Search Results (623)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Phase-change microcapsules offer significant advantages for thermal energy storage and regulation. However, conventional mechanical agitation fabrication methods encounter difficulties in achieving monodispersity, precise size control, and structural uniformity. Droplet microfluidics emerges as a promising alternative, enabling controllable production of microcapsules with tunable sizes (1–1000 μm), programmable core–shell configurations, and high encapsulation efficiency. This review comprehensively summarizes recent advances in microfluidic strategies for phase-change microcapsules fabricating, including single encapsulation, multi-core encapsulation, and high-throughput parallelization and their applications in solar energy storage, building thermal regulation, electronics cooling, and smart textiles. The review highlights key challenges for future advancement which will unlock the full potential of microfluidics-engineered phase-change microcapsules in next-generation thermal energy technologies. Full article

Acoustic coupling agents serve as critical interfacial materials connecting piezoelectric transducers with microfluidic chips in acoustofluidic systems. Their performance directly impacts acoustic wave transmission efficiency, device reusability, and reliability in biomedical applications. Considering the rapidly growing body of research in the field of acoustic microfluidics, this review aims to serve as an all-in-one reference on the role of acoustic coupling agents and relevant considerations pertinent to acoustofluidic devices for anyone working in or seeking to enter the field of disposable acoustofluidic devices. To this end, this review seeks to summarize and categorize key aspects of acoustic couplants in the implementation of acoustofluidic devices by examining their underlying physical mechanisms, material classifications, and core applications of coupling agents in acoustofluidics. Gel-based coupling agents are particularly favored for their long-term stability, high coupling efficiency, and ease of preparation, making them integral to acoustic flow control applications. In practice, coupling agents facilitate microparticle trapping, droplet manipulation, and biosample sorting through acoustic impedance matching and wave mode conversion (e.g., Rayleigh-to-Lamb waves). Their thickness and acoustic properties (sound velocity, attenuation coefficient) further modulate sound field distribution to optimize acoustic radiation forces and thermal effects. However, challenges remain regarding stability (evaporation, thermal degradation) and chip compatibility. Further aspects of research into gel-based agents requiring attention include multilayer coupled designs, dynamic thickness control, and enhancing biocompatibility to advance acoustofluidic technologies in point-of-care diagnostics and high-throughput analysis. Full article

In this work, we investigate the fundamental usability of fluorescent DNA-templated silver nanoclusters (DNA-AgNCs) as sensors for Point-of Care-Testing (PoCT) applications. We developed a microfluidic platform for the generation of droplets containing DNA-AgNCs in defined, different chemical environments. The droplets are read out fluorescently at two different emission wavelengths. For the pre-evaluation for the usage of biologically relevant matrices with DNA-AgNCs, the response of two different DNA-AgNCs to a variation in pH and sodium chloride concentration was acquired. Our compact and simple setup can detect DNA-AgNCs well below 100 nM and allows the characterization of the fluorescence response of DNA-based biohybrid nanosensors to changes in the chemical environment within short measurement times. The model DNA-AgNCs remain fluorescent throughout the physiologically relevant chloride concentrations and up to 150 mM. Upon shifts in pH, the DNA-AgNCs showed a complex fluorescence intensity response. The model DNA-AgNCs differ strongly in their response characteristics to the applied changes in their environments. With our work, we show the feasibility of the use of DNA-AgNCs as sensors in a simple microfluidic setup that can be used as a building block for PoCT applications while highlighting challenges in their adaption for use with biologically relevant matrices. Full article

This study presents an innovative wedge-shaped inlet weir-type microfluidic chip designed to address common issues of clogging and inefficiency in microfiltration processes. Driven solely by centrifugal force, the chip integrates a crossflow separation mechanism and enables selective droplet sorting based on size, without the need for external pumps. Fabricated from PMMA, the device features a central elliptical chamber, a wedge-shaped inlet, and spiral microchannels. These structures leverage shear stress and Dean vortices under centrifugal fields to achieve high-throughput separation of droplets with different diameters. Using water-in-oil emulsions as a model system, we systematically investigated the effects of geometric parameters and rotational speed on separation performance. A theoretical model was developed to derive the critical droplet size based on force balance, accounting for centrifugal force, viscous drag, pressure differentials, and surface tension. Experimental results demonstrate that the chip can effectively separate droplets ranging from 0 to 400 μm in diameter at 200 rpm, achieving a sorting efficiency of up to 72% and a separation threshold (cutoff accuracy) of 98.2%. Fluorescence analysis confirmed the absence of cross-contamination during single-chip operation. This work offers a structure-guided, efficient, and contamination-free droplet sorting strategy with broad potential applications in biomedical diagnostics and drug screening. Full article

Microfluidics is a rapidly advancing field focused on optimizing microdevices for applications such as organ-on-a-chip systems and enhancing laboratory analyses. Understanding the physical parameters of droplet generation is crucial for these devices. Computational fluid dynamics (CFD) techniques are essential for providing insights into the limitations and efficiency of numerical methods for studying fluid dynamics and improving our understanding of various application conditions. However, the influence of different numerical methods on the analysis of physical parameters in problems involving droplet generation in microchannels remains an area of ongoing research. This study implements the Volume of Fluid (VOF) method to investigate key physical parameters, including droplet size and the effect of the capillary number on fluid regimes, in droplet generation within a microchannel featuring a T-junction geometry. We compare the VOF method with the widely used Level Set Method (LSM) to evaluate its suitability for this context. The results show that the VOF method agrees with the LSM in fundamental outcomes, such as the reduction in droplet diameter as the flow rate ratio increases and the identification of the capillary number’s influence on fluid regime classification. The VOF method provides a clearer understanding of transitions between fluid regimes by detecting stages of non-uniformity in droplet size. It identifies a transition region between regimes with variations in droplet size, proving to be effective at mapping fluid flow regimes. This study highlights the potential of the VOF method in offering more detailed insights into instabilities and transitions between fluid regimes at the microscale. Full article

Droplet microfluidics has emerged as a transformative technology that can substantially increase the throughput of antibody “hit” discovery. This review provides a comprehensive overview of the recent advances in this dynamic field, focusing primarily on the technological and methodological innovations that have enhanced the antibody discovery process. This investigation starts with the fundamental principles of droplet microfluidics, emphasizing its unique capabilities for precisely controlling and manipulating picoliter-volume droplets. This discussion extends to various assay types employed in droplet microfluidics, including binding assays, functional assays, Förster Resonance Energy Transfer (FRET) assays, internalization assays, and neutralization assays, each offering distinct advantages for antibody screening and characterization. A critical examination of methods to improve droplet encapsulation is presented, besides addressing challenges such as reducing the leakage of small molecules from droplets and explaining what a “hit” droplet looks like. Furthermore, we assess design considerations essential for implementing high-throughput fluorescence-activated droplet sorting (FADS) workstations and emphasize the need for automation. This review also delves into the evolving commercial landscape, identifying key market players and emerging industry trends. This review paper aims to catalyze further research and innovation, ultimately advancing the field towards more efficient and robust solutions for antibody identification and development. Full article

This study proposes a simple yet versatile microfluidic strategy for fabricating monodisperse alginate hydrogel microspheres using a symmetric flow-focusing device. The system integrates three key innovations: (1) Cost-effective mold fabrication: A paper-based positive master replaces conventional SU-8 photoresist, significantly simplifying device prototyping. (2) Surfactant-free droplet generation: Alginate hydrogel droplets are formed at the first flow-focusing junction without requiring interfacial stabilizers. (3) In situ solidification with coalescence suppression: Acetic acid-infused corn oil is introduced at the adjacent junction, simultaneously triggering ionic crosslinking of alginate via pH reduction while preventing droplet aggregation. Notably, the hydrogel microspheres can be efficiently harvested through oscillatory aqueous phase separation, removing post-fabrication washing steps (typically 6–8 cycles for surfactant and oil removal). This integrated approach demonstrates exceptional advantages in fabrication simplicity, process scalability, and operational robustness for high-throughput hydrogel microsphere production. Full article

Microdroplet formation in microfluidic systems plays a pivotal role in chemical engineering, biomedicine, and energy applications. Precise control over the droplet size and formation dynamics of microdroplets is essential for optimizing performance in these fields. This work explores a hybrid control strategy that combines an active electric field with passive rib structures to regulate the droplet formation in a ribbed T-junction microchannel under an electric field. Numerical simulations based on the phase-field method are employed to analyze the effects of the electric capillary number $C{a}_e$ and rib height $a/w_c$ on the droplet formation mechanism. The results reveal that increasing $C{a}_e$ induces three distinct flow regimes of the dispersed phase: unpinning, partially pinning, and fully pinning regimes. This transition from an unpinning to a pinning regime increases the contact area between the wall and dispersed phase, restricts the flow of the continuous phase, and induces the shear stress of the wall, leading to a reduction in droplet size with the enhanced $C{a}_e$. Furthermore, an increase in rib height $a/w_c$ enhances the shear stress of the continuous phase above the rib, causing a progressive shift from a fully pinning to an unpinning regime, which results in a linear decrease in droplet size. A new empirical correlation is proposed to predict droplet size $S/w_c^2$ as a function of rib height $a/w_c$ and two-phase flow rate ratio $Q_d/Q_c$: $S/w_c^2=(-0.62-1.8Q_d/Q_c)(a/w)+(0.64+0.99Q_d/Q_c)$. Full article

Flexographic printing, traditionally used in the packaging industry, has emerged as a promising technology for microfluidic device fabrication due to enabling high resolution and being commercially available at a low cost compared to conventional techniques. This review explores the adaptation of a photopolymer flexographic printing plate mold (FMold) for microfluidics, examining its advantages, challenges, and applications. It offers a state-of-the-art view of the application of FMold for microfluidic systems, which offers a unique opportunity in terms of cost-effectiveness, scalability, and rapid prototyping. Applications are diverse: FMold has enabled the fabrication of microfluidic devices used in enhanced oil recovery to prepare rock-on-a-chip models, droplet generation and storage, suspension cell culture, monoclonal antibody production, complex cell differentiation pattern creation, phage screening, drug screening, cell detection, and cancer stem cell culture. Since its first appearance in 2018, FMold has been utilized in 50 publications in different laboratories around the world. Key advancements, current research trends, and future prospects are discussed to provide a comprehensive overview of this evolving tool. Full article

This study presents a mobile-based sperm analysis system featuring a user-friendly, droplet-loaded microfluidic chip that enables non-specialist users to perform the rapid and accurate quantitative evaluation of boar semen directly on the farm. The iSperm system integrates a tablet, optical module, heater, and real-time image analysis app to deliver automated measurements of sperm concentration, motility, and progressive motility in under one minute. Precision and user variability tests demonstrated high concordance with CASA and the hemocytometer, with minimal differences between trained and untrained users. A method comparison using 77 farm-collected samples confirmed agreement through Passing–Bablok regression and Bland–Altman analysis. ROC curve analyses further validated diagnostic accuracy for all parameters, with AUC values exceeding 0.95. The iSperm platform offers a reliable, user-friendly, and field-deployable solution for on-site semen quality assessment, improving decision-making in swine artificial insemination. Full article

Rapid mixing is widely prevalent in the field of microfluidics, encompassing applications such as biomedical diagnostics, drug delivery, chemical synthesis, and enzyme reactions. Mixing efficiency profoundly impacts the overall performance of these devices. However, at the micro-scale, the flow typically presents as laminar flow due to low Reynolds numbers, rendering rapid mixing challenging. Leveraging the vortices within a droplet of the Taylor flow and inducing chaotic convection within the droplet through serpentine channels can significantly enhance mixing efficiency. Based on this premise, we have developed a droplet micromixer that integrates the T-shaped channels required for generating Taylor flow and the serpentine channels required for inducing chaotic convection within the droplet. We determined the range of inlet liquid flow rate and gas pressure required to generate Taylor flow and conducted experimental investigations to examine the influence of the inlet conditions on droplet length, total flow rate, and mixing efficiency. Under conditions where channel dimensions and liquid flow rates are identical, Taylor flow achieves a nine-fold improvement in mixing efficiency compared to single-phase flow. At low Reynolds number (0.57 ≤ Re ≤ 1.05), the chip can achieve a 95% mixing efficiency within a 2 cm distance in just 0.5–0.8 s. The mixer proposed in this study offers the advantages of simplicity in manufacturing and ease of integration. It can be readily integrated into Lab-on-a-Chip devices to perform critical functions, including microfluidic switches, formation of nanocomposites, synthesis of oxides and adducts, velocity measurement, and supercritical fluid fractionation. Full article

Diffusiophoresis of a weakly charged dielectric droplet in a cylindrical pore is investigated theoretically in this study. The governing fundamental electrokinetic equations are solved with a patched pseudo-spectral method based on Chebyshev polynomials, coupled with a geometric mapping scheme to take care of the irregular solution domain. The impact of the boundary confinement effect upon the droplet motion is explored in detail, which is most profound in narrow channels. We found, among other things, that the droplet moving direction may reverse with varying channel widths. Enhanced motion-inducing double-layer polarization due to the presence of a nearby channel wall is found to be responsible for it. In particular, an interesting and seemingly peculiar phenomenon referred to as the “solidification phenomenon” is observed here at some specific critical droplet sizes or electrolyte strengths in narrow channels, under which all the droplets move at identical speeds regardless of their viscosities. They move like a rigid particle without the surface spinning motions and the induced interior recirculating vortex flows. As the corresponding shear rate is zero at this point, the droplet is resilient to undesirable exterior shear stresses tending to damage the droplet in motion. This provides a helpful guideline in the fabrication of liposomes in drug delivery in terms of the optimal liposome size, as well as in the microfluidic and nanofluidic manipulations of cells, among other potential practical applications. The effects of other parameters of electrokinetic interest are also examined. Full article

Alginate hydrogels offer distinct advantages as ionically crosslinked, biocompatible networks that can be shaped into spherical beads with high compositional flexibility. These spherical architectures provide isotropic geometry, modularity and the capacity for encapsulation, making them ideal platforms for scalable, stimuli-responsive actuation. Their ability to respond to thermal, magnetic, electrical, optical and chemical stimuli has enabled applications in targeted delivery, artificial muscles, microrobotics and environmental interfaces. This review examines recent advances in alginate sphere-based actuators, focusing on fabrication methods such as droplet microfluidics, coaxial flow and functional surface patterning, and strategies for introducing multi-stimuli responsiveness using smart polymers, nanoparticles and biologically active components. Actuation behaviours are understood and correlated with physical mechanisms including swelling kinetics, photothermal effects and the field-induced torque, supported by analytical and multiphysics models. Their demonstrated functionalities include shape transformation, locomotion and mechano-optical feedback. The review concludes with an outlook on the existing limitations, such as the material stability, cyclic durability and integration complexity, and proposes future directions toward the development of autonomous, multifunctional soft systems. Full article

Droplet-based microfluidics (DBM) has emerged as a powerful tool for a wide range of biochemical applications, from single-cell analysis and drug screening to diagnostics and tissue engineering. This review provides a comprehensive overview of the latest advancements in droplet generation and trapping techniques, highlighting both passive and active approaches. Passive methods—such as co-flow, cross-flow, and flow-focusing geometries—rely on hydrodynamic instabilities and capillary effects, offering simplicity and integration with compact devices, though often at the cost of tunability. In contrast, active methods exploit external fields—electric, magnetic, thermal, or mechanical—to enable on-demand droplet control, allowing for higher precision and throughput. Furthermore, we explore innovative trapping mechanisms such as hydrodynamic resistance networks, microfabricated U-shaped wells, and anchor-based systems that enable precise spatial immobilization of droplets. In the final section, we also examine active droplet sorting strategies, including electric, magnetic, acoustic, and thermal methods, as essential tools for downstream analysis and high-throughput workflows. These manipulation strategies facilitate in situ chemical and biological analyses, enhance experimental reproducibility, and are increasingly adaptable to industrial-scale applications. Emphasis is placed on the design flexibility, scalability, and biological compatibility of each method, offering critical insights for selecting appropriate techniques based on experimental needs and operational constraints. Full article