Lab on a Chip最新文献

Efficient particle enrichment underpins microfluidic clinical diagnostics, yet many biologically relevant samples are non-Newtonian and their behaviour in acoustic-oscillatory systems remains incompletely understood. Here, we compare particle-enrichment kinetics in Newtonian glycerol-water (GW), viscoelastic poly(ethylene oxide) (PEO), and shear-thinning xanthan gum (XG) solutions using a common acoustic-oscillatory microfluidic platform. The enrichment rate followed the order PEO > water > XG > GW under representative conditions. At f_ac = 1 MHz, V_pp = 17 V, and f_flow = 12 Hz, 1.4 wt% PEO reduced the enrichment time by approximately 60% relative to water. Increased hydrodynamic resistance accounts for the slower response in GW, whereas shear thinning lowers the apparent viscosity of XG as the deformation rate increases. The faster response in PEO suggests an additional viscoelastic contribution. This contribution may assist migration toward the central node at 1 MHz but oppose migration locally between the centreline and the two off-centre nodes at 2 MHz. The voltage-dependent enrichment rate was described empirically by 1/t_e = aVbpp. Phase-resolved simulations based on the measured rheology and channel geometry showed fluid-dependent velocity, shear-rate, and apparent-viscosity fields. Fluid rheology must therefore be considered when designing acoustic-oscillatory enrichment systems for complex samples.

Hydrogel-integrated organ-on-a-chip (OoC) models have emerged as a promising platform for recapitulating the complexity of native human tissues. This review highlights the role of hydrogels as tissue-specific extracellular matrix (ECM) mimics, focusing on the physicochemical properties that regulate cellular behaviour and tissue function in three-dimensional (3D) systems. We also explore the contribution of microfluidic systems in further enhancing physiological relevance by integrating multiple microenvironmental cues, including dynamic biochemical gradients, biophysical stimuli, tissue architecture, temporal regulation, 3D cellular arrangements, and ECM incorporation. Following a discussion of different hydrogel-microfluidic integration strategies, along with their associated engineering challenges and design considerations, we examine how the synergistic integration of hydrogels with microfluidics enables the development of advanced OoC models that more faithfully reproduce native tissue organisation and physiology. These advances make hydrogel-integrated OoC models well suited to a broad range of applications, including studying fundamental biology, disease modelling, drug development, personalised medicine, and multi-organ system, helping bridge the gap between in vivo animal studies, traditional in vitro studies, and human physiology.

We present a unified digital-to-experimental workflow that advances the integration of single-image diffusion-based rock generation with connectivity conditioning, scalable texture synthesis, and microfluidic experimentation, enabling statistically realistic generated images to be converted into hydraulically functional, fabrication-ready porous media. For each reference rock image across multiple lithologies, a separate SinDiffusion model is trained to generate statistically consistent pore-scale realizations that preserve key features of the input structure. Quantitative evaluation using intensity statistics, porosity, Minkowski functionals, connectivity metrics, and pore-shape eccentricity confirms preservation of multi-scale morphological characteristics. The generated images are further processed through percolation-constrained thresholding and texture synthesis to produce fabrication-ready designs with controlled connectivity and arbitrary geometries. Additional geometric and flow-property analyses across the four workflow stages show that the final designs retain comparable structural and transport-relevant characteristics while satisfying microfluidic fabrication requirements. The digital layouts are translated into rock-on-chip microfluidics via maskless photolithography and used for CO₂ drying and salt precipitation experiments. Homogeneous and artificially fractured sandstone-like configurations demonstrate the workflow's ability to resolve structure-dependent drying and precipitation patterns, with fractures promoting localized deposition and delayed clogging. Experiments on multiple realizations generated from the same input image show a consistent qualitative sequence of CO₂ displacement, brine depletion, and salt accumulation, while capturing realization-specific variability in phase evolution.

Neutrophils, the innate immune system's first line of defense, function in pathogen removal through diverse cellular responses. One critical response is neutrophil extracellular trap (NET) formation, which, despite its importance in inflammation, remains poorly understood and lacks high-resolution tools to effectively study its multiple forms: vital and suicidal. To begin addressing this gap, we introduce a tunable micropatterned platform that enables single-cell analysis of NETosis with spatial precision. Using photopatterned bacterial extracellular vesicles (bEVs) on a functionalized surface, we achieved controlled alignment of human peripheral blood neutrophils and demonstrated that engineered patterns control key NETosis outcomes. Meanwhile, phorbol 12-myristate 13-acetate (PMA) stimulation induced uniform suicidal NETosis. This approach supports additional applications, enabling tunable neutrophil patterning and live-cell imaging for intracellular investigation. Additionally, there is flexibility for different extracellular vesicle and nanoparticle patterning and pre-stimulation studies. Here, we present a novel system to quantify and manipulate NETosis pathways at the single-cell level, opening new avenues to explore immune heterogeneity and develop targeted therapies.

The cardiac autonomic nervous system is a key driver of various cardiac disorders and arrhythmias. However, investigating neuronal regulation of the human heart has proven difficult due to the limited availability of reliable experimental models. Here, we present a novel microphysiological system using a compartmentalized microfluidic device (MFD) to integrate co-cultured human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) and sympathetic neurons (hiPSC-SNs). MFD is composed of two wide-open chambers separated by microfluidic microchannels. Patch-clamp electrophysiology, RT-qPCR, immunofluorescence, and video-motion recording were used to characterize the phenotype of hiPSC-SNs and their functional coupling with hiPSC-CMs in the MDF. Immunofluorescence and RT-qPCR demonstrated significantly increased expression of the sympathetic neuronal markers peripherin, tyrosine hydroxylase, βIII-tubulin, dopamine β-hydroxylase, and nicotinic acetylcholine receptors, confirming successful differentiation into a sympathetic neuronal phenotype. Patch-clamp electrophysiology further demonstrated functional maturation, with hiPSC-SNs exhibiting spontaneous action potentials and nicotine-triggered membrane depolarization in response to 1 μM nicotine. Co-culture of hiPSC-CMs and hiPSC-SNs within the MFD promoted axonal projection into the cardiomyocyte chamber, establishing a physical connection between the two cell types. After 10 days of co-culture, functional integration was confirmed by a significant increase in hiPSC-CMs action potential frequency and beating rate, as recorded by patch-clamp and video motion tracking, respectively. Furthermore, selective nicotine stimulation of the neuronal chamber increased both action potential frequency and beating rate in hiPSC-CMs, whereas β-adrenergic blockade with 5 μM propranolol significantly reduced the beating rate. Collectively, these data demonstrate the feasibility of differentiating hiPSCs into functional sympathetic neurons and establishing a robust neuro-cardiac interface. This microphysiological system represents a powerful platform for investigating disorders characterized by impaired neuro-cardiac interactions, offering a valuable tool for both disease modeling and pharmacological screening.

Frequent monitoring of prothrombin time and international normalized ratio (PT/INR) is essential for effective management of anticoagulation therapy, yet conventional laboratory-based testing remains costly, time-consuming, and difficult to access in decentralized settings. Addressing this challenge, a hybrid paper-based point-of-care (POC) platform is designed for rapid and affordable whole-blood PT/INR analysis. The assay is developed through systematic optimization of key parameters, including sample volume, blood-to-reagent ratio, reaction time, substrate type, assay geometry, and strip dimensions for both haematocrit (HCT) and PT/INR modules. The integrated system simultaneously estimates HCT using radial intensity-based detection on Whatman Grade 4 paper (R² = 0.9788) and measures PT/INR on high-porosity MF1 glass-fibre strips (R² ≈ 0.94), enabling correction of HCT-induced bias. Image-derived features were analyzed using AI/ML-based models, where support vector machine classifiers achieved diagnostic accuracies of 98.5% and 96.9% for non-anticoagulated and anticoagulated cohorts, respectively. Integrated with a custom desktop/web/smartphone application and an automated warfarin dosage calculator, the platform provides a low-cost, rapid, and user-friendly solution for accessible anticoagulation monitoring.

Metallic wear debris in lubricating oils can reflect abnormal wear conditions in rotating machinery, and the rapid analysis of chemical elements in wear particles can timely predict the exact fault positions, thereby enabling ordinary operation and maintenance support in diverse industrial applications. Emerging as a quick and convenient analytical tool, laser-induced breakdown spectroscopy (LIBS) is promising for directly detecting oil-borne metallic microparticles. However, its efficiency has been greatly hindered by the low concentration of micrometric particles sparsely distributed in the oil matrix. Here, we present an acoustic manipulation strategy for enhancing the LIBS detection of oil-borne metallic microparticles. A sandwich-type configuration was selected to build the acoustic manipulation chip with dual parallelized serpentine microchannels, and the acoustic radiation force dominates the quick enrichment of randomly distributed metallic particles. With increased particle concentration, the LIBS spectral intensity was significantly enhanced for 3 typical elements (Fe, Cu, and Ni). The experimental results illustrated that the large background noise interference from the oil matrix was effectively suppressed, and the metallic elements after enrichment could be accurately recognized. The proposed acoustic enrichment method lays a solid foundation for enhancing the LIBS detection of oil-borne metallic particles, offering a new alternative for quick fault diagnosis and in-time health management of mechanical rotating systems in practical applications.

It is well established that the tumor microenvironment (TME) plays a dynamic role in breast cancer progression. Stromal components of the TME, including fibroblasts and the extracellular matrix (ECM), provide biophysical and biochemical cues to drive tumor cell proliferation and invasion. However, how the interplay between activated fibroblast (CAF) subtypes and ECM composition impinges on breast cancer cell behavior is still not well understood. To address this gap, we leveraged microfluidic technologies to engineer a model of the breast TME that incorporates tumor cells, CAFs, and ECM components. Our model consists of a tubular duct filled with MDA-MB-231 or MCF-7 cells surrounded by a 3D collagen type I matrix with or without two human fibroblasts/CAFs. To further investigate how ECM composition affects the stromal compartment, we altered the matrix to include laminin-111 (LN) and thrombospondin-1 (TSP-1), which we previously found to be dysregulated in invasive ductal carcinoma compared to normal breast tissue. By incorporating LN or TSP-1 into the collagen matrix, we identified significant differences in collagen fiber metrics (fiber length, density, and width), matrix stiffness, and alterations in matrix remodeling by CAFs. Specifically, remodeling was more pronounced in LN- vs. TSP-1-enriched microenvironments populated by myofibroblast-like (myCAF-like) cells compared to inflammatory CAFs (iCAF-like). Notably, MDA-MB-231 cell proliferation and invasion were significantly enhanced under these same conditions, and invasion was dependent on the LN-binding receptor, α6-integrin.

Digital polymerase chain reaction (dPCR) enables absolute nucleic acid quantification with high sensitivity and has strong potential for decentralized and integrated analytical applications. However, most current dPCR platforms rely on bulky pressure-driven instrumentation and large-footprint cartridges, limiting their suitability for compact and fully integrated microfluidic systems that incorporate upstream sample processing. Here, we introduce a centrifugal multi-volume digital PCR (MV-dPCR) disk designed to perform dPCR assays. The disk incorporates two primary innovations: (i) a radially arranged, multi-scale partitioning array with four distinct microcavity volumes (60 nl, 12 nl, 2.4 nl, and 0.48 nl), achieving compact layout while preserving a broad dynamic range; and (ii) an integrated vapor-based pneumatic pressurization module (∼70 kPa) that maintains stable partition integrity during thermal cycling without requiring external pressure hardware. These features are implemented in a monolithic cyclic olefin copolymer (COC) cartridge fabricated via thermoforming and sealed through thermo-diffusive bonding, occupying only one-third of a standard 140 mm disk. This compact design preserves plentiful space for future integration of upstream sample preparation modules. The MV-dPCR disk consistently achieves uniform partition filling with volume coefficients of variation (CVs) below 12% and low dead volume (<9%), and covers a 4.6 log₁₀ dynamic range using only 720 partitions. Validation experiments using synthetic DNA over four ten-fold dilution series demonstrate excellent linearity (R² > 0.99) and quantification accuracy comparable to commercial dPCR systems. Collectively, these advancements render the MV-dPCR disk a versatile, affordable, and easily scalable platform with potential for integration into more complex automated microfluidic workflows.

The integration of electrochemical sensing with microfluidic platforms is essential for advancing lab-on-a-chip technologies; however, many existing approaches rely on electrodes fabricated using costly and complex techniques such as thin-film deposition and photolithography. Laser-induced graphene (LIG) offers a rapid and low-cost alternative for electrode fabrication, yet it is most commonly produced on polyimide substrates, which are not readily compatible with permanent bonding to microfluidic channels and typically require adhesives or mechanical clamping. Here, we present a novel approach to integrating LIG electrodes with microchannels fabricated in polydimethyl siloxane (PDMS), a common material for microfluidics. Electrodes were formed on SU-8 photoresist-coated glass slides using a CO₂ laser and then covalently bonded to PDMS via 3-aminopropyl triethoxysilane (APTES). Structural and spectroscopic characterization of the LIG on SU-8 demonstrate successful conversion into conductive turbostratic graphitic carbon, while mechanical studies demonstrate strong bond integrity between the electrode substrate and PDMS over 16 hours of continuous operation. Electrochemical validation of the electrodes both off- and on-chip demonstrate performance suitable for quantitative electroanalysis. Proof-of-principle application of the integrated device to the detection of acetaminophen (paracetamol) by differential pulse voltammetry under flow conditions reveals a clinically relevant limit of detection (0.08 mM) with high intra-device precision. The resulting platform enables seamless integration with microfluidic channels and exhibits robust electrochemical performance ideal for rapid prototyping.