Applications In Microfluidic Systems Research Articles

Magnetically-responsive microwall arrays with path-guide for directional transportation of droplets

This research provides a comprehensive exploration of the development and characterization of magnetically responsive microwall arrays (MRMAs), presenting a novel approach to precise droplet manipulation. The proposed fabrication process involves microscale wall arrays created using carbonyl iron particles embedded in polydimethylsiloxane through a replica molding process. The MRMAs demonstrate a unique response to magnetic fields, enabling precise control over droplet movement. Through superhydrophobic coatings and meticulously adjusted magnetic fields, the system facilitates the efficient movement of droplets along predefined routes, achieving outstanding accuracy in droplet directionality and positioning. The experiments highlight the capability of MRMAs to merge differently colored droplets, underscoring their potential in long-distance droplet transportation. The results suggest applications in microfluidic systems, lab-on-a-chip devices, and targeted drug delivery, marking a significant advancement in microfluidic research.

Computational analysis of a four-flap valveless micropump (FFVM) for low reynolds number applications in microfluidic systems

Microfluidic systems are crucial in various fields including biological fluid handling and microelectronic cooling. Micropumps play a vital role in microfluidics. Valveless micropumps are the preferred choice in microfluidics because of their ability to minimize the risk of clogging and gently handle biological materials. In this comprehensive Four-Flap Valveless Micropump (FFVM) simulation, the fluid flow and associated deformation in the valveless micropump are analyzed. The oscillatory fluid motion generated by a straightforward reciprocating pumping mechanism is transformed into a unidirectional net flow by the micropump. This pump eliminates the need for intricate actuation mechanisms found in valve-based pumps while offering precise direction control. The input is given in terms of the Reynolds number or inflow velocity. In this study, the Reynolds numbers were changed from 16 to 50, which resulted in a positive correlation with the net flow rates, yielding a maximum net flow rate of 20.81 μl min−1 at a Reynolds number of 50. The influence of the average flow velocity is evident, with a peak net flow rate of 29.16 μl min−1 at 50 cm s−1. The FFVM showcases adaptability by delivering fluid within microfluidic pathways, holding promising applications in precision drug delivery systems.

Development of Ni-Mn-Ga Enabled Micropumps for Hybrid Microdevices in Microelectromechanical Systems

This study selects a single crystalline Ni-Mn-Ga alloy by its exceptional actuator attributes, high actuation speed, precise position control, rapid response to external magnetic fields, and extended operational lifespan. Researchers venture into uncharted territory, aiming to harness the potential of Ni-Mn-Ga alloy to revolutionize micropump performance and refine fluid manipulation within miniature devices. The methodology at the heart of this endeavor involves the seamless integration of this specialized alloy with microdevice technology, giving rise to a set of unique pump components that substantially boost pump efficiency. Crucially, Ni-Mn-Ga is the chosen material for the active part of the micropump. At the same time, MEMS fabrication handles the passive elements, all facilitated by the 0.18 µm semiconductor technology and Sivalco TCAD simulation software. Computational simulations validate the alloy's suitability, impressively achieving an accumulated flow volume of 0.15 x 10e-4 µL in 10 microseconds. Beyond its scientific significance, this research bridges MEMS technology and magnetic-enabled smart materials, showcasing the remarkable capabilities of Ni-Mn-Ga alloy in significantly enhancing micropump performance. These innovative solutions promise to open doors to groundbreaking applications in microfluidic systems across many scientific and industrial domains.

Stability of Immobilized Chemosensor‐Filled Vesicles on Anti‐Fouling Polymer Brush Surfaces

AbstractThe characterization of phospholipid membrane permeability for small molecules is crucial for many applications in drug discovery and biomedical research in general. Here, chemosensor‐laden vesicles offer an attractive platform for permeability assays. In this work, the stability of immobilized chemosensor‐filled vesicles is explored on anti‐fouling polymer brush surfaces for potential use in monitoring small molecule membrane permeability. The study focuses on the development of a method for immobilizing sensor‐loaded vesicles into arbitrary patterns on surfaces and characterizing their stability under changing temperatures and compositions. As substrate to enable intact, long‐term stable vesicle immobilization reactive polymer brushes with anti‐fouling properties are used. Utilizing microchannel cantilever spotting, biotin moieties are introduced on the polymer brush surface, enabling stable tethering of vesicles through streptavidin‐biotin interactions. The immobilized vesicles are monitored through fluorescence microscopy for their response to analytes under changing environmental parameters and vesicle composition. A higher stability of immobilized vesicles compared to free‐floating ones is observed, with permeability only at elevated temperatures. By tuning vesicle compositions, permeability at lower temperatures can be raised again. Overall, the study provides insights into a novel approach for vesicle immobilization, showcasing the potential of surface‐bound vesicles for applications in microfluidic systems and as biosensors in various assays.

Manipulation of liquid transport and droplet switch using light-actuated surface tension

The manipulation of microfluidic systems plays a crucial role in various applications within biology, chemistry, and materials science. However, conventional driving techniques often involve complex setups or rely on external forces, which limits their potential for miniaturization and integration. In this study, we propose a novel method for manipulating microfluidic systems using an azobenzene photosensitive surfactant stimulated by light. This approach offers a simpler and more convenient alternative for controlling microfluidic devices. To demonstrate the effectiveness of our light-driven method, we apply it to control the transition between two bifurcations in a double droplet system (DDS) by surpassing its surface energy barrier. Experimental results demonstrate successful transitions between the bifurcations of the DDS using the light-driven approach. To gain a deeper understanding of the transition process, we establish a dynamic model that considers the surfactant absorption process during the experiment. Furthermore, we provide a simple application of the proposed driving method through a light-activated tunable liquid lens, demonstrating its potential for broader applications in microfluidic systems. This work is expected to contribute to the development of novel light-driven microfluidic manipulation techniques.

Solute-particle separation in microfluidics enhanced by symmetrical convection.

The utilization of microfluidic technology for miniaturized and efficient particle sorting holds significant importance in fields such as biology, chemistry, and healthcare. Passive separation methods, achieved by modifying the geometric shapes of microchannels, enable gentle and straightforward enrichment and separation of particles. Building upon previous discussions regarding the effects of column arrays on fluid flow and particle separation within microchips, we introduced a column array structure into an H-shaped microfluidic chip. It was observed that this structure enhanced mass transfer between two fluids while simultaneously intercepting particles within one fluid, satisfying the requirements for particle interception. This enhancement was primarily achieved by transforming the originally single-mode diffusion-based mass transfer into dual-mode diffusion-convection mass transfer. By further optimizing the column array, it was possible to meet the basic requirements of mass transfer and particle interception with fewer microcolumns, thereby reducing device pressure drop and facilitating the realization of parallel and high-throughput microfluidic devices. These findings have enhanced the potential application of microfluidic systems in clinical and chemical engineering domains.

Microfluidic approaches in microbial ecology.

Microbial life is at the heart of many diverse environments and regulates most natural processes, from the functioning of animal organs to the cycling of global carbon. Yet, the study of microbial ecology is often limited by challenges in visualizing microbial processes and replicating the environmental conditions under which they unfold. Microfluidics operates at the characteristic scale at which microorganisms live and perform their functions, thus allowing for the observation and quantification of behaviors such as growth, motility, and responses to external cues, often with greater detail than classical techniques. By enabling a high degree of control in space and time of environmental conditions such as nutrient gradients, pH levels, and fluid flow patterns, microfluidics further provides the opportunity to study microbial processes in conditions that mimic the natural settings harboring microbial life. In this review, we describe how recent applications of microfluidic systems to microbial ecology have enriched our understanding of microbial life and microbial communities. We highlight discoveries enabled by microfluidic approaches ranging from single-cell behaviors to the functioning of multi-cellular communities, and we indicate potential future opportunities to use microfluidics to further advance our understanding of microbial processes and their implications.

Hydraulic-electric analogy for design and operation of microfluidic systems.

Microfluidic systems have been investigated as practical tools in the fields of biomedical engineering, analytical chemistry, materials science, and biological research. Yet the widespread applications of microfluidic systems have been hindered by the complexity of microfluidic design and the reliance on bulky external controllers. Hydraulic-electric analogy provides a powerful method to design and operate microfluidic systems with minimal requirement of control equipment. Here, we summarize recent development of microfluidic components and circuits based on the hydraulic-electric analogy. In a manner similar to electric circuits, microfluidic analogue circuits with a continuous flow or pressure input actuate fluids in a predetermined way to enable singular tasks such as flow- or pressure-driven oscillators. Microfluidic digital circuits consisting of logic gates are activated by a programmable input to perform complex tasks including on-chip computation. In this review, the design principles and applications of a variety of microfluidic circuits are overviewed. The challenges and future directions of the field are also discussed.

Droplet Detection and Sorting System in Microfluidics: A Review.

Since being invented, droplet microfluidic technologies have been proven to be perfect tools for high-throughput chemical and biological functional screening applications, and they have been heavily studied and improved through the past two decades. Each droplet can be used as one single bioreactor to compartmentalize a big material or biological population, so millions of droplets can be individually screened based on demand, while the sorting function could extract the droplets of interest to a separate pool from the main droplet library. In this paper, we reviewed droplet detection and active sorting methods that are currently still being widely used for high-through screening applications in microfluidic systems, including the latest updates regarding each technology. We analyze and summarize the merits and drawbacks of each presented technology and conclude, with our perspectives, on future direction of development.

Comparative application of microfluidic systems in circulating tumor cells and extracellular vesicles isolation; a review

Cancer is a prevalent cause of mortality globally, where early diagnosis leads to a reduced death rate. Many researchers' common strategies are based on personalized diagnostic methods with rapid response and high accuracy. This technology was developed by applying liquid biopsy instead of tissue biopsies in the case of tumor cell analysis that facilitates point-of-care testing for cancer diagnosis and treatment. In recent years, significant progress in microfluidic technology led to the successful isolation, analysis, and monitoring of cancer biomarkers in body liquid biopsy with merits like high sensitivity and flexibility, low sample usage, cost effective, and the ability of automation. The most critical and informative markers in body liquid refer to circulating tumor cells (CTCs) and extracellular vesicles derived from tumors (EVs) that carry various biomarkers in their structure (DNAs, proteins, and RNAs) as compared to ctDNA. The released ctDNA has a low half-life and decreased sensitivity due to large amounts of nucleic acid in serum. This review intends to highlight different cancer screening tests with a particular focus on the details regarding the only FDA-approved and awaiting technologies for FDA clearance to isolate CTCs and EVs based on microfluidics systems.

Microfluidic devices: The application in TME modeling and the potential in immunotherapy optimization.

With continued advances in cancer research, the crucial role of the tumor microenvironment (TME) in regulating tumor progression and influencing immunotherapy outcomes has been realized over the years. A series of studies devoted to enhancing the response to immunotherapies through exploring efficient predictive biomarkers and new combination approaches. The microfluidic technology not only promoted the development of multi-omics analyses but also enabled the recapitulation of TME in vitro microfluidic system, which made these devices attractive across studies for optimization of immunotherapy. Here, we reviewed the application of microfluidic systems in modeling TME and the potential of these devices in predicting and monitoring immunotherapy effects.

Supercritical CO2 applications in microfluidic systems

Supercritical CO2 applications in microfluidic systems

Spontaneous transport of water nanodroplets on graphene and hexagonal boron nitride in-plane heterostructure

Developing a surface inducing water droplets to transport spontaneously is very important to energy conversion. Here we demonstrate by the molecular dynamics simulations that a water nanodroplet on graphene and hexagonal boron nitride (h-BN) in-plane heterostructure can move spontaneously from the narrower end of the wedge-shaped h-BN track to the wider end. The driving force comes from the capillary force caused by the surface energy gradient at the edge of the connection, which is attributed to the different interactions of the water nanodroplet with graphene and h-BN. The energy analysis shows that the h-BN acts as a driving force, while graphene as a hindrance. We analyze the forces exerted on the water droplet and propose a theoretical model which indicates that the moving speed of the water nanodroplet can be controlled by the wedge angle and temperature. The present study suggests that the graphene/h-BN heterostructure is a potential material for driving droplets motion and can be explored to find applications in microfluidic systems.

On-board reagent storage and release by solvent-selective, rotationally opened membranes: a digital twin approach

Decentralized bioanalytical testing in resource-poor settings ranks among the most common applications of microfluidic systems. The high operational autonomy in such point-of-care/point-of-use scenarios requires long-term onboard storage of liquid reagents, which also need to be safely contained during transport and handling, and then reliably released just prior to their introduction to an assay protocol. Over the recent decades, centrifugal microfluidic technologies have demonstrated the capability of integrated, automated and parallelized sample preparation and detection of bioanalytical protocols. This paper presents a novel technique for onboard storage of liquid reagents which can be issued by a rotational stimulus of the system-innate spindle motor, while still aligning with the conceptual simplicity of such “Lab-on-a-Disc” (LoaD) systems. In this work, this highly configurable reagent storage technology is captured by a digital twin, which permits complex performance analysis and algorithmic design optimization according to objectives as expressed by target metrics.

Design and flow simulation of a micro steam jet pump

The development of micropump is directly related to the popularization and application of microfluidic systems. Recently, microfluidic systems have more urgent requirements for stable operation and simple structure of micropumps. For these purposes, a novel micro steam jet pump which uses planar induction heating to evaporate the initial fluid is presented. This new micropump could generate continuous flow with merits of no moving parts, stable operation and easy integration. A negative pressure is formed flowed with high-speed flow of vapor in the chamber to pump and eject liquid, and then realize continuous pumping. The working chamber of the micropump is calculated with aerodynamic function, and the simulation analysis is carried on with COMSOL Multiphysics 5.5. By changing key working parameters, appropriate working conditions are adopted with simulation analysis. When the primary vapor temperature is 403.15 K, the inlet width of the tapered section of the mixing chamber is 0.4 mm and the outlet width of the diffuser is 0.5 mm, the mingling and enhancing pressure performance of the micro steam jet pump is better. The optimization of design and simulation involved in this paper provided a good guidance for the design and experimental study of the micro steam jet pump.

Application of Microfluidic Systems for Breast Cancer Research.

Cancer is a disease in which cells in the body grow out of control; breast cancer is the most common cancer in women in the United States. Due to early screening and advancements in therapeutic interventions, deaths from breast cancer have declined over time, although breast cancer remains the second leading cause of cancer death among women. Most deaths are due to metastasis, as cancer cells from the primary tumor in the breast form secondary tumors in remote sites in distant organs. Over many years, the basic biological mechanisms of breast cancer initiation and progression, as well as the subsequent metastatic cascade, have been studied using cell cultures and animal models. These models, although extremely useful for delineating cellular mechanisms, are poor predictors of physiological responses, primarily due to lack of proper microenvironments. In the last decade, microfluidics has emerged as a technology that could lead to a paradigm shift in breast cancer research. With the introduction of the organ-on-a-chip concept, microfluidic-based systems have been developed to reconstitute the dominant functions of several organs. These systems enable the construction of 3D cellular co-cultures mimicking in vivo tissue-level microenvironments, including that of breast cancer. Several reviews have been presented focusing on breast cancer formation, growth and metastasis, including invasion, intravasation, and extravasation. In this review, realizing that breast cancer can recur decades following post-treatment disease-free survival, we expand the discussion to account for microfluidic applications in the important areas of breast cancer detection, dormancy, and therapeutic development. It appears that, in the future, the role of microfluidics will only increase in the effort to eradicate breast cancer.

Application of microfluidic systems in modelling impacts of environmental structure on stress-sensing by individual microbial cells

Environmental structure describes physical structure that can determine heterogenous spatial distribution of biotic and abiotic (nutrients, stressors etc.) components of a microorganism’s microenvironment. This study investigated the impact of micrometre-scale structure on microbial stress sensing, using yeast cells exposed to copper in microfluidic devices comprising either complex soil-like architectures or simplified environmental structures. In the soil micromodels, the responses of individual cells to inflowing medium supplemented with high copper (using cells expressing a copper-responsive pCUP1-reporter fusion) could be described neither by spatial metrics developed to quantify proximity to environmental structures and surrounding space, nor by computational modelling of fluid flow in the systems. In contrast, the proximities of cells to structures did correlate with their responses to elevated copper in microfluidic chambers that contained simplified environmental structure. Here, cells within more open spaces showed the stronger responses to the copper-supplemented inflow. These insights highlight not only the importance of structure for microbial responses to their chemical environment, but also how predictive modelling of these interactions can depend on complexity of the system, even when deploying controlled laboratory conditions and microfluidics.

Anti-Cancer Drug Screening with Microfluidic Technology

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high-throughput drug screening, require a small number of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. Many attempts have been made in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.

Viscous micropump of immiscible fluids using magnetohydrodynamic effects and a power-law conducting fluid

Small-scale fluid transport methods have grown significantly in recent years, mainly in applications in microfluidic systems. Therefore, the present study analyzes the movement of two-layers of immiscible fluids within a parallel flat plates microchannel. The fluid layers are composed of a Newtonian fluid and a power-law fluid. The pumping is produced by magnetohydrodynamics effects that act on the non-Newtonian conducting fluid dragging the non-conducting Newtonian fluid by viscous forces. Under the consideration of a laminar, incompressible, and unidirectional flow, the dimensionless mathematical model is established by the momentum equations for each fluid, together with the corresponding boundary conditions at solid-liquid and liquid-liquid interfaces. The problem formulation is semi-analytically solved using the Newton-Raphson method. The results are presented as a function of the velocity profiles and flow rate, showing interesting behaviors that depend on the physical and electrical properties of each fluid and flow conditions via the dimensionless parameters such as the flow behavior index, a magnetic parameter related to Lorenz forces, the fluids viscosity ratios and the dimensionless liquid-liquid interface position. This work contributes to the understanding of the various immiscible non-conducting fluids pumping techniques that can be used in microdevices.

Neuroscience Research using Small Animals on a Chip: From Nematodes to Zebrafish Larvae

Implementation of microfluidic technology to study small animal models such as Caenorhabditis elegans worms (soil-dwelling nematodes), Drosophila melanogaster (fruit fly) and larvae of Danio rerio (zebrafish) provides great opportunities for in vivo quantification of neuronal activities and behavioral responses. By controlling the internal environment, microfluidic devices can manipulate animal models with precision and cause minimal damage to the specimen. Due to these advantages, microfluidic devices have been applied to high-throughput drug screening, high-throughput brain-wide activity mapping, analyzing animals’ neuronal and behavioral responses to different external stimuli, microinjection, and neuronal regeneration. In this paper, we review different microfluidic devices and techniques that allow the manipulation of small animal models to study brain functions and behavioral responses. Furthermore, biomedical applications of microfluidic systems, technical challenges, and future directions in the whole brain and animal research on a chip will be discussed.