scholarly journals An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes

2019 ◽  
Author(s):  
Michael Schaich ◽  
Jehangir Cama ◽  
Kareem Al Nahas ◽  
Diana Sobota ◽  
Kevin Jahnke ◽  
...  

The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. We integrate the microfluidic octanol-assisted liposome assembly platform with an optofluidic transport assay to create a complete microfluidic total analysis system for quantifying drug permeability. Our system enables us to form liposomes with charged lipids mimicking the negative charge of bacterial membranes at physiological salt and pH levels, which proved difficult with previous liposome formation techniques. Furthermore, the microfluidic technique yields an order of magnitude more liposomes per experiment than previous assays. We demonstrate the feasibility of the assay by determining the permeability coefficient of norfloxacin across biomimetic liposomes.

2021 ◽  
Vol 11 (4) ◽  
pp. 1399
Author(s):  
Jure Oder ◽  
Cédric Flageul ◽  
Iztok Tiselj

In this paper, we present uncertainties of statistical quantities of direct numerical simulations (DNS) with small numerical errors. The uncertainties are analysed for channel flow and a flow separation case in a confined backward facing step (BFS) geometry. The infinite channel flow case has two homogeneous directions and this is usually exploited to speed-up the convergence of the results. As we show, such a procedure reduces statistical uncertainties of the results by up to an order of magnitude. This effect is strongest in the near wall regions. In the case of flow over a confined BFS, there are no such directions and thus very long integration times are required. The individual statistical quantities converge with the square root of time integration so, in order to improve the uncertainty by a factor of two, the simulation has to be prolonged by a factor of four. We provide an estimator that can be used to evaluate a priori the DNS relative statistical uncertainties from results obtained with a Reynolds Averaged Navier Stokes simulation. In the DNS, the estimator can be used to predict the averaging time and with it the simulation time required to achieve a certain relative statistical uncertainty of results. For accurate evaluation of averages and their uncertainties, it is not required to use every time step of the DNS. We observe that statistical uncertainty of the results is uninfluenced by reducing the number of samples to the point where the period between two consecutive samples measured in Courant–Friedrichss–Levy (CFL) condition units is below one. Nevertheless, crossing this limit, the estimates of uncertainties start to exhibit significant growth.


Kinesiology ◽  
2018 ◽  
Vol 50 (1) ◽  
pp. 104-111 ◽  
Author(s):  
İlker Özcan ◽  
Çağatay Şahan

The aim of this study was to investigate the effects of small-sided game training (SSGT) versus conventional aerobic interval training (CAIT) on soccer-specific endurance performance, lactate threshold levels (mmol·L-1), short-passing ability and defensive and offensive skills of a soccer match. Before and after a 6-week training intervention period, eighteen amateur soccer players (age 21.8±4.8 years) were tested. The tests included the anaerobic threshold (AnT) test, the Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IR1), and the Loughborough Soccer Passing Test (LSPT). A manual notational match analysis system was utilized to evaluate the defensive and offensive skills of players during the matches. Both the SSGT and CAIT were performed two days a week and consisted of five sets of 6-minute periods of work at the individualized exercise intensity corresponding to the individual anaerobic threshold, with 3-minute of recovery periods between sets. Mann-Whitney U and Wilcoxon signed rank tests were used to examine the between- and within-group differences, respectively. Statistical analyses revealed that the SSGT group players exhibited significantly better in terms of the LSPT scores (p<.01) and the number of defensive and offensive skills (p<.05). However, no other significant differences in the other variables were observed (p>.05). The results of the study suggested that SSGT improved short-passing ability, various soccer skills and physiological parameters, while CAIT only improved physiological parameters. SSGT improves soccer-specific endurance and technical ability of players at the same time, meaning it is a time efficient way of training.


1997 ◽  
Vol 119 (4) ◽  
pp. 551-556 ◽  
Author(s):  
C. Barratt

A mechanism is proposed for synchronizing the chaotic vibrations of an externally forced array of oscillators with nearest-neighbor viscoelastic coupling. The proposed mechanism involves the application of small time-dependent perturbations to the individual oscillators. The perturbations required to preserve the coherence are of the order of magnitude of any noise present. The mechanism works with any form of external forcing. A modification of the mechanism is used to control the forced chaotic vibrations of a single Duffing oscillator allowed to vibrate out of the vertical plane.


2020 ◽  
Vol 90 (2) ◽  
pp. 250-267 ◽  
Author(s):  
Sergio A. Marenssi ◽  
Carlos O. Limarino ◽  
Laura J. Schencman ◽  
Patricia L. Ciccioli

ABSTRACT Two episodes of lacustrine sedimentation, separated by an erosional surface and fluvial sedimentation, took place in the southern part of the broken foreland Vinchina basin (NW Argentina) between 11 and 5 Ma. The lacustrine deposits, 768 and 740 meters thick, are recorded in the upper part of the Vinchina Formation (“Vinchina lake”) and the lower part of the Toro Formation (“Toro Negro lake”) respectively. According to sedimentological features, four sedimentary facies associations (FAs) are recognized in the lacustrine deposits: 1) thinly laminated mudstones facies association (FA 1), 2) coarsening- and thickening-upward muddy to sandy cycles (FA 2), 3) medium- to coarse-grained sandstones (FA 3), and 4) mudstones, sandstones, and oolitic limestones (FA 4). Altogether, these facies correspond to ephemeral, shallow, lacustrine systems including saline mudflats. The total thickness of each lacustrine interval, the thickness of the individual cycles and their lithology, and the overall aggradational facies arrangement suggest that both lakes developed during underfilled stages of the basin. The coarsening-upward cycles can be regarded as lacustrine parasequences representing cyclic episodes of expansion and contraction of the lake, but unlike marine parasequences these cycles do not correlate to water depth. The development of lacustrine conditions and continuous base-level rise, together with the coeval southward-directed paleoflow indicators, suggest axial drainages and that the basin was externally closed (endorheic) at that time. The large thicknesses of each lacustrine interval also points to high accommodation in the southern part of the Vinchina basin during these times. Lake filling cycles are one order of magnitude thicker than lake depth, so we postulate that subsidence (tectonic) and rise of the spill point (geomorphology) increased accommodation but not water depth. Thus, unlike marine parasequences, the analyzed coarsening-upward cycles do not correlate to water depth, but rather they are controlled by more complex basinal accommodation processes. We hypothesize that the coeval uplift of the Umango and Espinal basement block to the south, coupled with the initial doming of the Sierra de Los Colorados to the east, may have generated the damming of the southward-directed drainage and a zone of maximum accommodation, then controlling the location of the two lakes and the preservation of their thick sedimentary records. Therefore, localized accommodation was enhanced by a combination of tectonic subsidence and topographic growth. The two lacustrine intervals and the intervening fluvial deposits record changing contributions from axial to transverse drainages and different cycles of closed and open conditions in the basin. A low-frequency, closed to open and back to closed (axial to transverse and return to axial drainage) basin evolution, is envisaged by the development of the two lakes (closed stages) and the erosional surface followed by the interval of fluvial sedimentation that separates them (open stage). In addition, several high-frequency lake fluctuations (expansion–contraction) are represented by the coarsening-upward cycles within each lacustrine interval. The thick lacustrine intervals and their intermediate incision surfaces record cyclic filling and re-excavation stages and localized episodes of increased subsidence in the Vinchina basin, which seem to be a common feature of tectonically active broken foreland basins.


Author(s):  
Toshifumi Ohkubo ◽  
Nobuyuki Terada ◽  
Yoshikazu Yoshida

A resin-based optical total analysis system (O-TAS) which consists both of microfluidic channels and light waveguides [1] is thought to be one of the most promising components in developing a “ubiquitous human healthcare system” in the near future. Along with this technology trend, we have already developed a transparent epoxy-resin-based optical TAS chip which has a specially prepared light waveguide structure of radially arranged configuration at an intersection portion with a microfluidic channel, in order to detect directivity of fluorescence from fluorescent substance attached micro particles [2],[3]. Schematic diagram of the optical TAS is shown in Figure 1. In the latest research, utilizing an AC modulated laser source and time-series averaging function on detected signal waveforms, we could have successfully obtained directivities of fluorescence from 5-μm-diameter particles with higher signal to noise (S/N) ratio [3].


Author(s):  
Paul Chiarot ◽  
Pierre Sullivan ◽  
Ridha Ben Mrad

In this work, micro particle imaging velocimetry (micro-PIV) was performed on the fundamental components of a micro total analysis system. Specifically, high aspect ratio passive valves and mixers were designed, fabricated, and characterized. The components were built using Micralyne Protolyne technology on a glass substrate and operated at reasonably achievable pressures. The flows through the components were analyzed both qualitatively and quantitatively with the goal of developing a more complete understanding of internal device performance. Using the results of the micro-PIV developed velocity fields it was found that the high aspect ratio passive valves are able to perform at reasonably achievable pressures. However, it was determined that the high aspect ratio passive mixers offer limited performance enhancements because of the low Reynolds number flows. The results of this work contribute to the understanding of passive component operation and address some of the challenges associated with developing completely integrated micro total analysis systems that use passive devices.


1982 ◽  
Vol 28 (4) ◽  
pp. 861-866 ◽  
Author(s):  
J Taylor ◽  
N L Anderson ◽  
A E Scandora ◽  
K E Willard ◽  
N G Anderson

Abstract This paper describes information-handling aspects of the TYCHO I analysis system (Clin, Chem. 27: 1807--1820, 1981), which analyzes two-dimensional electrophoresis gels, matches the individual protein spots with those in a reference pattern, and stores various information--including spot measurements, identifications, treatment profiles, set memberships, and comments--in a computerized database. This and additional information such as amino acid composition and cellular localization is then accessible from an interactive program that includes a pictorial user interface and presents much of the data in graphical form. Use of the TYCHO I system is illustrated by examples drawn from analyses of gel patterns from human leukocytes.


1995 ◽  
Vol 27 (04) ◽  
pp. 1144-1185
Author(s):  
Kimon P. Kontovasilis ◽  
Nikolas M. Mitrou

This paper considers fluid queuing models of Markov-modulated traffic that, due to large differences in the time-scales of events, possess structural characteristics that yield a nearly completely decomposable (NCD) state-space. Extension of domain decomposition and aggregation techniques that apply to approximating the eigensystem of Markov chains permits the approximate subdivision of the full system to a number of small, independent subsystems (decomposition phase), plus an ‘aggregative' system featuring a state-space that distinguishes only one index per subsystem (aggregation phase). Perturbation analysis reveals that the error incurred by the approximation is of an order of magnitude equal to the weak coupling of the NCD Markov chain. The study in this paper is then extended to the structure of NCD fluid models describing source superposition (multiplexing). It is shown that efficient spectral factorization techniques that arise from the Kronecker sum form of the global matrices can be applied through and combined with the decomposition and aggregation procedures. All structural characteristics and system parameters are expressible in terms of the individual sources multiplexed together, rendering the construction of the global system unnecessary. Finally, besides providing efficient computational algorithms, the work in this paper can be recast as a conceptual framework for the better understanding of queueing systems under the presence of events happening in widely differing time-scales.


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