Field Of Microfluidics Research Articles

Mechanisms of Hydrophobic Recovery of Poly(dimethylsiloxane) Elastomers after Plasma/Corona Treatments: A Minireview.

Plasma/corona treatment could alter the wettability of a poly(dimethylsiloxane) (PDMS) surface from being hydrophobic to being hydrophilic, which has attracted many researchers' attention. However, the treated surface will gradually recover its hydrophobicity as it ages. To understand the recovery, many studies have been performed. Although there is still no general consensus on the recovery mechanisms, several models have been proposed that can explain the reported wetting behavior of hydrophobic recovery. In this minireview, we summarized the reported mechanisms underlying the hydrophobicity-recovery of oxidized PDMS surfaces, which are certainly affected by varied factors including temperature, aging time, stored conditions, and treatment conditions. We hope this minireview can give beginners in the field of microfluidics a better understanding on the various mechanisms that contribute to the hydrophobic recovery of PDMS surfaces and thus take appropriate measures to efficiently maintain the surface wettability of oxidized PDMS chips to prolong their performance.

Molecular and microbiological methods for the identification of nonreplicating Mycobacterium tuberculosis.

Chronic tuberculosis (TB) disease, which requires months-long chemotherapy with multiple antibiotics, is defined by diverse pathological manifestations and bacterial phenotypes. Targeting drug-tolerant bacteria in the host is critical to achieving a faster and durable cure for TB. In order to facilitate this field of research, we need to consider the physiology of persistent MTB during infection, which is often associated with the nonreplicating (NR) state. However, the traditional approach to quantifying bacterial burden through colony enumeration alone only informs on the abundance of live bacilli at the time of sampling, and provides an incomplete picture of the replicative state of the pathogen and the extent to which bacterial replication is balanced by ongoing cell death. Modern approaches to profiling bacterial replication status provide a better understanding of inter- and intra-population dynamics under different culture conditions and in distinct host microenvironments. While some methods use molecular markers of DNA replication and cell division, other approaches take advantage of advances in the field of microfluidics and live-cell microscopy. Considerable effort has been made over the past few decades to develop preclinical in vivo models of TB infection and some are recognized for more closely recapitulating clinical disease pathology than others. Unique lesion compartments presenting different environmental conditions produce significant heterogeneity between Mycobacterium tuberculosis populations within the host. While cellular lesion compartments appear to be more permissive of ongoing bacterial replication, caseous foci are associated with the maintenance of M. tuberculosis in a state of static equilibrium. The accurate identification of nonreplicators and where they hide within the host have significant implications for the way novel chemotherapeutic agents and regimens are designed for persistent infections.

High-throughput generation of monodisperse double emulsions via controllable symmetric splitting in Y-shaped microchannels

To achieve high-throughput generation of monodisperse double emulsions via controllable symmetric splitting, the splitting dynamics of double emulsions in Y-shaped microchannels are systematically investigated by the combination of experimental study and numerical simulation. Four distinct breakup flow patterns of double emulsions splitting are initially identified, namely non-breakup, once uneven breakup, twice uneven breakup and twice even breakup, and the underlying hydrodynamic mechanisms of each flow pattern are further elucidated through the flow field structures and pressure distributions. The results show that the upstream pressure created by the flow obstruction of continuous phase governs the stable and symmetric splitting of double emulsions in Y-shaped microchannels. Effects of the flowrates of continuous phase, the outer and inner diameters of double emulsions, the physical properties of all the inner, middle and outer fluids as well as the angle of Y-shaped microchannel on the flow pattern transition laws are systematically clarified, and the corresponding universal flow pattern diagrams for predicting the critical boundary for the transition of flow patterns are established. Based on controllable symmetric splitting of double emulsions, three-level splitting microfluidic networks are rationally designed to achieve high-throughput generation of monodisperse double emulsions as well as monodisperse microcapsules via template synthesis. The results in this study not only advance the deep understanding of the breakup dynamics of double emulsions in Y-shaped microchannels, but also offer valuable guidance for the rational design of microfluidic devices for mass production of monodisperse double emulsions, thus providing a significant contribution to the fields of micro-chemical engineering and droplet microfluidics.

Enhanced microscale hydrodynamic near-cloaking using electro-osmosis

Abstract In this paper, we develop a general mathematical framework for enhanced hydrodynamic near-cloaking of electro-osmotic flow for more complex shapes, which is obtained by simultaneously perturbing the inner and outer boundaries of the perfect cloaking structure. We first derive the asymptotic expansions of perturbed fields and obtain a first-order coupled system. We then establish the representation formula of the solution to the first-order coupled system using the layer potential techniques. Based on the asymptotic analysis, the enhanced hydrodynamic near-cloaking conditions are derived for the control region with general cross-sectional shape. The conditions reveal the inner relationship between the shapes of the object and the control region. Especially, for the shape of a deformed annulus or confocal ellipses cylinder, the relationship of shapes is quantified more accurately by recursive formulas. Our theoretical findings are validated and supplemented by a variety of numerical results. The results in this paper also provide a mathematical foundation for more complex hydrodynamic cloaking. Additionally, the concept of cloaking has efficient applications in the field of microfluidics, including drag reduction, microfluidic manipulation, and biological tissue coculture.

Advances in textile-based microfluidics for biomolecule sensing.

Textile-based microfluidic biosensors represent an innovative fusion of various multidisciplinary fields, including bioelectronics, material sciences, and microfluidics. Their potential in biomedicine is significant as they leverage textiles to achieve high demands of biocompatibility with the human body and conform to the irregular surfaces of the body. In the field of microfluidics, fabric coated with hydrophobic materials serves as channels through which liquids are transferred in precise amounts to the sensing element, which in this case is a biosensor. This paper presents a condensed overview of the current developments in textile-based microfluidics and biosensors in biomedical applications over the past 20 years (2005-2024). A literature search was performed using the Scopus database. The fabrication techniques and materials used are discussed in this paper, as these will be key in various modifications and advancements in textile-based microfluidics. Furthermore, we also address the gaps in the application of textile-based microfluidic analytical devices in biomedicine and discuss the potential solutions. Advances in textile-based microfluidics are enabled by various printing and fabric manufacturing techniques, such as screen printing, embroidery, and weaving. Integration of these devices into everyday clothing holds promise for future vital sign monitoring, such as glucose, albumin, lactate, and ion levels, as well as early detection of hereditary diseases through gene detection. Although most testing currently takes place in a laboratory or controlled environment, this field is rapidly evolving and pushing the boundaries of biomedicine, improving the quality of human life.

Recent Advances in Dielectrophoretic Manipulation and Separation of Microparticles and Biological Cells.

Dielectrophoresis (DEP) is an advanced microfluidic manipulation technique that is based on the interaction of polarized particles with the spatial gradient of a non-uniform electric field to achieve non-contact and highly selective manipulation of particles. In recent years, DEP has made remarkable progress in the field of microfluidics, and it has gradually transitioned from laboratory-scale research to high-throughput manipulation in practical applications. This paper reviews the recent advances in dielectric manipulation and separation of microparticles and biological cells and discusses in detail the design of chip structures for the two main methods, direct current dielectrophoresis (DC-DEP) and alternating current dielectrophoresis (AC-DEP). The working principles, technical implementation details, and other improved designs of electrode-based and insulator-based chips are summarized. Functional customization of DEP systems with specific capabilities, including separation, capture, purification, aggregation, and assembly of particles and cells, is then performed. The aim of this paper is to provide new ideas for the design of novel DEP micro/nano platforms with the desired high throughput for further development in practical applications.

Dual-control of incubation effect for efficiently fabricating surface structures in fused silica

Abstract Fused silica with surface structures has potential applications in microfluidic, aerospace and other fields. To fabricate structures with high dimensional accuracy and surface quality is of paramount importance. However, it is indeed a challenge to strike a balance between accuracy and efficiency at the same time. Here, a temporally shaped femtosecond laser Bessel-beam-assisted etching method with dual-control of incubation effect is proposed to achieve this balance. Instead of layer-by-layer ablation continuously with Gaussian pulses, silica is modified discretely by double pulse Bessel beam with one single layer. During the modification process, incubation effect is dual-controlled in single shot process and spatial scanning process to generate even modified region efficiently. Then, the modified region is etched to form designed structures such as microholes, grooves, etc. The proposed method exhibits high efficiency for fabrication of surface structures in fused silica.

Time-dependent invasion laws for a liquid–liquid displacement system

Capillary-driven flow of fluids occurs frequently in nature and has a wide range of technological applications in the fields of industry, agriculture, medicine, biotechnology, and microfluidics. By using the Onsager variational principle, we propose a model to systematically study the capillary imbibition into a tube and find different laws of time-dependent capillary invasion length for liquid–liquid displacement system other than Lucas–Washburn type under different circumstances. The good agreement between our model and experimental results shows that the imbibition dynamics in a capillary tube with a prefilled liquid slug can be well captured by the dynamic equation derived in this paper. Our results bear important implications for macroscopic descriptions of multiphase flows in microfluidic systems and porous media.

Elasto-inertial focusing and particle migration in high aspect ratio microchannels for high-throughput separation

The combination of flow elasticity and inertia has emerged as a viable tool for focusing and manipulating particles using microfluidics. Although there is considerable interest in the field of elasto-inertial microfluidics owing to its potential applications, research on particle focusing has been mostly limited to low Reynolds numbers (Re<1), and particle migration toward equilibrium positions has not been extensively examined. In this work, we thoroughly studied particle focusing on the dynamic range of flow rates and particle migration using straight microchannels with a single inlet high aspect ratio. We initially explored several parameters that had an impact on particle focusing, such as the particle size, channel dimensions, concentration of viscoelastic fluid, and flow rate. Our experimental work covered a wide range of dimensionless numbers (0.05 < Reynolds number < 85, 1.5 < Weissenberg number < 3800, 5 < Elasticity number < 470) using 3, 5, 7, and 10 µm particles. Our results showed that the particle size played a dominant role, and by tuning the parameters, particle focusing could be achieved at Reynolds numbers ranging from 0.2 (1 µL/min) to 85 (250 µL/min). Furthermore, we numerically and experimentally studied particle migration and reported differential particle migration for high-resolution separations of 5 µm, 7 µm and 10 µm particles in a sheathless flow at a throughput of 150 µL/min. Our work elucidates the complex particle transport in elasto-inertial flows and has great potential for the development of high-throughput and high-resolution particle separation for biomedical and environmental applications.

Charting the course of blood flow: vessel-on-a-chip technologies in thrombosis studies

Cardiovascular diseases, primarily driven by thrombosis, remain the leading cause of global mortality. Although traditional cell culture and animal models have provided foundational insights, they often fail to capture the complex pathophysiology of thrombosis, which hinders the development of targeted therapies for cardiovascular diseases. The advent of microfluidics and vascular tissue engineering has propelled the advancement of vessel-on-a-chip technologies, which enable the simulation of the key aspects of Virchow’s Triad: hypercoagulability, alteration in blood flow, and endothelial wall injury. With the ability to replicate patient-specific vascular architectures and hemodynamic conditions, vessel-on-a-chip models offer unprecedented insights into the mechanisms underlying thrombosis formation and progression. This review explores the evolution of microfluidic technologies in thrombosis research, highlighting breakthroughs in endothelialized devices and their roles in emulating conditions such as vessel stenosis, flow reversal, and endothelial damage. The limitations and challenges of the current vessel-on-a-chip systems are addressed, and future perspectives on the potential for personalized medicine and targeted therapies are presented. Vessel-on-a-chip technology holds immense potential for revolutionizing thrombosis research, enabling the development of targeted, patient-specific diagnostic tools and therapeutic strategies. Realizing this potential will require interdisciplinary collaboration and continued innovation in the fields of microfluidics and vascular tissue engineering.

Preparation of Cross-Linked Sodium Alginate Microspheres with Different Metal Ions Using the Microfluidic Electrospray Technology.

Microspheres are micrometer-sized particles that can load and gradually release drugs via physical encapsulation or adsorption onto the surface and within polymers. In the field of biomedicine, hydrogel microspheres have been extensively studied for their application as drug carriers owing to their ability to reduce the frequency of drug administration, minimize side effects, and improve patient compliance. Sodium alginate (ALG) is a naturally occurring linear polysaccharide with three backbone glycosidic linkages. There are two auxiliary hydroxyl groups present in each of the moieties of the polymer, which have the characteristics of an alcohol hydroxyl moiety. The synthetic ALG units can undergo chemical cross-linking reactions with metal ions, forming a cross-linked network structure of polymer stacks, ultimately forming a hydrogel. Hydrogel microspheres can be prepared using a simple process involving the ionic cross-linking properties of ALG. In this study, we prepared ALG-based hydrogel microspheres (ALGMS) using a microfluidic electrodeposition strategy. The prepared hydrogel microspheres were uniformly sized and well-dispersed, owing to accurate control of the microfluidic electrospray flow. ALGMS cross-linked with different metal ions were prepared using a microfluidic electrospray technique combining microfluidic and high electric field, and its antimicrobial properties, slow drug release ability, and biocompatibility were investigated. This technology holds promise for application in advanced drug development and production.

Wide-Size Range and High Robustness Self-Assembly Micropillars for Capturing Microspheres.

Capillary force driven self-assembly micropillars (CFSA-MP) holds immense promise for the manipulation and capture of cells/tiny objects, which has great demands of wide size range and high robustness. Here, we propose a novel method to fabricate size-adjustable and highly robust CFSA-MP that can achieve wide size range and high stability to capture microspheres. First, we fabricate a microholes template with an adjustable aspect ratio using the spatial-temporal shaping femtosecond laser double-pulse Bessel beam-assisted chemical etching technique, and then the micropillars with adjustable aspect ratio are demolded by polydimethylsiloxane (PDMS). We fully demonstrated the advantages of the Bessel optical field by using the spatial-temporal shaping femtosecond laser double-pulse Bessel beams to broaden the height range of the micropillars, which in turn expands the size range of the captured microspheres, and finally achieving a wide range of capturing microspheres with a diameter of 5-410 μm. Based on the inverted mold technology, the PDMS micropillars have ultrahigh mechanical robustness, which greatly improves the durability. CFSA-MP has the ability to capture tiny objects with wide range and high stability, which indicates great potential applications in the fields of chemistry, biomedicine, and microfluidics.

Programmable spin and transport of a living shrimp egg through photoacoustic pressure.

In the fields of biomedicine and microfluidics, the non-contact capture, manipulation, and spin of micro-particles hold great importance. In this study, we propose a programmable non-contact manipulation technique that utilizes photoacoustic effect to spin and transport living shrimp eggs. By directing a modulated pulsed laser toward a liquid-covered stainless-steel membrane, we can excite patterned Lamb waves within the membrane. These Lamb waves occur at the interface between the membrane and the liquid, enabling the manipulation of nearby particles. Experimental results demonstrate the successful capture, spin, and transport of shrimp eggs in diameter of 220 µm over a distance of about 5 mm. Calculations indicate that the acoustic radiation force and torque generated by our photoacoustic manipulation system are more than 299.5 nN and 41.0 nN·mm, respectively. The system surpasses traditional optical tweezers in terms of force and traditional acoustic tweezers in terms of flexibility. Consequently, this non-contact manipulation system significantly expands the possibilities for applications in various fields, including embryo screening, cell manipulation, and microfluidics.

Computational and experimental microfluidics: Total analysis system for mixing, sorting, and concentrating particles and cells.

Body fluids can potentially indicate the presence of non-small cancer cells. Studying these fluids is an emerging field that could be crucial for cancer detection and monitoring treatment effectiveness. Meanwhile, the examination of fluids on a microscopic level is part of the field of microfluidics. This study focuses on the development of a total analysis system that consists of various interconnected structures that are designed to mix, classify, concentrate, and isolate particles in fluids that mimic the behavior of cancer and normal cells. Using the COMSOL Multiphysics software, the device's performance was optimized to use a pressure input of 35 kPa for water or serum and 29.4 kPa for a mixture of liquid and serum samples, which are the optimal pressure inputs. The numerical models were validated by experiments using two types of polystyrene particles, with diameters of 5 and 20 μm. Moreover, the developed system was applied to monitor the behavior of red blood cells. The microfluidic chip is capable of addressing several challenges through visual detections, including mixing tests of two fluids with similar densities, proper particle size classification using Dean flow fractionation, and single-step recovery of large, labeled particles. Finally, the collected particles were examined using an environmental scanning electron microscope to determine their size, and the results demonstrated that successful size separation was achieved, with particles around 20 μm completely separated from the smaller ones.

High‐Resolution 3D Printing of Dual‐Curing Thiol‐Ene/Epoxy System for Fabrication of Microfluidic Devices for Bioassays

AbstractThe customized processing of polymer materials in the microscale by high‐resolution 3D printing provides an easy access to advanced applications in the fields of optics, microfluidics, tissue engineering, and life science. However, the 3D printing of enclosed structures in the scale of tens of microns such as closed microfluidic channels remains a challenge as channel structures often are clogged by residual cured resin. Dual‐curing systems based on off‐stoichiometric thiol‐ene and thiol‐ene/epoxy chemistry are well‐known for adhesive‐free bonding in the fabrication of cast or injection molded microfluidic devices. Herein, the first high‐resolution stereolithography 3D printing of a dual‐curing thiol‐ene/epoxy system in the microscale for the fabrication of customized microfluidic devices is presented. In the first curing step, by high‐resolution 3D printing open microfluidic structures are produced. Consecutively, the microchannels are sealed by adhesive‐free dry bonding upon thermal initiation, producing well‐controlled structures with channel sizes down to 80 µm. Before bonding, the intermediate material allows for tailored surface modification with biotin, which allows for consecutive immobilization of various biomolecules. A DNA‐bioassay with specific patterning is shown in the sealed chip. The presented work paves the way toward the fabrication of customized microfluidic devices for a large range of specific bioassays.

Systematic evaluation of the radial polarized piezoelectric ceramic micro-tube for high-temperature microfluidics

Piezoelectric ceramic micro-tube (PCMT) featuring quick response and driving displacement resolution has been widely applied in the microfluidic field. With more and more microfluidic applications being conducted in high temperatures, there is an increased demand for high-temperature PCMTs. However, few reports were focused on evaluating the performance of PCMTs especially in high-temperature conditions, which hinders its applications greatly. In this paper, a radial polarized high-temperature PCMT with an inner diameter (ID) of 0.75 mm, an outer diameter (OD) of 1.2 mm and a length of 15 mm was fabricated first. Scanning electron microscope (SEM) test shows that this ceramic tube presents a homogenous and dense microstructure. Impedance spectrum tests at different temperatures show that the effective electromechanical coupling factor (keff) of this PCMT remains stable from room temperature to 250 °C, indicating good high-temperature stability. Quasi-steady axial displacement tests executed by the instrument constructed by our group show that this PCMT represents a linear driving response under 100 V. Based on systematic evaluations, the PCMT was used to fabricate a piezoelectric high-temperature nozzle for generating high-frequency droplets, through which tin droplet targets with a repetition frequency of 20 kHz and a diameter of 100 μm was obtained at 250 °C. The successful application demonstrates that the PCMT which was evaluated systematically can be used in practical high-temperature applications.

Performance and biocompatibility of OSTEMER 322 in cell-based microfluidic applications.

The Off-Stoichiometry Thiol-ene and Epoxy (OSTE+) polymer technology has been increasingly utilised in the field of microfluidics and lab-on-a-chip applications. However, the impact of OSTEMER polymers, specifically the OSTEMER 322 formulation, on cell viability has remained limited. In this work, we thoroughly explored the biocompatibility of this commercial OSTEMER formulation, along with various surface modifications, through a broad range of cell types, from fibroblasts to epithelial cells. We employed cell viability and confluence assays to evaluate the performance of the material and its modified variants in cell culturing. The properties of the pristine and modified OSTEMER were also investigated using surface characterization methods including contact angle, zeta potential, and X-ray photoelectron spectroscopy. Mass spectrometry analysis confirmed the absence of leaching constituents from OSTEMER, indicating its safety for cell-based applications. Our findings demonstrated that cell viability on OSTEMER surfaces is sufficient for typical cell culture experiments, suggesting OSTEMER 322 is a suitable material for a variety of cell-based assays in microfluidic devices.

Actuation for flexible and stretchable microdevices.

Flexible and stretchable microdevices incorporate highly deformable structures, facilitating precise functionality at the micro- and millimetre scale. Flexible microdevices have showcased extensive utility in the fields of biomedicine, microfluidics, and soft robotics. Actuation plays a critical role in transforming energy between different forms, ensuring the effective operation of devices. However, when it comes to actuating flexible microdevices at the small millimetre or even microscale, translating actuation mechanisms from conventional rigid large-scale devices is not straightforward. The recent development of actuation mechanisms leverages the benefits of device flexibility, particularly in transforming conventional actuation concepts into more efficient approaches for flexible devices. Despite many reviews on soft robotics, flexible electronics, and flexible microfluidics, a specific and systematic review of the actuation mechanisms for flexible and stretchable microdevices is still lacking. Therefore, the present review aims to address this gap by providing a comprehensive overview of state-of-the-art actuation mechanisms for flexible and stretchable microdevices. We elaborate on the different actuation mechanisms based on fluid pressure, electric, magnetic, mechanical, and chemical sources, thoroughly examining and comparing the structure designs, characteristics, performance, advantages, and drawbacks of these diverse actuation mechanisms. Furthermore, the review explores the pivotal role of materials and fabrication techniques in the development of flexible and stretchable microdevices. Finally, we summarise the applications of these devices in biomedicine and soft robotics and provide perspectives on current and future research.

Multi-step PDMS curing and a controlled separation method for mass manufacturing of high-performance and user-friendly micro-devices: valved micropumps.

Although valved micropumps have powerful performance, their popularized application is limited by high technical barriers and high costs brought by complex microstructures. Herein, we propose a multi-step PDMS curing method and a local PDMS separation strategy to achieve mass, standardized, and low-cost manufacturing of valved micropumps, solving their popularized problems by promoting role separation between manufacturers and users. The multi-step curing and the centralized structural layout enable a volume 20 times smaller than other valved micropumps. The lithography mold quality is the main reason for only 74% yield, and using metal molds would be a better alternative. Theoretical analysis shows that the thickness and diameter of the pump membrane are the main factors in designing different driving capabilities of the micropump. By driving the micropump through periodic fluid pressure, the results show that the flow rate is positively related to the input pressure and exhibits two flow rate formation mechanisms at high and low frequencies. Its powerful back pressure generating ability also indicates that the micropump has wide application prospects as injection pumps. The micropump also demonstrates tremendous flexibility and convenience in integration, driving, and application. The multi-step PDMS curing and controlled separating ideas show popularization value for other microfluidic components, such as one-way valves, hoping to innovate the microfluidics field.

Next generation microfluidics: fulfilling the promise of lab-on-a-chip technologies.

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches have stymied microfluidics from fulfilling this promise. We describe how accessibility, usability, and manufacturability of microfluidic technologies should be improved and how a shift in mindset and incentives within the field is also needed to address these issues. In this report, we discuss the state of the microfluidic field regarding current limitations and propose future directions and new approaches for the field to advance microfluidic technologies closer to translation and clinical use. While our report focuses on using blood as the prototypical biofluid sample, the proposed ideas and research directions can be extrapolated to other areas of hematology, oncology, biology, and medicine.