Effects Of Flow Rate Ratio Research Articles

Production of liposomes by microfluidics: The impact of post-manufacturing dilution on drug encapsulation and lipid loss

Microfluidic mixing is recognized as a convenient method to produce liposomes for its scalability and reproducibility. Numerous studies have described the effect of process parameters such as flow rate ratios and total flow rate on size and size distribution of vesicles. In this work, we focused our attention on the effect of flow rate ratios on the encapsulation efficiency of liposomes, as we hypothesized that different amount of residual organic solvent could affect the retention of lipophilic drug molecules within the bilayer. In a further step, we investigated how the liposomes integrity and loading were impacted by different methods of solvent removal: direct dialysis and dilution & dialysis. Liposomes were prepared by rapidly mixing an ethanolic solution of lipids and a model drug with buffer in a herringbone micromixer, employing four different flow rate ratios (FRR, 4:1, 7:3, 3:2, 1:1). Quercetin, resveratrol and ascorbyl palmitate were used as model antioxidant drugs with different lipophilicity. Data showed that liposomes produced using lower flow rate ratios (i.e., with more residual ethanol) had lower encapsulation efficiencies as well as a more prominent loss of lipids from the bilayer following purification with direct dialysis. If the amount of residual ethanol was reduced to 5% (dilution & dialysis method), the lipids and drug leakage was prevented. Such effect was correlated with the drug aggregation propensity in different ethanol/water mixtures measured by molecular dynamics simulations. Overall, these results highlight the need to tailor the purification method basing on the molecular properties of the loaded drug to ensure high encapsulation and limit the waste of material.

Numerical simulation of multi-functional droplet production in microfluidics

In this work, we have investigated numerically the formation of stable Janus droplets in microfluidics flow focusing device. We have examined the effect of continuous phase capillary number (Ca) as it influences the drop size and the stability of a Janus drop for a fixed dispersed phase flow rate. The effect of flow rate ratio of disperse phases has also been examined to understand the relative distribution of the material in a single Janus droplet. Numerical simulations have been performed using the commercial software Ansys Fluent 19.2 with the Volume of Fluid (VOF) method to solve discrete versions of governing equations. We have extended our method to study the formation and stability of a ternary droplet. For this, a third inlet is incorporated at the middle of the initial channel geometry and fluid combination. In the case of ternary drop, we find that different phases re-arrange themselves after drop formation before reaching the final stable configuration.

Effect of flow rate ratio and positioning on a lighthouse tip ECMO return cannula.

Extracorporeal membrane oxygenation is a life-saving support therapy in the case of cardiopulmonary refractory failure. Its use is associated to complications due to the presence of artificial surfaces and supraphysiological stress conditions. Thus, knowledge of the fluid structures associated to each component can give insight into sources of blood damage. In this study, an experimentally validated numerical study of a conventional lighthouse tip cannula in return configuration was carried out to characterize the flow structures using water or a Newtonian blood analog with different flow rate ratios and cannula positioning and their influence on hemolysis. The results showed that strong shear layers developed where the jets from the side holes met the co-flow. Stationary backflow regions at the vessel wall were also present downstream of the cannula. In the tilted case, the recirculation was much more pronounced on the wide side and almost absent on the narrow side. Small vortical backflow structures developed at the side holes which behaved like obstacles to the co-flow, creating pairs of counter-rotating vortices, which induced locally higher risk of hemolysis. However, global hemolysis index did not show significant deviations. Across the examined flow rate ratios, the holes on the narrow side consistently reinfused a larger fraction of fluid. A radial force developed in the tilted case in a direction so as to recenter the cannula in the vessel.

Simulation of Droplet Formation in T‐Inlet Microchannels with Different Junction Angle

AbstractThe level set method was used to numerically simulate the droplet formation process in T‐junction microchannels with different junction angle. The effects of flow rate ratio, capillary number, and contact angle on droplet formation under different junction angles were discussed. The numerical simulation results show that the dimensionless length and generation frequency of microdroplets increase with the flow rate ratio. It was observed that the droplet transforms from the squeezing regime to the dripping regime when the capillary number Ca is ≥ 0.02. For Ca ≤ 0.04, the smallest droplet was generated in the microchannel with 120° junction angle. Finally, the results also indicate that the effect of the contact angle is discrepant at different junction angles.

PIV Measurement of Velocity Field in T-junction Piping System and Effect of Flow Rate Ratio

PIV Measurement of Velocity Field in T-junction Piping System and Effect of Flow Rate Ratio

Characterization of Lipid Nanoparticles Containing Ionizable Cationic Lipids Using Design-of-Experiments Approach.

Lipid nanoparticles (LNPs) containing short-interfering RNA (LNP-siRNA systems) are a promising approach for silencing disease-causing genes in hepatocytes following intravenous administration. LNP-siRNA systems are generated by rapid mixing of lipids in ethanol with siRNA in aqueous buffer (pH 4.0) where the ionizable lipid is positively charged, followed by dialysis to remove ethanol and to raise the pH to 7.4. Ionizable cationic lipids are the critical excipient in LNP systems as they drive entrapment and intracellular delivery. A recent study on the formation of LNP-siRNA systems suggested that ionizable cationic lipids segregate from other lipid components upon charge neutralization to form an amorphous oil droplet in the core of LNPs. This leads to a decrease in intervesicle electrostatic repulsion, thereby engendering fusion of small vesicles to form final LNPs of increased size. In this study, we prepared LNP-siRNA systems containing four lipid components (hydrogenated soy phosphatidylcholine, cholesterol, PEG-lipid, and 1,2-dioleoyl-3-dimethylammonium propane) by microfluidic mixing. The effects of preparation parameters [lipid concentration, flow rate ratio (FRR), and total flow rate], dialysis process, and complex formation between siRNA and ionizable cationic lipids on the physicochemical properties [siRNA entrapment on the particle size and polydispersity index (PDI)] were investigated using a design of experiments approach. The results for the preparation parameters showed no impact on siRNA encapsulation, but lipid concentration and FRR significantly affected the particle size and PDI. In addition, the effect of FRR on the particle size was suppressed in the presence of anionic polymers such as siRNA as compared to the case of LNPs alone. More intriguingly, unlike empty LNPs, a decrease in the PDI and an increase in the particle size occurred after dialysis in the LNP-siRNA systems. Such changes by dialysis were suppressed at FRR = 1. These findings provide useful information to guide the development and manufacturing conditions for LNP-siRNA systems.

Synthesis of Polycaprolactone Nanoparticles through Flow‐Focusing Microfluidic‐Assisted Nanoprecipitation

AbstractPolycaprolactone nanoparticles (PCL NPs) were produced by a liquid nonsolvent nanoprecipitation process in a flow‐focusing microfluidic device and optimized in terms of particle size, polydispersity index (PDI), and zeta potential ζ. The effects of flow rate ratio (FRR), total flow rate (TFR), the organic solvents tetrahydrofuran and dimethylformamide (DMF), the surfactants polyvinyl alcohol and Tween 80, and polymer molecular weight on the size, PDI, and ζ of PCL NPs were investigated. A stability study was performed to compare the effect of the surfactants on the characteristics of PCL NPs over 7 d. The smallest particles are produced at the highest FRR, TFR, and polymer molecular weight and lowest polymer concentration in DMF. The presence of both surfactants results in smaller NPs.

Liposome production and concurrent loading of drug simulants by microfluidic hydrodynamic focusing.

Liposomes are spherical vesicles enclosed by phospholipid bilayers. Nanoscale liposomes are widely employed for drug delivery in the pharmaceutical industry. In this study, nanoscale liposomes are fabricated using the microfluidic hydrodynamic focusing (MHF) approach, and the effects of flow rate ratio (FRR) on liposome size and drug loading efficiency are studied. Fluorescein isothiocyanate modified dextran is used as a hydrophilic drug simulant and Nile red is used as a hydrophobic drug simulant. The experiment results show that hydrophilic drug simulant loading efficiency increases as FRR increases and eventually plateaues at around 90% loading efficiency. The hydrophobic drug simulant loading efficiency and FRR have a positive linear correlation when FRR varies from 10 to 50. Concurrent loading of both hydrophilic and hydrophobic drug simulants maintains thesame loading efficiencies asthose of loading each drug simulant alone. A negative correlation between liposome size and FRR is also confirmed. Unloaded liposomes and hydrophilic drug-loaded liposomes are of the same sizes, and are smaller than the ones loaded with the hydrophobic drug simulants alone or combined. The results suggest tunable liposome size and drug loading efficiency with the MHF technique. This provides evidence to encourage further studies of microfluidic liposome fabrication in the pharmaceutical industry.

Examining the Effect of Flow Rate Ratio on Droplet Generation and Regime Transition in a Microfluidic T-Junction at Constant Capillary Numbers

The focus of this work is to examine the effect of flow rate ratio (quotient of the dispersed phase flow rate over the continuous phase flow rate) on a regime transition from squeezing to dripping at constant capillary numbers. The effect of the flow rate ratio on the volume of droplets generated in a microfluidic T-junction is discussed, and a new scaling law to estimate their volume is proposed. Existing work on a regime transition reported by several researchers focuses on the effect of the capillary number on regime transition, and the results that are presented in this paper advance the current understanding by indicating that the flow rate ratio is another parameter that dictates regime transition. In this paper, the transition between squeezing and dripping regimes is reported at constant capillary numbers, with a transition region identified between squeezing and dripping regimes. Dripping is observed at lower flow rate ratios and squeezing at higher flow rate ratios, with a transition region between the two regimes at flow rate ratios between 1 and 2. This is presented in a flow regime map that is constructed based on the observed mechanism. A scaling model is proposed to characterise droplet volume in terms of flow rate ratio and capillary number. The effect of flow rate ratio on the non-dimensional droplet volume is presented, and lastly, the droplet volume is expressed in terms of a range of parameters, such as the viscosity ratio between the dispersed and the continuous phase, capillary number, and the geometrical characteristics of the channels.

Magnetophoretic separation of diamagnetic particles through parallel ferrofluid streams

Particle separation based on microfluidic technology offers a simple, reliable, and low-cost approach for the diagnosis of diseases. The separation concept can be extended to genetic engineering, cell transplantation, and immunology. This paper reports a simple microfluidic platform for the separation of diamagnetic particles of different sizes utilizing parallel ferrofluid streams. The ferrofluid streams with predefined concentrations of magnetic nanoparticles promote negative magnetophoresis and are able to separate a particle mixture with a subtle size variation. Numerical simulation was used to optimise the magnetic field gradient, e.g. the number and position of the external permanent magnets. The effect of flow rate ratio and the concentration distribution were analyzed by the simulation and validated by experiments. Furthermore, two-stream and three-stream ferrofluid configurations were evaluated to find the optimum separation performance. The experimental results show a maximum separation efficiency of 78% and 75% with three-stream configuration for 3.2-μm and 4.8-μm particles, respectively.

Effects of flow rate ratio on loss reduction of T-junction pipe

Effects of flow rate ratio on loss reduction of T-junction pipe

223 T字形合流管内の流れの損失低減に対する流量比の影響(OS13-3 乱流現象の実験と数値シミュレーション(3),OS13 乱流現象の実験と数値シミュレーション)

223 T字形合流管内の流れの損失低減に対する流量比の影響(OS13-3 乱流現象の実験と数値シミュレーション(3),OS13 乱流現象の実験と数値シミュレーション)

Experimental characterization and multi-scale modeling of mixing in static mixers

Mixing in static mixers is studied using a set of competitive-parallel chemical reactions and computational fluid dynamics (CFD) in a wide range of operating conditions. Two kinds of mixers, a wide angle Y-mixer and a two jet vortex mixer, referred to as Roughton mixer, are compared in terms of reaction yields and mixing times. It is found that the Roughton mixer achieves a better mixing performance compared to the Y-mixer. The effect of flow rate ratio on mixing in the Roughton mixer has been studied as well and it is shown that the mixing efficiency is not affected by the flow rate ratio. Moreover, experimental results and model predictions are in good agreement for all mixer geometries and operating conditions. CFD is used to calculate absolute mixing times based on the residence time in the segregated zone and it is shown that mixing times of less than 1 ms can be achieved in the Roughton mixer. In addition, CFD provides insight in local concentrations and reaction rates and serves as a valuable tool to improve or to scale-up mixers.

Three-Dimensional Finite Element Simulation and Analysis of Half-Club Coextrusion Processes

The three-dimensional flow of non-Newtonian polymer melts in coextrusion dies was analyzed based on finite element simulations. Simulation results, especially the interface predictions were discussed. The effects of flow rate ratio and the roughness of die wall on the interface were examined farther. It is found that the flow rate affects the shape and location of the interface notably. The velocity of fluid flow mainly controls the shape and location of the interface. Increasing that the higher slipperiness of the fluid path can make the velocity field more uniform and the interfacial offset less.

Effects of flow-rate ratio on startup and cyclic steady-state behaviors of simulated moving bed under linear conditions

The influence of the flow-rate ratio ( m-value) on the startup and the cyclic steady-state performance of the simulated moving bed (SMB) process were studied under the condition of a fixed feed flow rate. Each system was evaluated from the viewpoint of four performance parameters (major product concentration, purity, eluent consumption, and productivity). Flow-rate ratios of zones II and III ( m 2 and m 3) played key roles in the startup and cyclic steady-state behaviors of the performance parameters compared to m-values of zones I and IV ( m 1 and m 4) in the four-zone SMB process. However, the performance parameters were steeply changed near the operating boundaries of m 1 and m 4 even though their variation was smaller than the results from m 2 and m 3. In addition, the effects of m 1 and m 4 on the major product concentration were substantial in the operating range. The startup periods of both product concentrations were increased as the operating point in the triangle region became far from the diagonal in terms of m 2 and m 3. On the other hand, the variation of m 1 and m 4 could lead to a change in performance without any adjustment to the startup period.

Flow and Mixing Characteristics in Counter-Type T-junction (Influence of Flow Ratio on Mixing Characteristics)

The effects of flow rate ratio on flow and mixing characteristics for turbulent flow in a countertype T-junction channel have been investigated experimentally. The T-junction was modeled by a mixing tee with square cross sections, in which the mixing channel was connected with the main and counter channels at right angles. Detail distributions of velocity and concentration after the flow merging have been measured using Particle Image Velocimetry (PIV) and Planer Laser Induced Fluorescence (PLIF). Mixing of two flows around X/D=2-5 is enhanced with increase of flow rate ratio, and the concentration fields of the region are largely related to the longitudinal vortices induced by the centrifugal forces. The distributions of the velocity fluctuation in the transverse direction are similar to those of concentration in the mixing layer just after the flow merging. Two-point correlations of velocity fluctuation around the mixing interface were compared with those of concentration fluctuation. These results show that the spatial pattern of concentration fluctuation connected with turbulent mixing is conveyed downstream with extension growth.

초기 횡방향 유동이 존재하는 충돌제트/유출냉각에서 요철이 설치된 유출면에서의 열/물질전달 특성

The present study is conducted to investigate the effect of rib arrangements on an impingement/effusion cooling system with initial cross flow. To simulate the impingement/effusion cooling system, two perforated plates are placed in parallel and staggered arrangements with a gap distance of 2 times of the hole diameter. Initial crossflow passes between the injection and effusion plates, and the square ribs (3mm) are installed on the effusion plate. Both the injection and effusion hole diameters are 10 mm and Reynolds number based on the hole diameter and hole-to-hole pitch are fixed to 10,000 and 6 times of the hole diameter, respectively. To investigate the effects of rib arrangements, various rib arrangements, such as 90˚transverse and 45°angled rib arrangements, are used. Also, the effects of flow rate ratio of cross flow to impinging jets are investigated. With the initial crossflow, locally low transfer regions are formed because the wall jets are swept away, and level of heat transfer rate get decreased with increasing flow rate of crossflow. When the ribs are installed on the effusion plate, the local distributions of heat/mass transfer coefficients around the effusion holes are changed. The local heat/mass transfer around the stagnation regions and the effusion holes are affected by the rib positions, angle of attack and rib spacing. For low blowing ratio, the ribs have adverse effects on heat/mass transfer, but for higher blowing ratios, higher and more uniform heat transfer coefficient distributions are obtained than the case without ribs because the ribs prevent the wall jets from being swept away by the crossflow and increase local turbulence of the flow near the surface. Average heat transfer coefficients with rib turbulators are approximately 10% higher than that without ribs, and the higher values are obtained with small pitch of ribs. However, the attack angle of the rib has little influence on the average heat/mass transfer.<br/>

Separation of La and Ce with PC-88A by counter-current mixer-settler extraction column

Abstract The separation of La and Ce with 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (commercially known as PC-88A) from nitrate media was studied with a multistage counter-current mixer-settler extraction column of seven stages developed by the authors. The effect of flow rate ratio of the aqueous phase ( Q w ) to the organic phase ( Q o ) on the separation was studied. The maximum separation was obtained at Q w / Q o =3.2 and the separation degree was 63. Scrubbing of the organic phase was also studied in order to enhance the separation. La was scrubbed from the organic phase with nitric acid at pH 2.7 and the separation degree during scrubbing was 45. Simulations of the extraction and scrubbing processes were carried out and compared with the obtained experimental results. Stripping of Ce was achieved by using 100 mol/m 3 nitric acid. The organic phase was successfully recycled during the experiments without any effect on the extraction efficiency.

Optimization and design considerations of two-phase continuous protein separation

Aqueous two-phase systems (ATPS) have begun to be used industrially for the isolation and separation of recombinant enzyme proteins. However, until now most studies have concentrated on investigating factors affecting the partition coefficients of molecules and even the pilot plant and scale-up developments have lacked engineering, optimization and design considerations. This paper investigates such considerations in the process of protein separation and purification in ATPS. A cost function for the process of protein extraction that takes into account the effect of variables in ATPS has been developed to study the influence of this extraction stage over the rest of the stages in the process (production, concentration and purification). The effect of the flow rate ratios, the relative sizes of the PEG and Phosphate phases and the NaCl concentration have been analysed. An extended mathematical model was used to describe the continuous, steady state operation of an aqueous two-phase system for protein extraction. The basic model is based on steady state mass balances of the main components and phase equilibrium data. Experimental data on the separation of α-amylase from Bacillus subtilis supernatant in a PEG/salt system was used. Simulations were carried out to study the effect of flow rate ratio as a function of NaCI concentration in the feed. At a flow rate ratio above 2.4 the extraction process was very sensitive to NaCl concentration. A rigorous optimization was carried out using the Sequential Quadratic Programming Method (SQP) with a fixed initial NaCI concentration of 8.8%. An optimal Flow Rate Ratio of 2.27 was obtained. Thus, the optimization strategy developed in this paper was mathematically implementable and successful. The optimal steady state process conditions corresponded to conditions of a large and continuous bottom phase in both the forward and back extractions. This is very favourable for phase separation as it results in fast settling rates which are also virtually independent of phase volume ratio, which are extremely favourable conditions for the design of appropriate settlers.

Three-dimensional viscoelastic numerical analysis of the encapsulation phenomena in coextrusion

In recent years coextrusion process had gained wide recognition as an approach to achieving high quality or quantity and low costs by multilayered system as well as an polymer alloy or blend. We performed a strict 3-D numerical simulation with viscoelastic model on the encapsulation phenomena which is one of the problems in the coextrusion process. The effects of material properties such as viscosity ratio, extensional viscosity and second normal stress difference and an effect of flow rate ratios on the encapsulation phenomena were examined. Numerical results showed that encapsulation phenomena were affected by not only viscous properties but also elastic properties or non-linear properties. It was found that the difference of second normal stress differences working on the interface between fluid I and fluid II (we defined it as DN2) had a correlation with the interface shape.