CFD analysis of the Ahmed Glaucoma Valve and design of an alternative device

Computational fluid dynamics (CFD) modelling based on a commercial package, FLUENT, has been used in the present study. The primary aim of this study is to develop a novel implant by employing CFD techniques. Firstly, CFD analyses on the best design commercially available, which is the Ahmed Glaucoma Valve (AGV^®), are accomplished. In the light of the results, the new design focus is selected as the valve. The new design is analysed using GAMBIT and FLUENT software. CFD analyses of the new design and the AGV^® are compared and the strengths of the new design are revealed. The results are also compared with the experimental studies AGV^® in the literature. It is deduced that the proposed model shows a nonlinear pressure drop response, which is quite similar to that of AGV^®. The optimum combination would be a flow rate of 2.5 μl/min and a pressure drop of 1054.58 Pa for the proposed model.     

Analytical model for managing hypotony after implantation surgery of a glaucoma drainage device

The main aim of glaucoma treatment is to reduce the intraocular pressure (IOP). One of the most common surgical treatments of glaucoma is the implantation of a glaucoma drainage device to drain the aqueous humor from the anterior chamber to a filtration bleb, where the aqueous humor is absorbed. In some cases, the excess of drainage causes ocular hypotony, which constitutes a sight-threatening complication. To prevent hypotony after this intervention, surgeons frequently introduce a suture into the device tube, which increases the hydraulic resistance of the tube and, therefore, the IOP. This study aims to provide an analytical model to correct hypotony following implantation surgery of a glaucoma drainage device, which may help glaucoma surgeons decide on hypotony treatment. The results indicate that the IOP after implanting a cylindrical tube around 300 μm in diameter is essentially the same as that built up in the filtering bleb and can hardly be controlled by introducing a straight suture unless the suture diameter is slightly lower than that of the tube. On the contrary, when the tube diameter is smaller than, for example, 100 μm, significant reductions of the IOP can be obtained by introducing a thin suture into the tube.

     

Experimental analysis of pulsatile flow through elastic collapsible tubes: application to cardiac assist device

This study presents a simulated analysis of Phased Compression Cardiac Assist Device (PCCAD) and evaluation of its applicability as a non-invasive temporary assist for a failing heart. The new technique is based on the chest pump mechanism for blood flow augmentation during external massage by phased compression of the abdominal and thoracic cavities. A semi-closed hydraulic system to simulate the systemic circulation was constructed; the system includes a left ventricle which functions according to the Starling principle and a pneumatic system which controls the pressures applied to the thoracic and abdominal cavities, in complete synchronization with the beating normal or failing heart. The possibility of manipulating the three pumps in series (venous, heart, and arterial) has been checked, and the principal parameters which effect the efficiency of the PCCAD were evaluated. This in vitro analysis shows the high potential of a non-invasive temporary cardiac assist device. It points to the necessary measures one has to take in order to achieve good synchronization and to interfere externally with the augmentation of cardiac output or with the augmentation of root aortic pressure.     

A fully coupled porous media and channels flow approach for simulation of blood and bile flow through the liver lobules

Two dimensional, steady state, and incompressible blood and bile flows through the liver lobules are numerically simulated. Two different geometric models A and B are proposed to study the effects of lobule structure on the fluid flow behaviour. In Model A, the lobule tissue is represented as a hexagonal shape porous medium with a set of flow channels at its vertices accounting for the hepatic artery, portal and central veins along with bile ductules. Model B is a channelized porous medium constructed by adding a set of flow channels, representing the bile canaliculies and lobule sinusoids, to Model A. The bile and blood flow through the lobule is simulated by the finite element approach, based on the Darcy/Brinkman equations in the lobule tissue and the Navier-Stokes (or Stokes) equations in the flow channels. In Model B, a transmission factor on the boundaries of the bile canaliculies is introduced to connect the bile and blood flows. First, a single regular lobule is utilized to exhibit the fluid flow pattern through the liver lobule represented by proposed geometric models. Then, the model is extended to a group of liver lobules to demonstrate the flow through a liver slice represented by irregular lobules. Numerical results indicate that the Darcy and Brinkman equations provide nearly the same solutions for Model A and similar solutions with a little difference for Model B. It is shown that the existence of sinusoids and bile canaliculies inside the liver lobules has noticeable effects on its fluid flow pattern, in terms of pressure and velocity fields.     

Detection of methyl parathion using immuno-chemiluminescence based image analysis using charge coupled device

A novel method based on immuno-chemiluminescence and image analysis using charge coupled device (CCD) for the qualitative detection of methyl parathion (MP) with high sensitivity (up to 10 ppt) is described. MP antibodies raised in poultry were used as a biological sensing element for the recognition of MP present in the sample. The immuno-reactor column was prepared by packing in a glass capillary column (150 microl capacity) MP antibodies immobilized on Sepharose CL-4B through periodate oxidation method. Chemiluminescence principle was used for the detection of the pesticide. Light images generated during the chemiluminescence reaction were captured by a CCD camera and further processed for image intensity, which was correlated with pesticide concentrations. K(3)Fe(CN)(6) was used as a light enhancer to obtain detectable light images. Different parameters including concentrations of K(3)Fe(CN)(6), luminol, urea H(2)O(2), antibody, addition sequence of reactants and incubation time to obtain best images were optimized. The results obtained by image analysis method showed very good correlation with that of competitive ELISA for methyl parathion detection. Competitive ELISA method was used as a reference to compare the results obtained by CCD imaging.     

Liquid drainage through the peritoneal diaphragmatic surface

In 14 spontaneously breathing anesthetized rabbits, we used cyanoacrylate to glue a hollow capsule, at end expiration or at end inspiration, to the peritoneal surface of the tendinous portion of the diaphragm. The capsule was connected to a pressure transducer and a pipette calibrated in microliters. We filled the system with fluid and measured flow into the diaphragmatic surface facing the capsule (Fcap, microliter/cm2), from liquid displacement in the pipette at different hydraulic pressures in the system (Pcap). Pleural liquid pressure was simultaneously measured in the supraphrenic region (Psup). Fcap was positively correlated to transdiaphragmatic pressure gradient (Psup-Pcap) and breathing frequency but was unaffected by protein concentration of capsular fluid. For a breathing frequency of 30 cycles/min and a Psup - Pcap = -2 cmH2O, Fcap was 0.54 microliter.min-1.cm-2 for capsules applied at end expiration and 10-fold greater for capsules applied at end inspiration. Data indicate that the diaphragmatic tendinous portion in rabbits is a draining site for peritoneal fluid and that the conductance of the draining pathways (lymphatic stomata) is related to diaphragmatic tension. In the intact rabbit the average peritoneal fluid drainage through the tendinous portion of the diaphragm (approximately 16 cm2) was estimated at 43 microliters/min.     

Small-volume rapid-mix device for subsecond kinetic analysis in flow cytometry.

BACKGROUND: Rapid-mix flow cytometry has emerged as a powerful tool for mechanistic analysis of ligand binding, cell response, and molecular assembly. Although progress has come from improving sample delivery capabilities, little attention has been paid to the volumetric requirements associated with precious biological reagents. METHODS: By using programmable syringes, valves, and other fluidic components, we created a modular, precisely regulated rapid-mix device for the delivery of small-volume samples to the flow cytometer. The device was tested using a bead-based assay in which the binding kinetics between native biotin and fluorescein biotin-bearing beads were characterized. RESULTS: Bead suspensions and reagents paired in 35- to 45-microl aliquots were efficiently mixed by the device and delivered to the flow cytometer. Kinetic data associated with the fluorescein biotin beads were analyzed and used to calibrate the performance characteristics of the device in terms of sample delivery and mixing efficiency. CONCLUSION: The rapid-mix device is capable of detecting subsecond kinetics of biological reactions using microliter volume of samples. Dimensions of the device have been minimized, and the quantitative aspects of sample delivery and analysis have been optimized. Further, the modular design has been optimized for adaptation to a variety of experimental protocols.     

Analysis of various sugars by means of immobilized enzyme coupled flow injection analysis

Glucose, maltose, sucrose, lactose, xylose, sorbose, galactose, fructose and gluconolactone were analyzed by means of immobilized pyranose oxidase as well as by the combination of immobilized glucose oxidase with immobilized glycoamylase, invertase, mutarotase, maltase (α-glucosidase) and glucose isomerase by flow injection analysis (FIA). For the simultaneous analysis of glucose and other sugars three different flow-injection configurations were applied and compared. The average error of prediction of the analyses were better than 3% in model media and better than 6% in yeast extract containing media.     

Plug flow cytometry: An automated coupling device for rapid sequential flow cytometric sample analysis.

BACKGROUND: The tools for high throughput flow cytometry have been limited in part because of the requirement that the samples must flow under pressure. We describe a simple system for sampling repetitively from an open vessel. METHODS: Under computer control, the sample is loaded into a sample loop in a reciprocating eight-way valve by the action of a syringe. When the valve position is switched, the plug of sample in the sample loop is transported to the flow cytometer by a pressure-driven fluid line. By coupling the plug-forming capability to a second multi-port valve, samples can be delivered sequentially from separate vessels. RESULTS: The valve is able to deliver samples at rates ranging up to about 9 samples per minute. Each plug of sample has uniform delivery characteristics with a reproducible coefficient of variation (CV). Even at the highest sampling rate, carryover between samples is limited. CONCLUSIONS: Plug-flow flow cytometry has the potential to automate the delivery of small samples from unpressurized sources at rates compatible with many screening and assay applications.     

Numerical analysis of flow through a severely stenotic carotid artery bifurcation

The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m2, proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-epsilon, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed.     

A multi-platform flow device for microbial (co-) cultivation and microscopic analysis

Novel microbial cultivation platforms are of increasing interest to researchers in academia and industry. The development of materials with specialized chemical and geometric properties has opened up new possibilities in the study of previously unculturable microorganisms and has facilitated the design of elegant, high-throughput experimental set-ups. Within the context of the international Genetically Engineered Machine (iGEM) competition, we set out to design, manufacture, and implement a flow device that can accommodate multiple growth platforms, that is, a silicon nitride based microsieve and a porous aluminium oxide based microdish. It provides control over (co-)culturing conditions similar to a chemostat, while allowing organisms to be observed microscopically. The device was designed to be affordable, reusable, and above all, versatile. To test its functionality and general utility, we performed multiple experiments with Escherichia coli cells harboring synthetic gene circuits and were able to quantitatively study emerging expression dynamics in real-time via fluorescence microscopy. Furthermore, we demonstrated that the device provides a unique environment for the cultivation of nematodes, suggesting that the device could also prove useful in microscopy studies of multicellular microorganisms.     

Role of the autotaxin-lysophosphatidic acid axis in glaucoma,aqueous humor drainage and fibrogenic activity

Ocular hypertension due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM) is a major risk factor for glaucoma, a leading cause of irreversible blindness. However, the etiology of ocular hypertension remains unclear. Although autotaxin, a secreted lysophospholipase D and its catalytic product lysophosphatidic acid (LPA) have been shown to modulate AH drainage through TM, we do not have a complete understanding of their role and regulation in glaucoma patients, TM and AH outflow. This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.     

Hydraulic analysis of water flow through leaves of sugar maple and red oak

Leaves constitute a substantial fraction of the total resistance to water flow through plants. A key question is how hydraulic resistance within the leaf is distributed among petiole, major veins, minor veins, and the pathways downstream of the veins. We partitioned the leaf hydraulic resistance (R(leaf)) for sugar maple (Acer saccharum) and red oak (Quercus rubra) by measuring the resistance to water flow through leaves before and after cutting specific vein orders. Simulations using an electronic circuit analog with resistors arranged in a hierarchical reticulate network justified the partitioning of total R(leaf) into component additive resistances. On average 64% and 74% of the R(leaf) was situated within the leaf xylem for sugar maple and red oak, respectively. Substantial resistance-32% and 49%- was in the minor venation, 18% and 21% in the major venation, and 14% and 4% in the petiole. The large number of parallel paths (i.e. a large transfer surface) for water leaving the minor veins through the bundle sheath and out of the leaf resulted in the pathways outside the venation comprising only 36% and 26% of R(leaf). Changing leaf temperature during measurement of R(leaf) for intact leaves resulted in a temperature response beyond that expected from changes in viscosity. The extra response was not found for leaves with veins cut, indicating that water crosses cell membranes after it leaves the xylem. The large proportion of resistance in the venation can explain why stomata respond to leaf xylem damage and cavitation. The hydraulic importance of the leaf vein system suggests that the diversity of vein system architectures observed in angiosperms may reflect variation in whole-leaf hydraulic capacity.     

Direct detection of nucleic acid hybridization on the surface of a charge coupled device.

A method is described for the detection of DNA hybrids formed on a solid support, based upon the pairing of oligonucleotide chemistry and the technologies of electronic microdevice design. Surface matrices have been created in which oligonucleotide probes are covalently linked to a thin SiO2 film. 32P labeled target nucleic acid is then hybridized to this probe matrix under conditions of high stringency. The salient feature of the method is that to achieve the highest possible collection efficiency, the hybridization matrix is placed directly on the surface of a charge coupled device (CCD), which is used to detect 32P decay from hybridized target molecules (1, Eggers, M.D., Hogan, M.E., Reich, R.K., Lamture, J.B., Beattie, K.L., Hollis, M.A., Ehrilich, D.J., Kosicki, B.B., Shumaker, J.M., Varma, R.S., Burke, B.E., Murphy, A., and Rathman, D.D., (1993), Advances in DNA Sequencing Technology, Proc. SPIE, 1891, 13-26). Two implementations of the technology have been employed. The first involves direct attachment of the matrix to the surface of a CCD. The second involves attachment of the matrix to a disposible SiO2 coated chip, which is then placed face to face upon the CCD surface. As can be predicted from this favorable collection geometry and the known characteristics of a CCD, it is found that as measured by the time required to obtain equivalent signal to noise ratios, 32P detection speed by the direct CCD approach is at least 10 fold greater than can be obtained with a commercial gas phase array detector, and at least 100 fold greater than when X-ray film is used for 32P detection. Thus, it is shown that excellent quality hybridization signals can be obtained from a standard hybridization reaction, after only 1 second of CCD data acquisition.     

An analysis of turbulent shear stresses in leakage flow through a bileaflet mechanical prostheses

In this work, estimates of turbulence were made from pulsatile flow laser Doppler velocimetry measurements using traditional phase averaging and averaging after the removal of cyclic variation. These estimates were compared with estimates obtained from steady leakage flow LDV measurements and an analytical method. The results of these studies indicate that leakage jets which are free and planar in shape may be more unstable than other leakage jets, and that cyclic variation does not cause a gross overestimation of the Reynolds stresses at large distances from the leakage jet orifice.     

On-line three-parameter data uptake, analysis, and display device for flow cytometry and other applications

Multiparameter flow cytometric measurements are of growing interest in the study of complex features of biological cells. With state of the art instrumentation, three-parameter (3-P) data handling is relatively complicated and time consuming and the display methods are not satisfactory. As an alternative, an interactive 3-P analyzing module, Cytomic 123 is described, which displays 3-P fields during and immediately after data uptake in the form of a cubic array of 32,768 channels. The fields can be randomly rotated by hardware and software. The event frequencies in the field are primarily visualized by brightness modulation of the display dots. Additionally, the display of the field may be confined to user selected ranges of event frequencies, which may also be superposed to mixed frequency displays. A set of preprogrammed functions is available for the following tasks: (a) uptake of 3-P histograms combined with on-line control of the transducer pulses, (b) automatic uptake of a series of 2-P time correlated histograms in the cube, (c) generation and numerical evaluation of sections and projections of cube histograms, (d) interactive generation and evaluation of spatial subfields for integration, or as sorting matrix by successive erosion of section planes, or reprojection of projection windows, and (e) isometric display of sections and projections and exchange of data sets with other Cytomic modules or other data systems, especially the Cytomic 12 module, whose 2-P capabilities can be used. The module is built with low cost Z80 microprocessor eurocards. A standard oscilloscope serves as a display unit.     

Morphodynamics of flow through sinuous curvatures of the heart

Through cardiac looping during embryonic development, human and other vertebrate hearts adopt sinuous curvatures with marked changes in direction of flow at atrial, ventricular and arterial levels. We used magnetic resonance phase velocity mapping to study flow through the hearts of resting volunteers, and Doppler ultrasound to record changes with exercise. We found asymmetric recirculation of blood during filling phases of all four heart cavities, with blood redirected appropriately for onward passage to the next cavity. Doppler traces showed that biphasic ventricular filling became rapid and monophasic on strenuous exercise. We propose that looped curvatures of the heart have fluidic and dynamic advantages. Intra-cavity flow appears to be asymmetric in a manner that preserves stability, and allows momentum of inflowing streams to be redirected towards rather than away from the next cavity. Direction-change at ventricular level is such that recoil away from ejected blood is in a direction that can enhance rather than inhibit ventriculo-atrial coupling. These factors may combine to allow a reciprocating, sling-like, 'morphodynamic' mode of action become effective when heart rate and output increase with exercise. Dynamic efficiency of the looped heart may have favoured evolution of large, complex, active species characteristic of the vertebrate line.