High-performance PCB-based capillary pumps for affordable point-of-care diagnostics

Capillary pumps are integral components of passive microfluidic devices. They can displace precise volumes of liquid, avoiding the need for external active components, providing a solution for sample preparation modules in Point-of-Care (PoC) diagnostic platforms. In this work, we describe a variety of high-performance capillary pump designs, suitable for the Lab-on-Printed-Circuit-Board technology (LoPCB). Pumps are fabricated entirely on Printed Circuit Board (PCB) substrates via commercially available manufacturing processes. We demonstrate the concept of LoPCB technology and detail the fabrication method of different architectures of PCB-based capillary pumps. The capillary pumps are combined with microfluidic channels of various hydraulic resistances and characterised experimentally for different micropillar shapes and minimum feature size. Their performance in terms of flow rate is reported. Due to the superhydrophilic properties of oxygen plasma treated FR-4 PCB substrate, the capillary pump flow rates are much higher (138 μL/min, for devices comprising micropillar arrays without preceding microchannel) than comparable devices based on glass, silicon or polymers. Finally, we comment on the technology’s prospects, such as incorporating more complicated microfluidic networks that can be tailored for assays.     

A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices

Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm²) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.     

Droplet generation in a microchannel with a controllable deformable wall

We report the droplet generation behavior of a microfluidic droplet generator with a controllable deformable membrane wall using experiments and analytical model. The confinement at the droplet generation junction is controlled by using external pressure, which acts on the membrane, to generate droplets smaller than junction size (with other parameters fixed) and stable and monodispersed droplets even at higher capillary numbers. A non-dimensional parameter, i.e., controlling parameter K _p, is used to represent the membrane deformation characteristics due to the external pressure. We investigate the effect of the controlled membrane deformation (in terms of K _p), viscosity ratio λ and flow rate ratio r on the droplet size and mobility. A correlation is developed to predict droplet size in the controllable deformable microchannel in terms of the controlling parameter K _p, viscosity ratio λ and flow rate ratio r. Due to the deflection of the membrane wall, we demonstrate that the transition from the stable dripping regime to the unstable jetting regime is delayed to a higher capillary number Ca (as compared to rigid droplet generators), thus pushing the high throughput limit. The droplet generator also enables generation of droplets of sizes smaller than the junction size by adjusting the controlling parameter.     

Viscosity-dependent enhancement of fluid resistance in water/glycerol micro fluid segments

The influence of the formation of micro fluid segments on the fluid resistance was studied in an example of water/glycerol mixture by pressure drop measurements in dependence on the flow rate and viscosity. Therefore, a micro fluidic arrangement consisting of two syringe pumps, a pressure sensor and an injector for segment generation was assembled. It was found that micro fluid segments generate a significant enhancement of flow-induced pressure drop. This enhancement depends on the flow rate as well as on the number of microfluid segments and viscosity. The resulting pressure drop can be described by an empirical equation reconsidering flow rate, viscosity, capillary size and number of segments.     

Output pressure and efficiency of electrokinetic pumping of non-Newtonian fluids

Theoretical expressions of the flow rate, output pressure and thermodynamic efficiency of electrokinetic pumping of non-Newtonian fluids through cylindrical and slit microchannels are reported. Calculations are carried out in the framework of continuum fluid mechanics. The constitutive model of Ostwald-de Waele (power law) is used to express the fluid shear stress in terms of the velocity gradient. The resulting equations of flow rate and electric current are nonlinear functions of the electric potential and pressure gradients. The fact that the microstructure of non-Newtonian fluids is altered at solid–liquid interfaces is taken into account. In the case of fluids with wall depletion, both the output pressure and efficiency are found to be several times higher than that obtained with simple electrolytes under the same experimental conditions. Apart from potential applications in electrokinetic pumps, these predictions are of interest for the design of microfluidic devices that manipulate non-Newtonian fluids such as polymer solutions and colloidal suspensions. From a more fundamental point of view, the paper discusses a relevant example of nonlinear electrokinetics.     

Development and characterization of a capillary-flow microfluidic device for nucleic acid detection

We have developed a capillary flow-driven microfluidic biosensor to meet the needs of diagnostics for resource-limited areas. The device combined elements of lateral flow assays and microfluidic technology resulting in a hybrid with benefits of both formats. The biosensor was achieved by bonding two pieces of polymethyl methacrylate with channels ablated by a CO₂ laser, and enclosing an absorbent pad. The channels were UV/ozone treated to increase hydrophilicity which enabled capillary flow. The absorbent pad allowed for continuous flow in the channels once filled. The application of biosensor was demonstrated by detection of DNA with a sandwich assay. The target DNA was hybridized with nucleic acid modified magnetic beads as well as Ru(bpy) ₃ ²⁺ doped silica nanoparticles. Fluorescent signals were quantified in a holder fabricated to fit in a fluorescent microtiter plate reader. The capillary flow microfluidic was capable to detect 1?pmol target. The assay format which features rapid analysis and does not require the use of pumps could allow for inexpensive point of care diagnostics in the future.     

A positive pressure-driven PDMS pump for fluid handling in microfluidic chips

By utilizing the high gas permeability of polydimethylsiloxane (PDMS), a simple positive pressure-driven pumping method was introduced. The pump was an aerated PDMS with a central channel in it and packing with a transfusion bottle. It could be attached to the inlet of microfluidic chip using a Teflon tube to release the air into the microfluidic system and then to create a positive pressure for driving fluid. In comparison with the degas-based PDMS pump, positive pressure-driven PDMS pump offered increased system flexibility and reduced individual device fabrication complexity due to its independence and versatility. More importantly, it offered the advantages that the PDMS pump could be wrapped in transfusion bottles to meet the readily available requirements, and it also easily assembled, which only required the user use a Teflon tube to connect a PDMS pump and a microfluidic chip. This assembly provided great freedom to meet different pumping requirements. Furthermore, this PDMS pump could offer many possible configures of pumping power by adjusting the geometries of the pump or by combining different pump modules, the adjustment of pumping capacity was investigated. To help design pumps with a suitable pumping performance, the sealing effect, pumping pressure and flow rate were also investigated. The results indicated that the performance of the positive pressure-driven PDMS pump was reliable. Finally, we demonstrated the utility of this pumping method by applying it to a PDMS-based viscometer microfluidic chip.     

Development of a capillary flow microfluidic Escherichia coli biosensor with on-chip reagent delivery using water-soluble nanofibers

Although the potential role of microfluidics in point of care diagnostics is widely acknowledged, the practical limitations to their use still limit deployment. Here, we developed a capillary flow microfluidic with on-chip reagent delivery which combines a lateral flow assay with microfluidic technology. The horseradish peroxidase tagged antibody was electrospun in a water-soluble polyvinylpyrrolidone nanofibers and stored in a microfluidic poly(methyl methacrylate) chip. During the assay, the sample containing Escherichia coli on immunomagnetic beads came in contact with the nanofibers causing them to dissolve and release the reagents for binding. Following hybridization, the solution moved by capillary flow toward a detection zone where the analyte was quantified using chemiluminescence. The limit of detection was found to be approximately 10⁶ CFU/mL of E. coli O157. More importantly, the ability to store sensitive reagents within a microfluidic as nanofibers was demonstrated. The fibers showed almost instant hydration and dissemination within the sample solution.     

短叶片长度对固液离心泵内流场影响的模拟研究

为了研究短叶片长度对长短叶片离心泵叶轮内固液两相流场的影响,应用CFD软件对5种不同短叶片长度的离心泵中的固液两相流场进行数值模拟,分析并对比5种离心泵中压力及固相体积浓度变化规律.结果显示:5种离心泵中的压力沿着半径增大方向呈增大趋势;且相同半径处,工作面压力总是大于吸力面;在一定程度上减小短叶片长度,压力分布更均匀,颗粒浓度的变化曲线更平缓,同时叶轮中固相颗粒的高浓度区域大大减小,从而能够减弱各种不稳定因素的影响,保持良好的流动状态,提高离心泵的水力性能和抗磨损性能.所得结论为离心泵的改良和设计提供非常有价值的理论基础.     

Generating high-pressure sub-microliter flow rate in packed microchannel by electroosmotic force: potential application in microfluidic systems

We have developed a liquid delivery pump, known as an electroosmotic pump (EOP), based on the electrically induced osmosis principle, which is mainly made of one or several microchannels packed with porous fine dielectric material and connected in parallel. The EOP is tested with methanol, phosphate sodium buffer and their mixture, which can generate pressures from 0.1 to 15 MPa and flow rates of tens of nanoliters per minute to several microliters per minute. Constant and pulsation-free flow from the EOP adapts well to microfluidic systems.     

The design of an in-plane compliance structure for microfluidical systems

Two compliance structures for the use in liquid-based microfluidic systems have been realized with the aid of silicon micromachining. The basic principle is that these structures contain air bubbles that dampen the flow and pressure variations that may arise from a micropump. The compliance structures were specifically designed to work with the no moving parts valve (NMPV) pump [Proc. ASME Fluids Eng. Division, 1995, in press]. The structures were modeled and simulated. From the results of these simulations and the model, design rules for the compliance are formulated.Measurements on the compliance structures could only be performed for the steady state. These measurements were in very good agreement with the model. Working with two sets of pumps showed that pumps without the compliance structure needed an external compliance in order to get them to work, whereas the pumps with the on-chip compliance pumped right away.     

Valves for autonomous capillary systems

Autonomous capillary systems (CSs) are microfluidic systems inside which liquids move owing to capillary forces. CSs can in principle bring the high-performances of microfluidic-based analytical devices to near patient and environmental testing applications. In this paper, we show how wettable capillary valves can enhance CSs with novel functionalities, such as delaying and stopping liquids in microchannels. The valves employ an abruptly changing geometry of the flow path to delay a moving liquid filling front in a wettable microchannel. We show how to combine delay valves with capillary pumps, prevent shortcuts of liquid along the corners of microfluidic channels, stop liquids filling microchannels from a few seconds to over 30 min, trigger valves using two liquid fronts merging, and time a liquid using parallel microfluidic paths converging to a trigger valve. All together, these concepts should add functionality to passive microfluidic systems without departing from their initial simplicity of use. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Microfluidic systems for the analysis of viscoelastic fluid flow phenomena in porous media

In this study, two microfluidic devices are proposed as simplified 1-D microfluidic analogues of a porous medium. The objectives are twofold: firstly to assess the usefulness of the microchannels to mimic the porous medium in a controlled and simplified manner, and secondly to obtain a better insight about the flow characteristics of viscoelastic fluids flowing through a packed bed. For these purposes, flow visualizations and pressure drop measurements are conducted with Newtonian and viscoelastic fluids. The 1-D microfluidic analogues of porous medium consisted of microchannels with a sequence of contractions/expansions disposed in symmetric and asymmetric arrangements. The real porous medium is in reality, a complex combination of the two arrangements of particles simulated with the microchannels, which can be considered as limiting ideal configurations. The results show that both configurations are able to mimic well the pressure drop variation with flow rate for Newtonian fluids. However, due to the intrinsic differences in the deformation rate profiles associated with each microgeometry, the symmetric configuration is more suitable for studying the flow of viscoelastic fluids at low De values, while the asymmetric configuration provides better results at high De values. In this way, both microgeometries seem to be complementary and could be interesting tools to obtain a better insight about the flow of viscoelastic fluids through a porous medium. Such model systems could be very interesting to use in polymer-flood processes for enhanced oil recovery, for instance, as a tool for selecting the most suitable viscoelastic fluid to be used in a specific formation. The selection of the fluid properties of a detergent for cleaning oil contaminated soil, sand, and in general, any porous material, is another possible application.     

Two-layer multiplexed peristaltic pumps for high-density integrated microfluidics

The integration and operation of a large number of components is needed to enable ever more complex and integrated chemical and biological processes on a single microfluidic chip. The capabilities of these chips are often limited by the maximum number of pumps and valves that can be controlled on a single chip, a limitation typically set by the number of pneumatic interconnects available from ancillary hardware. Here, we report a multiplexing approach that greatly reduces the number of external pneumatic connections needed for the operation of a large number of peristaltic pumps. The utility of the approach is demonstrated with a complex microfluidic network capable of generating and routing liquid droplets in a two-phase flow. We also report a set of design rules for the design and operation of multiplexed peristaltic pumps, based on a study of the effect of the number of valves per pump and the valve-to-valve distance on the performance of peristaltic pumps. The multiplexing approach reported here may find application in a wide range of microfluidic chips for chemical and biological applications, especially those that require the integration of many different operations on a single chip and those that need to perform similar operations massively in parallel, in sub-nanoliter volumes.     

An automatic microfluidic system for rapid screening of cancer stem-like cell-specific aptamers

This study reports a microfluidic system which automatically performs the systematic evolution of ligands by exponential enrichment (SELEX) process for rapid screening of aptamers which are specific to cancer stem-like cells. The system utilizes magnetic bead-based techniques to select DNA aptamers and has several advantages including a rapid, automated screening process, and less consumption of cells and reagents. By integrating a microfluidic control module, a magnetic bead-based aptamer extraction module, and a temperature control module, the entire Cell-SELEX process can be performed in a shorter period of time. Compared with the traditional Cell-SELEX process, this microfluidic system is more efficient and consumes fewer sample volumes. It only takes approximately 3 days for an entire Cell-SELEX process with 15 screening runs, which is relatively faster than that of a traditional Cell-SELEX process (1 week for 15 rounds). The binding affinity of this resulting specific aptamer was measured by a flow cytometric analysis to have a dissociation constant (K _d) of 15.32 nM. The capture rate for cancer stem-like cells using the specific aptamer-conjugated bead is better than that using Ber-EP4 antibody-conjugated bead. This microfluidic system may provide a powerful platform for the rapid screening of cell-specific aptamers.     

Electrohydrodynamics around single ion-permselective glass beads fixed in a microfluidic device

This work demonstrates by direct visualization using confocal laser scanning microscopy that the application of electrical fields to a single-fixed, ion-permselective glass bead produces a remarkable complexity in both the coupled mass and charge transport through the bead and the coupled electrokinetics and hydrodynamics in the adjoining bulk electrolyte. The visualization approach enables the acquisition of a wealth of information, forming the basis for a detailed analysis of the underlying effects (e.g., ion-permselectivity, concentration polarization, nonequilibrium electroosmotic slip) and an understanding of electrohydrodynamic phenomena at charge-selective interfaces under more general conditions. The device used for fixing single beads in a microfluidic channel is flexible and allows to investigate the electrohydrodynamics in both transient and stationary regimes under the influence of bead shape, pore size and surface charge density, mobile phase composition, and applied volume forces. This insight is relevant for the design of microfluidic/nanofluidic interconnections and addresses the ionic conductance of discrete nanochannels, as well as nanoporous separation and preconcentration units contained as hybrid configurations, membranes, packed beds, or monoliths in lab-on-a-chip devices.     

The manufacturing of packaged capillary action microfluidic systems by means of CO2 laser processing

In this article we demonstrate a simple yet robust rapid prototyping manufacturing technique for the construction of autonomous microfluidic capillary systems by means of CO₂ laser processing. The final packaging of the microfluidic device is demonstrated using thermal lamination bonding and allows for a turnaround time of approximately 30 min to 3 h from activation of the laser system to device use. The low-cost CO₂ laser system is capable of producing repeatable microfluidic structures with minimum feature sizes superior than 100–150 μm over channel depths of more than 100 μm. This system is utilised to create capillary pump and valve designs within poly (methyl methacrylate) (PMMA) substrates. Such components are part of advanced systems that can self initiate and maintain the flow of various volumes of fluids from an input to a collection reservoir, whilst also controlling the progression of the flow through the various demonstrated valve type structures. The resulting systems could prove a very useful alternative to traditional, non-integrated, fluidic actuation and flow control systems found on-chip, which generally require some form of energy input, have limited portable capabilities and require more complex fabrication procedures.     

A magnetophoresis-based microfluidic detection platform under a static-fluid environment

Microfluidic cell separations and immunoassays exploit a dynamic flow environment by electrical pumps to manipulate fluids containing biomolecules and microbeads. In particular, the magnetophoresis-based microfluidics requires a delicate flow control of pumps because the flow rate affects the result sensitively. Consequently, the dynamic flow environment requiring pumps prevents the magnetophoresis-based microfluidics from popularization and miniaturization. Herein, we present a magnetophoresis-based microfluidic platform under a static-fluid environment for the detection of microbeads labeled with magnetic nanoparticles (MNPs) by simple manual operation of fluids. To overcome the residual flow caused by the manual operation, we designed a microfluidic device having a pair of microchannels; one for detecting the target and the other for a reference. The deviations due to the residual flow were corrected by comparing the difference between the mean velocities of microbeads in each microchannel where microbeads labeled with five different concentrations of MNPs could be classified. On the basis of the convenience and portability of magnetophoresis under a static-fluidic environment, this new microfluidic platform enabled semiquantitative detection of labeled particles without any complex electrical devices and could thus be used as a portable detection platform.     

A new electro-osmotic pump based on silica monoliths

A high-pressure electro-osmotic (EO) micro-pump fabricated by a sol–gel process is shown to be potentially effective as a fluid-driving unit on chip-scale analytical systems. A silica monolithic matrix with a morphology of micron-scaled through pores was synthesized within the 100 μm inner diameter (i.d.) fused-silica capillary of the micro-pump. The monolith bonds directly with the capillary wall such that frits with large pressure loss are unnecessary. This pump uses electro-osmotic flow to propel liquid solution with no moving parts. The Nafion^® housing design in the cathode chamber prevents flow leakage into the electrode reservoir from the flow channel and hence maximizes the pressure build-up. It also eliminates electrolytic bubble interference from the flow channels and provides ionic channels for current penetration simultaneously. As the monolith is silica-based, this pump can be used for a variety of fluids, especially for organic solvents, such as acetonitrile and methanol, without swelling and shrinking problems. The maximum flow rate and maximum pressure generated by the 100 μm i.d. monolithic pump are 2.9 μL/min and 3 atm for deionized water at 6 kV applied voltage. These results indicate that the pump can provide sufficient pressure and flow for miniaturized HPLC and micro-total-analysis systems (μ-TAS). A simple universal pressure pump curve collapses the data for a variety of working fluids and voltage.