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Free-flow electrophoresis (FFE) enables the continuous separation and collection of charged solutes, and as a result, it has drawn interest as both a preparative and an analytical tool for biological applications. Recently, a free-flow counterflow gradient focusing (FF-CGF) mechanism has been proposed with the goal of improving the resolution and versatility of FFE. To realize this potential, the factors that influence solute dispersion deserve further attention, including the gradient strength and the parabolic profile of the counterflow. Therefore, the goal of this work is to develop a theoretical model to study the interplay between these factors and molecular diffusion. Overall, an asymmetric solute distribution emerges for a wide range of parameters, and this behavior can be characterized with an exponentially modified Gaussian function. Results show that FF-CGF can achieve high-resolution separations, with the potential for high-throughput protein purification. Moreover, this work provides a practical guide for optimizing experimental conditions, as well as a strong framework for understanding and developing FF-CGF further.

Free-flow electrophoresis (FFE) has the ability to continuously separate charged solutes from complex biological mixtures. Recently, a free-flow counterflow gradient focusing (FF-CGF) mechanism has been introduced to FFE, and it offers the potential for improved resolution and versatility. However, further investigation is needed to understand the solute dispersion at the focal position. Therefore, the goal of this work is to model the impact of electroosmotic flow (EOF), which is found to produce a pressure-driven backflow to maintain the fixed counterflow inputs. Like the counterflow, this backflow has a parabolic velocity profile that must be considered when predicting the concentration distribution of a given solute. After the model is established, preliminary experimental results are presented for a qualitative comparison. Results demonstrate a reasonable agreement at low applied voltages and provide a strong framework for future experimental validation. This article is protected by copyright. All rights reserved.

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in an unprecedented economic and societal impact. Developing simple and accurate testing methods for point-of-care (POC) diagnosis is crucial not only for the control of COVID-19, but also for better response to similar outbreaks in the future. In this work, we present a novel proof-of-concept of a microfluidic microwave sensing method for POC diagnosis of the SARS-CoV-2 virus. This method relies on the antibody immobilized on the microwave sensor to selectively capture and concentrate the SARS-CoV-2 antigen or virus present in a buffer solution flowing through the sensor region in a microchannel. The capturing of the SARS-CoV-2 antigen or virus results in a change in the permittivity of the medium near the sensor region reflected by the resonance frequency shift which is used for detection. The use of microchannels offers precise control of the sample volume and the continuous flow nature also offers the potential to monitor the dynamic capturing process. The microwave-microfluidic device shows a good sensitivity of 0.1 ng ml

To evaluate the shear viscosity of contemporary, commercially available ocular lubricants at various shear rates and temperatures and to derive relevant mathematical viscosity models that are impactful for prescribing and developing eye drops to treat dry eye disease.The shear viscosity of 12 ocular lubricants was measured using a rheometer and a temperature-controlled bath at clinically relevant temperatures at which users may experience exposure to the drops (out of the refrigerator [4.3°C]; room temperature [24.6°C]; ocular surface temperature [34.5°C]). Three replicates for each sample at each temperature were obtained using a standard volume (0.5 mL) of each sample. The viscosity of each ocular lubricant was measured over the full range of shear rates allowed by the rheometer.The shear viscosity of the same ocular lubricant varied significantly among the three temperatures. In general, a higher temperature resulted in smaller viscosities than a lower temperature (an average of -48% relative change from 4.3°C to 24.6°C and -21% from 24.6°C to 34.5°C). At a constant temperature, the viscosity of an ocular lubricant over the studied shear rates can be well approximated by a power-law model.Rheological analysis revealed that the ocular lubricants exhibited shear-thinning behavior at the measured temperatures. Differences in the ocular lubricants' formulations and measured temperatures resulted in different viscosities.When prescribing eye drops, eye care professionals can select the optimal one for their patients by considering a variety of factors, including its rheological property at physiologically relevant shear rates and temperatures, which can improve residence time on the ocular surface, while ensuring appropriate comfort and vision. However, care must be taken when using the derived mathematical models in this study because the in vivo shear behavior of the ocular lubricants has not been examined and might show deviations from those reported when placed on the ocular surface.

Active control of individual picoliter- to nanoliter-sized droplets in a network of microchannels is vital to make droplet microfluidic platform an enabling technology for single-cell or single-particle analysis, which has found application in areas such as advanced manufacturing, material synthesis, life science research, and personalized medicine. The challenge manifests from the coupled dynamics between droplet motions and network inlet pressures, which must be overcome in order to control individual droplets successfully. In this article, we proposed a generalized approach for modeling and controlling droplet position. The model is validated experimentally and used in a series of multi-input multi-output linear–quadratic regulation controllers. The controllers obtain feedback from computer vision and actuate electropneumatic transducers to yield desired droplet movements. The ability to dynamically generate, trap, merge, split, and sort droplets according to real-time user demand is demonstrated with successful experimental results.

This work represents the second part of a two-part series on the dynamics of droplet formation in a T-junction generator under the squeezing regime when using solutions of red blood cells as the dispersed phase. Solutions containing red blood cells are non-Newtonian; however, these solutions do not behave in the same way as other non-Newtonian fluids currently described in the literature. Hence, available models do not capture nor predict important features useful for the design of T-junction microfluidic systems, including droplet volume. The formation of a red blood cell-containing droplet consists of three stages: a lag stage, a filling stage, and a necking stage, with the lag stage only observed in narrow dispersed phase channel setups. Unlike other shear-thinning fluids, thread elongation into the main channel at the end of the necking stage is not observed for red blood cell solutions. In this work, a model that predicts the final droplet volume of a red blood cell containing droplets in T-junction generators is presented. The model combines a detailed analysis of the geometrical shape of the droplet during the formation process, with force and Laplace pressure balances to obtain the penetration depth (b_{fill}^{*}) and the critical neck thickness (2r_{pinch}^{*}) of the droplet. The performance of the model was validated by comparing the operational parameters (droplet volume, the spacing between the droplet, and the generation frequency) with the experimental data across a range of the dimensionless parameters (flow rate ratios, continuous phase viscosities, and channel geometries).

One key factor that plays a significant role in the efficiency of on-chip electrophoresis separation is the initial shape of the sample plug at injection. For microchips involved in separat...

This work investigated a two-step surface modification of polyamide meshes and nonwoven fabrics for oil/water separation and looked into the durability of such modified polyamide. The two-step modification included 1) pre-etching the polyamide surface using plasma treatment and 2) coating the pre-etched surface by eco-friendly polydopamine (PDA)/cellulose. The pre-etching increased the surface roughness, which further improved the underwater superoleophobicity of the coating. Therefore, the modified polyamide was able to separate various oil/water mixtures and showed a higher intrusion pressure than the original sample and the samples which were only etched or only coated. The grooves on the surface that resulted from the pre-etching prevented the coating from peeling off. In durability tests, after 6 repeated uses, the modified nonwoven sample lost its underwater oleophobicity due to severe oil fouling, coming to a complete failure in oil/water separation. After 19 cycles, the modified mesh was still able to separate a certain amount of oil/water but showed reduced intrusion pressure because of slight oil contamination. Filters with different structures, like meshes with one layer of pores and nonwoven fabrics with complex three dimensional pores, had different oil fouling levels that affected oil/water separation. The recoverability of filters from oil contamination should be considered for practical applications.

Microfluidics is the science of miniaturization of conventional lab devices to microchips; electrophoresis is one of the techniques for on-chip DNA and protein separation. In this article, nondimen...

With the advent of microfluidics and lab-on-chip systems, DNA and protein separation technologies are being developed for biology, diagnostics, and health purposes. Fully realizing these applicatio...

Porous polyamide functionalized by plasma or various coatings has been investigated for oil/water separation. In literature, polyamide has rarely been studied for oil removal, and this work investigated the performance of bare polyamide 6.6 (nylon 6.6) in terms of the oil/water separation efficiency and the intrusion pressure, inspiring cost-effective solutions for large-scale oil removal in the industry. Both polyamide meshes possessing two-dimensional (2D) one-layer pores and nonwoven fabrics with three-dimensional (3D) irregular pores were found to be able to separate oil/water with a high efficiency above 98.5%. This finding was attributed to the dual underwater oleophobicity and underoil hydrophobicity of these polyamide samples. The roles of 2D and 3D structures in oil/water separation were illustrated, to provide a new insight into filter designing. Due to its greater intrusion pressure, the 3D netting structure was suggested as being more beneficial for oil/water separation than the 2D structure.

Non-invasive contactless simultaneous sensing and heating of individual droplets would allow droplet microfluidics to empower a wide range of applications. However, it is challenging to realize simultaneous sensing and heating of individual droplets as the resonance frequency of the droplet fluid, which is decided by its permittivity, must be known so that energy is only supplied at this frequency for droplet heating with one resonator. To tailor the energy transfer in real-life heating applications, the droplet has to be sensed first to identify its corresponding resonance frequency, which is used to dynamically tune the frequency for supplying the required energy for heating this particular droplet. To achieve this goal, two resonators are needed, with one for sensing and one for heating. Integrating multiple resonators into one typical microfluidic device limits placement of the resonators to be as close as possible, which would raise the concern of crosstalk between them. The crosstalk would result in inaccurate sensing and heating. This study focuses on numerically and experimentally investigating the effect of influencing parameters on the crosstalk between two adjacent resonators with the ultimate goal of providing guidance for multiplexing the resonators in a typical microfluidic device. ANSYS HFSS is used to perform the electromagnetic analysis based on the finite element method. Experimental studies are conducted on a microfluidic chip integrated with two resonators to validate the numerical results. An optimal distance between two resonators is suggested, with the recommendation for the resonator size and heating power towards simultaneous sensing and heating of individual droplets.

Polydimethylsiloxane (PDMS) is a widely used material for microfluidic devices due to its low cost, superior optical properties and fast iterative design process. Its softness however creates challenges for the device design and operation because part of the applied pressures contributes to deform chips instead of controlling the flow. The resulting dynamic behaviour is often ignored in passive microfluidic that focuses on the static behaviour of the chip, however, can cause low accuracy to active microfluidic that actuates flow frequently. Therefore, understanding the dynamic behaviour of microfluidic devices due to material compliance is of fundamental and practical importance. In this study, the microfluidic chip compliance is carefully considered by separating it from the sample tubing compliance. The capacitance is retrieved by assuming a symmetric RC circuit based on the experimentally determined time constant and chip resistance. The experimental capacitance is compared to a theoretical formula for chip designs with different height-to-width ratios and height-to-length ratios and for various fluids. The accuracy is within one order of magnitude that is much closer than previous approximations.

The extension of microfluidics to many bioassay applications requires the ability to work with non-Newtonian fluids. One case in point is the use of microfluidics with blood having different hematocrit levels. This work is the first part of a two-part study and presents the formation dynamics of blood droplets in a T-junction generator under the squeezing regime. In this regime, droplet formation with Newtonian fluids depends on T-junction geometry; however, we found that in the presence of the non-Newtonian fluid such as red blood cells, the formation depends on not only to the channel geometry, but also the flow rate ratio of fluids, and the viscosity of the phases. In addition, we analyzed the impact of the red blood cell concentration on the formation cycle. In this study, we presented the experimental data of the blood droplet evolution through the analysis of videos that are captured by a high-speed camera. During this analysis, we tracked several parameters such as droplet volume, spacing between droplets, droplet generation frequency, flow conditions, and geometrical designs of the T junction. Our analysis revealed that, unlike other non-Newtonian fluids, where the fourth stage exists (stretching stage), the formation cycle consists of only three stages: lag, filling, and necking stages. Because of the detailed analysis of each stage, a mathematical model can be generated to predict the final volume of the blood droplet and can be utilized as a guide in the operation of the microfluidic device for biochemical assay applications; this is the focus of the second part of this study [Phys. Rev. E 105, 025106 (2022)10.1103/PhysRevE.105.025106].

Microfluidics is an enabling technology that leverages smaller dimensions. The development of droplet microfluidics by introducing a second phase aimed to address challenges arising when using a single phase. The advantages of droplet microfluidics are used for various biomedical applications. Biomaterial applications are enabled by the complex structure capabilities, the encapsulation and effective isolation, and the high throughput allowing relevant production rates. The screening of isolated elements at the micrometer scale significantly improves the signal-to-noise ratio; moreover, the encapsulation and isolation within the droplets enable the study of large heterogeneous populations using high throughput devices. As for bioreactors, the small size is leveraged to achieve shorter reaction times and to save reagent; furthermore, the complex structures enabled by microfluidic devices are promising to achieve artificial cells.

In this note, we report a simple, new method for droplet generation in microfluidic systems using integrated microwave heating. This method enables droplet generation on-demand by using microwave heating to induce Laplace pressure change at the interface of the two fluids. The distance between the interface and junction and microwave excitation power have been found to influence droplet generation. Although this method is limited in generating droplets with a high rate, the fact that it can be integrated with microwave sensing that can be used as the feedback to tune the supply flow of materials presents unique advantages for applications that require dynamic tuning of material properties in droplets.

A review on microfluidic technology for antibacterial resistance study and antibiotic susceptibility testing (AST) is presented here. Antibiotic resistance has become a global health crisis in recent decades, severely threatening public health, patient care, economic growth, and even national security. It is extremely urgent that antibiotic resistance be well looked into and aggressively combated in order for us to survive this crisis. AST has been routinely utilized in determining bacterial susceptibility to antibiotics and identifying potential resistance. Yet conventional methods for AST are increasingly incompetent due to unsatisfactory test speed, high cost, and deficient reliability. Microfluidics has emerged as a powerful and very promising platform technology that has proven capable of addressing the limitation of conventional methods and advancing AST to a new level. Besides, potential technical challenges that are likely to hinder the development of microfluidic technology aimed at AST are observed and discussed. To conclude, it is noted that (1) the translation of microfluidic innovations from laboratories to be ready AST platforms remains a lengthy journey and (2) ensuring all relevant parties engaged in a collaborative and unified mode is foundational to the successful incubation of commercial microfluidic platforms for AST.

Microfluidics has progressed tremendously as a field over the last two decades. Various areas of microfluidics developed in fully-fledged domains of their own such as organ-on-a-chip, digital and paper microfluidics. Nevertheless, the technological advancement of microfluidics as a field has not yet reached end-users for independent use. This is the key objective that is kept as a lens throughout this review. The ultimate goal is for microfluidics to be simply considered as a tool for application-focused research. A modular automated platform is envisioned to provide the stacking and modularity required to lower the knowledge barrier for end-users. The literature considered in this review is limited to active microfluidics and the analysis focuses on the potential for end-users to independently leverage the platforms for research in various fields such as cell assays, biochemistry, materials, and environmental factors monitoring.

Microfluidics typically uses either a syringe pump that regulates the flow rate in microchannels or a pressure pump that controls the inlet pressures to drive the flow. In the context of pressure-driven flow, a reservoir holder containing liquid samples is normally used to interface the pressure pump with the microfluidic chip via soft tubing. The tubing connecting the pump and holder transports the pressurized air while the tubing connecting the holder and chip transports the liquid samples. The pressure output from the pump is usually assumed to be stable and the same as that applied to the liquid in the chip; however, in practice this assumption is often incorrect and may negatively impact chip performance. This assumption is critically challenged when applied to microfluidic chips involving dynamic control of fluids since the pressures are constantly varied (at > 10 Hz). This study presents a method for investigating, quantifying and modelling the pump stability and the dynamics of the air tubing using two pressure sensors. The relationship between the pressure output from the pump and the reservoir holder pressure is generalized as a first-order linear system. This relationship allows the software that controls the pressure pump to output the required pressure to the reservoir holder and thus to the microfluidic chip. These results should significantly improve the performance of microfluidic chips using active fluid control, and may also benefit passive fluid control applications.

A dynamic and low-profile unloader tibiofemoral knee brace is designed and prototyped by synergizing concepts from the fields of microfluidics and soft robotics. Microfluidics provides strategies for miniaturization and multiplexing while soft robotics afford the tools to create soft fluidic actuators and allow compliant and inherently safe robotic assistance as part of clothing. The unloader knee brace provides dynamic response during the gait cycle, where a three-point leverage torque is provided only during the stance phase to contribute to joint stability when required and enhance comfort and compliance.Clinical Relevance- This novel soft robotic brace has the potential to reduce device abandonment due to aesthetics, user non-compliance and discomfort due to a constant three-point leverage torque during the gait cycle. Also, this air microfluidics enabled soft robotic knee brace could be expanded upon to improve the efficacy of braces in general and augment the effects of physical therapy, rehabilitation and treatment of musculoskeletal conditions.

Quantum dot-DNA oligonucleotide (QD-DNA) conjugates have been used in many fields such as nucleic acid bioassays, intracellular probes, and drug delivery systems. A typical solid-phase method that achieves rapid loading of oligonucleotides on surfaces of QDs involves a two-step reaction and is performed in a batch-based approach. In contrast, droplet microfluidics offers many advantages that are unavailable when using batch processing, providing rapid and dense immobilized DNA oligonucleotides on QDs. The presented droplet microfluidic approach allows high-quality QD-DNA conjugates to be produced using one single device, which is designed to have two droplet generators, one droplet merger, and one mixer. One of the droplet generators coencapsulates QDs and magnetic beads (MBs) into nanoliter-sized droplets for the production of QD-MB conjugates and the other encapsulates oligonucleotides in nanoliter-sized droplets. These two streams of droplets then merge at a one-to-one ratio in a chamber. The merged droplets travel along the mixer, which is a serpentine microchannel with 30 turns, resulting in QD-DNA conjugation structures of high quality. This multifunctional microfluidic device provides advantages such as higher degree of control over the reaction conditions, minimized cross-contamination and impurities, and reduction of reagent consumption while eliminating any need for external vortexing and pipetting. To evaluate the quality of the QD-DNA conjugates, they were used as Forster resonance energy transfer (FRET) probes to quantify oligonucleic targets.

Manipulation of light transmission/absorbance and reflection/emission has a great significance in smart windows and displaying media like liquid crystal. Here, we report the usage of an external electric field to reversibly switch the molecular spectra of a model molecule on the basis of its interaction with an electroresponsible polymer brush. Both the UV-vis absorbance spectrum and the fluorescence emission spectrum of the model molecule were confirmed to be electroswitchable. The electroswitchable spectra were experimentally demonstrated to be induced by the electroswitchable statuses of medium anionic poly-allyloxy hydroxypropyl sulfonate (poly-AHPS) brush. Insightfully, the molecular aggregated status of model proflavine molecules could be electrically controlled via the electroresponsible poly-AHPS brushes and then the molecular spectra of the model proflavine molecule also could be electrically and controllably shifted. The success in the manipulation of molecular spectra opens up a wide range of applications not only for displaying but also for nonlinear optics, in vivo imaging, sensors, and environmental inspection.

The nanoparticle seed layer (a film) and vertically aligned nanorods of zinc oxide (ZnO) with different lengths were fabricated within a novel chamber-based microfluidic (microchamber) reactor with a varying height of 0.127–5 mm and characterized with their microstructures, photocatalytic performances as well as qualitative reaction kinetics. The ZnO seed layer was produced by a sol–gel procedure and the nanorods were hydrothermally grown on seed layer coated glass substrates. These ZnO samples were integrated into the microchamber reactor through a seven-layer sandwiched configuration. The aqueous methyl orange (MO) solution was chosen as a model polluted water. By comparing the ultraviolet–visible (UV–vis) absorbance of the original MO solution and the post-treatment sample, the reaction constants were calculated, representing the efficiencies of the reactors. The ZnO samples, usually possessing a large amount of defects, with a higher crystal quality showed an enhanced activity. The reaction constant was featured of a plateau with accelerating flow rates, exhibited an exponentially decreasing function of the chamber height, and declined with increasing the initial concentration of the MO solution. The efficiency of the microchamber reactor was found to be one to two orders of magnitude higher than that of a batch reactor. The rate determining step was suggested to be the mass transport related adsorption of MO on ZnO. The measured reaction properties and the reactor design should be of considerable significance to the scaling-up and optimization of microchamber catalytic reactors dedicated to water purification and other applications.

High throughput analysis is highly demanded in a variety of chemical reactions. Droplet microfluidics offers unique advantages over traditional multi-well plate systems for high throughput analysis such as providing a confined and more controllable environment for single particle or cell analysis. Driven by the need to improve the efficiency of encapsulating one particle or cell into one individual droplet without complicating geometric and operating conditions, this study experimentally investigated the effects of viscosity contrast between two miscible fluids that together serve the dispersed fluid on the ordering of particles before they are encapsulated into droplets by another immiscible fluid. Five scenarios with different viscosity contrast were systematically considered and a physical model of droplet size for each scenario was developed based on experimental results and scaling laws. The five different scenarios include two with pure 10% glycerol and pure 80% glycerol as the dispersed phase, respectively, and three others where these two fluids are either side by side or one is accompanied by the other. Droplet size and formation period for these scenarios were compared and analyzed considering the same geometric and flow conditions. It is found that the stratified flow structures formed in the first junction by the two miscible fluids (10% and 80% glycerol solutions) strongly influence droplet formation dynamics such as droplet size and formation frequency. Each scenario finds its own applications. The scenario with 80% glycerol surrounded by 10% glycerol provides the optimized means for particle encapsulation. However, the scenario with two fluids side by side in the first junction generates droplets with high monodispersity for the largest range of flow ratios, which is useful for high throughput reactions involving different reagents.

In this study, we present a microwave-based microfluidic mixer that allows rapid mixing within individual droplets efficiently. The designed microwave mixer is a coplanar design with a small footprint, which is fabricated on a glass substrate and integrated with a microfluidic chip. The mixer works essentially as a resonator that accumulates an intensive electromagnetic field into a spiral capacitive gap (around 200 μm), which provides sufficient energy to heat-up droplets that pass through the capacitive gap. This microwave actuation induces nonuniform Marangoni stresses on the interface, which results in three-dimensional motion inside the droplet and thus fast mixing. In order to evaluate the performance of the microwave mixer, droplets with highly viscous fluid, 75% (w/w) glycerol solution, were generated, half of which were seeded with fluorescent dye for imaging purposes. The relative importance of different driving forces for mixing was evaluated qualitatively using magnitude analysis, and the effect of the applied power on mixing performance was also investigated. Mixing efficiency was quantified using the mixing index, which shows as high as 97% mixing efficiency was achieved within the range of milliseconds. This work demonstrates a very unique approach of utilizing microwave technology to facilitate mixing in droplet microfluidics systems, which can potentially open up areas for biochemical synthesis applications.

Developing a microfluidic chip with multiple functions is highly demanded for practical applications, such as chemical analysis, diagnostics, particles synthesis and drug screening. This work demonstrates a microfluidic chip integrated with a series of functions including droplet generation, pairing, trapping, merging, mixing and releasing, and controlled entirely by liquid flow involving no electrodes, magnets or any other moving parts. This chip design is capable of trapping and merging droplets with different content on demand allowing the precise control of reaction time and eliminates the need for droplet synchronization of frequency, spacing or velocity. A compact model is developed to establish a set of design criterion. Experiments demonstrate that fast mixing in the merged droplets can be realized within several seconds benefiting from the flow fluctuation induced by droplets coming or leaving the trapping region. Additionally, it allows a concentration gradient of a reagent to be established. Finally, this design is applied to screen drug compounds that inhibit the tau-peptide aggregation, a phenomenon related to neurodegenerative disorders.

96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).

Automated control of individual droplets in microfluidic channels offers tremendous potential for applications requiring high accuracy and minimal user involvement. The feasibility of active droplet control has been previously demonstrated with pressure-driven flow control and visual feedback, but the manual operation required to perform droplet manipulations limited the accuracy, repeatability, and throughput. The present study improves upon the aforementioned challenges with a higher-level algorithm capturing the dynamics of droplet motion for a semi-automated control system. With a simple T junction geometry, droplets can now be automatically and precisely controlled on-demand. Specifically, there is ±10% accuracy for droplet generation, ±1.3% monodispersity for 500 μm long droplets and ±4% accuracy for splitting ratios. On-demand merging, mixing, and sorting are also demonstrated as well as the application of a drug screening assay related to neurodegenerative disorders. Overall, this system serves as a foundation for a fully automated system that does not require valves, embedded electrodes, or complex multi-layer fabrication.

Counterflow gradient electrofocusing uses the bulk flow of a liquid solution to counterbalance the electrophoretic migration of an analyte. When either the bulk velocity or the electrophoretic velocity of the analyte is made to vary across the length of the channel, there exists a unique zero-velocity point for the analyte. This focusing method enables simultaneous separation and concentration of different analytes. The high resolution and sensitivity achieved are similar to that of isoelectric focusing, which separates analytes based on their isoelectric points, but the key difference is that analytes will instead focus based on their electrophoretic mobility. Dynamically changing the applied voltage or the counterflow rate over time will shift the zero-velocity point, and therefore allows the focused analytes to pass through a fixed detection point, or elute from the separation channel. Throughout the review, a number of different counterflow gradient techniques will be discussed, along with their recent advancements and potential applications.

Microfluidic platform is an enabling technology for a wide range of applications such as life science research, material synthesis, drug discovery and environmental monitoring and protection. Most applications require separation or filtration of samples such as cell or particle separation which can be achieved by manipulating flow and channel geometries, leveraging external forces or integrating on-chip membranes. Membranes are convenient without the need of precise control of flow and channel dimensions or the need to use external forces. Polydimethylsiloxane (PDMS) which is one of the most widely used materials for making microfluidic devices has also been used to make on-chip membranes, but the integration appears to be tedious and have low reproducibility. Polycarbonate track-etched (PCTE) membranes which can be manufactured to a high standard are excellent alternatives and have demonstrated success in microfluidic applications. However, their use in microfluidics has been limited due to the lack of details for their integration with microfluidic devices. This study provides an improved understanding of the bond strength between PCTE membranes and PDMS and presents a detailed set of procedures for bonding them by aminosilane-mediated plasma treatment. Due to the manufacturing process, the membranes have a smooth and rough side, which were carefully evaluated in terms of their bonding strength with PDMS devices for a range of applied pressures. It was found that the smooth side should be preferentially chosen as the primary bonding surface, however, with proper procedures, the rough side can achieve similar results. Both procedures are provided in detail, which can have a significant impact on the performance of microfluidic devices that require a sandwiched membrane structure.

Soft robotics has gone through a decade of tremendous progress in advancing both fundamentals and technologies. It has also seen a wide range of applications such as surgery assistance, handling of delicate foods, and wearable assistive systems driven by its soft nature that is more human friendly than traditional hard robotics. The rapid growth of soft robotics introduces many challenges, which vary with applications. Common challenges include the availability of soft materials for realizing different functions and the precision and speed of control required for actuation. In the context of wearable systems, miniaturization appears to be an additional hurdle to be overcome in order to develop truly impactful systems with a high user acceptance. Microfluidics as a field of research has gone through more than two decades of intense and focused research resulting in many fundamental theories and practical tools that have the potentials to be applied synergistically to soft robotics toward miniaturization. This perspective aims to introduce the potential synergy between microfluidics and soft robotics as a research topic and suggest future directions that could leverage the advantages of the two fields.

Simple yet powerful clustered regularly-interspaced short palindromic repeats (CRISPR) technology has led to the advent of numerous developments in life sciences, biotechnology, therapeutics, and molecular diagnostics, enabled by gene editing capability. By exploiting the CRISPR-Cas system’s nucleic acid sequence detection abilities, CRISPR-based molecular diagnostics have been developed. Here, we review the development of rapid, sensitive, and inexpensive CRISPR-based molecular diagnostics. We introduce the transition of CRISPR technology to precision molecular diagnostic devices from tube to device. Next, we discuss the various nucleic acid (NA) detection methods by CRISPR. We address the importance of significant sample preparation steps for a future sample-to-answer solution, which is lacking in current CRISPR-based molecular diagnostic technology. Lastly, we discuss the extension of CRISPR-based molecular diagnostics to various critical applications. We envision CRISPR technology holds great promise for widespread use in precision NA detection applications after particular technical challenges are overcome.

It is widely believed that media surface roughness enhances particle deposition-numerous, but inconsistent, examples of this effect have been reported. Here, a new mathematical framework describing the effects of hydrodynamics and interaction forces on particle deposition on rough spherical collectors in absence of an energy barrier was developed and validated. In addition to quantifying DLVO force, the model includes improved descriptions of flow field profiles and hydrodynamic retardation functions. This work demonstrates that hydrodynamic effects can significantly alter particle deposition relative to expectations when only the DLVO force is considered. Moreover, the combined effects of hydrodynamics and interaction forces on particle deposition on rough, spherical media are not additive, but synergistic. Notably, the developed model's particle deposition predictions are in closer agreement with experimental observations than those from current models, demonstrating the importance of inclusion of roughness impacts in particle deposition description/simulation. Consideration of hydrodynamic contributions to particle deposition may help to explain discrepancies between model-based expectations and experimental outcomes and improve descriptions of particle deposition during physicochemical filtration in systems with nonsmooth collector surfaces.

Microwave resonator offers simultaneous sensing and heating of individual droplets in microchannels presenting unique advantages for applications requiring well-controlled reaction time. This study numerically investigates the effects of the temperature-dependent fluid properties including viscosity, density, diffusivity, and interfacial tension, on microwave heating induced mixing. A system consisting of a spiral resonator integrated with a microchannel with aqueous droplets moving with a carrier oil is considered. The electromagnetic field which provides heating to the droplets, and the flow and tracer concentration fields inside the droplet are obtained using commercial software, Ansys HFSS and Fluent, respectively. It is found that the mixing index can be increased from 0.4 to 0.84 within 320[ms] with microwave heating and it would be slightly increased to 0.47 when only the interfacial tension was made independent on temperature, which suggests that the temperature-dependent interfacial tension is the dominant factor for microwave heating induced mixing.

An open-source precision pressure pump system and control software is presented, primarily designed for the experimental microfluidics community, although others may find additional uses for this precision pressure source. This mechatronic system is coined ‘µPump,’ and its performance rivals that of commercially available systems, at a fraction of the cost. The pressure accuracy, stability, and resolution are 0.09%, 0.02%, and 0.02% of the full span, respectively. The settling time to reach 2 bar from zero and stabilize is less than 2 s. Material for building a four-channel µPump (approx. $3000 USD) or an eight-channel µPump (approx. $5000 USD) is approximately a quarter, or a third of the cost of buying a high-end commercial system, respectively. The design rationale is presented, together with documented design details and software, so that the system may be replicated or customized to particular applications. µPump can be used for two-phase droplet microfluidics, single-phase microfluidics, gaseous flow microfluidics and any other applications requiring precise fluid handling. µPump provides researchers, students, and startups with a cost-effective solution for precise fluid control.

Off-the-shelf planar strain gauges are ubiquitous and are generally designed for materials with a large elastic modulus such as steel or aluminum. Correspondingly, the strain gauges themselves are stiff and do not deform substantially under applied stress. Pairs of this type of strain gauge are typically used in a Wheatstone bridge circuit allowing the measurement of very small changes in resistance due to the changes in sensing element cross-sectional area to be measured. However, their use with softer low-modulus materials is limited due to the larger elastic deformations involved. The conductive property of graphene is leveraged to produce a different type of strain sensor that is sensitive yet also capable of significant elastic deformation. The graphene is dispersed in a silicone-based polymer matrix such that the deformation induces a change in resistance that can be measured using a voltage divider circuit. The target application for which this sensor is developed is to measure strain in a pressurized length of soft Tygon® tubing which is often used in pumping fluids through microfluidic devices. However, the silicone-based graphene polymer can easily be applied to a variety of other shapes and soft materials.

The functional performance of passively operated droplet microfluidics is sensitive with respect to the dimensions of the channel network, the fabrication precision as well as the applied pressure because the entire network is coupled together. Especially, the local and global hydrodynamic resistance changes caused by droplets make the task to develop a robust microfluidic design challenging as plenty of interdependencies which all affect the intended behavior have to be considered by the designer. After the design, its functionality is usually validated by fabricating a prototype and testing it with physical experiments. In case that the functionality is not implemented as desired, the designer has to go back, revise the design, and repeat the fabrication as well as experiments. This current design process based on multiple iterations of refining and testing the design produces high costs (financially as well as in terms of time). In this work, we show how a significant amount of those costs can be avoided when applying simulation before fabrication. To this end, we demonstrate how simulations on the 1D circuit analysis model can help in the design process by means of a case study. Therefore, we compare the design process with and without using simulation. As a case study, we use a microfluidic network which is capable of trapping and merging droplets with different content on demand. The case study demonstrates how simulation can help to validate the derived design by considering all local and global hydrodynamic resistance changes. Moreover, the simulations even allow further exploration of different designs which have not been considered before due to the high costs.

Quantum dots (QDs) provide opportunities for the development of bioassays, biosensors, and drug delivery strategies. Decoration of the surface of QDs offers unique functions such as resistance to non-specific adsorption, selective binding to target molecules, and cellular uptake. The quality of decoration has substantial impact on the functionality of modified QDs. Single-phase microfluidic devices have been demonstrated for decorating QDs with biological molecules. The device substrate can serve as a solid-phase reaction platform, with a limitation being difficulty in the realization of reproducible decoration at high density of coverage of QDs. Magnetic beads (MBs) have been explored as an alternative form of solid-phase reaction platform for decorating QDs. As one example, controlled decoration to achieve unusually high density can be realized by first coating MBs with QDs, followed by the addition of molecules such as DNA oligonucleotides. Uniformity and high density of coatings on QDs have been obtained using MBs for solid-phase reactions in bulk solution, with the further advantage that the MBs offer simplification of procedural steps such as purification. This study explores the use of a droplet microfluidic platform to achieve solid-phase decoration of MBs with QDs, offering control of local reaction conditions beyond that available in bulk solution reactions. A microchannel network with a two-junction in-series configuration was designed and optimized to co-encapsulate one single 1 µm MB and many QDs into individual droplets. The microdroplet became the reaction vessel, and enhanced conjugation through the confined environment and fast mixing. A high density of QDs was coated onto the surface of single MB even when using a low concentration of QDs. This approach quickly produced decorated MBs, and significantly reduced QD waste, ameliorating the need to remove excess QDs. The methodology offers a degree of precision to control conjugation processes that cannot be attained in bulk synthesis methods. The proposed droplet microfluidic design can be widely adopted for nanomaterial synthesis using solid-phase assays.

Hydrodynamic shrinkage of liquid CO

This study reports a new method for establishing an open tubular IPG in a microchip coupled with a whole column image detection (WCID) system for protein separation applications. This method allows a wider range of immobilized pH (2.6-9.5) to be established in a PDMS/quartz channel by controlling the diffusion of acidic and basic polymer solutions into the channel through well-designed channel dimensions. The developed pH gradient was experimentally validated by performing the separation of a mixture of standard pI markers. It was further validated by the separation of the hemoglobin control AFSC sample. This method is advantageous over existing IPG methods because it has a wider range of pH and maintains the open tubular feature that matches the UV WCID to improve the sensitivity.

Flow focusing generators have been widely used to generate droplets for many applications which call for accurate physical models that describe the droplet formation process in such configurations for design and operation purposes. Most existing models are empirical correlations obtained based on extensive experimental results and thus very sensitive to their own data sets. A comprehensive model that involves less parameter fitting by incorporating more theoretical arguments and thus has an improved applicability is urgently needed to guide the design and operation of flow focusing generators. This work presents a 3D physical model describing the droplet formation process in microfluidic flow focusing generators that operate in the squeezing regime where droplet size is usually larger than the channel width. This model incorporates an accurate geometric description of the 3D droplet shape during the formation process, an estimation of the time period for the formation cycle based on the conservation of mass and a semi-analytical model predicting the pressure drop over the 3D corner gutter between the droplet curvature and channel walls, which allow an accurate determination of the droplet size, spacing and formation frequency. The model considers the influences of channel geometry (height-to-width ratio), viscosity contrast, flow rate ratio and capillary number with a wide variety. This model is validated by comparing predictions from the model with experimental results obtained through high-speed imaging.

This is the first part of a two-part study on a partially miscible liquid-liquid flow (liquid carbon dioxide and deionized water) which is highly pressurized and confined in a microfluidic T-junction. Our main focuses are to understand the flow regimes as a result of varying flow conditions and investigate the characteristics of drop flow distinct from coflow, with a capillary number, Ca_{c}, that is calculated based on the continuous liquid, ranging from 10^{-3} to 10^{-2} (10^{-4} for coflow). Here in part I, we present our experimental observation of drop formation cycle by tracking drop length, spacing, frequency, and after-generation speed using high-speed video and image analysis. The drop flow is chronologically composed of a stagnating and filling stage, an elongating and squeezing stage, and a truncating stage. The common "necking" time during the elongating and squeezing stage (with Ca_{c}∼10^{-3}) for the truncation of the dispersed liquid stream is extended, and the truncation point is subsequently shifted downstream from the T-junction corner. This temporal postponement effect modifies the scaling function reported in the literature for droplet formation with two immiscible fluids. Our experimental measurements also demonstrate the drop speed immediately following their generations can be approximated by the mean velocity from averaging the total flow rate over the channel cross section. Further justifications of the quantitative analysis by considering the mass transfer at the interface of the two partially miscible fluids are provided in part II.

Droplet microfluidics has been proven to be a viable platform for a variety of reactions by using uniform droplets well encapsulated by an immiscible carrier medium as reaction vesicles. Merging as one of the most basic forms of droplet manipulation is highly demanded in controlling the concentration of reagents for reactions. After preliminary testing of several reported passive merging designs, it is found that most of them are prone to fabrication and operation uncertainties which limit their application for practical use. In this work, we present a simple design for merging variable numbers of droplets with a valve-type function which enables a critical volume limit to be imposed to the final product droplet. When the product droplet reaches the critical volume limit, it will block the exit of the merging chamber serving as the close mode of the valve. As a result, the pressure upstream is built up which forces the product droplet to exit the merger. The relationship between the numbers of droplets merged, the length of input droplets and the length of output droplets is used to tune the design parameters such as the chamber length, pillar array dimensions and bypass channel dimensions according to the desired set of reactions. The simplicity of the design allows for easier design and configuration to a desired purpose and lows down the risk of failures due to fabrication and operation uncertainties. The single-input–single-output design minimizes pressure disturbances from propagating downstream and reduces the complexity of integration into a larger LOC system. The geometry can be scaled up with little to no observable effect on the mode of operation.

Motivated by stabilizing a hydrophilic surface condition of polydimethylsiloxane (PDMS) and improving its zeta potential, several reported methods for treating PDMS surface were evaluated using two or more of the following techniques: capillary flow in dryly stored channels, static contact angle measurement, current monitoring technique and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The surface treatment methods that were evaluated include four groups: pre-doping PDMS with acrylic acid, extraction of uncured PDMS (oligomer), and monomer grafting using 2-hydroxyethyl methacrylate (HEMA) and monomer grafting using polyethylene glycol (PEG). This study also proposed a modified PEG grafting method. It was observed that the extraction and monomer grafting methods were capable of changing hydrophobic PDMS to the stable hydrophilic state. However, none of the evaluated methods were able to increase the zeta potential of PDMS to a value higher than that treated with a one-step plasma treatment based on the current monitoring measurement, where 1X Tris–Borate–EDTA (TBE) buffer was used as the liquid sample. It was found that combining extraction and one-step plasma treatment was the best approach to maintain the stable hydrophilic state of PDMS and gain a relatively high zeta potential. In addition, it was found that the extraction method provided the most consistent outcome in modified PDMS surfaces compared to other methods.