共查询到20条相似文献，搜索用时 62 毫秒
1.
In this paper, we demonstrate biphasic microfluidic droplets with broadly tunable internal structures, from simple near-equilibrium drop-in-drop morphologies to complex yet uniform non-equilibrium steady-state structures. The droplets contain an aqueous mixture of poly(ethylene glycol) (PEG) and dextran and are dispensed into an immiscible oil in a microfluidic T-junction device. Above a certain well-defined threshold droplet speed, the inner dextran-rich phase is "stirred" within the outer PEG-rich phase. The stirred polymer mixture is observed to exhibit a near continuum of speed and composition-dependent phase morphologies. There is increasing interest in the use of such aqueous two-phase systems in microfluidic devices for biomolecular applications in a variety of contexts. Our work presents a method to go beyond equilibrium phase morphologies in generating microfluidic "multiple" emulsions and at the same time raises the possibility of biochemical experimentation in benign yet complex biomimetic milieus. 相似文献
2.
Yun Suk Huh Chang-Moon Jeong Ho Nam Chang Sang Yup Lee Won Hi Hong Tae Jung Park 《Biomicrofluidics》2010,4(1)
A protein separation technology using the microfluidic device was developed for the more rapid and effective analysis of target protein. This microfluidic separation system was carried out using the aqueous two-phase system (ATPS) and the ionic liquid two-phase system (ILTPS) for purification method of the protein sample, and the three-flow desalting system was used for the removal of salts from the sucrose-rich sample. Partitioning of the protein sample was observed in ATPS or ILTPS with the various pHs. The microdialysis system was applied to remove small molecules, such as sucrose and salts in the microfluidic channel with the different flow rates of buffer phase. A complex purification method, which combines microdialysis and ATPS or ILTPS, was carried out for the effective purification of bacteriorhodopsin (BR) from the purple membrane of Halobacterium salinarium, which was then analyzed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and matrix-assisted laser desorption∕ionization time-of-flight. Furthermore, we were able to make a stable three-phase flow controlling the flow rate in the microfluidic channel. Our complex purification methods were successful in purifying and recovering the BR to its required value. 相似文献
3.
In this study, we show the importance of extensional rheology, in addition to the shear rheology, in the choice of blood analog solutions intended to be used in vitro for mimicking the microcirculatory system. For this purpose, we compare the flow of a Newtonian fluid and two well-established viscoelastic blood analog polymer solutions through microfluidic channels containing both hyperbolic and abrupt contractions∕expansions. The hyperbolic shape was selected in order to impose a nearly constant strain rate at the centerline of the microchannels and achieve a quasihomogeneous and strong extensional flow often found in features of the human microcirculatory system such as stenoses. The two blood analog fluids used are aqueous solutions of a polyacrylamide (125 ppm w∕w) and of a xanthan gum (500 ppm w∕w), which were characterized rheologically in steady-shear flow using a rotational rheometer and in extension using a capillary breakup extensional rheometer (CaBER). Both blood analogs exhibit a shear-thinning behavior similar to that of whole human blood, but their relaxation times, obtained from CaBER experiments, are substantially different (by one order of magnitude). Visualizations of the flow patterns using streak photography, measurements of the velocity field using microparticle image velocimetry, and pressure-drop measurements were carried out experimentally for a wide range of flow rates. The experimental results were also compared with the numerical simulations of the flow of a Newtonian fluid and a generalized Newtonian fluid with shear-thinning behavior. Our results show that the flow patterns of the two blood analog solutions are considerably different, despite their similar shear rheology. Furthermore, we demonstrate that the elastic properties of the fluid have a major impact on the flow characteristics, with the polyacrylamide solution exhibiting a much stronger elastic character. As such, these properties must be taken into account in the choice or development of analog fluids that are adequate to replicate blood behavior at the microscale. 相似文献
4.
We demonstrate the generation of water-in-water (w/w) jets and emulsions by combining droplet microfluidics and aqueous two-phase systems (ATPS). The application of ATPS in microfluidics has been hampered by the low interfacial tension between typical aqueous phases. The low tension makes it difficult to form w/w droplets with conventional droplet microfluidic approaches. We show that by mechanically perturbing a stable w/w jet, w/w emulsions can be prepared in a controlled and reproducible fashion. We also characterize the encapsulation ability of w/w emulsions and demonstrate that their encapsulation efficiency can be significantly enhanced by inducing formation of precipitates and gels at the w/w interfaces. Our work suggests a biologically and environmentally friendly platform for droplet microfluidics and establishes the potential of w/w droplet microfluidics for encapsulation-related applications. 相似文献
5.
We exploited the viscoelasticity of biocompatible dilute polymeric solutions, namely, dilute poly(ethylene oxide) solutions, to significantly enhance mixing in microfluidic devices at a very small Reynolds number, i.e., Re≈0.023, but large Peclet and elasticity numbers. With an abrupt contraction microgeometry (8:1 contraction ratio), two different dilute poly(ethylene oxide) solutions were successfully mixed with a short flow length at a relatively fast mixing time of <10 μs. Microparticle image velocimetry was employed in our investigations to characterize the flow fields. The increase in velocity fluctuation with an increase in flow rate and Deborah number indicates the increase in viscoelastic flow instability. Mixing efficiency was characterized by fluorescent concentration measurements. Our results showed that enhanced mixing can be achieved through viscoelastic flow instability under situations where molecular-diffusion and inertia effects are negligible. This approach bypasses the laminar flow limitation, usually associated with a low Reynolds number, which is not conducive to mixing. 相似文献
6.
Chaitanya Kantak Qingdi Zhu Sebastian Beyer Tushar Bansal Dieter Trau 《Biomicrofluidics》2012,6(2):022006-022006-9
Here, we utilize microfluidic droplet technology to generate photopolymerizeable polyethylene glycol (PEG) hydrogel microbeads incorporating a fluorescence-based glucose bioassay. A microfluidic T-junction and multiphase flow of fluorescein isothiocyanate dextran, tetramethyl rhodamine isothiocyanate concanavalin A, and PEG in water were used to generate microdroplets in a continuous stream of hexadecane. The microdroplets were photopolymerized mid-stream with ultraviolet light exposure to form PEG microbeads and were collected at the outlet for further analysis. Devices were prototyped in PDMS and generated highly monodisperse 72 ± 2 μm sized microbeads (measured after transfer into aqueous phase) at a continuous flow rate between 0.04 ml/h—0.06 ml/h. Scanning electron microscopy analysis was conducted to analyze and confirm microbead integrity and surface morphology. Glucose sensing was carried out using a Förster resonance energy transfer (FRET) based assay. A proportional fluorescence intensity increase was measured within a 1–10 mM glucose concentration range. Microfluidically synthesized microbeads encapsulating sensing biomolecules offer a quick and low cost method to generate monodisperse biosensors for a variety of applications including cell cultures systems, tissue engineering, etc. 相似文献
7.
Immiscible aqueous phases, formed by dissolving incompatible solutes in water, have been used in green chemical synthesis, molecular extraction and mimicking of cellular cytoplasm. Recently, a microfluidic approach has been introduced to generate all-aqueous emulsions and jets based on these immiscible aqueous phases; due to their biocompatibility, these all-aqueous structures have shown great promises as templates for fabricating biomaterials. The physico-chemical nature of interfaces between two immiscible aqueous phases leads to unique interfacial properties, such as an ultra-low interfacial tension. Strategies to manipulate components and direct their assembly at these interfaces needs to be explored. In this paper, we review progress on the topic over the past few years, with a focus on the fabrication and stabilization of all-aqueous structures in a multiphase microfluidic platform. We also discuss future efforts needed from the perspectives of fluidic physics, materials engineering, and biology for fulfilling potential applications ranging from materials fabrication to biomedical engineering. 相似文献
8.
Kuo-yuan Chung Narayan Chandra Mishra Chen-chi Wang Feng-hui Lin Keng-hui Lin 《Biomicrofluidics》2009,3(2)
In this paper, we demonstrate for the first time the technique to using microfluidics to fabricate tissue engineering scaffolds with uniform pore sizes. We investigate both the bubble generation of the microfluidic device and the application of foam as a tissue engineering scaffold. Our microfluidic device consists of two concentric tapered channels, which are made by micropipettes. Nitrogen gas and aqueous alginate solution with Pluronic® F127 surfactant are pumped through the inner and the outer channels, respectively. We observe rich dynamic patterns of bubbles encapsulated in the liquid droplets. The size of the bubble depends linearly on the gas pressure and inversely on the liquid flow rate. In addition, monodisperse bubbles self-assemble into crystalline structures. The liquid crystalline foams are further processed into open-cell solid foams. The novel foam gel was used as a scaffold to culture chondrocytes. 相似文献
9.
We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. 相似文献
10.
Ultrafast microfluidics using surface acoustic waves 总被引：2，自引：0，他引：2
We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and micro∕bioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1–10 cm∕s velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel. If the flow is sufficiently quiescent, the nodes of the transverse standing wave that arises across the microchannel also allow for particle aggregation, and hence, sorting on nodal lines. In addition, the SAW also facilitates other microfluidic capabilities. For example, capillary waves excited at the free surface of a sessile drop by the SAW underneath it can be exploited for micro∕nanoparticle collection and sorting at nodal points or lines at low powers. At higher powers, the large accelerations off the substrate surface as the SAW propagates across drives rapid destabilization of the drop free surface giving rise to inertial liquid jets that persist over 1–2 cm in length or atomization of the entire drop to produce 1–10 μm monodispersed aerosol droplets, which can be exploited for ink-jet printing, mass spectrometry interfacing, or pulmonary drug delivery. The atomization of polymer∕protein solutions can also be used for the rapid synthesis of 150–200 nm polymer∕protein particles or biodegradable polymeric shells in which proteins, peptides, and other therapeutic molecules are encapsulated within for controlled release drug delivery. The atomization of thin films behind a translating drop containing polymer solutions also gives rise to long-range spatial ordering of regular polymer spots whose size and spacing are dependent on the SAW frequency, thus offering a simple and powerful method for polymer patterning without requiring surface treatment or physical∕chemical templating. 相似文献
11.
Using a membrane emulsification method based on porous hollow-fiber membranes in combination with an aqueous two-phase system (ATPS), we are able to produce “water-in-water” droplets with narrow-dispersed size distributions. The equilibrium phases of the aqueous two-phase system polyethylene glycol-dipotassium hydrogen phosphate are used for this purpose. The droplet diameter of a given fluid system is determined by the flow rates of the continuous and disperse phase as well as the hollow fiber dimensions. When diluting the disperse phase and thus moving the ATPS system out of equilibrium, the droplet size can be further reduced in comparison to the equilibrium case. Generally, droplets formed with this method have diameters 20%–60% larger than the inner hollow fiber diameter. The new strategy of diluting the disperse phase allows the production of droplet diameter below the inner diameter of the membrane. 相似文献
12.
Definable surface chemistry is essential for many applications of microfluidic polymer systems. However, small cross-section channels with a high surface to volume ratio enhance passive adsorption of molecules that depletes active molecules in solution and contaminates the channel surface. Here, we present a one-step photochemical process to coat the inner surfaces of closed microfluidic channels with a nanometer thick layer of poly(ethylene glycol) (PEG), well known to strongly reduce non-specific adsorption, using only commercially available reagents in an aqueous environment. The coating consists of PEG diacrylate (PEGDA) covalently grafted to polymer surfaces via UV light activation of the water soluble photoinitiator benzoyl benzylamine, a benzophenone derivative. The PEGDA coating was shown to efficiently limit the adsorption of antibodies and other proteins to <5% of the adsorbed amount on uncoated polymer surfaces. The coating could also efficiently suppress the adhesion of mammalian cells as demonstrated using the HT-29 cancer cell line. In a subsequent equivalent process step, protein in aqueous solution could be anchored onto the PEGDA coating in spatially defined patterns with a resolution of <15 μm using an inverted microscope as a projection lithography system. Surface patterns of the cell binding protein fibronectin were photochemically defined inside a closed microfluidic device that was initially homogeneously coated by PEGDA. The resulting fibronectin patterns were shown to greatly improve cell adhesion compared to unexposed areas. This method opens for easy surface modification of closed microfluidic systems through combining a low protein binding PEG-based coating with spatially defined protein patterns of interest. 相似文献
13.
We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s–1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. 相似文献
14.
Improving methods for high-throughput combinatorial chemistry has emerged as a major area of research because of the importance of rapidly synthesizing large numbers of chemical compounds for drug discovery and other applications. In this investigation, a novel microfluidic chip for performing parallel combinatorial chemical synthesis was developed. Unlike past microfluidic systems designed for parallel combinatorial chemistry, the chip is a single-layer device made of poly(dimethylsiloxane) that is extremely easy and inexpensive to fabricate. Using the chip, a 2×2 combinatorial series of amide-formation reactions was performed. The results of this combinatorial synthesis indicate that the new device is an effective platform for running parallel organic syntheses at significantly higher throughput than with past methodologies. Additionally, a design algorithm for scaling up the 2×2 combinatorial synthesis chip to address more complex cases was developed. 相似文献
15.
BackgroundPEGylation, defined as the covalent attachment of polyethylene glycol, allows the synthesis of PEGylated therapeutic proteins with enhanced physicochemical properties. Traditional alkylating N-terminal PEGylation reactions on amine groups involve the use of modified linear mono-methoxy polyethylene glycol (mPEG) molecules looking for the synthesis of mono-PEGylated products. However, this approach requires different purification steps since inevitably undesired cross-linked products are synthesized. Herein, we propose the use of reactive aqueous two-phase systems (ATPS) to produce and purify PEGylated therapeutic conjugates using Ribonuclease A (RNase A) as a model protein.ResultsSelected linear 5 kDa and 20 kDa mPEG – potassium phosphate systems were produced according to equilibrium data obtained from constructed binodal curves. All reactive systems were able to generate biphasic systems and to PEGylate RNase A. Two 5 kDa and two 20 kDa systems were selected based on the reaction yield percentage and the feasibility of purifying the mono-PEGylated RNase A from the di-PEGylated and native RNase A by contrasting the differences in their partition behaviors. The remnant biological activity was of 94% and of 100% for the mono-PEGylated RNase A purified from the 5 kDa and 20 kDa mPEG systems when compared to the mono-PEGylated conjugate obtained by standard procurement methods.ConclusionsThis novel approach using reactive ATPS shows that it is feasible to simultaneously produce and purify PEGylated therapeutic proteins with conserved biological activity and presents another example where reactive ATPS can be successfully implemented.How to cite: Campos-García VR, Benavides J, González-Valdez J. Reactive aqueous two-phase systems for the production and purification of PEGylated proteins. Electron J Biotechnol 2021;54. https://doi.org/10.1016/j.ejbt.2021.09.003 相似文献
16.
AC Faradaic reactions have been reported as a mechanism inducing non-ideal phenomena such as flow reversal and cell deformation in electrokinetic microfluidic systems. Prior published work described experiments in parallel electrode arrays below the electrode charging frequency (fc), the frequency for electrical double layer charging at the electrode. However, 2D spatially non-uniform AC electric fields are required for applications such as in plane AC electroosmosis, AC electrothermal pumps, and dielectrophoresis. Many microscale experimental applications utilize AC frequencies around or above fc. In this work, a pH sensitive fluorescein sodium salt dye was used to detect [H+] as an indicator of Faradaic reactions in aqueous solutions within non-uniform AC electric fields. Comparison experiments with (a) parallel (2D uniform fields) electrodes and (b) organic media were employed to deduce the electrode charging mechanism at 5 kHz (1.5fc). Time dependency analysis illustrated that Faradaic reactions exist above the theoretically predicted electrode charging frequency. Spatial analysis showed [H+] varied spatially due to electric field non-uniformities and local pH changed at length scales greater than 50 μm away from the electrode surface. Thus, non-uniform AC fields yielded spatially varied pH gradients as a direct consequence of ion path length differences while uniform fields did not yield pH gradients; the latter is consistent with prior published data. Frequency dependence was examined from 5 kHz to 12 kHz at 5.5 Vpp potential, and voltage dependency was explored from 3.5 to 7.5 Vpp at 5 kHz. Results suggest that Faradaic reactions can still proceed within electrochemical systems in the absence of well-established electrical double layers. This work also illustrates that in microfluidic systems, spatial medium variations must be considered as a function of experiment time, initial medium conditions, electric signal potential, frequency, and spatial position. 相似文献
17.
Spherical and non-spherical wax microparticles are generated by employing a facile two-step droplet microfluidic process which consists of the formation of molten wax microdroplets in a flow-focusing microchannel and their subsequent off-chip crystallization and deformation via microdroplet impingement on an immiscible liquid interface. Key parameters on the formation of molten wax microdroplets in a microfluidic channel are the viscosity of the molten wax and the interfacial tension between the dispersed and continuous fluids. A cursory phase diagram of wax morphology transition is depicted depending on the Capillary number and the Stefan number during the impact process. A combination of numerical simulation and analytical modeling is carried out to understand the physics underlying the deformation and crystallization process of the molten wax. The deformation of wax microdroplets is dominated by the viscous and thermal effects rather than the gravitational and buoyancy effects. Non-isothermal crystallization kinetics of the wax illustrates the time dependent thermal effects on the droplet deformation and crystallization. The work presented here will benefit those interested in the design and production criteria of soft non-spherical particles (i.e., alginate gels, wax, and polymer particles) with the aid of time and temperature mediated solidification and off-chip crosslinking. 相似文献
18.
We summarize a recently developed microtechnology for printing biomaterials on biological surfaces. The technique is based on the use of immiscible aqueous solutions of two biopolymers and allows spatially defined placement of cells and biomolecules suspended in the denser aqueous phase on existing cell layers and extracellular matrix hydrogel surfaces maintained in the second phase. Printing takes place due to an extremely small interfacial tension and density difference between the two aqueous phases. The contact-free printing process ensures that both printed cells and the underlying cell monolayer maintain full viability and functionality. The technique accommodates both arbitrarily shaped patterns and microarrays of cells and bioreagents. The capability to print cells and small molecules on existing cell layers enables unique interrogations of the effects of cell-cell and cell-material interaction on cell fate and function. Furthermore, the very gentle conditions and the ability to directly pattern nongel embedded cells over cells make this technology appealing to tissue engineering applications where patterned multicellar organization with minimal scaffolding materials is needed, such as in dense tissues of the skeletal muscle and liver. 相似文献
19.
This paper reports the improvement of rectification effects in diffuser∕nozzle structures with viscoelastic fluids. Since rectification in a diffuser∕nozzle structure with Newtonian fluids is caused by inertial effects, micropumps based on this concept require a relatively high Reynolds numbers and high pumping frequencies. In applications with relatively low Reynolds numbers, anisotropic behavior can be achieved with viscoelastic effects. In our investigations, a solution of dilute polyethylene oxide was used as the viscoelastic fluid. A microfluidic device was fabricated in silicon using deep reactive ion etching. The microfluidic device consists of access ports for pressure measurement, and a series of ten diffuser∕nozzle structures. Measurements were carried out for diffuser∕nozzle structures with opening angles ranging from 15° to 60°. Flow visualization, pressure drop and diodicity of de-ionized water and the viscoelastic fluid were compared and discussed. The improvement of diodicity promises a simple pumping concept at low Reynolds numbers for lab-on-a-chip applications. 相似文献
20.
We present a novel image-based method to measure the on-chip microfluidic pressure and flow rate simultaneously by using the integrated optofluidic membrane interferometers (OMIs). The device was constructed with two layers of structured polydimethylsiloxane (PDMS) on a glass substrate by multilayer soft lithography. The OMI consists of a flexible air-gap optical cavity which upon illumination by monochromatic light generates interference patterns that depends on the pressure. These interference patterns were captured with a microscope and analyzed by computer based on a pattern recognition algorithm. Compared with the previous techniques for pressure sensing, this method offers several advantages including low cost, simple fabrication, large dynamic range, and high sensitivity. For pressure sensing, we demonstrate a dynamic range of 0-10 psi with an accuracy of ±2% of full scale. Since multiple OMIs can be integrated into a single chip for detecting pressures at multiple locations simultaneously, we also demonstrated a microfluidic flow sensing by measuring the differential pressure along a channel. Thanks to the simple fabrication that is compatible with normal microfluidics, such OMIs can be easily integrated into other microfluidic systems for in situ fluid monitoring. 相似文献