ACQUITY™ UPLC™ I-Class PLUS FL System, samples were injected onto a Waters™ XSelect™ Premier HSS T3 Column, eluted using a water/acetonitrile/formic acid gradient profile and quantified with both a Waters Xevo™ TQ-XS and Xevo TQ-S micro Mass Spectrometer. Results The method was shown to be linear from 2 - 100 µg/mL. Analytical sensitivity at lowest calibrator of 2µg/mL provided S/N (PtP) ≥15:1 for all tryptic peptides on both mass spectrometers. Coefficients of variation (CV) at 4 and 25µg/mL QC concentrations were all ≤ 10.0% (n = 5). The relative concentrations of the tryptic peptides were compared across 29 anonymized samples and good agreement was observed for GLE, SAV, DIL and ASA peptides. Conclusions We have demonstrated a clinical research method for quantifying Infliximab in plasma using a commercially available kit for sample preparation followed by LC-MS/MS analysis. The Promise Proteomics mAbXmise Kit aids in the day-to-day reproducibility of the immunocapture and tryptic digestion of IFX for targeted LC-MS/MS analysis with the correct peptide selection. Compared to a direct digest surrogate peptide workflow, the process used in the kit reduces matrix interference, improves analytical sensitivity, and enables the use of lower sample volumes. The method can be run on both the Xevo TQ-XS and Xevo TQ-S micro Mass Spectrometers which provide the dynamic range to quantify IFX across the expected range, and the selectivity and analytical sensitivity to obtain low-level quantification of the IFX surrogate peptide in plasma samples. The data presented combines the use of a kit dedicated to the preparation of samples and the use of liquid chromatography and mass spectrometry instrumentation to perform the quantitative analyses. The mAbXmise Kit described has not been cleared by any regulatory entity for diagnostic purposes outside of Europe. Analytical performance depends on the instrument characteristics and its settings. The end user is responsible for completion of the method development and validation. Proteomics mAbXmise Kits are not available for sale in all countries. For Research Use Only. Not for use in diagnostic procedures.

A study on the influence of material gradient index on bending and stress responses of FGM rectangular plates using the Finite Element Method

Functionally graded materials (FGMs) are advanced materials designed to achieve specific property gradients. The unique characteristic of these materials—variations in spatial dimensions—allows for integrating the advantages of different materials within a single component, where a combination of properties, such as mechanical strength, thermal resistance, and others, is needed. This paper utilizes finite element analysis to examine the deflection and stress responses of FGM rectangular plates with different material gradient profiles. Various boundary conditions, including clamped, simply supported, and free edges in different configurations, are considered. The plates are subjected to uniformly distributed, sinusoidally distributed, and concentrated loads. The study investigates the effects of boundary and loading conditions, along with the impact of the material gradient, on the deflections and stress responses of FGM rectangular plates. The results indicate variations in deflection and stress values for different material gradients, under varying boundary and loading conditions.

Flexural wave compression behaviors of programmable graded piezoelectric meta-beams

Active electromechanical metamaterials have drawn significant attention due to their remarkable tunability and adaptability in vibration and wave control. Exploiting the electromechanical coupling effect via controlled biased fields enables precise manipulation of the structural vibrations and wave transmissions. In this research, we have developed a programmable graded piezoelectric meta-beam that successfully imitates the wave compression behavior of an acoustic black hole without modifying the structural geometries. The effective parameters of the meta-beam are reshaped into a gradient distribution by tuning the electrical impedances of the digital shunting circuits. With such graded effective parameters, it becomes feasible to tailor the local wavenumber distribution of the meta-beam and hence achieve the desired wave compression. Numerical results validated our proposed paradigm of the programmable black hole in both straight and curved beams. In contrast to the straight beam, curvature of the curved beam reduces the tunable range of the local wavenumber. A comprehensive parametric study was conducted to investigate the influences of the gradient profile, electric damping, and curvature on the wave control function. For a given desired frequency, programmable control of wave compression location and amplified output of electrical signals are achieved.

Application of Deep Learning to Optimize Gradient Porosity Profile for Improved Energy Density of Lithium-Ion Batteries

Lithium-ion batteries with high active material loading can yield a high energy density at low C-rates. However, the sluggish ion transport caused by longer and more tortuous pathways hinders high energy delivery when extracting high power. This study presents the implementation of neural networks to optimize the gradient active material distribution profile throughout the thickness of electrodes to enhance energy density. The profiles were randomly generated, while maintaining a constant average active material in each electrode. An electrochemical–thermal model was used to investigate the impact of different profiles. A neural network model was then developed to establish the connection between the profiles and the resulting energy density for various electrode thicknesses and C-rates, utilizing a limited amount of simulation data. The neural network model could replicate the performance of the electrochemical–thermal model, but with significantly reduced computational time. This enabled the possibility of efficiently exploring a vast number of candidate profiles to identify the most optimal one for each of the positive and negative electrodes. The results showed that the gradient profiles were mostly influenced by the average active material, rather than the thickness of the electrode. Finally, at high currents, the optimal gradient profiles increased the energy density by over four times compared to uniform electrodes.

Study of Dependence of the Energy of the Field in Weakly Conductive Fiberlight-Guide with Gradient Refractive Index Profile Without Regard to Polarization

A round-in-cross-section weakly guiding fiber optic light guide is considered. The system of Maxwellian equations for electrically conductive transparent media without due regard to polarization with an index of refraction in the case under consideration is reduced to the homogeneous Helmholtz equation, a particular solution of which is found using the Green's function. For a unimodalmode a common decision was obtained for the field and energy inside the fiber in the general case of a gradient refractive index profile depending on the radial coordinate. The concept of normalized energy is introduced as the ratio of the energy inside a fiber with gradient refractive index profile to the energy inside a fiber with a step-index profile. Since in a single-mode regime the zero-order Bessel function, which describes the field inside a step-index profile fiber, can be replaced by a Gaussoid, then, when extending this replacement to the case of a single-mode gradient fiber, as a first approximation we shall obtain a finite expression for the normalized energy for a general gradient profile. The dependences of the normalized energy on the waveguide number were obtained for each of the degrees from the first to the fourth inclusive. It is shown that in the considered approximation, the energy increases up to a certain parameter values (for the first degree – a triangle profile) or slowly decreases (other profiles), after this value the energy increases for all profiles. The results obtained will help to select a suitable single-mode fiber for practical application.

Are the Carpathians tectonically active?: Geomechanical study in deep boreholes in the outer Carpathians (Poland)

Present-day tectonic stress state was investigated in three deep boreholes located in the eastern segment of the Polish Outer Carpathians (POC). Significant rotations of the maximum horizontal stress (SH) were observed in these boreholes, located at the hinge of the anticlines in the upper part of the nappes. For the deepest borehole, D-1 (5.5 km depth), 1D geomechanical modelling was performed to determine the stress gradient profiles. An optimal solution of the model, validated by numerous compressional and extensional failures (breakouts and drilling-induced fractures, respectively) of the borehole wall, was obtained for variable elastic horizontal strain. The strain varies stepwise across the Main Thrust Fault (MTF) and linearly within its walls. The dominance of a strike-slip faulting stress regime was determined for the Carpathian nappes, with contributions from thrust faulting above the MTF and normal faulting below the MTF. A critical stress state for reactivation of preferentially oriented pre-existing faults and fractures was inferred for the competent strata. A consistent interpretation of the variations in stress orientation and magnitude, suggests a contemporary refolding of the anticline at a shallower structural level, enhanced by the reactivation of the MTF and a lack of reactivation of the Carpathian Bottom Thrust. Integration of these results with measurements from previous studies in the eastern segment of the POC indicates a different regional orientation of SH in the autochthonous basement (N-S) and in the nappes (NE-SW). These results indicate a thin-skinned compressive reactivation of the upper part of the accretionary wedge, with the lower part of the nappes remaining passive, or locally prone to minor strike-slip or normal faulting. These results contradict the hypothesis of a contemporaneous extensional collapse of the POC.

Design of a metalens for beam collimation and angular amplification in optical phased array devices

We present an analytical design for increasing the beam sharpness (collimation) and field of view (FOV) of an optical phased array (OPA) device. In this work, a cylindrical metalens is used for collimation, while a set of metalens, with both concave and convex phase profiles, are incorporated to increase the FOV. Following the generalized vector law of reflection or refraction, the trajectories of the reflected or transmitted rays corresponding to the phase profile of phase gradient metasurfaces/metalens are obtained. Through the ray tracing method, the elliptical beam from the OPA device with a vertical beam (fast axis) width of 21 mm was collimated to a sharp spherical beam of width 1.5 mm by a metalens with a cylindrical phase profile. In addition, the incorporation of angular amplifier metalens with a 64-channel OPA device has shown an increased in FOV by almost threefold i.e., from 15 o to 41.96 o . Our results suggest that the use of metasurfaces/metalens can enhance the quality of output beam and provide significant advantages for compact on-chip integration with OPA devices in solid-state LiDAR applications.

Variable viscosity characteristics of two-layered isothermal calendering phenomena with non-Newtonian fluids

Two-layer calendering using non-Newtonian fluids is used frequently in different industries to improve the working and the quality of the products. In this article, two-layer calendering of incompressible non-Newtonian fluids, that is, couple stress fluid and viscoplastic fluid in the upper and lower layer respectively is investigated. For the simplified governing equations, Lubrication approximation theory is applied. By the use of no-slip condition and non-dimensional variables, the exact solution for pressure gradient, pressure, and velocity profiles for both layers of fluid is calculated. The parameters are important from an engineering point of view like roll separating force, power delivered by rollers, torque acting by each roller, and adiabatic temperature are also calculated analytically. Additionally, the results of a couple stress parameter, viscoplastic Casson parameter, and viscosity ratios on all the parameters are also discussed and investigated in detail. Moreover, all the effects investigated are also verified with the literature results of single-layer calendering of non-Newtonian fluids by using large numeric values for the couple stress parameter and viscoplastic Casson parameter.

A computational investigation for heat and fluid transport with electro-osmosis phenomenon in a scraped surface heat exchanger

Scraped surface heat exchangers (SSHEs) have prominently shown their eminence in various food, chemical and in pharmaceutical industries when the regular processing of fluids and pertinent materials is encountered. The heat transfer analysis of Williamson fluid flow with electro osmotic effects in a narrow-gap SSHE is designed by implementing constant temperature difference between the gaps of the rotor and the stator. A fluid model is established by using lubrication approximation theory and Debye-Huckel simplifications. The computational solution is elaborated by implementing renowned BVP4C technique in MATLAB. Exact solution of Poisson-Boltzmann equation for different scenarios of SSHE is gathered, whereas solution for velocity, stream functions and temperature in various parts of SSHE are explored computationally. Impact of various crucial physical flow parameters like, Weissenberg number, mobility of the medium number, electro osmotic parameter on the velocity profile, stream function, temperature profile, and pressure gradient has been explored graphically. The numerical solution is compared with artificial neural network (ANN) and an absolute alignment of BVP4C solution is observed with ANN solution. It is reported that fluid flow is lifted with enhancing the viscoelastic behavior and exhibits dual behavior for electroosmosis phenomenon and mobility of medium parameter. Also, it is seen that temperature of the fluid is significantly declines with Weissenberg number and is surges with enhancing mobility of medium and Brinkman number. By increasing the Brinkman number conduction phenomenon is slow down and heat produced due to viscous dissipation, raises the temperature of the fluid. The viscoelastic effect could be of enormous significance in applications, like Polymer processing in certain heat exchangers, and in mixing and blending foodstuffs etc.

Analysis of Gradient Profiles and Morphology of the Vela Jr. Supernova Remnant

Analysis of Gradient Profiles and Morphology of the Vela Jr. Supernova Remnant

Velocity-compensated intravoxel incoherent motion of the human calf muscle.

To determine whether intravoxel incoherent motion (IVIM) describes the blood perfusion in muscles better, assuming pseudo diffusion (Bihan Model 1) or ballistic motion (Bihan Model 2). IVIM parameters were measured in 18 healthy subjects with three different diffusion gradient time profiles (bipolar with two diffusion times and one with velocity compensation) and 17 b-values (0-600 s/mm2) at rest and after muscle activation. The diffusion coefficient, perfusion fraction, and pseudo-diffusion coefficient were estimated with a segmented fit in the gastrocnemius medialis (GM) and tibialis anterior (TA) muscles. Velocity-compensated gradients resulted in a decreased perfusion fraction (6.9% ± 1.4% vs. 4.4% ± 1.3% in the GM after activation) and pseudo-diffusion coefficient (0.069 ± 0.046 mm2/s vs. 0.014 ± 0.006 in the GM after activation) compared to the bipolar gradients with the longer diffusion encoding time. Increased diffusion coefficients, perfusion fractions, and pseudo-diffusion coefficients were observed in the GM after activation for all gradient profiles. However, the increase was significantly smaller for the velocity-compensated gradients. A diffusion time dependence was found for the pseudo-diffusion coefficient in the activated muscle. Velocity-compensated diffusion gradients significantly suppress the IVIM effect in the calf muscle, indicating that the ballistic limit is mostly reached, which is supported by the time dependence of the pseudo-diffusion coefficient.

Stabilization of magneto-Rayleigh-Taylor instability with non-uniform density and magnetic field profiles in Cartesian Geometry

Managing the Rayleigh–Taylor instability growth rate is one of the main challenges in inertial fusion. Among the proposed methods to tackle this issue, the application of a pre-embedded axial magnetic field and plasma density gradient of layers can be mentioned. Recent experimental evidence in Z-pinch devices shows that it is possible to suppress the growth rate of the Rayleigh-Taylor instability by applying a power law density gradient profile with exponent 2. In this work, in the framework of Cartesian coordinates, for a confined plasma between two fixed planes, the dispersion relation of a magnetized plasma has been obtained using linearization of the ideal MHD equations. Here, plasma with a power-law density profile of ∝r3 and magnetic field with the exponential profile is used. It is shown that for the relative strength of the magnetic field with a value of, ωf*=0.4 and more, the growth rate of instability appears only in a limited range of the range of reduced wave numbers, k*. By increasing this ratio, stability conditions are much improved. On the other hand, recent experimental studies show that self-generated plasma rotation is produced in an imploding Z-pinch device with an initial axial magnetic field. In the second part, the effect of plasma rotation on plasma stability conditions is investigated. Again, a new dispersion relation of the rotating magnetized plasma was derived. It is shown that in the non-magnetized case, a large relative angular velocity, Ω, is necessary to suppress the instability. However, for relative magnetic field strength, ωf*=0.4 and more, stable conditions can be achieved with a relatively lower angular velocity of about 5.

Simulation of triggering and evolution of ELM by pellet injection in EAST under BOUT++ framework

A BOUT ++ three-field magnetohydrodynamic model is employed to study the triggering and evolution of edge localized mode (ELM) by Li pellets injected along the outer mid-plane in the EAST configuration. The linear simulation shows that compared with a large deposition on the pedestal top (scenario I), a smaller deposition within the steep-gradient pedestal region (scenario II) can stimulate much larger linear growth rates of all-n peeling-ballooning modes (PBMs). The nonlinear simulation shows that there exists a pellet size threshold for ELM triggering for two deposition locations; the threshold for scenario I predicted in the present study matches the EAST observation well. Comparison of the two scenarios reveals that a smaller deposition is sufficient to trigger an ELM in a much shorter time in scenario II, whose ELM size is comparable to that in scenario I. This conclusion confirms previous DIII-D and ASDEX-Upgrade observations, suggesting that the steep-gradient pedestal region is a favorable deposition location for ELM triggering with minimum pellet size. Simulation analyses also find that the positive radial gradient of the hump-like pressure profile in the outer mid-plane induced by the pellet deposition plays a different role in the two scenarios. In scenario I, the force resulting from the gradient hinders the outflow of core plasmas and in return, the perturbation is suppressed from spreading inwards after ELM crashes. In scenario II, with a sizable deposition, the gradient results in another competitive perturbation growth region during the linear phase, thus dispersing the free energy and reducing the efficiency of destabilizing PBMs by pellet injection. The suppressing effect of saturated zonal flow on other modes, the short ELM fast crash phase, and the restricting transport effect of the positive radial pressure gradient work together to constrain the pedestal energy loss, especially when the pellet deposition amount is high.

Study of salt free-diffusion by 1D transport numerical simulations and shadowgraph experiments

Applying the Nernst-Planck formalism of 1D diffusive flux equations for ionic species of salts dissolved in water, Pitzer formalism for activity coefficients and PHREEQC software for species diffusion coefficients, with ionic strength-dependence coefficients optimized, we obtained expressions for apparent diffusion coefficients of sodium chloride, calcium chloride, and sodium sulphate, prevalent in deep aquifers. PHREEQC 1D transport simulations of free-diffusion experiments yielded temporal evolution of the concentration and gradient vertical profiles. The dynamics of concentrations non-equilibrium fluctuations during the free-diffusion experiments have been recorded by shadowgraphy. Thanks to the calculated gradient profiles the thickness of the sample has been integrated in the analysis equations of the structure functions. From the earliest stages of the diffusion process we measured the diffusion coefficients for the three salts, in very good agreement with reference measurements, validating the technique and method of analysis for studying free-diffusion in reservoirs targeted for CO2 and energy vectors storage.

Non‐isothermal flow dynamics during reverse roll coating phenomena of non‐Newtonian polymer

AbstractRoll coating plays a major role in industrial coating, including wallpapers, plastic and photographic films, sticky tapes, magnetic recordings, wrapping magazines and books, and so on. The current study proposes a mathematical model for a non‐isothermal, incompressible Sutterby fluid flowing through a narrow gap between two heated, counterrotating rollers. Lubrication approximation theory is used to simplify nondimensional expressions. The perturbation technique provides exact results for velocity profile, temperature, flow rate, and pressure gradient, whereas the numerical technique (Simpson rule) is used to compute the pressure profile and flow rate, respectively. The effects of the involved parameters on various physical characteristics like pressure, flow rate, temperature, pressure gradient, force, and power input are depicted in graphs and tabular form. A mechanism for controlling the coating thickness, power input, flow rate, separation force, and pressure distribution is provided by the material properties involved. With variations to a Sutterby fluid parameter and the velocity ratio K, both the pressure gradient and pressure decrease. It is significant to note that the temperature distribution is controlled by the velocities ratio and Brinkman number. Moreover, the separation point is shifted towards the nip area and the coating thickness on the web reduces with increasing velocities ratio K.

A high-throughput flowless microfluidic single and multi-solute concentration gradient generator: Design and parametric study.

Microfluidic concentration gradient generators (μ-CGGs) are critical in various biochemical assays, including cell migration, drug screening, and antimicrobial susceptibility testing. However, current μ-CGGs rely on integration with flow systems, limiting their scalability and widespread adoption owing to limited infrastructure and technical expertise. Hence, there is a need for flowless diffusional gradient generators capable of standalone operation, thereby improving throughput and usability. In this study, we model such a diffusional μ-CGG as an infinite source-sink system to capture two characteristic timescales: (i) gradient generation dictated by the diffusion timescale and (ii) stability determined by the rate of change in reservoir concentrations. Through finite-element simulations, we explored the influence of various geometric parameters such as the channel length, cross-sectional area, node and reservoir volumes, and the solute diffusivity on these timescales, along with experimental confirmation using fluorescent tracer diffusion. Our results show that while the gradient stability strongly depends on the reservoir volumes, diffusion length, and solute diffusion coefficient, they are independent of the node shape or the shape of the channel cross section. However, gradient profiles were found to be the strong functions of the diffusion length, solute diffusivity, and the geometric pattern of the microfluidic grid. Additionally, we showcased the versatility of the design by generating discrete gradient profiles and combinatorial gradients of two and three solutes, thus improving throughput in a wide range of on-chip biological assays. These findings underscore the potential of our microfluidic device as an easy-to-use, inexpensive, efficient, and high-throughput platform for various on-chip biological assays.