Generation of concentration gradient by controlled flow distribution and diffusive mixing in a microfluidic chip

We have developed a simple method to generate a concentration gradient in a microfluidic device. This method is based on the combination of controlled fluid distribution at each intersection of a microfluidic network by liquid pressure and subsequent diffusion between laminas in the downstream microchannel. A fluid dynamic model taking into account the diffusion coefficient was established to simulate the on-chip flow distribution and diffusion. Concentration gradients along a distance of a few hundred micrometers were generated in a series of microchannels. The gradients could be varied by carefully regulating the liquid pressure applied to the sample injection vials. The observed concentration gradients of fluorescent dyes generated on the microfluidic channel are consistent with the theoretically predicted results. The microfluidic design described in this study may provide a new tool for applications based on concentration gradients, including many biological and chemical analyses such as cellular reaction monitoring and drug screening.     

Photo‐crosslinkable hydrogel‐based 3D microfluidic culture device

We developed the photo‐crosslinkable hydrogel‐based 3D microfluidic device to culture neural stem cells (NSCs) and tumors. The photo‐crosslinkable gelatin methacrylate (GelMA) polymer was used as a physical barrier in the microfluidic device and collagen type I gel was employed to culture NSCs in a 3D manner. We demonstrated that the pore size was inversely proportional to concentrations of GelMA hydrogels, showing the pore sizes of 5 and 25 w/v% GelMA hydrogels were 34 and 4 μm, respectively. It also revealed that the morphology of pores in 5 w/v% GelMA hydrogels was elliptical shape, whereas we observed circular‐shaped pores in 25 w/v% GelMA hydrogels. To culture NSCs and tumors in the 3D microfluidic device, we investigated the molecular diffusion properties across GelMA hydrogels, indicating that 25 w/v% GelMA hydrogels inhibited the molecular diffusion for 6 days in the 3D microfluidic device. In contrast, the chemicals were diffused in 5 w/v% GelMA hydrogels. Finally, we cultured NSCs and tumors in the hydrogel‐based 3D microfluidic device, showing that 53–75% NSCs differentiated into neurons, while tumors were cultured in the collagen gels. Therefore, this photo‐crosslinkable hydrogel‐based 3D microfluidic culture device could be a potentially powerful tool for regenerative tissue engineering applications.     

键合方法对聚二甲基硅氧烷液滴型微流控芯片的影响

液滴型微流控芯片表面性质是影响其性能的重要因素. 研究了不同键合方法对基于聚二甲基硅氧烷(PDMS)的液滴型微流控芯片微管道表面性质的影响, 并分别观察和评价了不同键合方法所制作液滴型微流控芯片应用于制备油包水和水包油两种液滴分散体系的效果. 结果显示热扩散键合方法适用于制作油包水型PDMS液滴型微流控芯片, 而等离子键合方法制作的PDMS芯片适于形成水包油型的液滴分散体系.     

Conductivity detection for monitoring mixing reactions in microfluidic devices

A conductivity detector was coupled to poly(dimethylsiloxane)-glass capillary electrophoresis microchips to monitor microfluidic flow. Electroosmotic flow was investigated with both conductivity detection (CD) and the current monitoring method. No significant variation was observed between these methods, but CD showed a lower relative standard deviation. Gradient mixing experiments were employed to investigate the relationship between the electrolyte conductivity and the electrolyte concentration. A good linear response of conductivity to concentration was obtained for solutions whose difference in concentrations were less than 27 mM. The new system holds great promise for precision mixing in microfluidic devices using electrically driven flows.     

Potentiometric investigation of protonation reactions at aqueous-aqueous boundaries within a dual-stream microfluidic structure

The laminar flow regime prevailing in pressure-driven flow through a Y-shaped microfluidic channel was utilized to create a stable boundary between two aqueous liquids. Transverse transport of ions between these two liquids gave rise to a diffusion potential, which was monitored by measurement of the open circuit potential. In this report, the influence on the cross-channel potential distribution of protonation reactions occurring in the boundary zone between the two co-flowing liquids is presented. The proton source was present in one of the co-flowing streams, and an uncharged proton acceptor was present in the other aqueous stream. The time-dependent transport equation for diffusion and migration was augmented by chemical reaction terms and was solved for all species present in both streams as a theoretical basis for the analysis. Within this model, the system was assumed to be homogeneous along the channel height, and effects of nonuniform velocity profiles were neglected. A reduction in potential by several millivolts was predicted for a protonation reaction occurring close to the boundary between the two aqueous streams, provided that the mobility of the protonated species was lower than the mobility of the co-cation in the background electrolyte (alkali metal cation in this case). The magnitude of the decrease in the potential was greater for protonated molecules with lower mobility or if the mobility of the background electrolyte cation was increased. Experimental results are presented for imidazole and D-histidine as proton acceptors present in 10 mM KCl, 10 mM NaCl, or 10 mM CsCl solution and co-flowing with a stream of 10 mM hydrochloric acid, which served as the proton source. Decreases in measured potential, in line with the predicted diminished potential, were obtained.     

Microfluidic voltammetry: simulation of the chronoamperometric response of microband electrodes sited within microreactors

A computationally efficient fully implicit approach to the simulation of the chronoamperometric response of microband electrodes sited within microscale rectangular ducts is reported. The current response is reported for stagnant solution and where electrolyte is pumped through the cell under microfluidic control. The generality of the method is illustrated with reference to the simple case of a reversible one-electron-transfer reaction. The influence of flow rate and the effects of axial, lateral and normal diffusion upon the electrolysis current are examined and the results compared to approximate analytical behaviour where appropriate.Dedicated to Professor Dr. Alan Bond on the occasion of his 60th birthday.     

Diffusion characteristics of a T-type microchannel with different configurations and inlet angles.

A series of symmetrical and asymmetrical microfluidic T-sensors with different inlet angles were fabricated to study the mixing characteristics of a T-type microstructure for generating concentration gradient. Computational fluid dynamics (CFD) simulations showed that the concentration gradient, transition zone and diffusion length were different for various configurations and inlet angles. Quick mix and sharp concentration gradient occurred in the asymmetrical structure with large inlet angle. The observed concentration gradients in the fabricated microchannel were consistent with the theoretical prediction. In this microstructure, stagnant zone and z-direction diffusion also affected the concentration gradient. Based on the simulation results, the microfluidic structure was optimized to generate desired concentration gradient for a cell-based study.     

Microfluidic chip of concentration gradient and fluid shear stress on a single cell level

Concentration gradient and fluid shear stress(FSS) for cell microenvironment were investigated through microfluidic technology. The Darcy–Weisbach equation combined with computational fluid dynamics modeling was exploited to design the microfluidic chip, and the FSS distribution on the cell model with varying micro-channels(triangular, conical, and elliptical). The diffusion with the incompressible laminar flow model by solving the time-dependent diffusion–convection equation was applied to simu...     

Microfluidic chip for electrochemically-modulated liquid∣liquid extraction of ions

A microfluidic device with integrated electrodes for the electrochemically-modulated extraction of ions across immiscible aqueous–organic liquid–liquid interfaces is presented. Using a Y-shaped microfluidic channel with in situ electrodes and co-flowing aqueous and organic immiscible electrolyte solutions, the manipulation of the applied interfacial potential enabled the extraction of ions from the aqueous phase into the organic phase. Data for the extraction of tetraethylammonium cations from aqueous electrolyte into 1,2-dichloroethane electrolyte are presented. The device demonstrates the benefits of combination of microfluidics and liquid–liquid electrochemistry.     

A microfluidic diffusion chamber for reversible environmental changes around flaccid lipid vesicles

The reversible environmental changes around flaccid lipid vesicles represent a considerable experimental challenge, particularly because of remarkable softness of flaccid membranes, which can warp irreversibly under the slightest hydrodynamic flow. As a result, we have developed a microfluidic device for the controlled analysis of individual flaccid, giant lipid vesicles in a changing chemical environment. The setup combines the advantages of a flow-free microfluidic diffusion chamber and optical tweezers, which are used to load the sample vesicles into the chamber. After a vesicle is loaded into the diffusion chamber, its chemical environment is controllably and reversibly changed solely by means of diffusion. The chamber is designed as a 250 micrometres-long and 100 micrometres-wide dead-end microchannel, which extends from a T-junction of the main microchannels. Measurements of the flow-velocity profile in the chamber show that the flow rate decreases exponentially and scales linearly with the flow rate in the main channel. The characteristic length of the exponential decrease is 15 (1 ± 0.13) micrometres, meaning that a large part of the diffusion chamber is effectively flow-free. The diffusion properties are assessed by monitoring the diffusion of a dye into the chamber. It was found that a simple 1D diffusion model fits well to the experimental data. The time needed for the exchange of solutes in the chamber is of the order of minutes, depending on the solute's molecular weight. Here, we demonstrate how the diffusion chamber can be used for reversible environmental changes around flaccid, giant lipid vesicles and membrane tethers (nanotubes).     

Impedance spectroscopy studies of changes in the properties of lithium-sulfur cells in the course of cycling

Changes in the properties of lithium-sulfur cells during cycling were studied by impedance spectroscopy. The electric conductivity of the electrolyte changed during the charging and discharging of the lithium-sulfur cells as a result of the dissolution of lithium polysulfides formed in electrochemical reactions. The maximum resistance of the electrolyte and the surface layers on the sulfur and lithium electrodes was achieved in the region of the transition between the low- and high-voltage areas on the charge and discharge curves of the cells. This region corresponded to the highest concentration of lithium polysulfides in the electrolyte. For nearly charged or discharged lithium-sulfur cells, the impedance spectra contained linear segments which could be attributed to diffusion limitations at low frequencies. An analysis of the results of impedance studies suggested that the electrochemical processes in lithium-sulfur cells were controlled by diffusion in the surface layer on the sulfur electrode at high degrees of charge or discharge and by the transport properties of the electrolytic system at moderate degrees of charging.     

Determination of Activation Energy for the Diffusion of Fe<Superscript>3+</Superscript> Ions in Agar Gel Medium Containing Various Transition Metal Sulfates

The study of the diffusion of ferric ions in agar gel containing transition metal sulfates was carried out. The effect of gel concentration, electrolyte concentration and temperature on the diffusion of Fe³⁺ ions in various transition metal sulfates was studied with a view to verify Wang’s model of diffusion and the applicability of transition state theory to diffusion in a gel medium. The diffusion coefficients were measured using the zone diffusion technique. For a given concentration of electrolyte the activation energy (E) is found to decrease with an increase in the charge density of the cation of the supporting electrolyte and for a given system it is found to decrease with increasing electrolyte concentration in agreement with Wang’s model. This observation is explained on the basis of the distortion in the water structure caused by ions and agar molecules. At a given electrolyte concentration the magnitude of the Arrhenius parameters, E and D _o, is found to decrease with increasing gel concentration in agreement with the transition state theory of diffusion.     

Gas diffusion electrodes for polymer electrolyte fuel cell using sulfonated polyimide

Gas diffusion electrodes for high temperature polymer electrolyte fuel cells (PEFCs) have been prepared by using a novel proton conductive sulfonated polyimide (SPI) electrolyte. The catalyst layer was composed of Pt-loaded carbon black (Pt-CB) and SPI ionomer. The polarization properties and the microstructure of the catalyst layer were investigated as a function of the SPI/CB weight ratio. The anodic polarization was found to be negligibly small for all the compositions examined. The highest cathode performance was obtained at SPI/CB = 0.5 (by weight), where the best balance of high catalyst utilization and oxygen gas diffusion rate through the ionomer was obtained.     

Anisotropic diffusion of water in perfluorosulfonic acid membrane and hydrocarbon membranes

Polymer electrolyte membranes that are applied for polymer electrolyte fuel cell (PEFC) retain water in their three-dimensional network structure. Diffusion behavior of water in the membranes was analyzed by pulsed field gradient (PFG)-NMR method to estimate diffusion coefficient of proton species as water or hydronium ion. The membrane samples were put in a sample tube vertically or horizontally toward to the field gradient axis under determined temperature and humidity conditions. As the results, anisotropic diffusion behavior of water in the membranes was indicated. Anisotropic properties depended on the sample type, preparation conditions of the wet membranes, and measurement conditions. A perfluorosulfonic acid membrane tended to have smaller anisotropy while hydrocarbon membranes showed greater anisotropy.     

An electrochemically driven poly(dimethylsiloxane) microfluidic actuator: oxygen sensing and programmable flows and pH gradients

We describe the fabrication and performance of an integrated microelectrochemical reactor-a design possessing utility for multiple applications that include electrochemical sensing, the generation and manipulation of in-channel microfluidic pH gradients, and fluid actuation and flow. The device architecture is based on a three-electrode electrochemical cell design that incorporates a Pt interdigitated array (IDA) working (WE), a Pt counter (CE), and Ag pseudo-reference (RE) electrodes within a microfluidic network in which the WE is fully immersed in a liquid electrolyte confined in the channels. The microchannels are made from a conventional poly(dimethylsiloxane)(PDMS) elastomer, which serves also as a thin gas-permeable membrane through which gaseous reactants in the external ambient environment are supplied to the working electrode by diffusion. Due to the high permeability of oxygen through PDMS, the microfluidic cell supports significantly (>order of magnitude) higher current densities in the oxygen reduction reaction (ORR) than those measured in conventional (quiescent) electrochemical cells for the same electrode areas. We demonstrate in this work that, when operated at constant potential under mass transport control, the device can be utilized as a membrane-covered oxygen sensor, the response of which can be tuned by varying the thickness of the PDMS membrane. Depending on the experimental conditions under which the electrochemical ORR is performed, the data establish that the device can be operated as both a programmable pH gradient generator and a microfluidic pump.     

Microfluidic pool structure for cell docking and rapid mixing

A microfluidic pool structure for cell docking and rapid mixing is described. The pool structure is defined as a microchamber on one structural layer of a bilayer chip and connects with two or more individual microchannels on the other structural layer. In contrast to the turbulent flow in a macroscale pool, laminar streams enter and exit this microfluidic pool structure with definite and controllable direction that may be influenced by the location and geometry of the pool. A simple microfluidic model was used to validate this hypothesis. In this model, a microscale pool structure was made on the lower layer of a chip and connected with three parallel microchannels in the upper layer. Simulation and experimental results indicated that the flow profile within the pool structure was determined by its geometry and location. This could be used as a flow control method and it was simpler than designs based on microvalve, hydraulic pressure, or electrokinetic force, and has some important applications. For example, controllable streams within this structure were used to immobilize biological cells along the microchannel walls. When different solution streams flowed through the pool, rapid diffusion of analytes occurred for short diffusion distance between vertical flow laminas. Furthermore, desired dilution (mixing) ratio could be obtained by controlling the geometry of the microfluidic pool.     

Ionic diffusion and salt dissociation conditions of lithium liquid crystal electrolytes

Salt dissociation conditions and dynamic properties of ionic species in liquid crystal electrolytes of lithium were investigated by a combination of NMR spectra and diffusion coefficient estimations using the pulsed gradient spin-echo NMR techniques. Activation energies of diffusion (Ea) of ionic species changed with the phase transition of the electrolyte. That is, Ea of the nematic phase was lower than that of the isotropic phase. This indicates that the aligned liquid crystal molecules prepared efficient conduction pathways for migration of ionic species. The dissociation degree of the salt was lower compared with those of the conventional electrolyte solutions and polymer gel electrolytes. This is attributed to the low concentration of polar sites, which attract the dissolved salt and promote salt dissociation, on the liquid crystal molecules. Furthermore, motional restriction of the molecules due to high viscosity and molecular oriented configuration in the nematic phase caused inefficient attraction of the sites for the salt. With a decreased dissolved salt concentration of the liquid crystal electrolyte, salt dissociation proceeded, and two diffusion components attributed to the ion and ion pair were detected independently. This means that the exchange rate between the ion and the ion pair is fairly slow once the salt is dissociated in the liquid crystal electrolytes due to the low motility of the medium molecules that initiate salt dissociation.     

Skin‐worn Soft Microfluidic Potentiometric Detection System

A flexible skin‐mounted microfluidic potentiometric device for simultaneous electrochemical monitoring of sodium and potassium in sweat is presented. The wearable device allows efficient natural sweat pumping to the potentiometric detection chamber, containing solid‐contact ion‐selective Na⁺ and K⁺ electrodes, during exercise activity. The fabricated microchip electrolyte‐sensing device displays good analytical performance and addresses sweat mixing and carry‐over issues of early epidermal potentiometric sensors. Such soft skin‐worn microchip platform integrates potentiometric measurement, microfluidic technologies with flexible electronics for real‐time wireless data transmission to mobile devices. The new fully integrated microfluidic electrolyte‐detection device paves the way for practical fitness and health monitoring applications.     

The enhanced diffusional mixing for latex immunoagglutination assay in a microfluidic device

Latex immunoagglutination assay in a microfluidic device is expected to be even easier than its large-sized, commercialized counterpart. However, such demonstration has had a limited success due to the difficulties in mixing in a microfluidic device, especially for the microparticles used in latex immunoagglutination assay. The primary goal of this work is to improve diffusional mixing towards the successful latex immunoagglutination in a microfluidic devices without any non-specific binding. To this end, SDS (sodium dodecyl sulfate, an ionic surfactant) or Tween 80 (polyethylene sorbitol ester, a non-ionic surfactant) was added to the antibody-conjugated polystyrene (PS) microparticle suspension. These surfactant-added particle suspensions were mixed with the target antigen solution at the Y-junction of a microfluidic device. The immunoagglutination and the diffusion behavior were visually identified with an inverted light microscope. Both surfactants showed some problems such as non-specific binding (with SDS) or very poor diffusion (with Tween 80). As an alternative approach, therefore, highly carboxylated PS microparticles, where the surface is saturated with carboxyl-terminated side chains, were evaluated without using any surfactants. These particles showed very low non-specific binding comparable to that with Tween 80 and good diffusional mixing equivalent to that with SDS.