A microfluidic flow distributor generating stepwise concentrations for high-throughput biochemical processing

In this paper, we describe a microfluidic device in which solutions with stepwise concentrations can be accurately generated by continuously introducing two kinds of miscible liquids from each inlet, and biochemical processing can be conducted at the various conditions. Introduced liquid flows are geometrically divided into a number of downstream flows through multiple distribution channels, and each divided flow is then mixed with the divided flow of another liquid at a confluent point. The lengths of the precisely designed distribution channels determine the mixing ratio of the two liquids, without the influence of flow rate. In this study, a PDMS microfluidic device able to generate nine different concentrations was fabricated, and the performance of this device was estimated via colorimetric assay. As a biological application of this device, cell cultivation was performed under different concentration conditions. Due to its simplicity of operation, this microfluidic flow distributor will be applied to various kinds of biological analysis and screening systems.     

A microfluidic-based hydrodynamic trap: design and implementation

We report an integrated microfluidic device for fine-scale manipulation and confinement of micro- and nanoscale particles in free-solution. Using this device, single particles are trapped in a stagnation point flow at the junction of two intersecting microchannels. The hydrodynamic trap is based on active flow control at a fluid stagnation point using an integrated on-chip valve in a monolithic PDMS-based microfluidic device. In this work, we characterize device design parameters enabling precise control of stagnation point position for efficient trap performance. The microfluidic-based hydrodynamic trap facilitates particle trapping using the sole action of fluid flow and provides a viable alternative to existing confinement and manipulation techniques based on electric, optical, magnetic or acoustic force fields. Overall, the hydrodynamic trap enables non-contact confinement of fluorescent and non-fluorescent particles for extended times and provides a new platform for fundamental studies in biology, biotechnology and materials science.     

Continuous separation of particles using a microfluidic device equipped with flow rate control valves

We propose herein an improved microfluidic system for continuous and precise particle separation. We have previously proposed a method for particle separation called "pinched flow fractionation." Using the previously reported method, particles can be continuously separated according to differences in their diameters, simply by introducing liquid flows with and without particles into a specific microchannel structure. In this study, we incorporated PDMS membrane microvalves for flow rate control into the microfluidic device to improve the separation accuracy. By adjusting the flow rates distributed to each outlet, target particles could be precisely collected from the desired outlet. We succeeded in separating micron and submicron-size polymer particles. This method can be used widely for continuous and precise separation of various kinds of particles, and can function as an important part of microfluidic systems.     

Three-dimensional multihelical microfluidic mixers for rapid mixing of liquids

Rapid mixing of liquids is important for most microfluidic applications. However, mixing is slow in conventional micromixers, because, in the absence of turbulence, mixing here occurs by molecular diffusion. Recent experiments show that mixing can be enhanced by generating transient flow resulting in chaotic advection. While these are planar microchannels, here we show that three-dimensional orientations of fluidic vessels and channels can enhance significantly mixing of liquids. In particular, we present a novel, multihelical microchannel system built in soft gels, for which the helix angle, helix radius, axial length, and even the asymmetry of the channel cross section are easily tailored to achieve the desired mixing. Mixing efficiency increases with helix angle and asymmetry of channel cross section, which leads to orders of magnitude reduction in mixing length over conventional mixers. This new scheme of generating 3D microchannels will help in miniaturization of devices, process intensification, and generation of multifunctional process units for microfluidic applications.     

An inertia enhanced passive pumping mechanism for fluid flow in microfluidic devices

We describe and characterize a pumping mechanism that leverages the momentum present in small droplets ejected from a micro-nozzle to drive flow in an open microfluidic device. This approach allows driving flow in a microfluidic device in a regime that offers unique features different to those achievable with typical passive pumping or syringe-pump driven flow. Two flow regimes with specific flow characteristics are described: inertia enhanced passive pumping, in which fluid exchange times in the channel are significantly reduced, and inertia actuated flow, in which it is possible to initiate flow in an empty channel or against natural pressure gradients. Momentum is leveraged to create rapid fluid exchanges, instantaneous flow reversal, filling and mixing inside the microfluidic device.     

Controllable Synthesis of Multicompartmental Particles Using 3D Microfluidics

A microfluidic assembly method based on a microfluidic chip and capillary device was developed to create multicompartmental particles. The microfluidic chip design endows the particles with regulable internal structure. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components, and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely varied. As a proof of concept, we have produced some complicated particles that even contain 20 compartments. Furthermore, the potential applications of the anisotropic particles are explored by encapsulating magnetic beads, fluorescent nanoparticles, and the cells into different compartments of the microparticles. We believe that this method will open new avenues for the design and application of multicompartmental particles.     

A simple mechanism for reliable particle sorting in a microdevice with combined electroosmotic and pressure-driven flow

Selective transport and sorting of particles in microfluidic devices by electroosmosis is complicated due to superposition of uncontrolled hydrodynamic pressure contributions on the electroosmotic force. In this paper, we present a microfluidic concept for the reliable and simple separation and sorting of particles in a microchip by electroosmosis combined with pressure-driven flow. The presented device allows fluid quantities to be switched and particles to be sorted within a channel manifold using only a single power supply with fixed voltage and an electric switch. Consequently, chip operation and fluid switching procedure are greatly simplified compared to a situation, in which several independent power sources are used for flow balancing, as is the common procedure. With the triple-T channel design presented, backpressure flow disturbing the electrokinetic fluid and particle separation process is eliminated by introducing controlled opposed hydrodynamic flow of buffer from side channels. This pressure-driven flow is generated on-chip by setting up differences in the reservoir pressures in a defined manner. A detailed flow analysis based on the equivalence of fluid flow and electric current is performed and the conditions for reliable chip function are worked out.     

An optically driven pump for microfluidics

We demonstrate a method for generating flow within a microfluidic channel using an optically driven pump. The pump consists of two counter rotating birefringent vaterite particles trapped within a microfluidic channel and driven using optical tweezers. The transfer of spin angular momentum from a circularly polarised laser beam rotates the particles at up to 10 Hz. We show that the pump is able to displace fluid in microchannels, with flow rates of up to 200 microm(3) s(-1) (200 fL s(-1)). The direction of fluid pumping can be reversed by altering the sense of the rotation of the vaterite beads. We also incorporate a novel optical sensing method, based upon an additional probe particle, trapped within separate optical tweezers, enabling us to map the magnitude and direction of fluid flow within the channel. The techniques described in the paper have potential to be extended to drive an integrated lab-on-chip device, where pumping, flow measurement and optical sensing could all be achieved by structuring a single laser beam.     

Microfluidic synthesis of colloidal silica

We demonstrate the design, fabrication, and operation of microfluidic chemical reactors for the synthesis of colloidal silica particles. Two reactor configurations are examined: laminar flow reactors and segmented flow reactors. We analyze particle sizes and size distributions and examine their change with varying linear flow velocity and mean residence time. Laminar flow reactors are affected by axial dispersion at high linear velocities, thus leading to wide particle size distributions under these conditions. Gas is used to create a segmented flow, consisting liquid plugs separated by inert gas bubbles. The internal recirculation created in the liquid plugs generates mixing, which eliminates the axial dispersion effects associated with laminar flow reactors and produces a narrow size distribution of silica nanoparticles.     

Microfluidic system for dielectrophoretic separation based on a trapezoidal electrode array

This paper presents a novel microfluidic device for dielectrophoretic separation based on a trapezoidal electrode array (TEA). In this method, particles with different dielectric properties are separated by the device composed of the TEA for the dielectrophoretic deflection of particles under negative dielectrophoresis (DEP) and poly(dimethylsiloxane)(PDMS) microfluidic channel with a sinuous and expanded region. Polystyrene microparticles are exposed to an electric field generated from the TEA in the microfluidic channel and are dielectrophoretically focused to make all of them line up to one sidewall. When these particles arrive at the region of another TEA for dielectrophoretic separation, they are separated having different positions along the perpendicular direction to the fluid flow due to their different dielectrophoretic velocities. To evaluate the separation process and performance, both the effect of the flow rate on dielectrophoretic focusing and the influence of the number of trapezoidal electrodes on dielectrophoretic separation are investigated. Now that this method utilizes the TEA as a source of negative DEP, non-specific particle adhering to the electrode surface can be prevented; conventional separation approaches depending on the positive DEP force suffer from this problem. In addition, since various particle types are continuously separated, this method can be easily applicable to the separation and analysis of various dielectric particles with high particle recovery and selectivity.     

Micro-impedance cytometry for detection and analysis of micron-sized particles and bacteria

The sensitivity of a microfluidic impedance flow cytometer is governed by the dimensions of the sample analysis volume. A small volume gives a high sensitivity, but this can lead to practical problems including fabrication and clogging of the device. We describe a microfluidic impedance cytometer which uses an insulating fluid to hydrodynamically focus a sample stream of particles suspended in electrolyte, through a large sensing volume. The detection region consists of two pairs of electrodes fabricated within a channel 200 μm wide and 30 μm high. The focussing technique increases the sensitivity of the system without reducing the dimensions of the microfluidic channel. We demonstrate detection and discrimination of 1 μm and 2 μm diameter polystyrene beads and also Escherichia coli. Impedance data from single particles are correlated with fluorescence emission measured simultaneously. Data are also compared with conventional flow cytometry and dynamic light scattering: the coefficient of variation (CV) of size is found to be comparable between the systems.     

Continuous flow separation of particles within an asymmetric microfluidic device

A microfluidic based device has been developed for the continuous separation of polymer microspheres, taking advantage of the flow characteristics of systems. The chip consists of an asymmetric cavity with variable channel width which enables continuous amplification of the particle separation for different size particles within the laminar flow profile. The process has been examined by varying the sample inlet position, the sample to media flow rate ratio, and the total flow rate. This technique can be applied for manipulating both microscale biological and colloidal particles within microfluidic systems.     

Elastic-inertial separation of microparticle in a gradually contracted microchannel

Separation of microparticle in viscoelastic fluid is highly required in the field of biology and clinical medicine. For instance, the separation of the target cell from blood is an important prerequisite step for the drug screening and design. The microfluidic device is an efficient way to achieve the separation of the microparticle in the viscoelastic fluid. However, the existing microfluidic methods often have some limitations, including the requirement of the long channel length, the labeling process, and the low throughput. In this work, based on the elastic-inertial effect in the viscoelastic fluid, a new separation method is proposed where a gradually contracted microchannel is designed to efficiently adjust the forces exerted on the particle, eventually achieving the high-efficiency separation of different sized particles in a short channel length and at a high throughput. In addition, the separation of WBCs and RBCs is also validated in the present device. The effect of the flow rate, the fluid property, and the channel geometry on the particle separation is systematically investigated by the experiment. With the advantage of small footprint, simple structure, high throughput, and high efficiency, the present microfluidic device could be utilized in the biological and clinical fields, such as the cell analysis and disease diagnosis.     

Pipette-friendly laminar flow patterning for cell-based assays

Laminar flow patterning (LFP) is a characteristic method of microfluidic systems that allows two (or more) different solutions to flow side-by-side in a channel without convective mixing. This fluid behavior can be used to pattern cell suspensions, particles, and treatments as well as to create chemical gradients. LFP is typically implemented using syringe pumps and, for this reason, is most effective in constant flow scenarios such as long-term gradient generation. However, the complexity of using syringe pumps for patterning cell suspensions typically makes it a less attractive option than other standard patterning methods. We present a passive microfluidic method that enables short-term LFP of multiple fluids using a single pipette and allows each sample to be loaded in any sequence, at any point in time relative to one another. The proposed method is well-suited for cell-based assays, reduces the complexity of LFP to be on a similar level as other cell patterning methods, can be scaled to include more than two streams of fluid, and enables arrays of individually addressable devices for LFP on a single chip.     

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.     

Simultaneous particle counting and detecting on a chip

This paper reports a lab-on-a-chip device that performs particle detection and number counting by coupling the fluorescent detection and particle counting simultaneously. The particle number counting is realized by a resistive pulse sensor (RPS) and fluorescent particle detection is achieved by a miniaturized laser-fiber optic detection system. By using a single microfluidic channel with two detecting arm channels placed at the two ends of the sensing section, the RPS signal-to-noise ratio is improved significantly. Two-stage differential amplification is used to further increase the signal-to-noise ratio for both the RPS and fluorescent signals. This method is also highly sensitive, so that we were able to realize the RPS and fluorescent detection of 0.9 microm (mean diameter) fluorescent particles. Excellent agreement was achieved by comparing the results obtained by our system with the results from a commercial flow cytometer for a variety of samples of mixed fluorescent and non-fluorescent particles. The method described in this paper is simple and can be applied to develop a compact device without the need of lock-in amplifier or similar bulky supplemental equipment.     

Orthogonal optical force separation simulation of particle and molecular species mixtures under direct current electroosmotic driven flow for applications in biological sample preparation

Presented here are the results from numerical simulations applying optical forces orthogonally to electroosmotically induced flow containing both molecular species and particles. Simulations were conducted using COMSOL v4.2a Multiphysics® software including the particle tracking module. The study addresses the application of optical forces to selectively remove particulates from a mixed sample stream that also includes molecular species in a pinched flow microfluidic device. This study explores the optimization of microfluidic cell geometry, magnitude of the applied direct current electric field, EOF rate, diffusion, and magnitude of the applied optical forces. The optimized equilibrium of these various contributing factors aids in the development of experimental conditions and geometry for future experimentation as well as directing experimental expectations, such as diffusional losses, separation resolution, and percent yield. The result of this work generated an optimized geometry with flow conditions leading to negligible diffusional losses of the molecular species while also being able to produce particle removal at near 100% levels. An analytical device, such as the one described herein with the capability to separate particulate and molecular species in a continuous, high‐throughput fashion would be valuable by minimizing sample preparation and integrating gross sample collection seamlessly into traditional analytical detection methods.     

Rapid droplet mixers for digital microfluidic systems

The mixing of analytes and reagents for a biological or chemical lab-on-a-chip is an important, yet difficult, microfluidic operation. As volumes approach the sub-nanoliter regime, the mixing of liquids is hindered by laminar flow conditions. An electrowetting-based linear-array droplet mixer has previously been reported. However, fixed geometric parameters and the presence of flow reversibility have prevented even faster droplet mixing times. In this paper, we study the effects of varying droplet aspect ratios (height:diameter) on linear-array droplet mixers, and propose mixing strategies applicable for both high and low aspect ratio systems. An optimal aspect ratio for four electrode linear-array mixing was found to be 0.4, with a mixing time of 4.6 seconds. Mixing times were further reduced at this ratio to less than three seconds using a two-dimensional array mixer, which eliminates the effects of flow reversibility. For lower aspect ratio (相似文献   

A pneumatic micromixer facilitating fluid mixing at a wide range flow rate for the preparation of quantum dots

A novel fluid micromixer based on pneumatic perturbation and passive structures was developed. This micromixer facilitates integration and is applicable to fluid mixing over a wide range of flow rates. The microfluidic mixing device consists of an S-shaped structure with two mixing chambers and two barriers, and two pneumatic chambers designed over the S-shaped channel. The performance of the micromixer for fluids with wide variation of flow rates was significantly improved owing to the integration of the pneumatic mixing components with the passive mixing structures. The mixing mechanism of the passive mixing structures was explored by numerical simulation, and the influencing factors on the mixing efficiency were investigated. The results showed that when using a gas pressure of 0.26 MPa and a 100 m-thick polydimethylsiloxane (PDMS) pneumatic diaphragm, the mixing of fluids with flow rates ranging from 1 to 650 L/min was achieved with a pumping frequency of 50 Hz. Fast synthesis of CdS quantum dots was realized using this device. Smaller particles were obtained, and the size distribution was greatly improved compared with those obtained using conventional methods.     

A water-activated pump for portable microfluidic applications

An on-chip micropump for portable microfluidic applications was investigated using mathematical modeling and experimental testing. This micropump is activated by the addition of water, via a dropper, to ionic polymer particles that swell due to osmotic effects when wetted. The resulting particle volume increase deflects a membrane, forcing a separate fluid from an adjacent reservoir. The micropump components, along with the microfluidic components, are fabricated using the contact liquid photolithographic polymerization (CLiPP) method. The maximum flow rate achieved with this pump is 17 microL per minute per mg of dry polymer particles of 355-425 microm in diameter. The pump flow rate may be controlled by adjusting the particle size and amount, the membrane properties, and the channel dimensions. The experimental results demonstrate good agreement with an analytical model describing the particle swelling and its coupling with resistive forces from the bending membrane, viscous flow in the microchannel, and interfacial effects. Key features of this micropump are that it can be placed directly on a microdevice, and that it requires only a small amount of water and no external power supply to function. Therefore, this pumping system is useful for applications in which a highly portable device is required.