Development of cup shaped microneedle array for transdermal drug delivery

Microneedle technology is one of the attractive methods in transdermal drug delivery. However, the clinical applications of this method are limited owing to: complexity in the preparation of multiple coating solutions, drug leakage while inserting the microneedles into the skin and the outer walls of the solid microneedle can hold limited quantity of drug. Here, the authors present the fabrication of an array of rectangular cup shaped silicon microneedles, which provide for reduced drug leakage resulting in improvement of efficiency of drug delivery and possibility of introducing multiple drugs. The fabricated solid microneedles with rectangular cup shaped tip have a total height of 200 mu m. These cup shaped tips have dimensions: 60 x 60 mu m (length x breadth) with a depth of 60 mu m. The cups are filled with drug using a novel in-house built drop coating system. Successful drug dissolution was observed when the coated microneedle was used on mice. Also, using the above method, it is possible to fill the cups selectively with different drugs, which enables simultaneous multiple drug delivery. (C) 2015 American Vacuum Society.

NON-COERCIVE RICCI FLOW INVARIANT CURVATURE CONES

This note is a study of nonnegativity conditions on curvature preserved by the Ricci flow. We focus on a specific class of curvature conditions which we call non-coercive: These are the conditions for which nonnegative curvature and vanishing scalar curvature does not imply flatness. We show, in dimensions greater than 4, that if a Ricci flow invariant nonnegativity condition is satisfied by all Einstein curvature operators with nonnegative scalar curvature, then this condition is just the nonnegativity of scalar curvature. As a corollary, we obtain that a Ricci flow invariant curvature condition, which is stronger than a nonnegative scalar curvature, cannot be strictly satisfied by curvature operators (other than multiples of the identity) of compact Einstein symmetric spaces. We also investigate conditions which are satisfied by all conformally flat manifolds with nonnegative scalar curvature.

Studies on RF Magnetron Sputtered HfO2 Thin Films for Microelectronic Applications

We investigated the effect of oxygen flow rate during the reactive magnetron sputtering on the compositional, structural, optical and electrical properties of HfO2 films. We also studied the influence of annealing temperature on the structural and electrical properties of optimized HfO2 films of 25 to 30 nm thick. X-ray photoelectron study reveals that the films deposited at 15 SCCM of oxygen flow rate are stoichiometric and have an optical band gap of 5.86 eV. X-ray diffraction indicates that films without oxygen flow are amorphous, and beyond an oxygen flow rate of 5 SCCM exhibit polycrystalline monoclinic structure. At an annealing temperature of 600 degrees C, tetragonal phase was observed besides the monoclinic phase. The dielectric constant of 11 and low leakage currents of 1 x 10(-7) A/cm(2) were achieved for the stoichiometric films. As-deposited films show significant frequency dispersion due to the presence of defect states at the HfO2/Si interface, and it reduces after annealing.

Surface motions and intraplate continental deformation in Alaska driven by mantle flow

The degree to which the lithosphere and mantle are coupled and contribute to surface deformation beneath continental regions remains a fundamental question in the field of geodynamics. Here we use a new approach with a surface deformation field constrained by GPS, geologic, and seismicity data, together with a lithospheric geodynamic model, to solve for tractions inferred to be generated by mantle convection that (1) drive extension within interior Alaska generating southward directed surface motions toward the southern convergent plate boundary, (2) result in accommodation of the relative motions between the Pacific and North America in a comparatively small zone near the plate boundary, and (3) generate the observed convergence within the North American plate interior in the Mackenzie mountains in northwestern Canada. The evidence for deeper mantle influence on surface deformation beneath a continental region suggests that this mechanism may be an important contributing driver to continental plate assemblage and breakup.

Experimental studies on the flow through soft tubes and channels

Experiments conducted in channels/tubes with height/diameter less than 1 mm with soft walls made of polymer gels show that the transition Reynolds number could be significantly lower than the corresponding value of 1200 for a rigid channel or 2100 for a rigid tube. Experiments conducted with very viscous fluids show that there could be an instability even at zero Reynolds number provided the surface is sufficiently soft. Linear stability studies show that the transition Reynolds number is linearly proportional to the wall shear modulus in the low Reynolds number limit, and it increases as the 1/2 and 3/4 power of the shear modulus for the `inviscid' and `wall mode' instabilities at high Reynolds number. While the inviscid instability is similar to that in the flow in a rigid channel, the mechanisms of the viscous and wall mode instabilities are qualitatively different. These involve the transfer of energy from the mean flow to the fluctuations due to the shear work done at the interface. The experimental results for the viscous instability mechanism are in quantitative agreement with theoretical predictions. At high Reynolds number, the instability mechanism has characteristics similar to the wall mode instability. The experimental transition Reynolds number is smaller, by a factor of about 10, than the theoretical prediction for the parabolic flow through rigid tubes and channels. However, if the modification in the tube shape due to the pressure gradient, and the consequent modification in the velocity profile and pressure gradient, are incorporated, there is quantitative agreement between theoretical predictions and experimental results. The transition has important practical consequences, since there is a significant enhancement of mixing after transition.

Taming Control Divergence in GPUs through Control Flow Linearization

Branch divergence is a very commonly occurring performance problem in GPGPU in which the execution of diverging branches is serialized to execute only one control flow path at a time. Existing hardware mechanism to reconverge threads using a stack causes duplicate execution of code for unstructured control flow graphs. Also the stack mechanism cannot effectively utilize the available parallelism among diverging branches. Further, the amount of nested divergence allowed is also limited by depth of the branch divergence stack. In this paper we propose a simple and elegant transformation to handle all of the above mentioned problems. The transformation converts an unstructured CFG to a structured CFG without duplicating user code. It incurs only a linear increase in the number of basic blocks and also the number of instructions. Our solution linearizes the CFG using a predicate variable. This mechanism reconverges the divergent threads as early as possible. It also reduces the depth of the reconvergence stack. The available parallelism in nested branches can be effectively extracted by scheduling the basic blocks to reduce the effect of stalls due to memory accesses. It can also increase execution efficiency of nested loops with different trip counts for different threads. We implemented the proposed transformation at PTX level using the Ocelot compiler infrastructure. We evaluated the technique using various benchmarks to show that it can be effective in handling the performance problem due to divergence in unstructured CFGs.

Stability of Poiseuille flow in a fluid overlying an anisotropic and inhomogeneous porous layer

We present the linear stability analysis of horizontal Poiseuille flow in a fluid overlying a porous medium with anisotropic and inhomogeneous permeability. The generalized Darcy model is used to describe the flow in the porous medium with the Beavers-Joseph condition at the interface of the two layers and the eigenvalue problem is solved numerically. The effect of major system parameters on the stability characteristics is addressed in detail. It is shown that the anisotropic and inhomogeneous modulation of the permeability of the underlying porous layer provides an effective means for passive control of the flow stability.

Field-Portable Microfluidics-Based Imaging Flow Cytometer

Clinical microscopy is a versatile and robust tool used for the diagnosis of a plethora of diseases. However, due to various reasons, it remains inaccessible in resource limited settings. In this paper, we present an automated and cost-effective alternative to microscopy for use in clinical diagnostics. With the use of custom optics and microfluidics, we demonstrate a field-portable imaging flow cytometry system. Using the presented system, we have been able to image 586 cells per second. We demonstrate the clinical relevance of the proposed system by differentiating between suspensions of healthy and sphered RBCs based on high-throughput morphometric analysis. The instrument presented here is a major advancement in the domain of field portable diagnostics as it enables fast and robust quantitative diagnostic testing at the point-of-care.

Deformability Measurement of Single-Cells at High-Throughput With Imaging Flow Cytometry

Disease conditions like malaria, sickle cell anemia, diabetes mellitus, cancer, etc., are known to significantly alter the deformability of certain types of cells (red blood cells, white blood cells, circulating tumor cells, etc.). To determine the cellular deformability, techniques like micropipette aspiration, atomic force microscopy, optical tweezers, quantitative phase imaging have been developed. Many of these techniques have an advantage of determining the single cell deformability with ultrahigh precision. However, the suitability of these techniques for the realization of a deformability based diagnostic tool is questionable as they are expensive and extremely slow to operate on a huge population of cells. In this paper, we propose a technique for high-throughput (800 cells/s) determination of cellular deformability on a single cell basis. This technique involves capturing the image(s) of cells in flow that have undergone deformation under the influence of shear gradient generated by the fluid flowing through the microfluidic channels. Deformability indices of these cells can be computed by performing morphological operations on these images. We demonstrate the applicability of this technique for examining the deformability index on healthy, diabetic, and sphered red blood cells. We believe that this technique has a strong role to play in the realization of a potential tool that uses deformability as one of the important criteria in disease diagnosis.

Investigation of schemes for incorporating generator Q limits in the fast decoupled load flow method

Fast Decoupled Load Flow (FDLF) is a very popular and widely used power flow analysis method because of its simplicity and efficiency. Even though the basic FDLF algorithm is well investigated, the same is not true in the case of additional schemes/modifications required to obtain adjusted load flow solutions using the FDLF method. Handling generator Q limits is one such important feature needed in any practical load flow method. This paper presents a comprehensive investigation of two classes of schemes intended to handle this aspect i.e. the bus type switching scheme and the sensitivity scheme. We propose two new sensitivity based schemes and assess their performance in comparison with the existing schemes. In addition, a new scheme to avoid the possibility of anomalous solutions encountered while using the conventional schemes is also proposed and evaluated. Results from extensive simulation studies are provided to highlight the strengths and weaknesses of these existing and proposed schemes, especially from the point of view of reliability.

Atmospheric pressure plasma chemical vapor deposition reactor for 100 mm wafers, optimized for minimum contamination at low gas flow rates

Gas discharge plasmas used for thinfilm deposition by plasma-enhanced chemical vapor deposition (PECVD) must be devoid of contaminants, like dust or active species which disturb the intended chemical reaction. In atmospheric pressure plasma systems employing an inert gas, the main source of such contamination is the residual air inside the system. To enable the construction of an atmospheric pressure plasma (APP) system with minimal contamination, we have carried out fluid dynamic simulation of the APP chamber into which an inert gas is injected at different mass flow rates. On the basis of the simulation results, we have designed and built a simple, scaled APP system, which is capable of holding a 100 mm substrate wafer, so that the presence of air (contamination) in the APP chamber is minimized with as low a flow rate of argon as possible. This is examined systematically by examining optical emission from the plasma as a function of inert gas flow rate. It is found that optical emission from the plasma shows the presence of atmospheric air, if the inlet argon flow rate is lowered below 300 sccm. That there is minimal contamination of the APP reactor built here, was verified by conducting an atmospheric pressure PECVD process under acetylene flow, combined with argon flow at 100 sccm and 500 sccm. The deposition of a polymer coating is confirmed by infrared spectroscopy. X-ray photoelectron spectroscopy shows that the polymer coating contains only 5% of oxygen, which is comparable to the oxygen content in polymer deposits obtained in low-pressure PECVD systems. (C) 2015 AIP Publishing LLC.

Kinematic flow patterns in slow deformation of a dense granular material

The kinematic flow pattern in slow deformation of a model dense granular medium is studied at high resolution using in situ imaging, coupled with particle tracking. The deformation configuration is indentation by a flat punch under macroscopic plane-strain conditions. Using a general analysis method, velocity gradients and deformation fields are obtained from the disordered grain arrangement, enabling flow characteristics to be quantified. The key observations are the formation of a stagnation zone, as in dilute granular flow past obstacles; occurrence of vortices in the flow immediately underneath the punch; and formation of distinct shear bands adjoining the stagnation zone. The transient and steady state stagnation zone geometry, as well as the strength of the vortices and strain rates in the shear bands, are obtained from the experimental data. All of these results are well-reproduced in exact-scale non-smooth contact dynamics simulations. Full 3D numerical particle positions from the simulations allow extraction of flow features that are extremely difficult to obtain from experiments. Three examples of these, namely material free surface evolution, deformation of a grain column below the punch and resolution of velocities inside the primary shear band, are highlighted. The variety of flow features observed in this model problem also illustrates the difficulty involved in formulating a complete micromechanical analytical description of the deformation.

Flow Cytometry Analysis of Cytotoxicity In Vitro and Long-Term Toxicity of HA-40wt% BaTiO3 Nanoparticles In Vivo

The development of new implantable biomaterials requires bone-mimicking physical properties together with desired biocompatible property. In continuation to our earlier published research to establish compositional dependent multifunctional bone-like properties and cytocompatibility response of hydroxyapatite (HA)-BaTiO3 composites, the toxicological property evaluation, both invitro and invivo, were conducted on HA-40wt% BaTiO3 and reported in this work. In particular, this work reports invitro cytotoxicity of mouse myoblast cells as well as invivo long-term tissue and nanoparticles interaction of intra-articularly injected HA-40wt% BaTiO3 and BaTiO3 up to the concentration of 25mg/mL in physiological saline over 12weeks in mouse model. The careful analysis of flow cytometry results could not reveal any statistically significant difference in terms of early/late apoptotic cells or necrotic cells over 8d in culture. Extensive histological analysis could not record any signature of cellular level toxicity or pronounced inflammatory response in vital organs as well as at knee joints of Balb/c mice after 12weeks. Taken together, this study establishes nontoxic nature of HA-40wt% BaTiO3 and therefore, HA-40wt% BaTiO3 can be used safely for various biomedical applications.

Two-Phase Flow With Phase Change in Porous Channels

Phase change heat transfer in porous media finds applications in various geological flows and modern heat pipes. We present a study to show the effect of phase change on heat transfer in a porous channel. We show that the ratio of Jakob numbers based on wall superheat and inlet fluid subcooling governs the liquid-vapor interface location in the porous channel and below a critical value of the ratio, the liquid penetrates all the way to the extent of the channel in the flow direction. In such cases, the Nusselt number is higher due to the proximity of the liquid-vapor interface to the heat loads. For higher heat loads or lower subcooling of the liquid, the liquid-vapor interface is pushed toward the inlet, and heat transfer occurs through a wider vapor region thus resulting in a lower Nusselt number. This study is relevant in the designing of efficient two-phase heat exchangers such as capillary suction based heat pipes where a prior estimation of the interface location for the maximum heat load is required to ensure that the liquid-vapor interface is always inside the porous block for its operation.

Effect of Channel Confinement on Mixed Convective Flow Past an Equilateral Triangular Cylinder

The present work investigates the mixed convective flow and heat transfer characteristics past a triangular cylinder placed symmetrically in a vertical channel. At a representative Reynolds number, Re = 100, simulations are carried out for the blockage ratios beta = 1/3; 1/4; and 1/6. Effect of aiding and opposing buoyancy is brought about by varying the Richardson number in the range -1.0 <= Ri <= 1.0. At a blockage ratio of 1/3, suppression of vortex shedding is found at Ri = 1, whereas von Karman vortex street is seen both at beta = 1/4 and 1/6, respectively. This is the first time that such behavior of blockage ratio past a triangular cylinder in the present flow configuration is reported. Drag coefficient increases progressively with increasing Ri and a slightly higher value is noticed at beta = 1/3. For all b, heat transfer increases with increasing Ri. Flattening of Nu(avg)-Ri curve beyond Ri > 0: 75 is observed at beta = 1/3.