Lab on a Chip最新文献

筛选
英文 中文
A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy. 可灌注的第一代子宫内膜微血管模型用于研究妊娠期人螺旋动脉重构。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-09 DOI: 10.1039/d6lc00513f
Sebastian Naranjo, Madison E Fletcher, Noo Li Jeon, Joyce Y Wong, Catherine Klapperich
{"title":"A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.","authors":"Sebastian Naranjo, Madison E Fletcher, Noo Li Jeon, Joyce Y Wong, Catherine Klapperich","doi":"10.1039/d6lc00513f","DOIUrl":"10.1039/d6lc00513f","url":null,"abstract":"<p><p>Invasive placental cells, extravillous trophoblasts (EVT), remodel maternal vasculature to meet metabolic needs of the growing fetus. Dysregulation of spiral artery remodeling (SAR) is a characteristic of preeclampsia (PE), a severe pregnancy-related condition. We developed a modular new approach methodology (NAM) of human endometrial-specific vascular networks in a polystyrene (PS) microfluidic chip to recapitulate the intricate endometrial vascular microenvironment to investigate SAR. We leveraged the self-assembly of human endometrial microvascular endothelial cells (HEMEC) and normal human lung fibroblasts (NHLF) to successfully develop patent endometrial vascular networks after 3 days of culture. Exogenous proangiogenic factors significantly improved vascular density while maintaining intrinsic endometrial vascular properties. Treatments of menstrual cycle phase-specific hormones differentially affected endometrial vascular density, diameter, permeability, and endogenous secretions of proangiogenic proteins. We evaluated integration potential of EVT cell lines HTR8/SVneo and JEG-3. We measured decreased barrier function and observed increased presence of apoptotic HEMECs after 3 days of tri-culture with JEG-3 cells, whereas HTR8/SVneo-induced apoptosis remained statistically unchanged across days 1 and 3 of integration. Moreover, we confirm HTR8/SVneo and JEG-3 cells differentially interact with HEMEC vasculature and the surrounding perivascular niche. These studies demonstrate the utility of our model to study endometrial vascularization and EVT remodeling.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microfluidic channel engineering for mRNA-LNPs: a systematic review of mixing strategies, nanostructures, and biological performance. mRNA-LNPs的微流控通道工程:混合策略、纳米结构和生物性能的系统综述。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-08 DOI: 10.1039/d6lc00477f
Hyejoong Jeong, Cheol Hui Park, Bookun Kim, Junsang Doh, Heebeom Koo
{"title":"Microfluidic channel engineering for mRNA-LNPs: a systematic review of mixing strategies, nanostructures, and biological performance.","authors":"Hyejoong Jeong, Cheol Hui Park, Bookun Kim, Junsang Doh, Heebeom Koo","doi":"10.1039/d6lc00477f","DOIUrl":"https://doi.org/10.1039/d6lc00477f","url":null,"abstract":"<p><p>mRNA-lipid nanoparticles (mRNA-LNPs) have revolutionized nucleic acid therapeutics, yet their clinical success relies heavily on precise manufacturing processes. This review comprehensively explores the critical intersection between microfluidic channel design, lipid self-assembly biophysics, and the subsequent biological performance of mRNA-LNPs. First, we analyze the fundamental fluid mechanics driving representative microfluidic mixers, elucidating how different channel architectures dictate solvent exchange rates and nanoparticle assembly kinetics. We then systematically examine how these specific mixing regimes modulate essential physicochemical characteristics, including lipid distribution, internal nanostructure, particle morphology, size distribution, and overall colloidal stability. Crucially, we bridge the gap between manufacturing and pharmacology by evaluating how mixing-induced physicochemical differences directly translate into distinct biological outcomes, such as cellular uptake mechanisms, endosomal escape efficiency, and systemic pharmacokinetics. By integrating microfluidic engineering principles with biological evaluation, this review provides a mechanistic framework for understanding how continuous-flow assembly processes program the functional behavior of mRNA-LNP systems. Ultimately, we highlight emerging design principles essential for developing the next generation of robust, highly efficient nucleic acid delivery platforms.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Motility patterns of Euglena species in confining microfluidic geometries. 限制微流体几何形状的藻属植物运动模式。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-07 DOI: 10.1039/d6lc00471g
Kavya Rajendran, Gala Montiel-Rubies, Narvada Bhurosah, Karine Baassiri, Henry Shum, Ayyappasamy Sudalaiyadum Perumal, Dan V Nicolau
{"title":"Motility patterns of <i>Euglena</i> species in confining microfluidic geometries.","authors":"Kavya Rajendran, Gala Montiel-Rubies, Narvada Bhurosah, Karine Baassiri, Henry Shum, Ayyappasamy Sudalaiyadum Perumal, Dan V Nicolau","doi":"10.1039/d6lc00471g","DOIUrl":"https://doi.org/10.1039/d6lc00471g","url":null,"abstract":"<p><p>Protists rely on motility to explore their environment, enabling them to access resources such as nutrients and light, while avoiding unfavorable conditions and predators. To advance the current understanding of how motility and morphological adaptations modulate spatial navigation and interactions with confining physical environments, this work analysed the motility of <i>E. gracilis</i> and <i>E. acus</i>, which share a similar overall body plan but differ in flagellum length and pellicle configuration. Cell motility was quantified under progressively increasing confinement in microfluidic devices comprising quasi-open spaces (0D), single-wall interactions (1D), and two-wall confinement (2D), including corners and channels with varying geometries and complexities. The motility of <i>Euglenids</i> was characterized using single-cell swimming trajectories, wall-scattering dynamics, trapping time, switching of propulsion mode, swimming velocity, and quantification of successful navigation through structured environments. Five distinct wall-scattering behaviors were observed in low-confinement conditions. Both species mainly escaped geometrical confinements through collision-mediated scattering. <i>E. gracilis</i> exhibited larger average deflection angles and greater variability in its trajectory angles. In 2D corner confinement, <i>E. gracilis</i> presented extended trapping times and larger deflection angles, consistent with an increased interaction with walls. Under strong lateral confinement (channel widths approximately 1-2× the cell diameter), both species shifted from flagellar swimming to friction-assisted back-and-forth motion accompanied by pellicle-driven deformation (metaboly). These transitions in motility behavior were geometry-dependent and species-specific. <i>E. acus</i> exhibited higher metaboly incidence in highly tortuous channels, whereas <i>E. gracilis</i> relied more on flagellar propulsion and back-and-forth motility. Upon exiting channels with quasi straight channels (lower tortuosity), <i>E. gracilis</i> adopted curvilinear trajectories, while <i>E. acus</i> presented straighter trajectories. Our results suggest that <i>E. gracilis</i> did not show significant conditioning to confining environments, while <i>E. acus</i> presented a 'directional memory'-like movement, with trajectories in open spaces strongly influenced by the geometry of the preceding channel. These observations are consistent with the hypothesis that morphological traits, such as flagellum length and pellicle organization, modulate the observed differences in behavioral motility. These findings also provide a framework for understanding how morphological features may influence navigation in structured microenvironments and inform the design of microfluidic systems for applications such as motility-based cell sorting, photo-microbioreactors, and biocomputation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A confining microfluidic platform for disparate density coculture reveals the dynamics of macrophage-mediated adipocyte clearance. 不同密度共培养的封闭微流控平台揭示了巨噬细胞介导的脂肪细胞清除的动力学。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-07 DOI: 10.1039/d6lc00433d
Yuan Bin Lim, Jessica Evangeline Tan Kabigting, Mei Shan Cheam, Yusuke Toyama, Andrew W Holle
{"title":"A confining microfluidic platform for disparate density coculture reveals the dynamics of macrophage-mediated adipocyte clearance.","authors":"Yuan Bin Lim, Jessica Evangeline Tan Kabigting, Mei Shan Cheam, Yusuke Toyama, Andrew W Holle","doi":"10.1039/d6lc00433d","DOIUrl":"https://doi.org/10.1039/d6lc00433d","url":null,"abstract":"<p><p>Co-culturing cells with mismatched densities, where one cell type adheres to surfaces while the other floats, represents a fundamental challenge in cell biology. This is particularly evident in studying macrophage-adipocyte interactions, where macrophages must engage and clear the apoptotic adipocytes, a process critical to understanding chronic inflammation in obesity and metabolic disease. The density disparity between macrophages, which sink and adhere to culture surfaces, and adipocytes, which float due to their lipid content, has prevented conventional co-culture approaches from achieving sustained cell-cell contact. To address this challenge, we developed a microfluidic system that confines adipocyte-derived lipid droplets in close proximity to macrophages. This platform features recessed micro-traps within the upper surface of a microfluidic chamber that trap buoyant objects while allowing media exchange and delivery of reagents for live-cell and immunofluorescence imaging. Time lapse imaging revealed that the dynamic process of macrophages-dead corpse interactions, showing that individual macrophages cannot engulf entire corpses but instead mechanically deform them. Furthermore, the platform reproduces the Crown-Like Structure (CLS), which is a unique configuration of multiple macrophages enveloping a single dead adipocyte. Long-term culture revealed that CLS effectively clear lipids compared to partial macrophage engagement, providing insights that were previously unattainable with standard histological approaches. Beyond the macrophage-lipid interaction, this platform has potential for studying interactions between adherent cells and buoyant targets, such as microplastics, opening new avenues for research where density mismatch poses a major barrier.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lab-on-a-capillary: instrument-free compartmentalization using photopatterned hydrogel rings embedded inside a glass capillary for amplified bioassays. 毛细管上实验室:使用嵌入在玻璃毛细管内的光图案水凝胶环进行扩增生物测定的仪器无区隔化。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-07 DOI: 10.1039/d6lc00591h
Yimin Yang, Muhammad Usman Akhtar, Mehmet Akif Sahin, Yibo Huang, Liusu Wang, Xinpei Song, Ghulam Destgeer
{"title":"Lab-on-a-capillary: instrument-free compartmentalization using photopatterned hydrogel rings embedded inside a glass capillary for amplified bioassays.","authors":"Yimin Yang, Muhammad Usman Akhtar, Mehmet Akif Sahin, Yibo Huang, Liusu Wang, Xinpei Song, Ghulam Destgeer","doi":"10.1039/d6lc00591h","DOIUrl":"10.1039/d6lc00591h","url":null,"abstract":"<p><p>Sensitive and low-cost protein biomarker detection is critical for disease diagnosis. Advanced microfluidic systems can generate miniature reaction compartments for a high-sensitivity assay. However, these platforms often require external instruments, skilled operators, and complex setups. Here, we develop a lab-on-a-capillary (LabCap) platform that integrates photopatterned hydrogel rings within a glass capillary using a reconfigurable stop-flow lithography system. During sample loading and unloading steps, nanoliter-scale aqueous droplets (torodrops) are spontaneously formed around the hydrogel rings, creating isolated reaction compartments without the need for external instruments or an immiscible oil phase. The LabCap platform enables detection of clinically relevant biomarkers, including C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). By adjusting the incubation protocol, the detection performance can be tuned to meet different analytical requirements. A 16 min periodic medium exchange protocol yielded calculated limits of detection of 1.3 ng mL<sup>-1</sup> for CRP and 1.8 ng mL<sup>-1</sup> for NT-proBNP, whereas static incubation yielded 0.5 ng mL<sup>-1</sup> for both biomarkers after 1 h and 0.14 ng mL<sup>-1</sup> for CRP at a matched 16 min incubation. In addition, LabCap offers practical advantages, including a low consumable material cost for fabricating one device (<€1), low reagent consumption (<100 μL per assay step), and minimal wash-buffer usage (1 mL). These results demonstrate that LabCap is a simple, cost-effective, and versatile platform for compartmentalized biomarker detection.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Programming flow anisotropy in hydrodynamic metamaterials via series-parallel equivalent fluidic networks. 基于串并联等效流体网络的流体力学超材料流动各向异性规划。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-06 DOI: 10.1039/d6lc00753h
Haixiang Pang, Yijia Ma, Yu-Hong Dong, Yiyun Cui, Kang-Kang Zhang
{"title":"Programming flow anisotropy in hydrodynamic metamaterials <i>via</i> series-parallel equivalent fluidic networks.","authors":"Haixiang Pang, Yijia Ma, Yu-Hong Dong, Yiyun Cui, Kang-Kang Zhang","doi":"10.1039/d6lc00753h","DOIUrl":"https://doi.org/10.1039/d6lc00753h","url":null,"abstract":"<p><p>Precise microflow control underpins microfluidic technologies in precision medicine, yet conventional approaches rely on anisotropic materials or external fields, limiting fabrication simplicity and scalability. Unlike transformation-based or data-driven approaches, we demonstrate that flow anisotropy can be programmed through the layered organization of locally homogeneous, isotropic media <i>via</i> a series-parallel equivalent fluidic network (SPEFN) realized as single-medium metamaterials (SMMs). SPEFN provides an analytically invertible mapping from network topology to the macroscopic effective-viscosity tensor, from which a connectivity-controlled anisotropy law and an exact non-disturbance condition emerge as direct analytical consequences. We experimentally realize three monolithic SMM devices: a spiral-layered director, an annular cloak, and a fan-shaped concentrator. Particle-tracking velocimetry confirms the predicted responses across all devices, including ≈30° streamline reorientation and a concentrator velocity ratio of 1.37 <i>versus</i> a predicted value of 1.38. The cloak exhibits higher apparent suppression than predicted; tracer retention or adhesion visible in Movie S1 may partly explain this difference. The system further shows robust performance under strongly non-uniform inflow and sub-percent fabrication tolerances.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic evaluation of deep learning design choices for image-based organ-on-chip quality assessment. 基于图像的片上器官质量评估中深度学习设计选择的系统评价。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-06 DOI: 10.1039/d6lc00731g
Ayse B Oktay, Arpit Tandon, Brian E Howard, Ruchir R Shah
{"title":"Systematic evaluation of deep learning design choices for image-based organ-on-chip quality assessment.","authors":"Ayse B Oktay, Arpit Tandon, Brian E Howard, Ruchir R Shah","doi":"10.1039/d6lc00731g","DOIUrl":"https://doi.org/10.1039/d6lc00731g","url":null,"abstract":"<p><p>Label-free brightfield microscopy is widely used to monitor organ-on-chip (OOC) cultures, but manual quality assessment can be subjective, labor-intensive, and difficult to standardize across biological conditions. Using a public dataset of 3072 microscopy images from six cell lines, we systematically evaluated four questions relevant to automated OOC quality assessment: (1) how model architecture and image resolution affect performance, (2) whether predictive information is localized or distributed across the image, (3) whether biological metadata provides complementary information beyond the image, and (4) how well learned quality representations transfer across cell lines. We found that (1) both architecture and input resolution influenced performance, with increasing resolution from 224 × 224 to 768 × 768 improving ConvNeXt-Tiny accuracy from 0.852 to 0.910 and improving performance for five of six evaluated convolutional neural networks (CNNs); (2) multiple instance learning and saliency analyses indicated that quality relevant information was distributed across multiple image regions rather than dominated by isolated local defects; (3) biological metadata provided only modest additional benefit, with the best metadata-conditioned model achieving an accuracy of 0.915 compared with 0.910 for image-only classification; and (4) transfer to previously unseen cell lines varied substantially (ROC-AUC 0.783-0.999), while finetuning models with target-cell-line data substantially recovered performance, increasing pooled accuracy from 0.791 to 0.890. Domain-adversarial training did not consistently improve transfer. Rather than introducing a new deep learning architecture, the novelty of this work lies in systematically evaluating these OOC-specific design and generalization factors within a common framework. These findings highlight image resolution, biological-domain validation, and target-domain adaptation as important considerations for robust automated OOC quality assessment.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NanoSpacer: a confinement-based label-free microscopy platform for particle detection, counting, and sizing from nano- to microscale for microbiology and marine applications. NanoSpacer:一个基于空间的无标签显微镜平台,用于颗粒检测、计数和从纳米到微米的微生物学和海洋应用。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-05 DOI: 10.1039/d6lc00655h
Farzin Chougani, Inga Skjevdal, Roman Netzer, Lara Ambrosio Leal Dutra, Mário Araújo, Isabel Benta Oliveira, Ellinor O Alseth, Florian Ströhl, Hans-Matti Blencke, Gabriel Magno de Freitas Almeida, Oliver Vanderpoorten
{"title":"NanoSpacer: a confinement-based label-free microscopy platform for particle detection, counting, and sizing from nano- to microscale for microbiology and marine applications.","authors":"Farzin Chougani, Inga Skjevdal, Roman Netzer, Lara Ambrosio Leal Dutra, Mário Araújo, Isabel Benta Oliveira, Ellinor O Alseth, Florian Ströhl, Hans-Matti Blencke, Gabriel Magno de Freitas Almeida, Oliver Vanderpoorten","doi":"10.1039/d6lc00655h","DOIUrl":"https://doi.org/10.1039/d6lc00655h","url":null,"abstract":"<p><p>Label-free particle analysis across micro- and nanoscale particle systems requires multiple specialized instruments, making it difficult to compare measurements across scales within a single workflow. Here we show the use of NanoSpacer/MicroSpacer, a glass-based confinement platform, for particle detection, relative particle counting, and diffusion-based sizing at the single particle level. The platform confines liquid samples between spacer-defined glass surfaces, restricting the vertical observation volume while allowing particles to move freely within the imaging plane. This improves particle visibility under darkfield illumination and supports more reliable particle tracking for diffusion-based sizing in solutions. Diffusion coefficients are obtained from mean-squared displacement (MSD) analysis using open-source software and converted to hydrodynamic size <i>via</i> the Stokes-Einstein relationship. The platform was evaluated across four model systems spanning micro- to nanoscale: (i) binary GFP/mKate bacterial mixtures were quantified at the single-cell level, with GFP ratios of 59%, 18%, and 89% in agreement with correlative flow cytometry (65%, 23%, 86%) and colony-forming unit counts (54%, 17%, 86%); (ii) bacteriophages <i>Polaria</i> and <i>Mystique</i> were detected by darkfield and apparent size estimates returned modal hydrodynamic diameters of approximately 250 nm and 190 nm, consistent with electron microscopy; (iii) putative nanobubbles were produced by chemical and mechanical methods, with modal diameters of approximately 170 nm and 600 nm; (iv) polystyrene nanoplastic particles (100, 200, and 1000 nm) were imaged in freshwater and seawater, where salt-induced aggregation produced clusters spanning orders of magnitude in size. Together, these results establish NanoSpacer/MicroSpacer as a cost-efficient, microscopy-compatible workflow for particle metrology across micro- and nanoscale systems relevant to marine science and microbiology.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor-on-a-chip with single-cell microfluidics reveals distinct NK cell immunosuppression by hypoxia versus lipid accumulation. 肿瘤芯片与单细胞微流体显示明显NK细胞免疫抑制低氧与脂质积累。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-05 DOI: 10.1039/d6lc00668j
Aoling Wang, Yunting Wang, Xiahe Han, Qiurui Chen, Wu Liu
{"title":"Tumor-on-a-chip with single-cell microfluidics reveals distinct NK cell immunosuppression by hypoxia <i>versus</i> lipid accumulation.","authors":"Aoling Wang, Yunting Wang, Xiahe Han, Qiurui Chen, Wu Liu","doi":"10.1039/d6lc00668j","DOIUrl":"https://doi.org/10.1039/d6lc00668j","url":null,"abstract":"<p><p>Immunosuppression induced by metabolic stress within the solid tumor microenvironment (TME) critically limits the efficacy of cancer immunotherapies. Here, we develop a tumor microenvironment-on-a-chip (TMoC) platform integrated with single-cell microfluidic analysis to precisely model both hypoxic and lipid-enriched conditions commonly found in solid tumors. Utilizing this system, we elucidate the distinct effects of these two metabolic stressors on natural killer (NK) cell function. Hypoxia broadly suppresses NK cell cytotoxicity and downregulates multiple functional molecules. In contrast, lipid accumulation exerts a selective inhibitory effect, reducing granzyme B and IL-10 expression while relatively preserving IFN-γ mRNA expression. Single-cell analysis reveals stress-induced functional heterogeneity and secretory synergy among NK cells. Notably, we identified a relatively high-IFN-γ-secreting subpopulation retained under lipid-rich conditions despite an overall reduction in IFN-γ secretion at the single-cell level. Furthermore, single-cell pairing assays dissociate global killing efficacy from killing kinetics, revealing that hypoxia and lipid accumulation impair NK cells through distinct kinetic modes. Using the TMoC platform to evaluate combination therapies targeting both hypoxia and lipid metabolism, we show that dual intervention synergistically restores NK cell cytolytic function. The platform demonstrates superior screening sensitivity compared to conventional <i>in vitro</i> models. Collectively, this work highlights the potential of integrating engineered microphysiological systems with single-cell analysis to decipher complex TME interactions and guide the development of immunotherapeutic strategies.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-time integrated and multiplexed electrochemical sensor for reactive oxygen species in a high-throughput microphysiological system. 高通量微生理系统中活性氧的实时集成多路电化学传感器。
IF 6.3 2区 工程技术
Lab on a Chip Pub Date : 2026-10-02 DOI: 10.1039/d6lc00601a
William C Records, Brian P Cain, Norman F Sheppard, Michael J Matranga, Carlos A Segura, Cáit Ní Chléirigh, Anthony J Quinnert, WeiXuan Lai, Stephan Pretorius, Christian E Wells, Daniel T Conroy, Landys Lopez-Quezada, Zachary R Tranchemontagne, Brenna Rosso, Rebeccah J Luu, Anjana Jeyaram, Halee Kim, Rose Keating, Jeffrey Ma, Liana Kramer, Vidhya Vijayakumar, Jeffrey T Borenstein, Jonathan R Coppeta, Hesham Azizgolshani
{"title":"Real-time integrated and multiplexed electrochemical sensor for reactive oxygen species in a high-throughput microphysiological system.","authors":"William C Records, Brian P Cain, Norman F Sheppard, Michael J Matranga, Carlos A Segura, Cáit Ní Chléirigh, Anthony J Quinnert, WeiXuan Lai, Stephan Pretorius, Christian E Wells, Daniel T Conroy, Landys Lopez-Quezada, Zachary R Tranchemontagne, Brenna Rosso, Rebeccah J Luu, Anjana Jeyaram, Halee Kim, Rose Keating, Jeffrey Ma, Liana Kramer, Vidhya Vijayakumar, Jeffrey T Borenstein, Jonathan R Coppeta, Hesham Azizgolshani","doi":"10.1039/d6lc00601a","DOIUrl":"https://doi.org/10.1039/d6lc00601a","url":null,"abstract":"<p><p>The integration of real-time sensors in microphysiological systems (MPS) faces steep challenges due to the mass transport limitations inherent to microfluidic environments, complex microdevice fabrication methods, and maintenance of long-term performance at high throughput. Reactive oxygen species (ROS) represent attractive yet elusive sensing targets for MPS due to their integral role in cellular metabolism, oxidative homeostasis, and response to disease and injury. Nevertheless, without real-time measurement, their short-lived nature limits practical investigations of ROS as biomarkers in biomedical research. In this work, we have integrated a 96-plex, real-time ROS measurement system into PREDICT96, a high-throughput MPS platform, as a first demonstration of a highly multiplexed electrochemical sensor capability. The ROS measurement system comprises a miniaturized amperometric sensor array capable of rapidly measuring H<sub>2</sub>O<sub>2</sub>, a prototypical ROS, at micromolar concentrations (1-10 μM) with high sensitivity and selectivity across 96 microphysiological devices. Integrated microfluidic pumping enables active mixing during measurement and supports the detection of targets with low concentrations or short lifetimes. This novel capability will enable future work investigating ROS as biomarkers for disease modeling and medical countermeasure evaluation, targeting viral respiratory infections of lung-immune tissue models.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书