Viscoelastic microfluidics has emerged as a powerful, label-free platform for submicron particle manipulation by exploiting the intrinsic rheological properties of polymeric fluids without the need for external fields. However, achieving precise focusing at the submicron scale remains challenging due to the significantly weakened hydrodynamic forces acting on small particles. In this study, we present a high-performance microfluidic system that integrates high-aspect-ratio (HAR) straight channels with hydrodynamic pinching to enhance elasto-inertial focusing of micro- (2.1 μm) and submicron-sized (0.87 μm and 0.5 μm) particles. Using devices with physical aspect ratios (ARphys = H/W) of 3.3, 5, and 10, we systematically investigated the transition of particle migration behavior across varying PEO concentrations and flow conditions. To unify the combined effects of static channel geometry and dynamic flow-induced confinement, we introduce the concept of the effective aspect ratio (AReff). Our results show that while an ARphys of 10 enables stable sheathless focusing, devices with lower ARphys can achieve comparable performance by increasing the flow rate ratio (FRR), thereby elevating AReff. This synergistic coupling amplifies the lateral elastic stress gradient by confining particles within an intensively compressed sample stream, effectively overcoming the volume-dependent force scaling limitations (Fel ∝ d3). By optimizing the flow configuration within the ARphys = 10 device (FRR = 4, Qtotal = 40 µL/min, AReff ≈ 50), we successfully suppressed the Brownian diffusion, achieving the highest focusing quality (FWHM ≈ 10 μm for 0.5 μm particles). By quantitatively evaluating focusing performance through the AReff, this work provides a robust physical framework and practical design guidelines for the manipulation of sub-micrometer targets in relatively short channels (L/Dh ≈ 255). The proposed device offers a high-resolution, high-throughput solution for future analytical and diagnostic applications.
Biofilm associated infections represent a significant clinical challenge due to their inherent tolerance to antibiotics, ability to evade host immune responses, and persistence in chronic disease settings. Conventional therapies often fail to eradicate mature biofilms, particularly in polymicrobial infections or on medical devices, highlighting the urgent need for innovative interventions. Nanomedicine has emerged as a promising strategy, offering platforms such as polymeric nanoparticles, liposomes, metallic, and hybrid systems capable of enhancing drug penetration, targeting microbial communities, and enabling controlled release of antimicrobials. Comparative studies suggest that combination approaches, including enzyme functionalized or stimuli responsive nanoparticles paired with antibiotics, may outperform single modality treatments by simultaneously disrupting the biofilm matrix and delivering active agents. Despite encouraging preclinical findings, several barriers hinder clinical translation. These include challenges in large scale synthesis, reproducibility, stability, regulatory approval, and comprehensive safety assessment, as well as the complexity of accurately modeling biofilm heterogeneity and host interactions. Additionally, nanoparticle biodistribution, protein corona formation, and potential microbial adaptation present further translational hurdles. Future research should focus on optimizing multifunctional nanoplatforms, refining preclinical biofilm models, assessing long term safety, and integrating strategies to anticipate resistance. Addressing these interconnected scientific, technical, and regulatory challenges will likely be critical for harnessing nanomedicine as a transformative tool in the management of persistent biofilm related infections.
Label-free cell sorting technology holds significant value in fundamental biomedical research and clinical precision diagnostics. However, existing dielectrophoresis sorting chips generally face the challenge of balancing high throughput with high resolution, while traditional metal electrodes are prone to bubble formation and sample contamination. To address these issues, this study proposes a ring-array dielectrophoresis microfluidic chip based on liquid electrodes. Through the synergistic design of semicircular flow channels and 36 circumferentially arranged liquid electrodes, the effective selection region of the electric field is significantly extended within the limited chip area, while a gradient electric field is formed along the flow direction, enabling continuous and dynamic deflection separation of particles of similar size. Key parameters such as voltage, frequency, and flow rate were optimized using a multiphysics simulation system, and the chip was fabricated via 3D printing. Fluorescent polystyrene microspheres of 5 μm and 15 μm were used to simulate non-target and target cells, respectively, and sorting experiments were conducted under various optimized parameter conditions. Compared to existing dielectrophoresis chips, this design maintains excellent resolution during high-throughput operations while fundamentally eliminating bubble formation and sample contamination caused by liquid electrodes, featuring a simple structure and convenient fabrication. This study provides a novel solution that balances performance and practicality for label-free, high-activity cell sorting, with subsequent efforts focused on validation with real-cell samples and exploration of integration with point-of-care diagnostic systems.
Capillaric microfluidics offer miniaturization and simplified liquid handling without the need for peripheral equipment. Paper materials like cellulose and nitrocellulose are commonly used as passive pumps in capillaric microfluidics due to their porous structure capable of wicking relatively large volumes of liquid in a compact device footprint. Growing interest in capillaric microfluidics over the past four decades has provided a wide range of self-powered fluidic control elements and expanded the range of available applications. However, the integration of paper pumps with microchannels is an often overlooked and delicate process with tips and tricks – often spread via word of mouth – that can significantly impact the performance and reproducibility of capillaric microfluidics. In this work, we compared fabrication and connection strategies between a 3D printed microfluidic device, nitrocellulose substrate, and cellulose wicking pump to determine the optimal design for reliable and user-friendly handling. Leveraging prior work in the field, we found that a thick cellulose wicking pump, secured to the device and connected to the nitrocellulose substrate using adhesive tape to apply pressure resulted in low variation of the fluid flow within the system. We also showed that overlapping the nitrocellulose with the outlet microchannel produced repeatable results for users of various training levels. These results demonstrate an effective, reliable, and user-friendly microchannel-paper interface that could prove suitable for a broad range of applications, including diagnostic immunoassays. Our characterization and conclusions also offer transparency into a crucial yet under-discussed aspect of capillaric microfluidics design and fabrication.
We numerically investigate wettability-gradient-driven propulsion of a shear-thinning droplet on micro-textured and confined substrates. The droplet rheology is modelled using the Carreau–Yasuda constitutive relation, and interfacial dynamics are resolved using a finite-element level-set framework incorporating consistent slip regularization and mesh-independent resolution. We develop a scaling analysis from the numerical framework, establishing the coupled dependence of droplet propulsion on wettability gradient, confinement, roughness, and contact-line dynamics. This is achieved through non-dimensional parameters including capillary number (Ca), roughness height ( ), and rescaled slip length ( ε ), providing mechanistic insights into wettability-driven transport of non-Newtonian fluids. A theoretical scaling relation describing roughness-dependent propulsion is further developed and validated against numerical results. Droplet propulsion exhibits a non-monotonic dependence on the flow behaviour index, with optimal transport arising in shear-thinning regimes that enhance internal circulation while balancing kinetic energy generation and viscous dissipation. Surface texture strongly modulates contact-line stresses; triangular asperities generate the highest propulsion by amplifying local shear and sustaining pressure imbalance. Roughness height and confinement ratio both display optimal intermediate ranges, beyond which contact-line distortion, curvature-induced resistance, and increased hydrodynamic resistance suppress motion. The results identify the coupled roles of rheology, texture, confinement, and energetics in governing passive droplet transport on wettability-graded surfaces.
Continuously rotating a single microdroplet within a circular loop channel keeps the droplet in motion while holding it within a fixed field of view. Existing approaches to droplet rotation, however, typically rely on multi-layer devices equipped with pneumatic control valves, which complicate both fabrication and operation. In this study, we present a method, free of embedded pneumatic valves, in which a single droplet is rotated in a circular loop microchannel by applying three pressure waveforms, analogous to the driving currents of a three-phase synchronous motor, to three radially arranged control channels. The operating principle is formulated using this motor analogy, and an equation of motion is derived that explicitly accounts for the time delays arising from the pressure pumps and the feedback loop. Computational fluid dynamics simulations and experiments consistently show that the measured optimal lead angle closely matches the theoretical prediction of 90° across a range of system parameters, including tubing length. The proposed framework simplifies the integration of loop-based droplet manipulation into existing lab-on-a-chip devices and provides a practical design guide for controlling such systems.
Microflows like Knudsen pumps often include rarefied gases featuring different degrees of rarefaction. This different modeling complexity requires space- and time-adaptive rarefied gas models that resolve the physical effects efficiently in each subdomain of the microflow. Different-order moment models are effective at describing rarefied gases in microflows with respective levels of complexity in each subdomain. In this work, analytical model-error estimators for the Hyperbolic Moment Equations (HME) model are derived that are then used to define a space- and time-adaptive moment model for microflows of rarefied gases. First, a domain decomposition strategy of the microflow into subdomains, each modelled by an HME model of an appropriate order, is presented, using domain decomposition criteria that are based on the exact model difference between a higher-order HME model and a lower-order HME model and on chosen error thresholds. Secondly, a non-linear adaptation of a recently developed padded buffer cell approach is presented to couple these varying-order HME models using a single finite volume scheme. Finally, a smoothing of the domain decomposition is proposed to limit oscillations generated by the coupling. While the performance depends on the thresholds and the smoothing parameter, the proposed adaptive moment model is able to capture the different degrees of rarefaction of the rarefied gas in the microflow and yields accurate numerical results compared to experimentally validated DVM benchmark data while obtaining computational speedups of up to 40 percent compared to using a high-order HME model in the entire domain.
Precise control of shear stress is essential for maintaining β -cell physiology in microfluidic perifusion assays, where transient pressure fluctuations can alter glucose-stimulated responses. In this work, we present a boundary-layer-driven microTesla ( μ Tesla) pump engineered to deliver stable, non-pulsatile flow for shear-sensitive biological studies. Using combined computational fluid dynamics and experimental validation, we examined how surface texturization, slip length, and fluid viscosity collectively influence boundary-layer development, shear distribution, and pump output. The μ Tesla II pump produced laminar, viscosity-adaptive flow across Newtonian and non-Newtonian regimes, maintaining consistent outlet velocity even under high-viscosity conditions. Surface textures modulated slip length to enhance viscous coupling, yielding smooth acceleration and reduced startup surges relative to conventional syringe and peristaltic pumps. When applied to β -cell perifusion, μ Tesla II minimized flow-induced artifacts, preserving physiological calcium and ATP dynamics during glucose stimulation. Overall, these findings establish the μ Tesla II as a low-shear perifusion platform that reduces flow-induced artifacts, improves the reproducibility of short-term flow-based cellular assays, and supports the advancement of organ-on-chip and diabetes research models.
Chronic kidney disease (CKD) is a progressive disorder that requires early diagnosis and continuous monitoring to prevent irreversible renal damage. Clinically significant indicators of kidney function and disease progression include urinary biomarkers, especially albumin and creatinine. Nevertheless, traditional analytical techniques for their determination are frequently laborious, necessitate centralized laboratory infrastructure, and are not ideal for quick or point-of-care (POC) examination. To address these limitations, this study presents the design and fabrication of a novel three-dimensional (3D) microfluidic device for the simultaneous detection of albumin protein and creatinine in human urine samples from CKD patients. In order to improve fluid handling, mass transfer, and analytical efficiency while reducing sample and reagent usage, the suggested 3D microfluidic design incorporates intricate channel designs. The device reduces operating complexity and analysis time by enabling multiplexed biochemical analysis inside a single compact system. The synthesis of silver nanoparticles AgNPs@BS and copper nanoparticles CuNPs@BS was achieved using Boswellia sacra (BS) as a dual-function phytochemical platform, acting concurrently as both a reducing and stabilizing (capping) agent. The detection process is then based on the aggregation of AgNPs@BS at pH = 11 induced by creatinine and the aggregation of CuNPs@BS induced by albumin, resulting in a distinct and visually observable colour shift. With a regression value (R2) of 0.9837 and a limit of detection (LOD) of 4.52 µg/mL, the AgNPs@BS sensor demonstrated a linear relationship between the A670/A403 extinction ratio and creatinine concentration range of 20 to 150 µg/mL. Additionally, the CuNPs@BS-based colorimetric assay exhibited a linear relationship between color intensity and albumin concentration over the range of 5–150 µg/mL, with LOD of 3.87 µg/mL. Overall, the developed 3D microfluidic device offers a promising approach for integrated urinary biomarker analysis and represents a step toward portable and POC diagnostic systems for chronic kidney disease monitoring.
The dynamic evolution of gas–solid–liquid interfaces exert a critical influence on reactive transport in subsurface engineering, including geological CO2 sequestration and unconventional energy development. However, the microscale interfacial processes by which reaction-induced bubbles regulate mineral dissolution remain poorly understood, owing to the challenge on visualizing in the opaque natural rock. In this work, emerging mineral microfluidic platform was employed to directly visualize and quantify the coupling between CO2 bubble generation and single calcite dissolution. Three distinct dissolution regimes were identified depending on flow rate and acid concentration, namely bubble-free, bubble-shielding, and bubble-sealing dissolution. At low acid concentration, dissolution proceeds smoothly without bubble formation, and the effective reaction rate increases with flow rate following a power-law trend. Once a critical acid concentration is exceeded, CO2 bubbles nucleate and grow on the reactive surface, sharply reducing the effective reactive area. Acid transport becomes confined to narrow channels surrounding the bubbles, suggesting a progressive shift from convection-dominated to diffusion-dominated mass transfer. Bubble shielding significantly decreases the effective reaction rate by 81.5
Non-poly(A) messenger ribonucleic acid (mRNA) purification remains a critical bottleneck for cell-free translation platforms like transcription-translation coupled with the association of puromycin linker (TRAP) display for peptide screening, where sub-optimal thermal release can compromise results. Herein, we demonstrate a “complex system response” approach for optimizing thermal elution from probe-coated magnetic beads. Using an orthogonal array composite design with two optimization rounds (17 three-factor + 9 two-factor experiments), we systematically explored temperature (60–95 °C), time (5–30 min), pH (7–9), and their interactions, revealing an unanticipated optimum of 60 °C for 23.5 min at pH 9 (vs. conventional protocols of 90 °C for 10 min). These conditions were associated with a maximum release efficiency of 71 ± 7
The influence of the flow rate ratio on plug hydrodynamics is investigated experimentally in a rectangular T-junction microchannel under different conditions, where water plugs are dispersed in a silicone oil carrier phase. The study examines plug length, generation frequency, velocity, and shape. The results show that the resultant forces at the junction, characterised by the two-phase capillary number CaTP, predominantly govern all plug characteristics. Under constant CaTP, the plug length increases linearly with the flow rate ratio, while the generation frequency remains within the range of 41–55 Hz. Plug velocity is primarily controlled by the liquid film thickness, which varies with the flow rate ratio, whereas plug shape is only weakly influenced by this parameter. These findings enhance understanding of two-phase plug flow in microchannels and provide valuable insights for controlling plug flow regimes in microelectronic cooling applications.
This paper examines deformation and transport behavior of compound droplets when transported through microchannels with different geometries, including sinusoidal, sawtooth, diffuser, nozzle obstructions. The effect of capillary number (varying between 0.025 and 1) and obstruction size (0.4 Ro -0.8 Ro) on transition behaviour of compound droplets is studied systematically. The results indicate that capillary number is significant factor in deformation and stability of droplets. One of the values tested gave reliable outcomes with capillary number of 0.1 and even more accurate with 0.025. This implies that lower capillary numbers result in more accurate simulations, as they are precise in capturing interface dynamics and droplet-obstruction interactions. Transit time of outer and inner droplets decreases with obstruction ratio of 0.4–0.8, which means that obstructions of higher size facilitate faster droplet passage. This suggests that a lower capillary number enhances the precision of simulations by better capturing interface dynamics and droplet–obstruction interactions. The transit time for both outer and inner droplets decreases with increasing obstruction ratio from 0.4 to 0.8, indicating that larger obstructions facilitate faster droplet passage.
The equivalent circuit design method has evolved into a relatively mature technique for designing microfluidic devices. This approach simplifies microfluidic device design by approximating fluid behavior within the devices as analogous to electron behavior in electrical circuits, thereby leveraging the analogy between microfluidic hydraulics and electrical circuits. Based on this technique, scientists have developed microfluidic devices with various functionalities, such as multi-concentration mixing, cell capture, flow distribution, concentration gradient generation, and droplet generation. However, due to the disparity in physical properties between microfluidic systems and electrical circuits, the impedance effect experienced by fluids during the analogical design process is not pronounced—specifically, when mapping fluidic characteristics like high and low Reynolds numbers to circuit properties such as high and low current frequencies. This gap has resulted in a lack of microchannel design methods analogous to inductive components in electrical circuits when applying the equivalent circuit approach to microfluidic chip design. Here, we propose a design strategy for microfluidic valves with inductive properties and their topological optimization. The valve structures designed by this method exhibit high flow resistance under high Reynolds number conditions and low resistance under low Reynolds number conditions. Consequently, this work enriches the equivalent circuit design methodology by introducing the equivalent inductive microfluidic module—Microfluidic inductor as a new available module, along with its corresponding design method.
This work presents a physics-guided design, optimization, fabrication, and experimental validation of Fresnel-ring-based single-transducer acoustic tweezers capable of precise three-dimensional manipulation of microparticles in liquid without reliance on (or being hampered by) standing waves. A planar piezoelectric transducer patterned with concentric half-wavelength annular electrodes is engineered to generate three axially separated focal points whose constructive interference forms a spatially enclosed radiation-force potential well. By systematically optimizing the inter-focal spacing using Finite Element Modeling (FEM), we establish quantitative design rules that link the primary focal length, inter-focal distance, trapping-zone geometry, and particle-size selectivity. Hydrophone-based three-dimensional pressure mapping validates the simulated acoustic field and confirms the formation of a well-defined low-pressure region bounded by surrounding high-pressure lobes. Experimental results demonstrate robust, size-selective confinement of microspheres and stable trapping of large biological specimens, including a 700 μm zebrafish embryo, at user-defined axial distances from the transducer surface. The observed trapping behavior agrees with theoretical predictions based on acoustic radiation force scaling and streaming-induced drag. By explicitly correlating focal configuration, radiation potential landscape, and particle-size-dependent stability, this study establishes a scalable, microfabrication-compatible framework for single-transducer acoustic tweezers. The technology based on multi-focal acoustic tweezers enables programmable trapping size, trapping position, selective manipulation, and controlled particle lifting and ejection, providing a versatile platform for advanced BioMEMS applications and next-generation contactless micromanipulation systems.
Colloidal particle-laden inks are increasingly used in additive manufacturing to produce functional components with tailored properties, and droplet-based microfluidics enables precise generation of high-viscosity, particle-rich droplets. Despite extensive studies on particle-free shear-thinning fluids, the coupled influence of particle concentration on both flow regimes and droplet size in microfluidic systems remains insufficiently understood. Here, we showed that particle concentration in shear-thinning, alumina-laden inks governs droplet formation dynamics through a dual effect on viscosity and interfacial tension. We investigated the droplet formation of a solvent-free, alumina-laden acrylate ink dispersed in a continuous aqueous phase using a flow-focusing microfluidic device. Inks containing 10
In this study, bovine serum albumin-stabilized gold nanoclusters (BSA@AuNCs) were synthesized using a microfluidic droplet system. Compared with traditional flask-based synthesis methods, the microfluidic droplet system yielded AuNCs with uniform nucleation, enhanced fluorescence properties, improved stability, and a significantly shortened preparation time (24 min). Selectivity analysis demonstrated that BSA@AuNCs exhibit high specificity toward Cu(II), and a linear relationship was observed between the Cu(II) concentration (0–5000.0 µM) and the fluorescence intensity of BSA@AuNCs, with a detection limit of 20.0 µM. Upon the addition of Cu(II), the binding of Cu(II) to BSA@AuNCs led to increased particle size and aggregation, which was macroscopically manifested as fluorescence quenching. Finally, BSA@AuNCs were innovatively applied to the detection of Cu(II) levels in zebrafish embryos. Confocal laser scanning microscopy (CLSM) imaging revealed a gradual decrease in fluorescence intensity within BSA@AuNC-incubated zebrafish embryos as the Cu(II) concentration increased. This method provides a viable strategy for detecting metal ions in living organisms and lays an experimental foundation for investigating the effects of Cu(II) and their related mechanisms in vivo.
An infrared thermal imager and a digital microscope are employed to observe the spreading behavior of oil droplets that are subject to various temperature fields in this study. The spreading characteristics of oil droplets are analyzed by adjusting the temperature field, temperature gradient, liquid viscosity and volume. Experimental results show that when an oil droplet is placed on a solid surface that is subject to a temperature field, the oil droplet always spreads forward in the opposite direction of the temperature gradient. During the spreading process, the front end of the droplet advances while the rear end remains fixed, forming an oil film whose shape is constrained by the temperature field. Moreover, when the temperature field keeps unchanged, a larger temperature gradient will cause the droplet to spread more rapidly, expand the oil film area and promote the morphological evolution. Furthermore, as the viscosity increases, the spreading velocity decreases, and the response of the droplet to the temperature field weakens, resulting in a reduction in the oil film area and suppression of the shape evolution. Finally, the spreading velocity rises with the increase of droplet volumes, and the oil film area expands while preserving morphological similarity. A theoretical model for the spreading speed is established based on the force analysis, and the theoretical results agree well with the experimental values. These findings contribute to the understanding of wear mechanisms caused by lubricant depletion or starvation in mechanical equipment and provide a guide for preventing lubricant accumulation.
Gas transport through nanochannels is critical to applications ranging from gas separation to shale gas extraction. Accurately predicting flow rates under non-adsorbing or weak-physisorption conditions requires the generalized Knudsen theory, which accounts for the full spectrum of gas-wall scattering mechanisms. However, its broad validation across diverse gases and surfaces remains incomplete, largely because the key parameter quantifying scattering, the diffuse reflection fraction (f) or tangential momentum accommodation coefficient (TMAC), is notoriously difficult to determine. Here, we employ molecular dynamics (MD) simulations to develop a robust approach for calculating f. Using this method, we systematically validate the generalized Knudsen theory for a wide range of gases, including all noble gases and common polyatomic species (H2, O2, H2O, CO2 and CH4). Our results show that f or TMAC is predominantly a surface property: it clusters around 0.1 for graphene and 0.8 for SiO2, with only weak dependence on the gas species. By incorporating these f values, the theory achieves remarkable accuracy in predicting flow rates, as confirmed by direct MD simulations across all tested gas-channel combinations. This work establishes a general and predictive framework for gas transport in nanochannels, paving the way for the rational design of nanofluidic devices and advanced separation membranes.
Nitrofurantoin, a broad-spectrum nitrofuran-class antibiotic, persists in food and aquatic environments, posing risks of hepatotoxicity and contributing to antibiotic resistance. Although LC-MS/MS and HPLC-based provide exceptional sensitivity, they are incompatible for rapid and on-site analysis. Beyond trace on-site detection, effective management of antibiotic load requires scalable and efficient remediation strategies to prevent indirect entry and minimize secondary toxicity. While conventional UV-photodegradation is extensively studied for antibiotic removal, it often leads to formation of toxic intermediates raising concerns about environmental safety. Thus, exists a need for alternate photodegradation approach with less toxic intermediates. This study comprehensively investigates the Near-infrared (NIR) light-based degradation of nitrofurantoin (NFT) coupled with surface-enhanced Raman spectroscopy (SERS)-based toxicity profiling. To ensure rigorous comparison, identical power of 37 W was used with UV and NIR irradiations for constant exposure duration. To investigate the field deployability of this strategy, we developed a low-cost paper-based microfluidic platform integrated with silver nanorods for simultaneous degradation and SERS-based detection of the non-toxic intermediates. SERS fingerprint of the UV degraded samples corresponded to 1-aminohydantoin (AHD), a toxic and carcinogenic metabolite, while NIR irradiation favours the formation of a less toxic 5-nitro-2-furaldehyde (NFA). Time-resolved Raman analysis demonstrated systematic degradation of NFT with R2 > 0.95 upon NIR irradiation. These results establish NIR-assisted degradation as a safer alternative to UV degradation and signify the potential of SERS-based paper microfluidics as a field-deployable device for Sustainable Development Goals 3 and 6 through sustainable water management and improved public health safety.
