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1.
Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μBlood/μPBS) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (QPBSSS/QBloodL). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (ABlood (t) = Aα + Aβ exp [−(t − t0)/λBlood]) is selected based on the pressure difference (ΔP = PA − PB) at each junction (A, B) of both side channels. The characteristic time of blood (λBlood) is measured by analyzing the area (ABlood) filled with blood in the bridge channel by selecting an appropriate detection window in the microscopic images captured by a high-speed camera (frame rate = 200 Hz, total measurement time = 7 s). The elasticity of blood (GBlood) is identified using the relationship between the characteristic time and the viscosity of blood. For practical demonstrations, the proposed method is successfully applied to evaluate the variations in viscosity and elasticity of various blood samples: (a) various hematocrits form 20% to 50%, (b) thermal-induced treatment (50 °C for 30 min), (c) flow-induced shear stress (53 ± 0.5 mL/h for 120 min), and (d) normal rat versus spontaneously hypertensive rat. Based on these experimental demonstrations, the proposed method can be effectively used to monitor variations in viscosity and elasticity of bloods, even with the absence of fully integrated sensors, tedious labeling and calibrations. 相似文献
2.
The selective cell separation is a critical step in fundamental life sciences, translational medicine, biotechnology, and energy harvesting. Conventional cell separation methods are fluorescent activated cell sorting and magnetic-activated cell sorting based on fluorescent probes and magnetic particles on cell surfaces. Label-free cell separation methods such as Raman-activated cell sorting, electro-physiologically activated cell sorting, dielectric-activated cell sorting, or inertial microfluidic cell sorting are, however, limited when separating cells of the same kind or cells with similar sizes and dielectric properties, as well as similar electrophysiological phenotypes. Here we report a label-free density difference amplification-based cell sorting (dDACS) without using any external optical, magnetic, electrical forces, or fluidic activations. The conceptual microfluidic design consists of an inlet, hydraulic jump cavity, and multiple outlets. Incoming particles experience gravity, buoyancy, and drag forces in the separation chamber. The height and distance that each particle can reach in the chamber are different and depend on its density, thus allowing for the separation of particles into multiple outlets. The separation behavior of the particles, based on the ratio of the channel heights of the inlet and chamber and Reynolds number has been systematically studied. Numerical simulation reveals that the difference between the heights of only lighter particles with densities close to that of water increases with increasing the ratio of the channel heights, while decreasing Reynolds number can amplify the difference in the heights between the particles considered irrespective of their densities.Separating specific cells from heterogeneous or homogeneous mixtures has been considered as a key step in a wide variety of applications ranging from biomedicine to energy harvesting. For example, the separation and sorting of rare circulating tumor cells (CTCs) from whole blood has gained significant importance in the potential diagnosis and treatment of metastatic cancers.1,2 Similarly, malaria detection relies on the collection of infected red blood cells (RBCs) from whole blood.3,4 In addition, the selective separation of lipid-rich microalgae from homogeneous mixtures of microalgae is a promising technique in biomass conversion.5To date, conventional cell separation can be done by labelling cells with biomolecules to induce differences in physical properties. For instance, in a fluorescence-activated cell sorter (FACS), cells to be separated are labelled with antibodies or aptamers with fluorescent molecules, and then sorted by applying an electrical potential.6,7 Similarly, magnetic-activated cell sorter (MACS) uses magnetic.8,9 Alternatively, label-free cell separation methods have exploited inherent differences in the physical properties (e.g., size and dielectric properties) of different kinds of cells. For example, acoustophoresis forces particles larger than a desired size to move into the center of a fluidic channel by using ultrasonic standing waves.10–12 Inertial microfluidics takes advantage of curved fluidic channels in order to amplify the size differences between particles.13,14 Mass-dependent separation of particles based on gravity and hydrodynamic flow was also reported.15 Particles with different dielectric properties can also be sorted by dielectrophoresis which induces the movement of polarizable particles.16–18The disadvantage of these methods, however, is that they require external forces and labels that may cause unexpected damage to biological cells.19–21 More importantly, most methods are limited in separating cells of the same kind or cells with similar sizes and dielectric properties.Here we designed a novel, label-free density difference amplification-based cell sorting (dDACS) that allows the separation of particles with the same size and charge by exploiting subtle differences in density without the use of external forces. Figure 1(a) illustrates the proposed microfluidic model and its underlying mechanism. The conceptual microfluidic system consists of an inlet, a separation chamber (hydraulic jump cavity), and multiple outlets. Particles entering through the inlet experience gravity (FG), buoyancy (FB), and drag (FD) forces in the separation chamber. The net force acting on the particles can be described as
F = FG + FB + FD.(1)As particles enter the separation chamber (i.e., hydraulic jump cavity), FD acting on the particles changes its direction along the streamline. The particles experience additional forces in the y direction due to large tangential angle (Fig. 1(b)). For lighter particles, whose densities are close to that of the surrounding water, FD becomes comparable to FG (i.e., in the y direction), while the net force for heavier particles is less affected by this additional contribution of FD due to a large FG. As a result, the height (H) and distance (D) that each particle can travel are different depending on its density. The difference in the maximum height (ΔHmax) between two particles with different density (ρp1 and ρp2) can be further approximated as
(2)where vyp0 and vyf represent the velocity of particle and fluid along the y direction at the entrance of hydraulic jump cavity, respectively.Open in a separate windowFIG. 1.Schematic illustration of label-free density difference amplification-based cell sorting (dDACS), which exploits differences in the densities (ρ1 > ρ2) of particles with similar diameters (d) and charge. (a) The conceptual microfluidic design consists of an inlet, a separation chamber (hydraulic jump cavity), and multiple outlets. Incoming particles experience gravity (FG), buoyancy (FB), and drag (FD) forces in the separation chamber, and depending on their densities, the height (H) and distance (D) that each particle is able to reach will be different, allowing the particles to be separated into multiple outlets. (b) Possible microfluidic channel configurations for density-based separation: Uniform channel height (left), gradual channel expansion (middle), and hydraulic jump cavity with sudden channel expansion (right). The height difference between particles with different densities can be amplified by the sudden channel expansion compared to the other two cases due to the relatively large tangential angle, θ of FD. (|θ1|≪ |θ2|) (see Fig. S1 in the supplementary material22).In comparison with the other two cases (Fig. 1(b) uniform channel height and gradual channel expansion), the height difference between the particles with different densities can be amplified by the sudden channel expansion in the hydraulic jump cavity due to relatively large tangential angle (see supplementary material22). Therefore, the particles can be separated through the multiple outlets, depending on their height and distance.In order to analyze the separation behavior of particles in the chamber according to differences in their densities, H and D are systematically investigated. The numerical simulations are performed using a commercial CFD software (CFX 14.0; ANSYS 14.0; ANSYS, Inc.). Particles with the same density may have different trajectories in the separation chamber depending on their inlet positions (Fig. 2(a)). Prior to this investigation, the maximum height (Hmax) and distance (Dmax) for each particle are compared by examining H and D of 100 identical particles at different inlet positions since the inlet position of particles could be controlled.20 Fig. 2(b) shows Hmax and Dmax of particles with respect to density at a fixed Reynolds number (Re = 0.1). Note that Reynolds number is defined as Re = ρfvfDh/μ, where ρf, vf, Dh, μ are density of fluid, velocity of the fluid, hydraulic diameter of a channel, and dynamic viscosity of the fluid, respectively. The hydraulic diameter in the Reynolds number is determined with the inlet channel. Particle densities in the range of 1.1 to 2.0 g/cm3 are chosen with the increase of 0.1 g/cm3. These values are quite reasonable in that the densities of many microorganisms such as microalgae are typically within this range and their densities can be varied by 0.2 g/m3 depending on their cellular context.23 The lighter particles travel with a higher Hmax, and longer Dmax. With the separation chamber, the height difference between particles with densities of 1.1 and 1.2 g/cm3 can be amplified by about 10 times as compared to that in a channel without the chamber, judging from the position where the 1.1 g/cm3 particle reaches its Hmax.Open in a separate windowFIG. 2.Microfluidic particle separation with respect to Reynolds number (Re). (a) Trajectories in the separation chamber of a hundred particles with the same density starting from inlet positions chosen arbitrarily in order to investigate the effect of the inlet positions on the maxima of the height (Hmax) and distance (Dmax) prior to further simulation. (b) Representative trajectories of particles having different densities from 1.1 to 2.0 g/cm3. (c) The maximum height (Hmax) of each particle with respect to Re. (d) Representative maximum distance (Dmax) of each particle at Re = 0.1. (Left) Streamline of fluid and representative trajectories of particles with densities of 1.1 and 2.0 g/cm3 in the separation chamber at Re = 0.1 (right).In Fig. 2(c), the values for Hmax of particles with respect to Reynolds number (Re) are presented. Since in our study, the maximum height (Hmax) and distance (Dmax) for each particle were compared by examining H and D of 100 identical particles that are randomly distributed in the channel (throughout all figures), there is little variation in Hmax and Dmax between each simulation. However, the standard deviation between each simulation is quite small and can be negligible. The Hmax values particles at Re = 0.5 with densities of 1.1 g/cm3 and 1.2 g/cm3 are 2.21 × 103 μm and 2.17 × 103 μm, respectively. The difference between Hmax of different particles, ΔHmax, increases with decreasing Re. For example, ΔHmax between particles with densities of 1.1 and 2.0 g/cm3 becomes 0.26 × 103 μm at Re = 1.0, but increases to 1.38 × 103 μm as Re decreases to 0.1. As Re increases (velocity of fluid increases), the relative velocity in the y direction between the fluid and the particle increases resulting in increasing of FD in the y direction since the velocity of particle in the y direction is very small at the entrance of the separation chamber. Thus, contribution of FD becomes comparable to the net force in the y direction. As a result, most of the particles even in the case of heavier ones travel quite similarly with the streamline, and ΔHmax subsequently decreases. On the other hand, as Re decreases, the contribution of FG becomes dominant due to the decrease of FD in the y direction. Consequently, the particles start to cross downwards streamlines as the density of the particles increases and Hmax gradually decreases. In addition, irrespective of their densities, ΔHmax of the particles increases with decreasing Re.Fig. 2(d) shows Dmax with respect to the density of the particles (left). Different densities of particles show different trajectories due to the relative contribution of FD to the net force in the y direction depending on the particle density (right). At Re = 0.1, Dmax of particles with densities of 1.1 cm3 and 1.2 g/cm3 are 2.91 × 104 μm and 1.43 × 104 μm, respectively. As the density of a particle increases, its Dmax dramatically decreases. The difference in Dmax between particles with densities of 1.1 and 1.2 g/cm3 is 1.48 × 104 μm, and 0.0037 × 104 μm for particles with densities of 1.9 and 2.0 g/cm3. The effect of FD is stronger compared to that of FG on lighter particles. Thus, lighter particles travel quite similarly with the streamline and finally have a large Dmax. On the other hand, heavier particles where effect of FG is stronger compared to that of FD cross downwards streamlines and finally have a small Dmax.Next, in order to investigate the separation behavior of particles with respect to the geometry of the microfluidic device, the effect of the ratio of the height of the separation chamber (hc) to the inlet (hi) on Hmax is investigated as shown in Fig. Fig.3.3. Interestingly, Hmax of particles with density of 1.1 g/cm3 increases from 1.93 × 103 μm to 6.48 × 103 μm while that of particles with density of 1.9 g/cm3 slightly changes from 0.70 × 103 μm to 0.73 × 103 μm as hc/hi increases from 5 to 20.Open in a separate windowFIG. 3.Microfluidic particle separation with respect to the ratio of the height of the inlet (hi) to the separation chamber (hc).This result can be attributed to two effects: (1) the change in the streamline and (2) the relative contribution of drag force to the net force depending on the density. With increasing hc/hi, dramatic increase in Hmax for lighter particles is because the streamline for the lighter ones experiences more vertical displacement in the separation chamber and the contribution of FD to the net force acting on the lighter one is more significant (see Fig. S2 in the supplementary material22).Based on this approach, we propose a microfluidic device for the selective separation of the lightest particle. Fig. 4(a) shows one unit (with three outlets) of the proposed microfluidic device that can be connected in series. The ratio of channel heights (hc/hi) is set to 20, and the particle densities are in the range of 1.1 ∼ 1.5 g/m3. Fig. 4(b) shows the representative separation behavior of the particles. A portion of the lightest particles (1.1 g/cm3) is selectively separated into the upper and middle outlets, while remaining light particles together with four other heavier particles with densities in the range of 1.2 to 1.5 g/cm3 leave through the lowest outlet. With a single operation of this unit, 40% of the lightest particles are recovered. In addition, the yield increases with increasing number of cycles (Fig. 4(c)).Open in a separate windowFIG. 4.(a) One unit of the proposed microfluidic device for the selective separation of the lightest particle based on the simulation results. Particles are separated into two outlets based on differences in both the height and distance travelled stemming from differences in density. (b) Representative separation behavior of particles observed in the device. (c) The yield of the lightest particle (1.1 g/cm3) with the proposed microfluidic device according to the number of cycles (i.e., this unit is assumed to be connected in series).In summary, we have demonstrated a label-free microfluidic system for the separation of particles according to subtle differences in their densities without external forces. Our microfluidic design consists simply of an inlet, a separation chamber, and multiple outlets. When entering the separation chamber, the particles experience an additional drag force in the y direction, amplifying the difference in both the height and the distance that the particles with different densities can travel within the chamber. At a fixed Reynolds number, with increasing particle density, Hmax decreases monotonously, and Dmax decreases dramatically. On the other hand, as Reynolds number increases, the difference between the heights of particles with different densities is attenuated. In addition, the simulation reveals that increasing the ratio of the channel heights increases the difference between the heights of particles only when their densities are close to that of the surrounding water. Based on this approach, a microfluidic device for the separation of the lightest particles has been proposed. We expect that our density-based separation design can be beneficial to the selective separation of specific microorganisms such as lipid-rich microalgae for energy harvesting application. 相似文献
3.
Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs. 相似文献
4.
In this paper, we present an on-chip hand-powered membrane pump using a robust patient-to-chip syringe interface. This approach enables safe sample collection, sample containment, integrated sharps disposal, high sample volume capacity, and controlled downstream flow with no electrical power requirements. Sample is manually injected into the device via a syringe and needle. The membrane pump inflates upon injection and subsequently deflates, delivering fluid to downstream components in a controlled manner. The device is fabricated from poly(methyl methacrylate) (PMMA) and silicone, using CO2 laser micromachining, with a total material cost of ∼0.20 USD/device. We experimentally demonstrate pump performance for both deionized (DI) water and undiluted, anticoagulated mouse whole blood, and characterize the behavior with reference to a resistor-capacitor electrical circuit analogy. Downstream output of the membrane pump is regulated, and scaled, by connecting multiple pumps in parallel. In contrast to existing on-chip pumping mechanisms that typically have low volume capacity (∼5 μL) and sample volume throughput (∼1–10 μl/min), the membrane pump offers high volume capacity (up to 240 μl) and sample volume throughput (up to 125 μl/min). 相似文献
5.
Understanding the mechanical properties of optically transparent polydimethylsiloxane (PDMS) microchannels was essential to the design of polymer-based microdevices. In this experiment, PDMS microchannels were filled with a 100 μM solution of rhodamine 6G dye at very low Reynolds numbers (∼10−3). The deformation of PDMS microchannels created by pressure-driven flow was investigated by fluorescence microscopy and quantified the deformation by the linear relationship between dye layer thickness and intensity. A line scan across the channel determined the microchannel deformation at several channel positions. Scaling analysis widely used to justify PDMS bulging approximation was allowed when the applied flow rate was as high as 2.0 μl/min. The three physical parameters (i.e., flow rate, PDMS wall thickness, and mixing ratio) and the design parameter (i.e., channel aspect ratio = channel height/channel width) were considered as critical parameters and provided the different features of pressure distributions within polymer-based microchannel devices. The investigations of the four parameters performed on flexible materials were carried out by comparison of experiment and finite element method (FEM) results. The measured Young''s modulus from PDMS tensile test specimens at various circumstances provided reliable results for the finite element method. A thin channel wall, less cross-linker, high flow rate, and low aspect ratio microchannel were inclined to have a significant PDMS bulging. Among them, various mixing ratios related to material property and aspect ratios were one of the significant factors to determine PDMS bulging properties. The measured deformations were larger than the numerical simulation but were within corresponding values predicted by the finite element method in most cases. 相似文献
6.
For the first time, we report on the preliminary evaluation of gold coated optical fibers (GCOFs) as three-dimensional (3D) electrodes for a membraneless glucose/O2 enzymatic biofuel cell. Two off-the-shelf 125 μm diameter GCOFs were integrated into a 3D microfluidic chip fabricated via rapid prototyping. Using soluble enzymes and a 10 mM glucose solution flowing at an average velocity of 16 mm s−1 along 3 mm long GCOFs, the maximum power density reached 30.0 ± 0.1 μW cm−2 at a current density of 160.6 ± 0.3 μA cm−2. Bundles composed of multiple GCOFs could further enhance these first results while serving as substrates for enzyme immobilization. 相似文献
7.
We report the successful fabrication and testing of 3D printed microfluidic devices with integrated membrane-based valves. Fabrication is performed with a low-cost commercially available stereolithographic 3D printer. Horizontal microfluidic channels with designed rectangular cross sectional dimensions as small as 350 μm wide and 250 μm tall are printed with 100% yield, as are cylindrical vertical microfluidic channels with 350 μm designed (210 μm actual) diameters. Based on our previous work [Rogers et al., Anal. Chem. 83, 6418 (2011)], we use a custom resin formulation tailored for low non-specific protein adsorption. Valves are fabricated with a membrane consisting of a single build layer. The fluid pressure required to open a closed valve is the same as the control pressure holding the valve closed. 3D printed valves are successfully demonstrated for up to 800 actuations. 相似文献
8.
Stefanie Demming Gena Peterat Andreu Llobera Hannah Schmolke Alexander Bruns Michael Kohlstedt Ala‘aldeen Al-Halhouli Claus-Peter Klages Rainer Krull Stephanus Büttgenbach 《Biomicrofluidics》2012,6(3)
This paper presents a vertically positioned microfluidic system made of poly(dimethylsiloxane) (PDMS) and glass, which can be applied as a microbubble column (μBC) for biotechnological screening in suspension. In this μBC, microbubbles are produced in a cultivation chamber through an integrated nozzle structure. Thus, homogeneous suspension of biomass is achieved in the cultivation chamber without requiring additional mixing elements. Moreover, blockage due to produced carbon dioxide by the microorganisms—a problem predominant in common, horizontally positioned microbioreactors (MBRs)—is avoided, as the gas bubbles are released by buoyancy at the upper part of the microsystem. The patterned PDMS layer is based on an optimized two-lithographic process. Since the naturally hydrophobic PDMS causes problems for the sufficient production of microbubbles, a method based on polyelectrolyte multilayers is applied in order to allow continuous hydrophilization of the already bonded PDMS-glass-system. The μBC comprises various microelements, including stabilization of temperature, control of continuous bubble formation, and two optical configurations for measurement of optical density with two different sensitivities. In addition, the simple and robust application and handling of the μBC is achieved via a custom-made modular plug-in adapter. To validate the scalability from laboratory scale to microscale, and thus to demonstrate the successful application of the μBC as a screening instrument, a batch cultivation of Saccharomyces cerevisiae is performed in the μBC and compared to shake flask cultivation. Monitoring of the biomass growth in the μBC with the integrated online analytics resulted in a specific growth rate of 0.32 h−1, which is almost identical to the one achieved in the shake flask cultivation (0.31 h−1). Therefore, the validity of the μBC as an alternative screening tool compared to other conventional laboratory scale systems in bioprocess development is proven. In addition, vertically positioned microbioreactors show high potential in comparison to conventional screening tools, since they allow for high density of integrated online analytics and therefore minimize time and cost for screening and guarantee improved control and analysis of cultivation parameters. 相似文献
9.
Pascal Wettstein Craig Priest Sameer A. Al-Bataineh Robert D. Short Paul M. Bryant James W. Bradley Suet P. Low Luke Parkinson Endre J. Szili 《Biomicrofluidics》2015,9(1)
Spatially varied surface treatment of a fluorescently labeled Bovine Serum Albumin (BSA) protein, on the walls of a closed (sealed) microchannel is achieved via a well-defined gradient in plasma intensity. The microchips comprised a microchannel positioned in-between two microelectrodes (embedded in the chip) with a variable electrode separation along the length of the channel. The channel and electrodes were 50 μm and 100 μm wide, respectively, 50 μm deep, and adjacent to the channel for a length of 18 mm. The electrode separation distance was varied linearly from 50 μm at one end of the channel to a maximum distance of 150, 300, 500, or 1000 μm to generate a gradient in helium plasma intensity. Plasma ignition was achieved at a helium flow rate of 2.5 ml/min, 8.5 kVpk-pk, and 10 kHz. It is shown that the plasma intensity decreases with increasing electrode separation and is directly related to the residual amount of BSA left after the treatment. The plasma intensity and surface protein gradient, for the different electrode gradients studied, collapse onto master curves when plotted against electrode separation. This precise spatial control is expected to enable the surface protein gradient to be tuned for a range of applications, including high-throughput screening and cell-biomolecule-biomaterial interactions. 相似文献
10.
Recent advances in microscale flow propulsion through bioinspired artificial cilia provide a promising alternative for lab-on-a-chip applications. However, the ability of actuating artificial cilia to achieve a time-dependent local flow control with high accuracy together with the elegance of full integration into the biocompatible microfluidic platforms remains remote. Driven by this motive, the current work has constructed a series of artificial cilia inside a microchannel to facilitate the time-dependent flow propulsion through artificial cilia actuation with high-speed (>40 Hz) circular beating behavior. The generated flow was quantified using micro-particle image velocimetry and particle tracking with instantaneous net flow velocity of up to 101 μm/s. Induced flow patterns caused by the tilted conical motion of artificial cilia constitutes efficient fluid propulsion at microscale. This flow phenomenon was further measured and illustrated by examining the induced flow behavior across the depth of the microchannel to provide a global view of the underlying flow propulsion mechanism. The presented analytic paradigms and substantial flow evidence present novel insights into the area of flow manipulation at microscale. 相似文献
11.
The T-shaped microchannel system is used to mix similar or different fluids, and the laminar flow nature makes the mixing at the entrance junction region a challenging task. Acoustic streaming is a steady vortical flow phenomenon that can be produced in the microchannel by oscillating acoustic transducer around the sharp edge tip structure. In this study, the acoustic streaming is produced using a triangular structure with tip angles of 22.62°, 33.4°, and 61.91°, which is placed at the entrance junction region and mixes the inlets flow from two directions. The acoustic streaming flow patterns were investigated using micro-particle image velocimetry (μPIV) in various tip edge angles, flow rate, oscillation frequency, and amplitude. The velocity and vorticity profiles show that a pair of counter-rotating streaming vortices were created around the sharp triangle structure and raised the Z vorticity up to 10 times more than the case without acoustic streaming. The mixing experiments were performed by using fluorescent green dye solution and de-ionized water and evaluated its performance with the degree of mixing (M) at different amplitudes, flow rates, frequencies, and tip edge angles using the grayscale value of pixel intensity. The degree of mixing characterized was found significantly improved to 0.769 with acoustic streaming from 0.4017 without acoustic streaming, in the case of 0.008 μl/min flow rate and 38 V oscillation amplitude at y = 2.15 mm. The results suggested that the creation of acoustic streaming around the entrance junction region promotes the mixing of two fluids inside the microchannel, which is restricted by the laminar flow conditions. 相似文献
12.
Shimul C. Saha Andrew M. Powl B. A. Wallace Maurits R. R. de Planque Hywel Morgan 《Biomicrofluidics》2015,9(1)
We describe a scalable artificial bilayer lipid membrane platform for rapid electrophysiological screening of ion channels and transporters. A passive pumping method is used to flow microliter volumes of ligand solution across a suspended bilayer within a microfluidic chip. Bilayers are stable at flow rates up to ∼0.5 μl/min. Phospholipid bilayers are formed across a photolithographically defined aperture made in a dry film resist within the microfluidic chip. Bilayers are stable for many days and the low shunt capacitance of the thin film support gives low-noise high-quality single ion channel recording. Dose-dependent transient blocking of α-hemolysin with β-cyclodextrin (β-CD) and polyethylene glycol is demonstrated and dose-dependent blocking studies of the KcsA potassium channel with tetraethylammonium show the potential for determining IC50 values. The assays are fast (30 min for a complete IC50 curve) and simple and require very small amounts of compounds (100 μg in 15 μl). The technology can be scaled so that multiple bilayers can be addressed, providing a screening platform for ion channels, transporters, and nanopores. 相似文献
13.
This paper presents a spheroid chip in which three-dimensional (3D) tumor spheroids are not only formed by gravity-driven cell aggregation but also cultured at the perfusion rates controlled by balanced droplet dispensing without fluidic pumps. The previous spheroid chips require additional off-chip processes of spheroid formation and extraction as well as bulky components of fluidic pumps. However, the present spheroid chip, where autonomous medium droplet dispensers are integrated on a well array, achieves the on-chip 3D tumor spheroid formation and perfusion culture using simple structure without bulky fluidic pumps. In the experimental study, we demonstrated that the spheroid chip successfully forms 3D tumor spheroids in the wide diameter range of 220 μm–3.2 mm (uniformity > 90%) using H358, H23, and A549 non-small cell lung cancer cells. At the pump-less perfusion culture (Q = 0.1–0.3 μl/min) of spheroids, the number of H358 cells in the spheroid increased up to 50% from the static culture (Q = 0 μl/min) and the viability of the cultured cells also increased about 10%. Therefore, we experimentally verified that the perfusion environment created by the spheroid chip offers a favourable condition to the spheroids with high increase rate and viability. The present chip achieves on-chip 3D tumor spheroid formation and pump-less perfusion culture with simple structure, thereby exhibiting potential for use in integrated in-vivo-like cell culture systems. 相似文献
14.
Acoustic trapping of minute bead amounts against fluid flow allows for easy automation of multiple assay steps, using a convenient aspirate/dispense format. Here, a method based on acoustic trapping that allows sample preparation for immuno-matrix-assisted laser desorption/ionization mass spectrometry using only half a million 2.8 μm antibody covered beads is presented. The acoustic trapping is done in 200 × 2000 μm2 glass capillaries and provides highly efficient binding and washing conditions, as shown by complete removal of detergents and sample processing times of 5-10 min. The versatility of the method is demonstrated using an antibody against Angiotensin I (Ang I), a peptide hormone involved in hypotension. Using this model system, the acoustic trapping was efficient in enriching Angiotensin at 400 pM spiked in plasma samples. 相似文献
15.
To sequentially handle fluids is of great significance in quantitative biology, analytical chemistry, and bioassays. However, the technological options are limited when building such microfluidic sequential processing systems, and one of the encountered challenges is the need for reliable, efficient, and mass-production available microfluidic pumping methods. Herein, we present a bubble-free and pumping-control unified liquid handling method that is compatible with large-scale manufacture, termed multilayer microfluidic sample isolated pumping (mμSIP). The core part of the mμSIP is the selective permeable membrane that isolates the fluidic layer from the pneumatic layer. The air diffusion from the fluidic channel network into the degassing pneumatic channel network leads to fluidic channel pressure variation, which further results in consistent bubble-free liquid pumping into the channels and the dead-end chambers. We characterize the mμSIP by comparing the fluidic actuation processes with different parameters and a flow rate range of 0.013 μl/s to 0.097 μl/s is observed in the experiments. As the proof of concept, we demonstrate an automatic sequential fluid handling system aiming at digital assays and immunoassays, which further proves the unified pumping-control and suggests that the mμSIP is suitable for functional microfluidic assays with minimal operations. We believe that the mμSIP technology and demonstrated automatic sequential fluid handling system would enrich the microfluidic toolbox and benefit further inventions. 相似文献
16.
Jeonghun Nam Justin Kok Soon Tan Bee Luan Khoo Bumseok Namgung Hwa Liang Leo Chwee Teck Lim Sangho Kim 《Biomicrofluidics》2015,9(6)
A novel microfluidic device which consists of two stages for particle focusing and separation using a viscoelastic fluid has been developed. A circular capillary tube was used for three-dimensional particle pre-alignment before the separation process, which was inserted in a polydimethylsiloxane microchannel. Particles with diameters of 5 and 10 μm were focused at the centerline in the capillary tube, and the location of particles was initialized at the first bifurcation. Then, 5 and 10 μm particles were successfully separated in the expansion region based on size-dependent lateral migration, with ∼99% separation efficiency. The proposed device was further applied to separation of MCF-7 cells from leukocytes. Based on the cell size distribution, an approximate size cutoff for separation was determined to be 16 μm. At 200 μl/min, 94% of MCF-7 cells were separated with the purity of ∼97%. According to the trypan blue exclusion assay, high viability (∼90%) could be achieved for the separated MCF-7 cells. The use of a commercially available capillary tube enables the device to be highly versatile in dealing with particles in a wide size range by using capillary tubes with different inner diameters. 相似文献
17.
Particle separation is important to many chemical and biomedical applications. Magnetic field-induced particle separation is simple, cheap, and free of fluid heating issues that accompany electric, acoustic, and optical methods. We develop herein a novel microfluidic approach to continuous sheath-free magnetic separation of particles. This approach exploits the negative or positive magnetophoretic deflection to focus and separate particles in the two branches of a U-shaped microchannel, respectively. It is applicable to both magnetic and diamagnetic particle separations, and is demonstrated through the sorting of 5 μm and 15 μm polystyrene particles suspended in a dilute ferrofluid. 相似文献
18.
In this paper, 3D particle focusing in a straight channel with asymmetrical expansion–contraction cavity arrays (ECCA channel) is achieved by exploiting the dean-flow-coupled elasto-inertial effects. First, the mechanism of particle focusing in both Newtonian and non-Newtonian fluids was introduced. Then particle focusing was demonstrated experimentally in this channel with Newtonian and non-Newtonian fluids using three different sized particles (3.2 μm, 4.8 μm, and 13 μm), respectively. Also, the effects of dean flow (or secondary flow) induced by expansion–contraction cavity arrays were highlighted by comparing the particle distributions in a single straight rectangular channel with that in the ECCA channel. Finally, the influences of flow rates and distances from the inlet on focusing performance in the ECCA channel were studied. The results show that in the ECCA channel particles are focused on the cavity side in Newtonian fluid due to the synthesis effects of inertial and dean-drag force, whereas the particles are focused on the opposite cavity side in non-Newtonian fluid due to the addition of viscoelastic force. Compared with the focusing performance in Newtonian fluid, the particles are more easily and better focused in non-Newtonian fluid. Besides, the Dean flow in visco-elastic fluid in the ECCA channel improves the particle focusing performance compared with that in a straight channel. A further advantage is three-dimensional (3D) particle focusing that in non-Newtonian fluid is realized according to the lateral side view of the channel while only two-dimensional (2D) particle focusing can be achieved in Newtonian fluid. Conclusively, this novel Dean-flow-coupled elasto-inertial microfluidic device could offer a continuous, sheathless, and high throughput (>10 000 s−1) 3D focusing performance, which may be valuable in various applications from high speed flow cytometry to cell counting, sorting, and analysis. 相似文献
19.
The flow of λ-DNA solutions in a gradual micro-contraction was investigated using direct measurement techniques. The effects on DNA transport in microscale flows are significant because the flow behavior is influenced by macromolecular conformations, both viscous and elastic forces dominate inertial forces at this length scale, and the fully extended length of the molecule approaches the characteristic channel length wc (L/wc ∼ 0.13). This study examines the flow of semi-dilute and entangled DNA solutions in a gradual planar micro-contraction for low Reynolds numbers (3.7 × 10−6 < Re < 3.1 × 10−1) and high Weissenberg numbers (0.4 < Wi < 446). The semi-dilute DNA solutions have modest elasticity number, El = Wi/Re = 55, and do not exhibit viscoelastic behavior. For the entangled DNA solutions, we access high elasticity numbers (7.9 × 103 < El < 6.0 × 105). Video microscopy and streak images of entangled DNA solution flow reveal highly elastic behavior evidenced by the presence of large, stable vortices symmetric about the centerline and upstream of the channel entrance. Micro-particle image velocimetry measurements are used to obtain high resolution, quantitative velocity measurements of the vortex growth in this micro-contraction flow. These direct measurements provide a deeper understanding of the underlying physics of macromolecular transport in microfluidic flow, which will enable the realization of enhanced designs of lab-on-a-chip systems. 相似文献
20.
Aarash Sofla Bojana Cirkovic Anne Hsieh Jason W. Miklas Nenad Filipovic Milica Radisic 《Biomicrofluidics》2013,7(1)
The majority of available cardiomyocyte markers are intercellular proteins, limiting our ability to enrich live cardiomyocytes from heterogeneous cell preparations in the absence of genetic labeling. Here, we describe enrichment of live cardiomyocytes from the hearts of adult mice in a label-free microfluidic approach. The separation device consisted of a vertical column (15 mm long, 700 μm diameter), placed between permanent magnets resulting in a field strength of 1.23 T. To concentrate the field at the column wall, the column was wrapped with 69 μm diameter nickel wire. Before passing the cells through the column, the cardiomyocytes in the cell suspension had been rendered paramagnetic by treatment of the adult mouse heart cell preparation with sodium nitrite (2.5 mM) for 20 min on ice. The cell suspension was loaded into the vertical column from the top and upon settling, the non-myocytes were removed by the upward flow from the column. The cardiomyocytes were then collected from the column by applying a higher flow rate (144 μl/min). We found that by applying a separation flow rate of 4.2 μl/min in the first step, we can enrich live adult cardiomyocytes to 93% ± 2% in a label-free manner. The cardiomyocytes maintained viability immediately after separation and upon 24 h in culture. 相似文献