Applications In Microfluidic Devices Research Articles

A metamaterial-free fluid-flow cloak.

The model of ideal fluid flow around a cylindrical obstacle exhibits a long-established physical picture, where originally straight streamlines are deflected over the whole space by the obstacle. Inspired by transformation optics and metamaterials, recent theories have proposed the concept of fluid cloaking, which is able to recover the straight streamlines, as if the obstacle did not exist. However, such a cloak, similar to all previous transformation-optics-based devices, relies on complex metamaterials with inhomogeneous parameters and is difficult to implement. Here we deploy the theory of scattering cancellation and report on the experimental realization of a fluid-flow cloak without metamaterials. This cloak is realized by engineering the geometry of the fluid channel, which effectively cancels the dipole-like scattering of the obstacle. The cloaking effect is demonstrated through the direct observation of recovered straight streamlines in the fluid flow. Our work sheds new light on conventional fluid control and may find application in microfluidic devices.

Optimization of Photooxygenation of Dihydroartemisinic Acid in a Continuous Micro-reactor utilizing Physically Immobilized Methylene Blue on Polystyrene Micro-particles

Extensive studies reported upon the application of microfluidic devices for photooxygenation reactions. Only a few researches, however, have studied the optimization of experimentally controllable parameters towards achieving the best reaction conversion. Accordingly, in the current study, the optimum values of operating parameters towards achieving the highest dihydroartemisinic acid (DHAA) conversion were determined through the response surface methodology (RSM) technique. In order to do that, first, heterogenized micro-photosensitizers were synthesized during a super facile procedure not requiring any chemical reaction or modifications. Then, these micro-photosensitizers were utilized to perform continuous photooxygenation of the DHAA by means of a glass micro-reactor at room temperature and atmospheric pressure. Finally, the impacts of experimental parameters such as the flow ratios of solution to oxygen as well as DHAA and micro-photosensitizers’ concentrations upon the DHAA conversions were examined by using Design of Experiments (DOE) software in order to optimize and statistically model the DHAA conversion. The optimum value for this conversion was predicted by the RSM technique to be 70 % which was in a very good agreement with that of the experimental value of 69 % obtained in this study. The optimal values for the flow rates ratio, DHAA initial concentration, and micro-photosensitizer’s concentration were obtained to be 0.5, 0.5 mg/ml, as well as 1.5 mg/ml, respectively.

Imbibition of Newtonian Fluids in Paper-like Materials with the Infinitesimal Control Volume Method

Paper-based microfluidic devices are widely used in point-of-care testing applications. Imbibition study of paper porous media is important for fluid controlling, and then significant to the applications of paper-based microfluidic devices. Here we propose an analytical approach based on the infinitesimal control volume method to study the imbibition of Newtonian fluids in commonly used paper-like materials. Three common paper shapes (rectangular paper strips, fan-shaped and circular paper sheets) are investigated with three modeling methods (corresponding to equivalent tiny pores with circle, square and regular triangle cross section respectively). A model is derived for liquid imbibition in rectangular paper strips, and the control equations for liquid imbibition in fan-shaped and circular paper sheets are also derived. The model is verified by imbibition experiments done using the mixed cellulose ester filter paper and pure water. The relation of imbibition distance and time is similar to that of the Lucas−Washburn (L−W) model. In addition, a new porosity measurement method based on the imbibition in circular paper sheets is proposed and verified. Finally, the flow rates are investigated. This study can provide guidance for the design of different shapes of paper, and for better applications of paper-based microfluidic devices.

Enhanced Fog Harvesting through Capillary-Assisted Rapid Transport of Droplet Confined in the Given Microchannel

A novel integrated bioinspired surface is fabricated by using an innovative capillarity-induced selective oxidation method, to achieve the combination of the fog-collecting characteristics of a variety of creatures, i.e., the micronanostructures of spider silk, the wettable patterns of desert beetle, the conical structure of cactus spine, and the hierarchical microchannel of Sarracenia trichome. The fog is captured effectively via multistructures on the cone tips, and captured droplet is collected and confined in the microchannel to realize rapid transport via the formation of wettable pattern on the surface and the introduction of wettable gradient in the microchannel. Consequently, the fog harvest efficiency reaches 2.48 g/h, increasing to nearly 320% compared to the normal surface. More interestingly, similar to Sarracenia trichome, the surface also presents two transport modes, namely, Mode I (water transport along dry microchannel) and Mode II (succeeding water slippage on the water film). In Mode II, the velocity of 34.10 mm/s is about three times faster than that on the Sarracenia trichome. Such a design of integrated bioinspired surface may present potential applications in high-efficiency water collection systems, microfluidic devices, and others.

A wearable, nozzle‑diffuser microfluidic pump based on high‑performance ferroelectric nanocomposites

New target applications for microfluidic devices have been focused on home usability, wearability and cost-effectiveness. Towards these goals, in this work, a controllable, bendable, and all‑organic, nozzle‑diffuser microfluidic pump was designed, fabricated and tested. First, to resolve the crucial issue of high driving voltage, the ferroelectric polymer poly(vinylidene fluoride‑trifluoroethylene) (P(VDF‑TrFE)) was optimized by adding core‑shell structured Al2O3@CNT nanofillers. The membrane so developed with 1.1 wt% Al2O3@CNT showed an increase by nearly 7 times in the induced strain in comparison to the neat P(VDF‑TrFE) at low electric fields, because the modified membrane simultaneously achieved a lower coercive electric field and a higher polarization. Accordingly, the required operating voltage of the microfluidic pump integrated with optimized membrane significantly decreased from 1000 V to 160 V. Meanwhile, this pump exhibited a wider range of flow rates (13–135 µL/min) than the reported results, associated with the higher output pressure in our membranes. Importantly, the designed pump still possessed an excellent controllability of the fluidic processes, though it underwent a large bending up to 74°. Consequently, the extremely promising application of the as‑prepared microfluidic pump in wearable, biomedical devices was demonstrated.

P–025 Sperm selection using a modified “swim up” technique in absence of sperm centrifugation improve sperm DNA fragmentation and decreases miscarriage rate

Abstract Study question Is it useful to avoid sperm centrifugation in laboratory routine work to improve sperm quality and reproductive outcome in Assisted Reproduction Techniques (ART)? Summary answer Exclusion of sperm centrifugation for sperm selection using neat sperm samples (IO-lix), increases sperm quality in the collected subpopulation decreasing miscarriage rate after using ICSI. What is known already Inclusion of sperm centrifugation in ART is an aggressive intervention for sperm selection with ineludible production iatrogenic damage affecting sperm integrity. The application of IMSI, PICSI or microfluidic devices avoid sperm centrifugation and may improve the quality of the subsample obtained. However, these methodologies may result time consuming, expensive or producing poor results when the quality of the sperm is limited. We have already shown that a modified swim-up avoiding centrifugation (called IO-lix) is a low-cost and efficient alternative to microfluidic devices, recovers 100 times more concentration and reduces sperm DNA fragmentation with no significant differences to other methodologies. Study design, size, duration This is a retrospective study from 2018 to 2020 which includes patients with an average of age of 38.2 years using their own oocytes with ICSI as fertilization technique. Two aleatory groups of patients were made: Group 1: 88 cycles with 503 fertilized oocytes and 206 blastocysts were obtained with sperm samples processed by IO-lix and Group 2: 303 cycles, 1451 fertilized oocytes and 591 blastocysts using a standard “swim up” technique to process sperm. Participants/materials, setting, methods A total of 391 ICSI cycles were included in this retrospective study. The male factor was similar in both groups and they showed altered SDF previously to the cycle. We compared data of the motility and SDF of sperm samples before and after applying IO-lix and we analyzed by X2 contingence test differences on miscarriage rates between groups 1 and 2. Main results and the role of chance General sperm parameter changes after IO-lix showed that averaged sperm concentration observed in neat ejaculated samples was 62M/SD=46.4. Values obtained after IO-lix in the same samples were 12.3M/SD8.0. Averaged sperm motility in neat samples was 54%/SD=9.3 and 70.9%/SD=13.2 after IO-lix. Finally, sperm DNA fragmentation in neat samples was 35.8%/SD17.3, while these values decreased to 9.2%/SD=3.9 after IO-lix. About reproductive outcome results, significant differences were not obtained on the development to blastocyst stage rate comparing both groups (X2=0.003; p value = 0.954; Alpha 0.05). In the case of IO-lix processed samples, the pregnancy rate was 59.42% in Group 1 and 44.72% in Group 2 (X2=0.651; p value =0.419; Alpha 0.05). A total of 9 miscarriages of 41 clinical pregnancies (21.95%) were observed after IO-lix, while this number increases to 59 out of 123 clinical pregnancies, which means the 47.96% of the embryo transfers, when “swim-up” was used. In this case significant differences were obtained (X2=3.935; p value = 0.0.047; Alpha 0.05). Limitations, reasons for caution Being a pilot study aimed to understand the results of IO-lix in ART, correlations have not been stablished between the levels of sperm improvement after IO-lix and paired results of ART. This study would be necessary, specially to identify the possible origin of miscarriage associated to the male factor. Wider implications of the findings: Elimination of sperm centrifugation using a combined strategy of gradients and “swim-up” for sperm isolation, reduce miscarriage rate and produce equivalent results of blastocyst development to those obtained with “swim-up”. Being a cost-effective and improving laboratory workload, its use for sperm selection is recommended. Trial registration number Not applicable

Anisotropic wetting surfaces machined by diamond tool with tips microstructured by focused ion beam

In recent years, there has been an increasing interest in methods to fabricate hydrophobic surfaces. Hydrophobic surfaces have been used in multiple applications in microfluidic devices to control fluid flow, as self-cleaning surfaces and also in de-icing or for drag reduction. Conventionally, hydrophobic surfaces were created by laser processing, self-assembly and other chemical processing methods. However, in many of these methods, hydrophobicity of the surface cannot be maintained for an extended time or restricted to limited set of materials. In some applications, creation of anisotropy in the hydrophobic property and the ability to pattern it, is important. Here, a low-cost, high-throughput method to generate highly hydrophobic and anisotropic surface has been developed. This method uses Computer Numerical Control machining employing diamond tools whose tips have been micro-structured using Focused Ion Beam that enables parallelization and achieves at least four times higher machining speed compared with other methods. The versatility of this method has been demonstrated by machining both metal and polymeric materials. Significant anisotropic wetting has been observed on the machined surface with the anisotropy in directional contact angle of up to 71.6°. Highly-hydrophobic surfaces with contact angle of 163.1° on 6061 Aluminum Alloy and 155.7° on polymethyl methacrylate surface were created.

Effects on droplet generation in step-emulsification microfluidic devices

Step emulsification technology is an important breakthrough for the industrial application of microfluidic devices. In this paper, the influences of microdevice structures and physical properties of fluids on the droplet (around 1 mm in size) generation in a step emulsificator with a single microchannel are studied. Through the analysis of the interface evolution process during droplet generation, we found that increasing the width of the terrace (0.4–1.0 mm) and the size of the collection cavity, decreasing the viscosity of the dispersed phase (0.89–54.61 mPa·s) result in the increase in the range of the dripping flow regime, obtaining a larger emulsion flux of the microdevice. The prediction equation for the droplet size is proposed by considering the inertial and viscous forces of the dispersed phase: Dh=1.63Oh0.17We0.14+D0h-0.47Oh0.24. Finally, the relationship between the satellite droplet size formed by the neck rupture and the manipulation variables is presented.

Application of microfluidic paper-based analytical device (μPAD) to detect COVID-19 in energy deprived countries.

SummaryCoronavirus disease (COVID‐19) has spread all across the world. Low‐ and medium‐income countries are more affected economically and socially compared to developed countries due to the lack of a rapid, robust, and affordable testing infrastructure. Furthermore, the high cost of real‐time polymerase chain reaction (PCR) system, sophisticated user‐handling procedure, and high expense of the conventional clinical tests are the root causes of the less accessibility of the testing systems to the users. In this study, a COVID‐19 Point‐of‐Care (POC) ecosystem model is proposed for the low‐ and medium‐income countries (or energy deprived countries) that will facilitate the technological development with locally available fabrication components. In addition, the nontechnological development phases have also been discussed, which encompasses the collaboration among academia, local as well as government bodies, and entrepreneurial ventures. In addition, a hypothetical design of a microfluidic paper‐based analytical (μPADs) POC platform is proposed to detect COVID‐19 analyte using unprocessed patient‐derived saliva, which is a miniaturized form‐factor of conventional real‐time polymerase chain reaction (PCR) technique. The device contains four major reaction zones, which are sample zone, buffer zone, loop‐mediated isothermal amplification (LAMP) Master Mix zone, Ethylenediamine tetraacetic acid (EDTA) zone, and sensor zone. To obtain quicker test results and easier operation, a handheld image acquisition technique is introduced in this study. It is hypothesized that in a remote setting, the proposed design could be used as an initial guideline to develop a POC COVID‐19 testing system, which may be simple, easy‐to‐use, and cost‐effective.

Effect of Surface Nanopatterning on Slip: The Case of Couette Flow of Long-Chain Polyethylene Melt Flowing Past Gold Surfaces.

The manifestation of slip during flow of a polymer melt past a solid surface depends on several parameters, such as film thickness, the strength of polymer-solid interactions compared to the cohesive energy of the polymer, and the roughness of the surface. Understanding the role of these molecular aspects for slip is crucial in microfluidics, friction-tuning, polymer extrusion, and nanocomposites applications. The present article investigates the effect of surface nanopatterning on slip, via Couette-flow simulations of long chain polyethylene melts past nanopatterned gold surfaces. Slip is quantified in terms of the true and effective slip velocity, and the slip length. When polymer chains are adsorbed to surfaces with periodic features (e.g., crystal planes), they develop preferential ordering in a way that enables them to minimize their free energy. The orientation of a chain is affected by that of its neighbors; thus, when several chains come together, they are prone to form regions with crystal-like orientation. We show that, in some cases, the introduction of nanopatterns on the surface can perturb and induce reorganization of these regions, and in turn affect slip. The nanopatterns are realized as periodic defect stripes of variable width, depth, areal density, and orientation angle. In situations in which the width of the defects becomes comparable to the diameter of individual chain backbones, slip is minimized (stick conditions). Cutting the nanopatterns in low symmetry directions can affect the quality of their edges and lead to enhanced friction. To characterize these edges we have devised a scheme for the quantification of the mean square roughness and mean position of the surface, which is general and applicable in 2 and 3 dimensions for any kind of material, either crystalline of amorphous. Applying the patterns on the opposing solid surfaces in a symmetric or antisymmetric manner has a profound effect on flow. We show that the application of nanopatterns in symmetric configurations generates zero net flow and induces additional shear along directions normal to the direction of the flow. The application of symmetry-breaking configurations can guide flow toward preferential directions, a result with possible applications in microfluidic devices.

Paper-based microfluidics: Simplified fabrication and assay methods

• Review of paper-based microfluidics. • Overview of current methods of fabrication. • Applications as diagnostic devices. • Limitations and opportunities. Paper-based microfluidics is the branch of microfluidics involving devices made out of paper, or other porous membranes, that wick fluids by capillary action. Paper-based microfluidic devices have several advantages over conventional microfluidic devices including simpler fabrication, lower cost, easier disposal, and the ability to operate without pumps or other supporting equipment. The most common application of paper-based microfluidic devices is in the development of point-of-care (POC) diagnostic devices, which could eliminate the need for costly and time-consuming laboratory-based analytical procedures. This review provides an overview of current methods of fabricating paper-based microfluidic devices, examples of applications of these devices, a discussion of their current limitations, and an outlook on their future.

Modular micropumps fabricated by 3D printed technologies for polymeric microfluidic device applications

In order to facilitate the implementation of microfluidic technology for rapid point-of-care analysis, there is a demand for self-powered microfluidics. The modular architecture of degas driven plug-and-play polymeric micropumps and microfluidic cartridges arose during last decade as a powerful strategy for autonomous flow control. So far, reported polymeric micropumps were made of poly-dimethyl siloxane and were fabricated by casting. In this work, we showed that the advantages of three-dimensional printing can greatly benefit the development of modular micropumps. In addition, micropumps were created with a geometry that cannot be manufactured with conventional techniques, making it easily assemblable to microfluidic devices. Four types of polymeric resins and three printing methods were used to create a set of functional micropumps. It was shown that the material and the design of the printed micropumps were related to their power, making them tuneable and programmable. Finally, as proof of concept, a self-powered colorimetric test for the detection of starch was demonstrated. Three-dimensional printed micropumps emerge as an innovative element in the field of self-powered microfluidics, which may be the key to develop integrated microsystems for several applications such as in rapid point-of-care analysis.

Fabrication of Miniaturized Microfluidic Paper-Based Analytical Devices for Sandwich Enzyme-Linked Immunosorbent Assays using INKJET Printing

Main application of microfluidic paper-based analytical devices (µPADs) is for low-cost and portable assays. In order to reduce the cost, miniaturization seems to be an effective way to save reagents, samples, materials, etc. Present study demonstrates that mini-µPADs based on nitrocellulose membrane with only 2 main channels can perform sandwich enzyme-linked immunosorbent assays (ELISA) for quantitative determination of human chorionic gonadotropin (hCG). Moreover, the width and the length of these devices are only about 4.0 and 33.4 mm, respectively. Inkjet printing technology, having the advantages of simple and material-saving process, was used to create hydrophobic barrier. Colorimetric signals from ELISA captured by digital camera and measured by ImageJ software shows that these µPADs can quantitative determine of hCG in the range from 5 to 10 000 ng/mL. Furthermore, duration for each tests is only about 5 min. The success in fabricating miniaturized µPADs shows the potentials to reduce the size of µPADs as well as the amount of needed samples, time and reagents. For all these reasons, this miniaturization concept can be applied to many further applications of analytical biochemical assays.

A Printable Thin Film‐Based Digital Peristaltic Sticker‐Pump for a Simple and Robust Integration into Microfluidics

AbstractA micropump is pivotal for routing and multiplexing fluids in microfluidic channels, especially for point‐of‐care diagnostic devices. In this regard, a simple and easily mountable micropump‐platform needs to be developed to expand the applications of microfluidic devices. Here, the sticker type‐peristaltic pump, called “sticker‐pump,” is developed by incorporating an array of biocompatible polymeric bimorph actuators. The sticker‐pump can be activated via digital input sequence to control the flow rate in response to the operating voltage and switching speed. Furthermore, the programmed digital sequence demonstrates the generation of pulsatile and continuous flows without any back pressure. The sticker‐pump is further studied through a systematic characterization to validate the working mechanism of one sticker‐pump (1‐bit) and the flow rates (3.77–36.90 µL min−1) attained by the combination of three sticker‐pumps (3‐bit) on microfluidics. Since the sticker‐pump is all solution‐processed, an inexpensive sticker‐pump can be manufactured by scalable printing technologies.

Fabrication and Applications of Microfluidic Devices: A Review.

Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science. Various materials can be processed into miniaturized chips containing channels and chambers in the microscale range. A diverse repertoire of methods can be chosen to manufacture such platforms of desired size, shape, and geometry. Whether they are used alone or in combination with other devices, microfluidic chips can be employed in nanoparticle preparation, drug encapsulation, delivery, and targeting, cell analysis, diagnosis, and cell culture. This paper presents microfluidic technology in terms of the available platform materials and fabrication techniques, also focusing on the biomedical applications of these remarkable devices.

Liquid Mixing Based on Electrokinetic Vortices Generated in a T-Type Microchannel.

This article proposes a micromixer based on the vortices generated in a T-type microchannel with nonuniform but same polarity zeta potentials under a direct current (DC) electric field. The downstream section (modified section) of the outlet channel was designed with a smaller zeta potential than others (unmodified section). When a DC electric field is applied in the microchannel, the electrokinetic vortices will form under certain conditions and hence mix the solution. The numerical results show that the mixing performance is better when the channel width and the zeta potential ratio of the modified section to the unmodified section are smaller. Besides, the electrokinetic vortices formed in the microchannel are stronger under a larger length ratio of the modified section to the unmodified section of the outlet channel, and correspondingly, the mixing performance is better. The micromixer presented in the paper is quite simple in structure and has good potential applications in microfluidic devices.

Exploring the Design Efficiency of Random Microfluidic Mixers

With the development of microfluidic technologies, the increasing application of microfluidic devices in various research fields has brought up the urgent need for device performance simulation before fabrication to increase the design efficiency and reduce unnecessary trials and errors. As a fundamental function unit, the mixing performance is critical for a successful microfluidic device. Here in this study, we present a method of increasing the design efficiency of random micromixers. We have first generated the random libraries of micromixers constrained to different rectilinear grid configurations from $3\times3$ to $8\times8$ using MATLAB, and finite element analysis was used to simulate the performance of the micromixers. Then the most appropriate grid configuration was investigated on the aspects of fluid velocity and concentration distribution, simulation cost, and micromixer chip size. Our study results showed that the $5\times5$ grid configuration of random micromixer is an optimal balance to achieve the most abundant fluid velocity and solute concentration, while has acceptable simulation cost and reduced chip size. In summary, the $5\times5$ grid configuration is appropriate to provide enough random micromixer designs to meet user desire, not only time-effective but also cost-effective.

Polydimethylsiloxane microfluidic films for in vitro engineering of small-scale neuronal networks

Polydimethylsiloxane microfluidic devices have become standard tools in cell engineering research. However, through-holes where cells access the microchannels are usually fabricated manually using biopsy punches, making it difficult to create a large array of sub-mm sized through-holes. Here, we present a fabrication process for a thin-film microfluidic device containing an array of through-holes, which are as small as 100 μm by 100 μm and span 10 mm by 10 mm. A proof-of-concept application of the device to neuronal patterning experiments shows that spatially complex network dynamics emerge when a non-random connectivity is imposed to cultured neuronal networks. We also demonstrate that the coupling strengths between neuronal modules, a major factor that defines the global network dynamics, can be effectively modulated by varying the microchannel widths. This work opens a new application of microfluidic devices to multicellular systems comprised of several tens to hundreds of neurons.

Inertial microfluidics: Recent advances.

Inertial microfluidics has attracted significant attentions in last decade due to its superior advantages of high throughput, label- and external field-free operation, simplicity, and low cost. A wide variety of channel geometry designs were demonstrated for focusing, concentrating, isolating, or separating of various bioparticles such as blood components, circulating tumor cells, bacteria, and microalgae. In this review, we first briefly introduce the physics of inertial migration and Dean flow for allowing the readers with diverse backgrounds to have a better understanding of the fundamental mechanisms of inertial microfluidics. Then, we present a comprehensive review of the recent advances and applications of inertial microfluidic devices according to different channel geometries ranging from straight channels, curved channels to contraction-expansion-array channels. Finally, the challenges and future perspective of inertial microfluidics are discussed. Owing to its superior benefit for particle manipulation, the inertial microfluidics will play a more important role in biology and medicine applications.

Thermal Effect on Poly(methyl methacrylate) (PMMA) Material Removal in the Micromilling Process.

Poly(methyl methacrylate) (PMMA) is of growing interest in the application of microfluidic devices and high precision optical elements due to its excellent moldability and formability. Micromilling is one of the micromachining methods which has been extensively used to manufacture polymer components. In this study, a high-speed micromilling method was used to manufacture polymer with high form accuracy and surface quality. The processing temperature effects on the surface quality were investigated in detail. The dynamic mechanical analysis (DMA) experiment was used to study the material mechanical property under different temperatures. According to the DMA results, the PMMA sample is in the glass and viscoelastic state during the milling process. The cutting chips under various processing temperatures are classified into three kinds according to their shapes: roll, sheet, and sinter. The surface roughness of samples with sheet and roll cutting chips is smaller than that of sinter cutting chips. To obtain a better machining bottom surface and edge shape, the processing temperature below 70 °C is recommended according to the results. This work is of great value for the study of polymer removal mechanism and optimization of processing parameters for the industry.