搜索结果：Lab on a chip

Osteocytes form an extensive dendritic network within bone tissue that senses mechanical and biochemical stimuli, critical for bone homeostasis. However, the complex interplay between mechanotransduction, oxygen tension, and osteocyte differentiation remains difficult to study due to the lack of physiologically relevant humanin vitromodels. Previously, we developed a microphysiological system (MPS) that integrates perfusion, mechanical loading, and oxygen control within a culture platform that enables the culture of bone-like three-dimensional (3D) constructs [1]. Here, we demonstrate the application of this MPS as Bonoid-on-a-chip (BoC)-platform to investigate osteoblast-to-early osteocyte transition and mechanosensitive signalling in a human-relevant 3D context, under different physical and chemical conditions. We generated bonoids by bioprinting primary human osteoblasts into a gelatine-hydrogel and cultured them under either static conditions or as dynamic BoC. Different BoC environments consisting in controlled perfusion (0.5 ml min-1), mechanical loading (0% or 10% compression, 1 Hz frequency), and physiological oxygen tension (21% or 12%) over a seven-day period were compared. These different models were additionally treated with dexamethasone (DEXA), to evaluate early osteocyte-targeted effects of drug exposure under these different conditions. We observed high cell viability across all conditions, but clear differences in metabolic activity, morphological changes, and mechanotransduction markers between static and dynamic cultures. Notably, cells within the BoC-platform exhibited extended dendritic processes and significantly increased secretion of prostaglandin E2 and nitrite in response to mechanical stimulation - hallmarks of osteocytic signalling in mechanotransduction. When testing the new BoC as platform for early osteocyte-targeted investigations, we found DEXA exposure disrupting this mechanoresponsive phenotype, highlighting the model's applicability for pharmacological screening. These findings demonstrate the value of our BoC-platform as a human-relevant model for studying bone mechanobiology and drug responsesin vitro. This approach offers a promising alternative to animal models in bone research and opens new avenues for investigating osteocyte function under physiologically dynamic conditions.

Brucellosis and echinococcosis are highly prevalent in pastoral areas, and traditional detection methods are limited because they are labor intensive, time consuming, and can only detect single-pathogens. This study aims to develop a magneto-immunofluorescent microfluidic chip for the rapid and simultaneous detection of serum antibodies against both brucellosis and echinococcosis and verify the detection performance and clinical application potential of the chip. In this study, a magneto-immunofluorescent microfluidic chip was designed, fabricated and optimized, with a focus on the conjugation ratios of Echinococcus/Brucella antigens/antibodies to microspheres and the binding ratios of samples to fluorescent microspheres. The 2D/3D structures of the chip were verified via computational fluid dynamics simulation, and the core detection performance of the chip (linear range, limit of detection (LOD), precision, and specificity) was validated using positive sera and reference materials. The detection consistency between the chip and the clinical enzyme-linked immunosorbent assay (ELISA) was evaluated by coincidence rate, Kappa test, and Bland-Altman analysis. The technical advantages and limitations of the chip were then summarized. The chip stably and reliably detected eight target antibodies (AgB IgG, Ag5 IgG, Em2 IgG, Em18 IgG, LPS IgM, LPS IgG, OMP25 IgM, OPM25 IgG), with all key performance indicators meeting clinical requirements. It showed high consistency with ELISA: the positive and negative coincidence rates of all target antibodies exceeded 90%, Em18 IgG and LPS IgG achieved 100% positive coincidence rate, and Em18 IgG also had 100% negative coincidence rate; Kappa values ranged from 0.88 to 0.98 (far higher than the 0.75 threshold for good consistency), and more than 90% of samples fell within the 95% confidence interval in Bland-Altman analysis. Compared with ELISA, the chip had advantages of being a "one-chip multi-test", with low sample consumption, rapid detection, and simple operation, suitable for on-site screening in pastoral areas. The magneto-immunofluorescent microfluidic chip developed in this study enables the rapid and simultaneous detection of antibodies against brucellosis and echinococcosis, featuring excellent detection performance and high consistency with the gold standard method. This chip is expected to provide critical technical support for the early diagnosis, epidemiological surveillance, and precise prevention and control of both brucellosis and echinococcosis, thereby improving public health and preventing economic losses in the animal husbandry industry in high-prevalence regions of these two diseases.

The lymphatic system is essential for fluid homeostasis and immune surveillance, yet its role in skeletal regeneration remains poorly defined. Here, we introduce a biomimetic organ-on-a-chip (OoC) model that recapitulates lymphatic endothelial cell (LEC) behavior under precisely controlled flow-mediated environments and elucidates their regulatory contribution in alveolar bone repair. Under flow-mediated shear stress, LECs exhibited enhanced sprouting, forming lumenized lymphatic structures in vitro. Furthermore, conditioned medium from perfused LECs significantly promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Mass spectrometry identified WISP1 as a key mechanoresponsive secreted factor with high levels in LECs that activated canonical Wnt signaling in BMSCs, thus contributing to enhanced osteogenic marker expression and mineralization. In vivo validation using a murine molar extraction model with controlled occlusal loading revealed that occlusal loading promoted lymphangiogenesis and accelerated alveolar bone regeneration, accompanied by elevated WISP1 expression within alveolar sockets. Conversely, pharmacological suppression of lymphatic expansion through MAZ51 administration impaired bone formation while reducing WISP1 levels, thereby confirming the functional contribution of lymphatic vessels in alveolar bone regeneration. Together, these findings demonstrate that LECs function as mechanoresponsive regulators that transduce shear-related cues into osteoinductive signals through WISP1-mediated paracrine communication. Our study uncovers a previously unrecognized lymphatic-osteogenic signaling axis and establishes a physiologically relevant OoC platform for systematic investigation of lymphatic mechanotransduction in bone regeneration.

Two dynamic lung-on-a-chip co-culture models were developed to recreate the airway-vascular interface by incorporating primary airway epithelial and pulmonary microvascular endothelial cells. One model uses commercially available cells from healthy donors, whereas the other employs cells derived from patients with chronic obstructive pulmonary disease (COPD), enabling direct comparison of healthy and diseased conditions under identical culture conditions. Both models support epithelial differentiation under continuous perfusion and air-liquid interface (ALI) conditions, resulting in a physiologically relevant epithelial barrier supported by an underlying endothelial layer. The workflow includes extracellular matrix coating, cell seeding, ALI establishment, barrier function assessment, cell phenotyping, and cell type-specific RNA extraction. Permeability assays demonstrated robust barrier integrity in both systems, while immunofluorescence confirmed continuous localization of Zonula Occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) at cell junctions. Epithelial differentiation was confirmed by β-tubulin IV staining and visualization of ciliary beating. High-quality RNA was obtained separately from each compartment, supporting cell type-specific molecular analyses. The COPD model recapitulated key features of the disease, notably enhanced mucus production, without compromising barrier function or cell viability. The use of patient-derived epithelial and endothelial cells preserves individual pathological characteristics, enabling investigation of intercellular mechanisms in COPD. This approach provides a physiologically relevant alternative to static in vitro and animal models and supports preclinical studies of inhaled drugs, pathogen exposure, and epithelial-endothelial interactions. Importantly, the healthy and COPD lung-on-a-chip models can be used either in combination for direct comparative studies or independently for mechanistic investigations, therapeutic testing, and drug discovery. The system can also be adapted to other respiratory conditions involving altered epithelial or endothelial compartments, offering a versatile and translational platform for respiratory research.

Reconfigurable robotic systems have emerged as platforms for particle manipulation owing to their adaptability and capability to alter structural configurations according to task requirements. However, achieving programmable particle capture, transportation, and release through cooperative interactions among untethered robots within microfluidic environments remains challenging. In the present study, reconfigurable cilia-based magnetic millirobots (CMMRs) were developed for cooperative particle manipulation through programmable assembly. The platform consisted of multiple CMMRs that were independently actuated using an electromagnetic coil array and assembled into a cooperative structure possessing a central cavity for particle confinement. Through sequential electromagnetic coil activation and pulse-width modulation-based control, programmable assembly, transportation, and disassembly of the CMMRs were achieved. During assembly, self-organization analysis demonstrated that the constituent CMMRs converged toward this configuration, enabling formation of the cooperative structure needed. Subsequently, particle transportation experiments demonstrated the confinement and transportation of particles along predefined trajectories, with trajectory deviations maintained below 5%. Furthermore, μPIV characterization revealed that the assembled structure generated a directional transport corridor with a flow velocity of 4.5 mm s-1, providing a hydrodynamic environment for particle transportation compared with individual CMMRs. The demonstrated capabilities can serve as a foundation for reconfigurable untethered robotic systems capable of microhandling operations in lab-on-a-chip environments.

Tricalcium silicate (TCS) is a clinically established calcium silicate-based material. However, its highly alkaline hydration environment limits cellular compatibility. This study investigated whether direct incorporation of phosphate solution during TCS hydration promotes calcium-deficient hydroxyapatite (CDHAp) formation, modulates solution chemistry, and enhances osteogenic biological responses. TCS was mixed with KH2PO4 solutions at 0, 5, 10, 15, and 20 wt% (TP0-TP20) at a fixed liquid-to-powder ratio. Crystalline phase evolution was characterised by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) after simulated body fluid (SBF) immersion for up to 28 days. Surface morphology was examined by scanning electron microscopy (SEM). Solution pH, solubility, and ion release (Ca2+, Si4+, PO43-) were quantified by ICP-OES. Osteogenic gene expression (RUNX2, OSX, COL1A1, OPN) was evaluated in MC3T3-E1 pre-osteoblasts by RT-qPCR. Cell viability and migration under physiological perfusion were assessed using a custom microfluidic Lab-on-a-Chip system. XRD and XPS confirmed concentration-dependent CDHAp formation in TP15 and TP20 from day 1, with peak intensity increasing progressively through day 28. TP0 showed CDHAp formation was insufficient to be clearly detected by XRD. Higher phosphate content progressively reduced solution pH and suppressed free Ca2+ accumulation, maintaining levels within 2-6 mM at early time points while elevating Si4+ release. TP15 and TP20 significantly upregulated RUNX2, OSX, and COL1A1 compared with TP0 (p < 0.05). Under microfluidic system, TP0 supported no viable cells, whereas TP20 demonstrated directional cell migration toward the specimen surface. Incorporating phosphate solution during TCS hydration accelerates CDHAp crystallisation, moderates excessive alkalinity, and enhances early osteogenic differentiation and cell migration under flow. These findings establish phosphate-modified TCS as a strategy to enhance HAp formation with enhanced chemical and biological properties.

The accurate assessment of the gastrointestinal fate of functional food ingredients is critical for substantiating health benefits. However, conventional in vitro models do not fully capture the dynamic, multicellular, and physicochemical environment of the human intestine, creating a predictive gap. Microfluidic gut-on-a-chip (GOC) technology provides a microphysiological approach by integrating fluid flow, mechanical cues, and multicellular co-cultures into a controllable biomimetic platform. This review critically examines the potential applications of GOC systems in evaluating food bioactives. We first summarize core design principles, including biomimetic architecture, material selection, mechanical stimulation, shear stress, and oxygen or chemical gradient control. We then discuss their applications in sequential digestion, intestinal absorption, barrier assessment, host-microbiota interactions, disease-specific modeling, and personalized nutrition. We provide a balanced analysis of the advantages and limitations of GOC systems, with emphasis on physiological relevance in selected contexts, real-time monitoring, material-related analytical bias, biological variability, throughput, standardization, regulatory acceptance, and industrial scalability. Finally, we discuss three application-oriented pathways for food-industry translation: high-throughput screening platforms, personalized formulation testing, and multi-organ microphysiological systems for systemic efficacy and safety assessment. As the field matures, GOC technology may serve as a supportive tool for evidence-based functional food development by bridging conventional in vitro assays and human intervention studies.

Wearable sweat sensors offer a promising technical approach for real-time personal health management due to their non-invasive, in situ, and continuous monitoring capabilities. This study presents a novel wearable non-enzymatic electrochemical sensor based on a PEDTM/rGO/AuNPs composite for continuous and non-invasive monitoring of sweat glucose. Leveraging the synergistic effects of hydroxymethyl-functionalized poly(3,4-ethylenedioxythiophene) (PEDTM), reduced graphene oxide (rGO), and gold nanoparticles (AuNPs), the sensor significantly improves the electrocatalytic oxidation efficiency of glucose. At a low working potential of 0.2&#xa0;V, the sensor demonstrates high sensitivity (362 &#xb5;A&#xb7;mM-&#x2009;1&#xb7;cm-&#x2009;2) and a low detection limit (6.2 &#xb5;M). Density functional theory (DFT) calculations reveal the synergistic catalytic mechanism of the composite at the oxidation pathway level. To achieve stable and efficient sweat collection and real&#x2011;time analysis, the sensor is integrated with a microfluidic chip based on SDS/NaOH/PI nanofibers and a portable point-of-care testing (POCT) system, enabling on&#x2011;site visual monitoring of sweat glucose. Real&#x2011;time monitoring results indicate a strong correlation between the sweat glucose levels measured by the sensor and blood glucose concentrations. This work provides an effective material and device design strategy for constructing high&#x2011;performance, integrated non&#x2011;invasive glucose monitoring systems, offering significant theoretical value and application potential in the field of wearable health monitoring.

Ulcerative colitis (UC) is characterized by disruptions of the gut microbiome and an exaggerated mucosal immune response in genetically susceptible individuals. Alterations in the composition of the intestinal metabolome associated with dysbiosis can trigger chronic inflammation. However, it remains unclear whether microbial dysbiosis is the cause or consequence of chronic mucosal inflammation. To address this gap, we aimed to investigate the potential pro-inflammatory effects of sterile fecal microbiome filtrate (FMF) using a microphysiological, immunocompetent intestine-on-chip (IoC) model. Sterile FMF from UC patients with active disease (n&#x2009;=&#x2009;6) or in remission (n&#x2009;=&#x2009;4) and non-UC individuals (n&#x2009;=&#x2009;5) were applied to IoC models. Cytokine responses of the epithelial and endothelial compartments were assessed after 24&#x2009; h, 48&#x2009; h, and 72&#x2009; h of incubation, while barrier permeability was evaluated after a period of 72 h. An artificial intelligence-driven image analysis pipeline was developed to quantify structural alterations of the epithelial tissue, including damage and thickness, as well as endothelial and immune cell densities in the IoC model in response to FMF exposure. FMF from active UC patients significantly increased proinflammatory cytokines (IL-1&#x3b2;, IL-6, IL-8, IL-23, and MCP-1) in the vascular IoC compartment in a time-dependent manner. In contrast, FMF from non-UC or UC patients in remission had no significant impact on the proinflammatory cytokine response compared to untreated media control. Luminal-vascular permeability was increased following the FMF treatment regardless of its origin. Image-based analysis revealed increased epithelial tissue damage and reduced tissue thickness following FMF exposure, alongside decreased endothelial cell density and altered macrophage morphology, independent of UC disease activity. FMF from UC patients with active disease induces a robust proinflammatory cytokine response in the IoC model, suggesting that UC-associated FMF-derived factors may contribute to the initiation of inflammatory processes relevant to UC pathogenesis. These findings are derived from a simplified intestinal barrier model and require further mechanistic and physiological validation. While image analysis revealed no significant microarchitectural differences among the three FMF groups, the pipelines established standardized metrics to evaluate the impact of FMF-derived factors on intestinal tissue integrity and immune responses, providing a framework for future IoC-based research in UC.

Biocompatible hydrogel encapsulation of model organisms, such as Caenorhabditis elegans, is highly desirable over chemical or mechanical immobilization methods that can harm health and hinder long term imaging studies. This study introduces an automated, gentle method for continuous immobilization within hydrogel blocks, achieved through flow lithography and machine learning-assisted vision detection. To optimize this automated worm immobilization, we investigated operating parameters, such as flow rate, solution composition, and worm loading concentration. With 90% precision in AI worm detection, we achieved 86% encapsulation efficiency at low to moderate worm-loading concentrations (1-7 worms per &#x3bc;L). Higher loading concentrations of 10-15 worms per &#x3bc;L reduced the encapsulation efficiency to 71%. Worm loading concentration, composition, and flow-rate ratios of the two input solutions-the worm-suspended aqueous solution (WSAS) and the polyethylene glycol diacrylate (PEGDA) solution (PEGS)-significantly affected worm throughput, worm dehydration during encapsulation, and the viability of encapsulated worms. The WSAS-to-PEGS flow-rate ratio was set at 0.5, with a minimum WSAS flow rate of 1 &#x3bc;L min-1 required to avoid backflow. The PEGDA concentration in PEGS was kept below 50% to avoid worm dehydration. By varying the concentrations of hydrogel precursor, PEGDA, we enabled both partial and complete immobilization suitable for short term and long-term studies, respectively. Results show the encapsulated worm's viability over 3 days, highlighting this method's potential for long-term studies without compromising worm health or movement.

Real-time quantification of concentric contractile force in engineered ring-shaped smooth muscle tissue remains challenging because conventional optical readouts provide indirect deformation-based measurements, whereas force-based systems often distort the circular tissue geometry. Here, we present a 3-dimensional flexible device for measuring the contractile force of in vitro ring-shaped smooth muscle tissue by electrical readouts while preserving its circular configuration. The device consists of a circular array of FEM-optimized n-shaped flexible pillars that convert tissue-derived contraction into n-shaped pillar bending and an electrical resistance change. To improve electrical robustness during bending, an air-sprayed SEBS polymer interlayer was introduced before Au deposition, reducing deformation-induced cracking and enabling continuous electrical response. The selected 300 &#x3bc;m pillar design showed a force-displacement relationship consistent with FEM prediction, and the calibrated &#x394;V-force relationship exhibited an approximately linear response up to &#x223c;200 &#x3bc;N. Ring-shaped human aortic smooth muscle tissues formed by collagen-based self-assembly showed spontaneous compaction and expression of &#x3b1;-SMA and calponin. During 15 h of spontaneous compaction, the device detected a progressive increase in single-pillar force, reaching 125.3 &#xb1; 44.2 &#x3bc;N at 15 h. The device also detected high-K+/Ca2+-evoked active contraction, with a peak single-pillar force of &#x223c;70 &#x3bc;N. These results demonstrate a calibrated electrical force-readout approach for ring-shaped smooth muscle tissue contractility and establish a device-level basis for future force-based evaluation of pharmacological responses and disease-associated contractile differences.

Hematogenous metastasis is initiated when tumor cells (TCs) intravasate into the vasculature, yet intravasation remains poorly understood because it is difficult to observein vivoand intravasated TCs are challenging to isolate. To address these challenges, we developed IntravChip, a continuously perfused microfluidic platform containing a vascularized primary tumor microenvironment (TME) enabling the observation of TC intravasation, and a downstream chamber to collect intravasated TCs. The IntravChip can support a high TC concentration in the TME while maintaining complete vascular perfusion, which we found was necessary to collect intravasated cells. Using MDA-MB-231 breast TCs, we identified an optimal initial TC seeding density that, by day 9, yields a densely populated TME and 100-440 collected intravasated TCs. We validated the IntravChip across several TC types, showing that MDA-MB-231 and MV3 TCs have the highest intravasation rates while MCF-7 TCs have low intravasation efficiency. We also show that the IntravChip is compatible with super-resolution nano-imaging. Our devices enabled high-quality STochastic Optical Reconstruction Microscopy imaging, which revealed that H3K9me3 nanodomains are significantly differentially distributed in intravasated MDA-MB-231 TCs compared to those residing in the TME. Finally, the IntravChip was validated as a platform to test the effects of anti-cancer drugs on TCs and on the vasculature. We showed that a 5&#x3bc;M concentration of sorafenib reduced intravasation events by 69% without impacting the morphology of the microvascular networks, while a 10&#x3bc;M concentration led to a significant decrease in vessel diameter. This platform enables quantitative analysis of TC intravasation, collection of intravasated TCs for characterization, and screening of anti-metastatic therapies.

Colon cancer is one of the leading causes of death, requiring advanced therapies that need models for developing new drugs. Conventional cell culture models do not accurately and precisely reproduce the complexity of the tumor microenvironment, limiting their usefulness in research and therapy development. To address this weakness, patient-derived organoids have emerged as promising in vitro models. The implementation of these organoid-based models into more physiologically relevant systems is expected to improve their clinical relevance. Thus, integrating these organoids into microfluidic chips acting as bioreactors will likely improve the predictive response of therapies in personalized medicine. In this article, we report the development of a new colon cancer organoid-on-a-chip model that enables the in vitro culture of patient-derived colon cancer organoids under continuous culture media flow. We demonstrate how the developed organoids were derived from tumor biopsies of patients with colorectal cancer, expanded in standard three-dimensional (3D) culture, and cultured inside the microfluidic chips. The microfluidic chip chambers are designed to house organoids in a controlled environment, allowing the injection of therapies and monitoring by optical microscopy in real time. The in vitro therapies tested were a combination of drugs based on 5-fluorouracil and oxaliplatin at different concentrations. As a result, we demonstrate for the first time that this model proves the capability of this technology for in vitro testing colon cancer therapies.

Thermochromic materials with temperature-dependent color changes and color memory are widely used in functional coatings, anti-counterfeiting, and smart architectures. Cholesteric liquid crystal (CLC) molecules undergo periodic helical twisting of their orientation, forming a unique helical superstructure with fluidity and long-range orientational order. When confined in microscale spherical droplets with interfacial anchoring, CLC assemblies exhibit dynamic optical response due to thermoresponsive molecular rearrangement. The helical defects within physical confinement and the interfacial molecular anchoring jointly interfere with the cholesteric reorganization, offering intelligent color modulation and structural stability but with limited color saturation and slow response. Herein, we construct molybdenum disulfide (MoS2)-doped double emulsion droplets with CLC as the core using droplet microfluidics, creating near-infrared-activated thermochromic microcapsules (NIR-TCMs) with enhanced response and color saturation. The microcapsules with controllable diameters (75.4-275.0 &#x3bc;m) and shell thicknesses (9.7-43.0 &#x3bc;m) are formed by polymerizing the middle phase of the double emulsion droplets. NIR-TCMs (136 &#x3bc;m core, 16 &#x3bc;m shell) of 0.5 wt% MoS2-doped CLC show approximately 3-fold reduction in total response time from 19.0 &#xb1; 2.35 s to 6.2 &#xb1; 0.84 s and an increase in excitation purity from 0.16 &#xb1; 0.03 to 0.55 &#xb1; 0.05. By tuning molecular arrangement via entropic and enthalpic effects and enhancing thermal transport via heat conduction, MoS2 mitigates the thermal resistance of the polymer shell, leading to a rapid thermochromic response. Additionally, MoS2 boosts color saturation and enables NIR photothermal chromism via broadband absorption. The NIR-TCM films display static patterns at room temperature, while they create new visible patterns via NIR excitation. These patternable NIR-TCMs enable remote modulation of the optical properties of individual microcapsules and the overall device, offering a photonic chip for information encryption and optical coatings.

Accurate measurement of height-averaged flow velocity from scalar signal transport is important for shallow microfluidic velocimetry. Conventional scalar imaging velocimetry (SIV) is sensitive to scalar-field noise, while deep neural network-assisted-SIV requires extensive labeled velocity data and may exhibit limited generalizability to unseen flow conditions. This study aims to develop an unsupervised physics-informed framework for accurately reconstructing pulsatile flow velocity from concentration signals in a shallow microfluidic channel. Multiscale perturbation-enhanced physics-informed neural network (MPE-PINN) was proposed by decomposing the scalar transport process into steady and pulsatile components and embedding the corresponding perturbation-based governing equations into the loss function. This method was evaluated using numerically generated concentration fields under different scalar transport and flow conditions, and its performance was compared with a conventional PINN using mean absolute percentage error (MAPE), convergence behavior, and noise robustness. Results show that MPE-PINN maintains MAPEs below 1% over a broad operating range with concentration signal frequency fC&#x2264;2 Hz and flow frequency fQ&#x2264;1.6 Hz. The proposed method also shows improved robustness under noisy concentration fields and better preservation of pulsatile velocity features than the conventional PINN. These results demonstrate that MPE-PINN provides an accurate and robust unsupervised approach for pulsatile velocity extraction in shallow microfluidic channels, offering practical potential for microfluidic flow characterization and biomedical lab-on-a-chip applications.

There is an unmet need for a versatile platform that enables flexible multi-drug combination screening with a wide concentration range and automated operation. Accordingly, an automated multi-drug combination screening platform (ISMMCGs) integrating elliptical baffle micromixers (EBMixers) and three types of microfluidic concentration gradient (MCG) chips was developed. The EBMixer achieves&#x2009;>&#x2009;90% mixing efficiency within a 40&#xa0;mm channel (Re&#x2009;=&#x2009;0-70), ensuring rapid uniform mixing. The MCG chips (linear, two-fold, ten-fold dilution), designed via the equivalent circuit method, spanning a four-order-of-magnitude concentration gradient (10&#x207b;&#x2074;-1). Automated switching via a micro-solenoid valve array enables "rough/fine/precise" screening. Validation with sodium fluorescein confirms gradient reliability; Screening experiments of vancomycin against MRSA demonstrate that this system can narrow the OD600-determined apparent MIC range down to 0.78-1.01&#xa0;&#xb5;g/mL, verifying the application potential of this platform in rapid screening of antimicrobial concentration ranges; and tigecycline-colistin sulfate combination screening for MDR-AB verifies the platform's flexibility for concentration-dependent combinatorial testing. This integrated platform addresses the limitations of traditional methods by balancing wide concentration coverage, multi-drug flexibility, and automation. It provides a refined, cost-effective tool for drug screening, facilitating the development of personalized treatment regimens and accelerating drug discovery processes, with broad applications in antimicrobial resistance research and pharmaceutical development.

Acoustofluidic buffer exchange enables continuous, contact-free replacement of the fluid surrounding suspended particles and cells, offering a gentle alternative to conventional centrifugation-based processing. Its performance is governed by the interplay between acoustic radiation-driven particle migration and streaming-induced fluid transport. Here, we investigate buffer exchange in a silicon-glass bulk acoustic wave microchannel actuated by a piezoelectric transducer, combining experimental characterization, numerical modeling, and biological validation. Particle transport was examined across a range of actuation voltages and flow rates to evaluate the competing effects of particle migration, interface displacement, and hydrodynamic residence time. No-flow calibration experiments confirmed the expected quadratic dependence of migration velocity on acoustic actuation, establishing a radiation-dominated reference independent of flow. Under continuous operation, however, finite residence time and acoustically induced interface motion limited achievable buffer exchange. Metrics relating particle migration to interface velocity and residence time enabled identification of operating regimes associated with efficient particle transfer and varying degrees of buffer preservation. Numerical simulations supported the experimental observations and clarified the distinct contributions of acoustic radiation forces and acoustic streaming. Biological validation using U2OS and INS-1 pancreatic &#x3b2;-cells demonstrated effective buffer exchange, high cell viability (>98%), and improved recovery compared with centrifugation-based processing. These findings provide practical design guidelines for balancing particle transfer, buffer retention, and biological compatibility in continuous acoustofluidic cell-processing systems.

Glioma progression is closely associated with vascular-related microenvironmental cues, but conventional in vitro models often lack spatial control over tumor spheroids, extracellular matrices, endothelial cells, and stromal support cells. Here, we developed a compartmentalized vascular-mimetic glioma spheroid-on-a-chip for visualizing glioma-vascular-associated cell interactions in a three-dimensional hydrogel microenvironment. The device integrates a central hydrogel channel for pre-formed glioma spheroids, two adjacent medium channels for human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs), and an L-shaped barrier for stable gel-medium interface confinement. Simulation and dye perfusion experiments confirmed improved hydrogel confinement and stable compartmentalization. Optimized HUVEC/NHDF co-culture supported vascular-like endothelial-stromal organization and invasion into the hydrogel compartment. In the integrated chip, the HUVEC/NHDF co-culture increased the diameters of U87 and U251 spheroids by 26.4% and 21.4%, respectively, and induced endothelial-associated cell accumulation around U87 spheroids. Transwell assays further indicated that glioma cells together with stromal cells promoted HUVEC vascular-like organization. This platform provides a simplified and reproducible model for studying selected reciprocal interactions between glioma spheroids and vascular-associated stromal components under spatially controlled three-dimensional culture conditions.