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The microfluidic measurement of capillary flow can be used to evaluate the response of biological samples to stimulation, where distance and velocity are altered. Melt-extruded multi-bored microfluidic capillaries allow for high-throughput testing with low device cost, but simple devices may limit control over sample flow when compared to the more complex "lab-on-a-chip" devices produced using advanced microfluidic fabrication methods. Previously, we measured the dynamics of global haemostasis stimulated by thrombin by dipping straight vertical microcapillaries into blood, but only the most rapid response could be monitored, as flow slowed significantly within 30 s. Here, we show an innovative method to extend both the stimulation process and flow measurement time without increasing the cost of the device by adding simple loops to the flexible extruded device. The loops enable longer time-scale measurements by increasing resistance to flow, thereby reducing the dependence on high stimulus concentrations for rapid reactions. The instantaneous velocity and equilibrium heights of straight and looped vertical microcapillary films were assessed with water, plasma and whole blood, showing that the loops create additional frictional resistances, reduce flow velocity and prolong residence times for increased time scales of the stimulation process. A modified pressure balance model was used to capture flow dynamics with the added loop. Looped devices loaded with thrombin and collagen showed an improved detection of blood stimulation responses even with lower stimulus concentrations, compared to straight vertical capillaries. Thrombin-activated blood samples in straight capillaries provided a maximum measurement zone of only 4 mm, while the looped design significantly increased this to 11 mm for much longer time scale measurements. Our results suggest that extending stimulation times can be achieved without complex microfluidic fabrication methods, potentially improving concentration–response blood stimulation assays, and may enhance the accuracy and reliability. We conclude adding a loop to low-cost extruded microfluidic devices may bring microfluidic devices closer to delivering on their promise of widespread, decentralized low-cost evaluation of blood response to stimulation in both research and clinical settings. [ABSTRACT FROM AUTHOR]

Understanding the propulsion of a swimmer in a large group of individuals holds the key to unravelling the intriguing dynamics of active matter collective motion. Here, we develop a two-dimensional (2-D) self-assembled rotor, powered by bacterial flagella. At a water–air interface, the average direction of rotation of a rotor is fixed. When the chiral rotor is put into a 2-D bacterial suspension, we examine the average and fluctuation of the angular velocity of the rotor. Remarkably, the average angular velocity of a rotor is found to increase up to 3 times when the density of surrounding bacterial suspension increases and the increase is nonlinear. In a dense suspension of bacteria, the existence of a rotor disrupts vortices in the surrounding active turbulence, and the acceleration of the rotor is independent of the activity level of the surrounding free bacteria. The nonlinear acceleration thus results from hydrodynamic interaction with surrounding crowdedness that can be quantitatively explained by hydrodynamic simulation. The simultaneity between the acceleration of rotor and free bacteria in active turbulence suggests that crowding-induced acceleration may promote the onset of instability. The result will inspire new active-matter-based microfluidic devices with improved transport properties. [ABSTRACT FROM AUTHOR]

Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution. We demonstrate the ability to resolve 50-µm microchannels, breaking the historical relationship between resin properties and negative space resolution. With this approach, we fabricated proof-of-concept 3D free-form microfluidic devices with improved design freedom over device material selection and resulting properties. [ABSTRACT FROM AUTHOR]

Increasing evidences demonstrate the role of sensory innervation in bone metabolism, remodeling and repair, however neurovascular coupling in bone is rarely studied. Using microfluidic devices as an indirect co-culture model to mimic in vitro the physiological scenario of innervation, our group demonstrated that sensory neurons (SNs) were able to regulate the extracellular matrix remodeling by endothelial cells (ECs), in particular through sensory neuropeptides, i.e. calcitonin gene-related peptide (CGRP) and substance P (SP). Nonetheless, still little is known about the cell signaling pathways and mechanism of action in neurovascular coupling. Here, in order to characterize the communication between SNs and ECs at molecular level, we evaluated the effect of SNs and the neuropeptides CGRP and SP on ECs. We focused on different pathways known to play a role on endothelial functions: calcium signaling, p38 and Erk1/2; the control of signal propagation through Cx43; and endothelial functions through the production of nitric oxide (NO). The effect of SNs was evaluated on ECs Ca2+ influx, the expression of Cx43, endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, p38, ERK1/2 as well as their phosphorylated forms. In addition, the role of CGRP and SP were either analyzed using respective antagonists in the co-culture model, or by adding directly on the ECs monocultures. We show that capsaicin-stimulated SNs induce increased Ca2+ influx in ECs. SNs stimulate the increase of NO production in ECs, probably involving a decrease in the inhibitory eNOS T495 phosphorylation site. The neuropeptide CGRP, produced by SNs, seems to be one of the mediators of this effect in ECs since NO production is decreased in the presence of CGRP antagonist in the co-culture of ECs and SNs, and increased when ECs are stimulated with synthetic CGRP. Taken together, our results suggest that SNs play an important role in the control of the endothelial cell functions through CGRP production and NO signaling pathway. [ABSTRACT FROM AUTHOR]

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSμC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSμC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 μm) toward the inner wall, while directing smaller ones (avg. diameter: 23 μm) outward. Utilizing ITSμC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSμC suggests its potential in differentiating a wide range of heterogeneous cell populations. [ABSTRACT FROM AUTHOR]

Microfluidic chips hold vast potential for applications in fields such as DNA analysis, drug screening, cell culture and biosensing. However, microfluidic chips are susceptible to disruption and damage from bubbles. Current bubble removal methods suffer from limitations including narrow applicability, poor biocompatibility, limited bubble containment volume, low degassing rates, manufacturing complexity and integration challenges. Addressing these issues, this study presents the development of a bubble filtration microfluidic chip inspired by the stomatal pore structure in plant leaves, which prevents air propagation between conduits. Surface wettability theory and surface tension principles were utilized to investigate the mechanism of bubble filtration by plant stomatal pores. A cellulose/PVA hydrogel was introduced to enable the microfluidic chip to effectively filter bubbles. The design and in situ formation method of the bubble filtration chip were developed, and the chip was fabricated using micro-nanofabrication processes. Performance evaluation of the bubble filtration microfluidic chip demonstrated that with a gel film thickness of 20 μm, the microfluidic chip exhibits high gas leak threshold and minimal flow loss. The resulting biomimetic bubble filtration microfluidic chip features a simple structure, compact size, and independence from auxiliary equipment, making it suitable for portable microfluidic devices. [ABSTRACT FROM AUTHOR]

Microfluidic devices with open lattice structures, equivalent to a type of porous media, allow for the manipulation of fluid transport processes while having distinct structural, mechanical, and thermal properties. However, a fundamental understanding of the design principles for the solid structure in order to achieve consistent and desired flow patterns remains a challenge, preventing its further development and wider applications. Here, through quantitative and mechanistic analyses of the behavior of multi-phase phenomena that involve gas–liquid–solid interfaces, we present a design framework for microfluidic devices containing porous architectures (referred to as poroFluidics) for deterministic control of multi-phase fluid transport processes. We show that the essential properties of the fluids and solid, including viscosity, interfacial tension, wettability, as well as solid manufacture resolution, can be incorporated into the design to achieve consistent flow in porous media, where the desired spatial and temporal fluid invasion sequence can be realized. Experiments and numerical simulations reveal that different preferential flow pathways can be controlled by solid geometry, flow conditions, or fluid/solid properties. Our design framework enables precise, multifunctional, and dynamic control of multi-phase transport within engineered porous media. [ABSTRACT FROM AUTHOR]

The paper-based culture platform developed by Whitesides readily incorporates tissue-like structures into laboratories with established workflows that rely on monolayer cultures. Cell-laden hydrogels are deposited in these porous scaffolds with micropipettes; these scaffolds support the thin gel slabs, allowing them to be evaluated individually or stacked into thick constructs. The paper-based culture platform has inspired many basic and translational studies, each exploring how readily accessible materials can generate complex structures that mimic aspects of tissues in vivo. Many of these examples have relied on static culture conditions, which result in diffusion-limited environments and cells experiencing pericellular hypoxia. Perfusion-based systems can alleviate pericellular hypoxia and other cell stresses by continually exposing the cells to fresh medium. These perfusion systems are common in microfluidic and organ-on-chip devices supporting cells as monolayer cultures or as 3D constructs. Here, we introduce a continuous flow delivery system, which uses parts readily produced with 3D printing to provide a self-contained culture platform in which cells in paper or other scaffolds are exposed to fresh (flowing) medium. We demonstrate the utility of this device with examples of cells maintained in single cell-laden scaffolds, stacks of cell-laden scaffolds, and scaffolds that contain monolayers of endothelial cells. These demonstrations highlight some possible experimental questions that can be enabled with readily accessible culture materials and a perfusion-based device that can be readily fabricated. [ABSTRACT FROM AUTHOR]

Electrochemical sensors provide an affordable and reliable approach towards the detection and monitoring of important biological species ranging from simple ions to complex biomolecules. The ability to miniaturize electrochemical sensors, coupled with their affordability and simple equipment requirements for signal readout, permits the use of these sensors at the point-of-care where analysis using non-invasively obtainable biofluids is receiving growing interest by the research community. This paper describes the design, fabrication, and integration of a 3D printed Mg2+ potentiometric sensor into a 3D printed microfluidic device for the quantification of Mg2+ in low-sample volume biological fluids. The sensor employs a functionalized 3D printable photocurable methacrylate-based ion-selective membrane affixed to a carbon-mesh/epoxy solid-contact transducer for the selective determination of Mg2+ in sweat, saliva and urine. The 3D printed Mg2+ ion-selective electrode (3Dp-Mg2+-ISE) provided a Nernstian response of 27.5 mV per decade with a linear range of 10 mM to 39 μM, covering the normal physiological and clinically relevant levels of Mg2+ in biofluids. 3Dp-Mg2+-ISEs selectively measure Mg2+ over other biologically present cations – sodium, potassium, calcium, ammonium – as well as provide high stability in the analytical signal with a drift of just 13 μV h−1 over 10 hours. Comparison with poly(vinylchloride)-based Mg2+-ISEs showed distinct advantages to the use of 3Dp-Mg2+-ISEs, with respect to stability, resilience towards biofouling and importantly providing a streamlined and rapid approach towards mass production of selective and reliable sensors. The miniaturization capabilities of 3D printing coupled with the benefits of microfluidic analysis (i.e., low sample volumes, minimal reagent consumption, automation of multiple assays, etc.), provides exciting opportunities for the realization of the next-generation of point-of-care diagnostic devices. [ABSTRACT FROM AUTHOR]

Compartmentalization is a vital aspect of living cells to orchestrate intracellular processes. In a similar vein, constructing dynamic and responsive sub-compartments is key to synthetic cell engineering. In recent years, liquid-liquid phase separation via coacervation has offered an innovative avenue for creating membraneless organelles (MOs) within artificial cells. Here, we present a lab-on-a-chip system to reversibly trigger peptide-based coacervates within cell-mimicking confinements. We use double emulsion droplets (DEs) as our synthetic cell containers while pH-responsive elastin-like polypeptides (ELPs) act as the coacervate system. We first present a high-throughput microfluidic DE production enabling efficient encapsulation of the ELPs. The DEs are then harvested to perform multiple MO formation-dissolution cycles using pH as well as temperature variation. For controlled long-term visualization and modulation of the external environment, we developed an integrated microfluidic device for trapping and environmental stimulation of DEs, with negligible mechanical force, and demonstrated a proof-of-principle osmolyte-based triggering to induce multiple MO formation-dissolution cycles. In conclusion, our work showcases the use of DEs and ELPs in designing membraneless reversible compartmentalization within synthetic cells via physicochemical triggers. Additionally, presented on-chip platform can be applied over a wide range of phase separation and vesicle systems for applications in synthetic cells and beyond. Compartmentalization within living cells is vital to orchestrate intracellular processes, but effective compartmentalization and organization within synthetic cells remains a key challenge. Here, the authors report a lab-on-a-chip system to reversibly trigger the formation of peptide-based coacervates as membraneless organelles via pH/temperature/osmolyte variations within cell-mimicking confinements. [ABSTRACT FROM AUTHOR]

The incorporation of engineered muscle‐tendon junction (MTJ) with organ‐on‐a‐chip technology provides promising in vitro models for the understanding of cell‐cell interaction at the interface between muscle and tendon tissues. However, developing engineered MTJ tissue with biomimetic anatomical interface structure remains challenging, and the precise co‐culture of engineered interface tissue is further regarded as a remarkable obstacle. Herein, an interwoven waving approach is presented to develop engineered MTJ tissue with a biomimetic "M‐type" interface structure, and further integrated into a precise co‐culture microfluidic device for functional MTJ‐on‐a‐chip fabrication. These multiscale MTJ scaffolds based on electrospun nanofiber yarns enabled 3D cellular alignment and differentiation, and the "M‐type" structure led to cellular organization and interaction at the interface zone. Crucially, a compartmentalized co‐culture system is integrated into an MTJ‐on‐a‐chip device for the precise co‐culture of muscle and tendon zones using their medium at the same time. Such an MTJ‐on‐a‐chip device is further served for drug‐associated MTJ toxic or protective efficacy investigations. These results highlight that these interwoven nanofibrous scaffolds with biomimetic "M‐type" interface are beneficial for engineered MTJ tissue development, and MTJ‐on‐a‐chip with precise co‐culture system indicated their promising potential as in vitro musculoskeletal models for drug development and biological mechanism studies. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by bacteria, viruses, fungi, and parasites pose a significant societal challenge. In response, scientists are developing advanced technology to enhance the prevention, diagnosis, and treatment of such diseases. One such promising technology is microfluidic systems, which are utilized in organ‐on‐a‐chip systems to replicate the microenvironments of organs. These systems have potential applications in drug screening, disease modeling, and personalized medicine. This review provides an overview of recent advances in organ‐on‐a‐chip platforms and their potential for preventing and diagnosing various infections. After discussing traditional techniques employed in studying infectious diseases, the role of microfluidic platforms in detecting infections is delved in. It is expound on advanced microfluidic‐based strategies for infection diagnosis, such as the polymerase chain reaction‐based microfluidic devices, enzyme linked immunosorbent assay‐based microfluidic devices, hierarchical nanofluidic molecular enrichment systemand µWestern blotting‐based microfluidic devices, and smartphone‐based microfluidic devices. Additionally, future research challenges and perspectives are discussed on microfluidic systems in biomedical and regenerative medicine applications. Consequently, microfluidic platforms have the potential to serve as fundamental frameworks for understanding infectious diseases, thereby leading to personalized regenerative medicine. hierarchical nanofluidic molecular enrichment system [ABSTRACT FROM AUTHOR]

Elements of microfluidic systems created by 3D printing offer numerous advantages, such as rapid manufacturing, low cost, and the ability to create complex 3D channel topologies. Their parameters and performance can be quickly adjusted by editing the model loaded into the printer. However, the mechanical properties of polymers used for printing are often poorly documented and can significantly change over time due to aging, relaxation, or creep effects, leading to unexpected behaviour of 3D-printed devices. To address this issue, we performed a complete mechanical characterization of the samples made by 3D printing, including stress relaxation and creep tests, at different time intervals after printing. The determined properties of the material allowed us to model the mechanical and hydrodynamical performance of the 3D-printed microfluidic device, which we demonstrate using an example of a fully printed check valve specially developed for use in microfluidic systems. This approach allows easy quantitative evaluation of the optimal production cycle and lifetime of 3D-printed microfluidic devices. [ABSTRACT FROM AUTHOR]

The Organ-on-a-Chip is a microfluidic device designed to replicate human organ and tissue conditions. Temperature regulation is crucial for mimicking physiological processes and ensuring cellular viability in Organ-on-a-Chip platforms. This article focuses on employing system identification to mathematically model thermal regulation in a new Organ-on-a-Chip. A controlled environment box was constructed for testing, using infrared and negative temperature coeficient sensors for intrim temperature analysis. Data collected from the cell culture chamber were processed and analyzed in MATLAB®. System identification led to the selection of a transfer function, and a descriptive equation for Organ-on-a-Chip temperature was obtained. The study revealed temperature differences between ambient and culture chamber temperatures, emphasizing the importance of real-time analysis. Mathematical modeling and in silico tests play a crucial role in predicting physiological behavior, allowing complex interactions to be simulated. The obtained temperature equation can be refined and applied in various 3D models. indicating innovation in the integration of Organ-on-a-Chip in medicine and biomedical engineering. [ABSTRACT FROM AUTHOR]

Filamentous fungi and fungal-like organisms contribute to a wide range of important ecosystem functions. Evidence has shown the movement of liquid across mycelial networks in unsaturated environments, such as soil. However, tools to investigate liquid movement along hyphae at the level of the single cell are still lacking. Microfluidic devices permit the study of fungal and fungal-like organisms with cellular resolution as they can confine hyphae to a single optical plane, which is compatible with microscopy imaging over longer timescales and allows for precise control of the microchannel environment. The aim of this study was to develop a method that enables the visualization and quantification of liquid movement on hyphae of fungal and fungal-like microorganisms. For this, the fungal–fungal interaction microfluidic device was modified to allow for the maintenance of unsaturated microchannel conditions. Fluorescein-containing growth medium solidified with agar was used to track liquid transported by hyphae via fluorescence microscopy. Our key findings highlight the suitability of this novel methodology for the visualization of liquid movement by hyphae over varying time scales and the ability to quantify the movement of liquid along hyphae. Furthermore, we showed that at the cellular level, extracellular movement of liquid along hyphae can be bidirectional and highly dynamic, uncovering a possible link between liquid movement and hyphal growth characteristics. We envisage that this method can be applied to facilitate future research probing the parameters contributing to hyphal liquid movement and is an essential step for studying the phenomenon of fungal highways. [ABSTRACT FROM AUTHOR]

Inertial microfluidic devices have gained attention for point-of-need (PoN) sample preparation. Yet, devices capable of simultaneous particle-bacteria solution exchange and separation are low in throughput, hindering their applicability to PoN settings. This paper introduces a microfluidic centrifuge for high-throughput solution exchange and separation of microparticles, addressing the need for processing large sample volumes at elevated flow rates. The device integrates Dean flow recirculation and inertial focusing of microparticles within 24 curved microchannels assembled in a three-layer configuration via in-plane and out-of-plane parallelization. We studied solution exchange and particle migration using singleplex and duplex samples across devices with varying curve numbers (2-curve, 8-curve, and 24-curve). Processing 5 and 10 μm microparticles at flow rates up to 16.8 ml/min achieved a solution exchange efficiency of 96.69%. In singleplex solutions, 10 and 5 μm particles selectively migrated to inner and outer outlets, demonstrating separation efficiencies of 99.7% and 90.3%, respectively. With duplex samples, sample purity was measured to be 93.4% and 98.6% for 10 and 5 μm particles collected from the inner and the outer outlets, respectively. Application of our device in biological assays was shown by performing duplex experiments where 10 μm particles were isolated from Salmonella bacterial suspension with purity of 97.8% while increasing the state-of-the-art particle solution exchange and separation throughput by 16 folds. This parallelization enabled desirable combinations of high throughput, low-cost, and scalability, without compromising efficiency and purity, paving the way for sample preparation at the PoN in the future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most severe form of brain cancer in adults, characterized by its complex vascular network that contributes to resistance to conventional therapies. Thermal therapies, such as magnetic hyperthermia (MHT), emerge as promising alternatives, using heat to selectively target tumor cells while minimizing damage to healthy tissues. The organ-on-a-chip can replicate this complex vascular network of GBM, allowing for detailed investigations of heat dissipation in MHT, while computational simulations refine treatment parameters. In this in silico study, tumor-on-a-chip models were used to optimize MHT therapy by comparing heat dissipation in normal and abnormal vascular networks, considering geometries, flow rates, and concentrations of magnetic nanoparticles (MNPs). In the high vascular complexity model, the maximum velocity was 19 times lower than in the normal vasculature model and 4 times lower than in the low-complexity tumor model, highlighting the influence of vascular complexity on velocity and temperature distribution. The MHT simulation showed greater heat intensity in the central region, with a flow rate of 1 µL/min and 0.5 mg/mL of MNPs being the best conditions to achieve the therapeutic temperature. The complex vasculature model had the lowest heat dissipation, reaching 44.15 °C, compared to 42.01 °C in the low-complexity model and 37.80 °C in the normal model. These results show that greater vascular complexity improves heat retention, making it essential to consider this heterogeneity to optimize MHT treatment. Therefore, for an efficient MHT process, it is necessary to simulate ideal blood flow and MNP conditions to ensure heat retention at the tumor site, considering its irregular vascularization and heat dissipation for effective destruction. [ABSTRACT FROM AUTHOR]

Open microfluidic systems offer significant advantages, including the elimination of external pumps and facilitating fluid access at any point along the channel. However, their deployment in harsh environments is commonly compromised due to the delicate nature of hydrophilic chemical coatings and the vulnerability of open microchannels to clogging and contamination. Here, a bioinspired, demand-responsive mode-switchable strategy is proposed to enhance the mechanical durability of open microfluidic systems. Specifically, under harsh conditions or when long-term storage is necessary, this strategy allows the open microfluidic device to transition to a protective mode simply through releasing the strain, thereby preserving the integrity of the structure and hydrophilic coatings. The stretched open microfluidic mode enables spontaneous liquid spreading along a hydrophilic microchannel scribed by femtosecond laser. This mode-switchable strategy provides the open microfluidic device with robustness to maintain spontaneous liquid flow, even under severe testing conditions such as 2000 cycles of cotton swab rubbing, sand impact, sandpaper abrasion, tape peeling, twisting, and finger rubbing. A proof-of-concept application involving blood type analysis on this mode-switchable open microfluidic device showcases its superior mechanical durability under severe environmental conditions. The proposed strategy paves the way for the broader use of open microfluidic devices in various practical applications. [ABSTRACT FROM AUTHOR]

The study of heat and mass transfer in a Hele-Shaw cell rotating around a perpendicular axis has various advanced technological applications. These include the design of microfluidic devices and continuous-flow chemical microreactors, to name a couple. In this setup configuration, the quasi-two-dimensional design allows for recording the density field using optical methods, and the rotation enables control of this field through spatially distributed inertial forces. As is known, in the limit of an infinitely thin layer, the Coriolis force vanishes within a standard mathematical model. However, experimental observations of fluid flow in a rotating Hele-Shaw cell indicate the opposite. In this paper, we show that the correct derivation of the equation of motion under the Hele-Shaw approximation leads to the appearance of a Boussinesq-type term for the Coriolis force. To study the effect of the Coriolis buoyancy, we consider the problem of fluid stability during the internal generation of a transfer component, which can be either the concentration of the dissolved substance or the temperature of the medium. The careful study of system dynamics involves linear stability analysis, weakly nonlinear analysis, and direct numerical simulation. The general properties of the disturbance spectrum are analyzed. The branching of solutions near the first bifurcation is studied using the technique of multiple time scales. A stationary convection is replaced by an oscillatory one under the action of the Coriolis force, as demonstrated by weakly nonlinear analysis. Finally, we investigate the nonlinear dynamics using direct numerical simulation. [ABSTRACT FROM AUTHOR]

This study introduces the first experimental analysis of shear cavitation in a microscale backward-facing step (BFS) configuration. It explores shear layer cavitation under various flow conditions in a microfluidic device with a depth of 60 μm and a step height of 400 μm. The BFS configuration, with its unique characteristics of upstream turbulence and post-reattachment pressure recovery, provides a controlled environment for studying shear-induced cavitation without the complexities of other microfluidic geometries. Experiments were conducted across four flow patterns: inception, developing, shedding, and intense shedding, by varying upstream pressure and the Reynolds number. The study highlights key differences between microscale and macroscale shear cavitation, such as the dominant role of surface forces on nuclei distribution, vapor formation, and distinct timescales for phenomena like shedding and shockwave propagation. It is hypothesized that vortex strength in the shear layer plays a significant role in cavity shedding during upstream shockwave propagation. Results indicate that increased pressure notably elevates the mean thickness, length, and intensity within the shear layer. Instantaneous data analysis identified two vortex modes (shedding and wake modes) at the reattachment zone, which significantly affect cavitation shedding frequency and downstream penetration. The wake mode, characterized by stronger and lower-frequency vortices, transports cavities deeper into the channel compared to the shedding mode. Additionally, vortex strength, proportional to the Reynolds number, affects condensation caused by shockwaves. The study confirms that nuclei concentration peaks in the latter half of the shear layer during cavitation inception, aligning with the peak void fraction region. [ABSTRACT FROM AUTHOR]

The present study focuses on the unsteady flow of a viscoelastic Maxwell nanofluid with couple stress in a circular microchannel under the combined action of periodic pressure and magnetic field. The Green's function method is applied to the unsteady Cauchy momentum equation to derive the velocity field. We strive to check out the analytical solutions of the current model by validating them with existing results. In addition, the effects of several dimensionless parameters (such as the couple stress parameter γ, the Deborah number De, and the dimensionless frequency ω) on the streaming potential and the electrokinetic energy conversion (EKEC) efficiency of the three waveforms (cosine, square, and triangular) are portrayed via graphical illustrations. Within the range of parameters chosen in this study, the results demonstrate that increasing the value of the Deborah number or decreasing the dimensionless frequency can effectively enhance the streaming potential. The velocity field and EKEC efficiency are improved with increasing couple stress parameters. Furthermore, our investigation is extended to compare the EKEC efficiency for square and triangular waveforms when the couple stress parameters are set to 20 and 40, respectively. The results also indicate that increasing the couple stress parameter significantly improves the EKEC efficiency, particularly in the context of the square waveform. These findings will provide valuable assistance in the design of periodic pressure-driven microfluidic devices. [ABSTRACT FROM AUTHOR]

In this study, a novel approach for enhancing the rapid spreading of free liquid film on lithium niobate (LiNbO3) substrate under megahertz (MHz) surface acoustic wave (SAW) excitation is presented by treating it with surfactants. Through the design of a specific interdigital transducer structure, it was discovered that exciting the SAW at a frequency of 32.3 MHz can achieve optimal spreading performance for water droplets on the surface of surfactant-treated LiNbO3 substrate. The maximum average velocity reaches 1.76 mm/s at position P2 = 1250 μm in the water film front, and the stable film spreading speed shows a 204.9% increase compared to the existing research. Simultaneously, through the investigation of the spreading experiment phenomenon of silicone oil and de-ionized water droplets at varying frequencies, we have discovered the dynamic mechanism of "reverse phase" propagation in liquid film for the first time. This entails that the advancing edge of the wetting film demonstrates a spreading motion law that is opposite to the traditional spreading phenomena, with the spreading velocity in the central exceeding that on both sides. Our research demonstrates that this microfluidic device developed by SAWs enhances the spreading efficiency of the free films, enabling rapid expansion of the target liquid to form a high-surface area film layer. This advancement holds promise for overcoming the limitations of low sensitivity and short response time in the field of rapid pathological diagnosis in contemporary medicine. [ABSTRACT FROM AUTHOR]

In this article, the role of slip-dependent (SD) zeta potential in the hydrodynamic characteristics of mixed electromagnetohydrodynamic (EMHD) and electroosmotic driven flow of couple stress fluid within a rotating microfluidic channel is theoretically investigated. This work is the first to analyze the hydrodynamic characteristics of slip-independent (SI) and slip-dependent (SD) zeta potentials in a rotating microchannel including a detailed analysis of Ekmann spirals in the microchannel. Ekmann spirals show the effect of rotational flow caused by different parameters, particularly, the slip parameter and the Hartmann number being the most significant ones. Ekmann plot variations, observed under both SI and SD model cases, show a significant effect on rotating flow dynamics. The effect of pertinent parameters on the rotational flow velocity, centerline velocity, and volumetric flow rate is graphically depicted. The findings of this research reveal that the SD zeta potential plays a crucial role in determining the rotating flow velocity and volume flow transport. The normalized transverse centerline in the magnitude flow velocity increases with the couple stress parameter and decreases with the slip parameter for both SI and SD model cases. Notably, the magnitude of the normalized transverse flow rate increases with rotational parameter values. In contrast, it decreases with an increase in the slip parameter under the SD model case. The outcomes of this study can be directly used in applications like transportation of biofluid models in Lab-On-a-Chip (LOC) devices and microfluidic systems under certain conditions. [ABSTRACT FROM AUTHOR]

This study provides a critical understanding of controlling solute distribution in microfluidic systems by examining the effects of symmetric and asymmetric zeta potentials under magnetohydrodynamic (MHD) pulsatile electroosmotic flow. These findings are vital for enhancing the efficiency of microfluidic devices used in lab-on-a-chip applications. The aim of this study is to explore the modulation of solute transport in MHD pulsatile electroosmotic microchannel flow, focusing on both symmetric and asymmetric wall zeta potentials. Using the Debye–Hückel approximation, the Poisson–Boltzmann equation is obtained. Subsequently, the convection–diffusion equation is solved using the velocity profile, with Aris's method of moments to derive the moment equations. These equations are then solved using a finite difference scheme. The mean concentration is calculated employing Hermite polynomials. We examined the effects of key parameters such as the electroosmotic parameter (κ), the Hartmann number (Ha), and zeta potentials on the dispersion coefficient (DT), mean concentration distribution (Cm), skewness, and kurtosis. We consider three situations: symmetric ( ζ 1 = ζ 2 ), partially asymmetric ( ζ 1 = 1.0 , ζ 2 = 0.0), and fully asymmetric ( ζ 1 = 1.0 , ζ 2 = − 1.0) zeta potentials. Our results reveal that asymmetric zeta potentials lead to faster dispersion, with DT decreasing with increasing κ for symmetric potentials and increasing for asymmetric ones. As the Hartmann number increases, dispersion decreases for both symmetric and asymmetric zeta potentials while the peak of mean concentration rises. The mean concentration profile exhibits Gaussian behavior at both small and large times, with anomalous behavior in the intermediate region. For symmetric zeta potentials, Gaussianity is observed at t = 0.001 in the diffusive regime and at t = 10.0 in Taylor's regime, while for asymmetric potentials, Gaussianity occurs at t = 0.03 and t = 3.0, indicating that large-time Gaussian behavior is approximately 3.33 times faster and dispersion becomes transient for asymmetric potentials. [ABSTRACT FROM AUTHOR]

A theoretical and numerical investigation of electrokinetic flow is performed in a nanochannel with the charged symmetric corrugated surfaces. The perturbation and numerical solutions of electrokinetic flow variables are given, and the effects of corrugation geometry, such as wave amplitude and wave number, on the electrokinetic flow characteristics are systematically examined. The results show that the electrokinetic flow recirculation may occur easily at wave crest due to the electroviscous effect. The velocity profile is strongly dependent on wave number, but the maximum or minimum velocity may be insusceptible to wave number. Furthermore, the distributions of streaming potential and energy conversion efficiency are also investigated. We find that, for some special geometry of corrugations, the streaming current and conversion efficiency obtained from the present corrugated nanochannel are higher than that from the smooth nanochannel. Specially, when the dimensionless wave number is 0.5/π, the magnitude of streaming potential is enhanced about 29% at δ = 0.5 and the peak value of conversion efficiency is enhanced about 2% at δ = 0.1. We believe that the optimal corrugation geometry parameters can be of benefit in designing a microfluidic device with higher streaming current and conversion efficiency. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have recently been used as nanocarriers in drug delivery systems for nucleic acid drugs. Their practical applications are currently primarily limited to the liver and specific organs. However, altering the type and composition ratio of phospholipids improves their distribution in organs other than the liver, such as the spleen and lungs. This study aimed to elucidate the effects of LNP components and particle size on in vivo distribution through systemic circulation to pancreatic islets to achieve better targeting of islets, which are a fundamental therapeutic target for diabetes. Fluorescence-labeled LNPs were prepared using three phospholipids: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), with particle sizes of 30–160 nm (diameter) using a microfluidic device. Baffled-structured iLiNP devices with adjusted flow-rate ratios and total flow rates were used. After the intravenous administration of LNPs to C57BL/6 J mice, the distribution of each LNP type to the major organs, including the pancreas and pancreatic islets, was compared using ex vivo fluorescence imaging and observation of pancreatic tissue sections. DSPC-LNPs- and DOPE-LNPs showed the highest distribution in the spleen and liver, respectively. In contrast, the DOPC-LNPs showed the highest distribution in the pancreas and the lowest distribution in the liver and spleen. In addition, smaller particles showed better distribution throughout the pancreas. The most significant LNP distribution in the islets was observed for DOPC-LNPs with a particle size of 160 nm. Furthermore, larger LNPs tended to be distributed in the islets, whereas smaller LNPs tended to be distributed in the exocrine glands. DOPC-LNPs were distributed in the islets at all cholesterol concentrations, with a high distribution observed at >40% cholesterol and > 3% PEG and the distribution was higher at 24 h than at 4 h. Thus, LNP composition and particle size significantly affected islet distribution characteristics, indicating that DOPC-LNPs may be a drug delivery system for effectively targeting the pancreas and islets. [Display omitted] • DOPC-LNP showed higher distribution in the pancreas. • Larger particle size showed higher distribution in islets. • Higher cholesterol content showed higher distribution in islets. • Higher DSG-PEG content showed higher distribution in islets. • Larger PEG-modified DOPC-LNPs are suitable drug delivery carriers to islets. [ABSTRACT FROM AUTHOR]

Pumping fluid is one of the crucial parts of any microfluidic system. Using electric and magnetic fields as a substitute for moving parts can have many advantages. In this study hydrodynamic and heat transfer characteristics of electroosmotic flow under influence of lateral electric and transverse magnetic field, are studied numerically. Results indicate that the dimensionless parameters such as Hartmann number, intensity of the lateral electric field, pressure gradient parameter and aspect ratio have an important role in controlling flow. It can be implied that the enhancement of pressure gradient leads to the decrease of critical Hartmann number, and this dependency can be reduced from 44% to 7% for S = 0:5 to S = 50 in two pressure gradients of = 1 and = 20. In addition, the reduction of aspect ratio of microchannel section leads to the increment of critical Hartmann number in a specified lateral electric field. At the end, thermal analysis is being done by consideration of the effects of magnetic and electric fields on the Nusselt number. [ABSTRACT FROM AUTHOR]

Additive manufacturing methods give the opportunity to produce interesting, new structures with a more complicated topology than would be possible using traditional methods. Using the selective laser sintering method, a disk with a high roughness and porous structure was produced. Studies of material surface were performed on microscopic devices. An in vitro experiment was performed on the manufactured disk using mice fibroblastic cells. The designed shape enabled the growth of the cell culture in the disc pores and ensured impermeability of the disc base. On the basis of the average viability of 79%, which is close to reference well (80%), preliminary results confirmed that the manufactured structures create sufficiently comfortable conditions for the cell cultures without the need to design their internal topography. Controlling the production parameters of SLS printing allows obtaining the structures characterized by spatial and surface porosity without designing inner geometry of the structure. Polyamide 2200 (PA2200) powder with a laser beam, offers new possibilities for producing surfaces used in the tissue engineering, bioreactors, and microfluidics devices. [ABSTRACT FROM AUTHOR]

Janus particles are popular in recent years due to their anisotropic physical and chemical properties. Even though there are several established synthesis methods for Janus particles, microfluidics-based methods are convenient and reliable due to low reagent consumption, monodispersity of the resultant particles and efficient control over reaction conditions. In this work a simple droplet-based microfluidic technique is utilized to synthesize magnetically anisotropic TiO2-Fe2O3 Janus microparticles. Two droplets containing reagents for Janus particle were merged by using an asymmetric device such that the resulting droplet contained the constituents within its two hemispheres distinct from each other. The synthesized Janus particles were observed under the optical microscope and the scanning electron microscope. Moreover, a detailed in vitro characterization of these particles was completed, and it was shown that these particles have a potential use for biomedical applications. [ABSTRACT FROM AUTHOR]

Microfluidic-based point-of-care diagnostics offer several unique advantages over existing bioanalytical solutions, such as automation, miniaturisation, and integration of sensors to rapidly detect on-site specific biomarkers. It is important to highlight that a microfluidic POC system needs to perform a number of steps, including sample preparation, nucleic acid extraction, amplification, and detection. Each of these stages involves mixing and elution to go from sample to result. To address these complex sample preparation procedures, a vast number of different approaches have been developed to solve the problem of reagent storage and delivery. However, to date, no universal method has been proposed that can be applied as a working solution for all cases. Herein, both current self-contained (stored within the chip) and off-chip (stored in a separate device and brought together at the point of use) are reviewed, and their merits and limitations are discussed. This review focuses on reagent storage devices that could be integrated with microfluidic devices, discussing further issues or merits of these storage solutions in two different sections: direct on-chip storage and external storage with their application devices. Furthermore, the different microvalves and micropumps are considered to provide guidelines for designing appropriate integrated microfluidic point-of-care devices. [ABSTRACT FROM AUTHOR]

This study investigates the fabrication of 3D-printed microfluidic devices for solid/liquid separation, focusing on additive manufacturing technologies. Stereolithography (SLA) and fused filament fabrication (FFF) were used to create microseparators with intricate designs optimized for separation efficiency. Model suspensions containing quartz sand, nano-calcium carbonate, and talc-based baby powder in water were prepared using an electric magnetic stirrer and conveyed into the microseparator via a peristaltic pump. Different flow rates were tested to evaluate their influence on the separation efficiency. The highest separation efficiency for the model systems was observed at a flow rate of 200 mL min−1. This was due to the increased turbulence at higher flow rates, which hindered the secondary flow perpendicular to the primary flow direction. The particle size distribution before and after separation was analyzed using sieve and laser diffraction, and particle morphology was inspected by scanning electron microscopy. The laser diffraction analysis revealed post-separation particle size distributions, indicating that Outlet 1 (external stream) consistently captured larger particles more effectively than Outlet 2 (internal stream). This work highlights the potential of additive manufacturing to produce customized microfluidic devices, enabling rapid prototyping and fine-tuning of complex geometries, thus enhancing separation efficiency across various industrial applications. [ABSTRACT FROM AUTHOR]

Gastrointestinal cell culture technology has evolved in the past decade with the integration of microfluidic technologies, bringing advantages with greater selectivity and cost effectiveness. Herein, these technologies are sorted into three categories, namely the cell-culture insert devices, conventional microfluidic devices, and 3D-printed microfluidic devices. Each category is discussed in brief with improvements also discussed here. Introduction of different companies and applications derived from each are also provided to encourage uptake. Subsequently, future perspectives of integrating microfluidics with trending topics like stool-derived in vitro communities and gut–immune–tumor axis investigations are discussed. Insights on modular microfluidics and its implications on gastrointestinal cell cultures are also discussed here. Future perspectives on point-of-care (POC) applications in relations to gastrointestinal microfluidic devices are also discussed here. In conclusion, this review presents an introduction of each microfluidic platform with an insight into the greater contribution of microfluidics in gastrointestinal cell cultures. [ABSTRACT FROM AUTHOR]

The rapid and sensitive detection of bacterial contaminants using low-cost and portable point-of-need (PoN) biosensors has gained significant interest in water quality monitoring. Cell-imprinted polymers (CIPs) are emerging as effective and inexpensive materials for bacterial detection as they provide specific binding sites designed to capture whole bacterial cells, especially when integrated into PoN microfluidic devices. However, improving the sensitivity and detection limits of these sensors remains challenging. In this study, we integrated CIP-functionalized stainless steel microwires (CIP-MWs) into a microfluidic device for the impedimetric detection of E. coli bacteria. The sensor featured two parallel microchannels with three-electrode configurations that allowed simultaneous control and electrochemical impedance spectroscopy (EIS) measurements. A CIP-MW and a non-imprinted polymer (NIP)-MW suspended perpendicular to the microchannels served as the working electrodes in the test and control channels, respectively. Electrochemical spectra were fitted with equivalent electrical circuits, and the charge transfer resistances of both cells were measured before and after incubation with target bacteria. The charge transfer resistance of the CIP-MWs after 30 min of incubation with bacteria was increased. By normalizing the change in charge transfer resistance and analyzing the dose–response curve for bacterial concentrations ranging from 0 to 107 CFU/mL, we determined the limits of detection and quantification as 2 × 102 CFU/mL and 1.4 × 104 CFU/mL, respectively. The sensor demonstrated a dynamic range of 102 to 107 CFU/mL, where bacterial counts were statistically distinguishable. The proposed sensor offers a sensitive, cost-effective, durable, and rapid solution for on-site identification of waterborne pathogens. [ABSTRACT FROM AUTHOR]

Lactate is a critical regulatory factor secreted by tumors, influencing tumor development, metastasis, and clinical prognosis. Precise analysis of tumor-cell-secreted lactate is pivotal for early cancer diagnosis. This study describes a paper-based microfluidic chip to enable the detection of lactate levels secreted externally by living cells. Under optimized conditions, the lactate biosensor can complete the assay in less than 30 min. In addition, the platform can be used to distinguish lactate secretion levels in different cell lines and can be applied to the screening of antitumor drugs. Through enzymatic chemical conversion, this platform generates fluorescent signals, enabling qualitative assessment under a handheld UV lamp and quantitative analysis via grayscale intensity measurements using ImageJ (Ver. 1.50i) software. The paper-based platform presented in this study is rapid and highly sensitive and does not necessitate other costly and intricate instruments, thus making it applicable in resource-constrained areas and serving as a valuable tool for investigating cell lactate secretion and screening various anti-cancer drugs. [ABSTRACT FROM AUTHOR]

Loop-mediated isothermal amplification (LAMP) has attracted significant attention for rapid and accurate point-of-care diagnostics. However, integrating sample introduction, lysis, amplification, and detection steps into an easy-to-use, disposable system has so far been challenging. This has limited the uptake of the technique in practical applications. In this study, we developed a colourimetric one-step LAMP assay that combines thermolysis and LAMP reaction, to detect the SARS-CoV-2 virus in nasopharyngeal swab samples from COVID-19-infected individuals. The limit of detection was 500 copies per reaction at 65 °C for 25 min in reaction tubes. Additionally, we developed a finger-operated capillary-driven microfluidic device with selective PVA coating. This finger-actuated microfluidic device could self-dose the required sample amount for the LAMP reaction and inhibit sample evaporation. Finally, we integrated the LAMP assay into the microfluidic device by short-term pre-storage of the LAMP master mix. Using this device, nasopharyngeal swab samples from COVID-19-infected individuals showed positive results at a reaction time of 35 min at 65 °C. This integrated device may be adapted to detect other RNA viruses of interest rapidly. [ABSTRACT FROM AUTHOR]

The reversible bonding of microfluidic chips has been developing rapidly with the requirement of reusable microfluidic devices or the need to obtain the samples inside the chip. Traditional bonding methods for polymer‐based microfluidics, e.g., thermal bonding, permanently attach the substrate and cover plate. Sometimes, once the chip flow channel is blocked, it is difficult to clean and affect the reusability of the chip. This study proposes a new reversible bonding method for poly (methyl methacrylate) (PMMA) microfluidic chips with the help of stretch release adhesive strips. The designed microchannels were fabricated on the surface of PMMA plates using CO2 laser irradiation. Then, stretch release adhesive strips were used as an intermediate layer between the substrate (with microchannels) and another flat PMMA/PS/PC plate to seal the microchannel. The assembled chip sets were bonded at room temperature with bonding strength comparable with other permanent bonding methods. Experimental results show that simply pulling the adhesive layer by applying a shear force can easily detach the intermediate adhesive layer from both the substrate and cover plate to separate the bonded chipset. The proposed reversible bonding method is simple, rapid and has low residue and high bonding strength. Bacterial culture experiments were also conducted to verify the biocompatibility of the proposed bonding method. The proposed reversible bonding technique can be used for polymer‐based microfluidic devices that require sample recovery or chip reuse. Highlights: The stretch release adhesive strip can provide high bond strength.It allows easy peeling for reversible bonding.It bonds at room temperature with simple operation.It has good transparency for easy observation of experiments.It has good biocompatibility. [ABSTRACT FROM AUTHOR]

Metal micro-droplet ejection technology has attracted attention for its potential applications in the rapid prototyping of micro-metal parts and microelectronic packaging. The current micro-droplet ejection device developed based on this technology faces challenges such as the requirement of a micro-oxygen ejection environment, a complex feeding structure, and high costs. Therefore, a drop-on-demand droplet generator for metallic pellets with impact feed ejection is designed in this paper. This device has a simple and compact structure, does not require a high-cost heat source, and can perform drop-on-demand ejection of metallic pellets in an atmospheric environment. A micro-channel feeding method based on piezoelectric ceramic actuator drives is proposed. A rigid dynamics metallic pellet flight trajectory model is established to analyze the relationships between the driving voltage and the flight trajectory of the pellets. With the help of Fluent to simulate and analyze the melting and ejection processes of the pellets inside the nozzle, the changes in the variable parameters of the flow field in the process of the melting and flight of a single molten drop are studied. The droplet generator produces stable droplets with a 500 µs pulse width and 1100 mm/s initial velocity of the projectile. The simulation results show that a single projectile has to go through three stages including feeding, melting, and ejecting, which take 39.5 ms, 7.85 ms, and 17.65 ms. The total simulation time is 65.0 ms. It is expected that the injection frequency of the metal projectile droplet-generating device will reach 15 Hz. [ABSTRACT FROM AUTHOR]

This review explores significant advancements in polymer science and fabrication processes that have enhanced the performance and broadened the application scope of microfluidic devices. Microfluidics, essential in biotechnology, medicine, and chemical engineering, relies on precise fluid manipulation in micrometer-sized channels. Recent innovations in polymer materials, such as flexible, biocompatible, and structurally robust polymers, have been pivotal in developing advanced microfluidic systems. Techniques like replica molding, microcontact printing, solvent-assisted molding, injection molding, and 3D printing are examined, highlighting their advantages and recent developments. Additionally, the review discusses the diverse applications of polymer-based microfluidic devices in biomedical diagnostics, drug delivery, organ-on-chip models, environmental monitoring, and industrial processes. This paper also addresses future challenges, including enhancing chemical resistance, achieving multifunctionality, ensuring biocompatibility, and scaling up production. By overcoming these challenges, the potential for widespread adoption and impactful use of polymer-based microfluidic technologies can be realized. [ABSTRACT FROM AUTHOR]

Lab-on-a-Chip microfluidic devices present an innovative and cost-effective platform in the current trend of miniaturization and simplification of imaging flow cytometry; they are excellent candidates for high-throughput single-cell analysis. In such microfluidic platforms, cell tracking becomes a fundamental tool for investigating biophysical processes, from intracellular dynamics to the characterization of cell motility and migration. However, high-throughput and long-term cell tracking puts a high demand on the consumption of computing resources. Here, we propose a novel strategy to achieve rapid 3D cell localizations along the microfluidic channel. This method is based on the spatiotemporal manipulation of recorded holographic interference fringes, and it allows fast and precise localization of cells without performing complete holographic reconstruction. Conventional holographic tracking is typically based on the phase contrast obtained by decoupling the calculation of optical axial and transverse coordinates. Computing time and resource consumption may increase because all the frames need to be calculated in the Fourier domain. In our proposed method, the 2D transverse positions are directly located by morphological calculation based on the hologram. The complex-amplitude wavefronts are directly reconstructed by spatiotemporal phase shifting to calculate the axial position by the refocusing criterion. Only spatial calculation is considered in the proposed method. We demonstrate that the computational time of transverse tracking is only one-tenth of the conventional method, while the total computational time of the proposed method decreases up to 54% with respect to the conventional approach. The proposed approach can open the route for analyzing flow cytometry in quantitative phase microscopy assays. [ABSTRACT FROM AUTHOR]

We developed an unconventional seed-mediated in situ synthetic method, whereby gold nanostars are formed directly on the internal walls of microfluidic reactors. The dense plasmonic substrate coatings were grown in microfluidic channels with different geometries to elucidate the impacts of flow rate and profile on reagent consumption, product morphology, and density. Nanostar growth was found to occur in the flow-limited regime and our results highlight the possibility of creating shape gradients or incorporating multiple morphologies in the same microreactor, which is challenging to achieve with traditional self-assembly. The plasmonic-microfluidic platforms developed herein have implications for a broad range of applications, including cell culture/sorting, catalysis, sensing, and drug/gene delivery.

Background: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. Methods: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. Results: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1–55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022). Conclusions: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

Algal growth depends strongly on phosphorus (P) as a key nutrient, underscoring the significance of monitoring P levels. Algal species display a sensitive response to fluctuations in P availability, notably through the expression of alkaline phosphatase (AP) when challenged with P-depletion. As such, alkaline phosphatase activity (APA) serves as a valuable metric for P availability, offering insights into how algae utilize and fix available P resources. However, current APA quantification methods lack single cell resolution, while also being time- and reagent consuming. Microfluidics offers a promising cost-effective solution to these limitations, providing a platform for precise single-cell analysis. In this study, a trap-based microfluidic device was integrated with a commercially available AP live stain to study the single cell APA response of a model algae strain, Chlamydomonas reinhardtii, when exposed to different exogenous P levels. A three-step culture-starve-spike process was used to induce APA in cells cultured under two different basal P levels (1 and 21 mM). When challenged with different spiked P levels (ranging from 0.1–41 mM), C. reinhardtii cells demonstrated a highly heterogeneous APA response. Two-way ANOVA confirmed that this response is influenced by both spiked and basal P levels. Utilizing an unsupervised machine learning approach (HDBSCAN), distinct subpopulations of C. reinhardtii cells were identified exhibiting varying levels of APA at the single-cell level. These subpopulations encompass significant groups of individual cells with either notably high or low APA, contributing to the overall behavior of the cohorts. Considerable intrapopulation differences in APA were observed across cohorts with similar average behavior. For instance, while some cohorts exhibited a concentrated distribution around the overall average APA, others displayed subpopulations dispersed across a wider range of APA levels. This underscores the potential bias introduced by analyzing a small number of cells in bulk, which may skew results by overrepresenting extreme behavioral subpopulations. The findings if this study highlight the need for analytical approaches that account for single cell heterogeneity in APA and demonstrate the utility of microfluidics as a well-suited means for such investigations. This study illuminates the complexities of APA regulation at the single cell level, providing crucial insights that advance our understanding of algal phosphorus metabolism and environmental responses. [ABSTRACT FROM AUTHOR]

The emergence of microfluidic devices integrated with nanostructures enables highly efficient, flexible and controllable biosensing, among which zinc oxide (ZnO) nanostructure-based fluorescence detection has been demonstrated to be a promising methodology due to its high electrical point and unique fluorescence enhancement properties. The optimization of microfluidic synthesis of ZnO nanostructures for biosensing on chip has been in demand due to its low cost and high efficiency, but still the flow-induced growth of ZnO nanostructures is not extensively studied. Here, we report a simple and versatile strategy that could manipulate the local flow field by creating periodically arranged micropillars within a straight microchannel. We have explored the effects of perfusion speed and flow direction of seed solution, localized flow variation of growth solution and growth time on the morphology of nanostructures. This provided a comprehensive understanding which governs nanostructure fabrication controlled by flow. The results demonstrated that localized flow in microfluidic devices was essential for the initiation and growth of zinc oxide crystals, enabling precise control over their properties and morphology. Furthermore, a model protein was used to demonstrate the intrinsic fluorescence enhancement of ZnO nanostructures as an example to reveal the morphology-related enhancement properties. [ABSTRACT FROM AUTHOR]