Lab on a Chip最新文献

{"title":"Evaluating migration and cytotoxicity of tissue-resident and conventional NK cells in a 3D microphysiological system using live-cell imaging.","authors":"Hyeri Choi,June Ho Shin,Hyeonsu Jo,John B Sunwoo,Nool Li Jeon","doi":"10.1039/d4lc01095g","DOIUrl":"https://doi.org/10.1039/d4lc01095g","url":null,"abstract":"Natural killer (NK) cells are critical components of the immune response against cancer, recognized for their ability to target and eliminate malignant cells. Among NK cell subsets, intraepithelial ILC1 (ieILC1)-like tissue resident NK (trNK) cells exhibit distinct functional properties and enhanced cytotoxicity compared to conventional NK (cNK) cells, positioning them as promising candidates for cancer immunotherapy. However, the specific roles and mechanisms of these cytotoxic trNK cells within the tumor microenvironment (TME) remain to be further explored. In this study, we utilized a three-dimensional (3D) microphysiological system (MPS) to model the tumor-vascular interface and investigate the distinct capabilities of cytotoxic ieILC1-like trNK and cNK cells within the TME. Through the integration of live-cell imaging and cell-tracking analysis, we quantitatively assessed NK cell migration, tumor infiltration, and cytotoxic activity in real time. Our findings revealed that trNK cells demonstrate enhanced motility, sustained tumor interactions, and superior tumor-killing efficiency compared to cNK cells. This study highlights the unique properties of trNK cells, providing a robust foundation for developing next-generation cancer therapies that harness their potent cytotoxic capabilities.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897454","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}

{"title":"Development of a novel point-of-care device to monitor arterial thrombosis.","authors":"Christopher A Bresette,Viviana Claveria,David N Ku","doi":"10.1039/d5lc00061k","DOIUrl":"https://doi.org/10.1039/d5lc00061k","url":null,"abstract":"Arterial thrombosis is a leading cause of heart attacks and strokes, representing a significant global health challenge. Microfluidic research studies have identified high shear stress, a thrombotic surface, and the presence of von Willebrand factor (vWF) and platelets as key conditions necessary for formation of arterial thrombi, termed shear-induced platelet aggregation (SIPA). However, current point-of-care (POC) assays of platelet function fail to incorporate these conditions, often relying on artificial agonists alone for stimulation. This study introduces a novel POC device designed to replicate high shear arterial thrombosis to create large platelet-rich clots reliably with small blood samples. The device was tested with blood from 10 healthy donors, with and without treatment with antiplatelet agents ASA, 2MeSAMPS and eptifibatide. The POC endpoint was compared with the PFA-100 to demonstrate novelty. A novel POC was successfully developed that can run with 5 mL of blood, had an intra-patient variability <15% and could distinguish differences in the healthy subjects tested. The POC was sensitive to antiplatelet agents acetyl-salicylic acid, 2-MeSAMPS and eptifibatide, showing an increase in end volume, a proxy for occlusion time, after treatment (p < 0.001). The novel POC device provides a unique endpoint that is uncorrelated with PFA-100 results. The ability of the novel POC to differentiate individual's thrombotic potential underscores its utility for clinical applications such as diagnosing platelet dysfunction, quantifying thrombotic risk, and optimizing antiplatelet therapies. This novel approach bridges the gap between research assays and practical clinical tools, offering a significant advancement in personalized cardiovascular care.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"8 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893314","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}

{"title":"Elevating single-particle encapsulation in droplet microfluidics by utilizing surface acoustic wave and flow control.","authors":"Chunhua He,Huasheng Zhuo,Canfeng Yang,Jianxin Wang,Xian Jiang,Fan Li,Chengxu Lin,Hai Yang,Tuying Yong,Xiangliang Yang,Zhiyong Liu,Yan Ma,Lei Nie,Guanglan Liao,Tielin Shi","doi":"10.1039/d4lc00787e","DOIUrl":"https://doi.org/10.1039/d4lc00787e","url":null,"abstract":"Target particle encapsulation is crucial in droplet microfluidics for high-throughput applications like single-cell sequencing and drug screening. However, it faces limitations, with encapsulation rates of only 10% to 30% due to suspension density and the inherent functionality of the chip being restricted by the Poisson distribution. This leads to reagent waste and reduced effectiveness in applications requiring ultra-high multiplexing or extensive particle analysis, due to the massive empty droplets. Here we propose a droplet microfluidic system integrating surface acoustic wave (SAW) and sheath flow control. Suspensions of varying concentrations within the channel are initially pre-focused by sheath fluid, and then acoustically focused into a linear arrangement by SAW. Spacing between particles can be regulated by modulating the sheath fluid, ensuring sequential encapsulation of cells or beads in individual droplets. Thermal shock generated by the SAW, particle and droplet frequency, and particle encapsulation ratio are all elaborately evaluated. The results demonstrate that our system reaches an exciting single-bead packing efficiency of up to 78%, and achieves a packing rate of more than 60% for both high and low concentrations of solutions for polystyrene microspheres, magnetic beads and H22 cells, 6 times higher than the theoretical upper limit of the conventional method and 1.8 times higher than the Poisson distribution. More importantly, our system is designed to be free of structural and parametric constraints, which is quite important in future practical application. Thus, our on-chip particle focusing control method and droplet microfluidic system provide great potential in biological applications needing a high single-particle encapsulation ratio in limited partitions, such as ultra-high multiplex digital biomolecular detection, single-cell analysis, drug screening, and single exosome detection.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"136 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893316","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}

{"title":"Generation of cell-sized liposomes using laser-induced microjets.","authors":"Jiajue Ji,Shuma Kawai,Rina Takagi,Keiichiro Koiwai,Ryuji Kawano,Yoshiyuki Tagawa","doi":"10.1039/d5lc00149h","DOIUrl":"https://doi.org/10.1039/d5lc00149h","url":null,"abstract":"Cell-sized liposomes are microcapsules composed of a lipid bilayer, with potential applications in membrane science and synthetic biology. In this study, we present a novel method that employs high-speed laser-induced microjets to penetrate a lipid-carrying oil phase, thereby generating cell-sized liposomes. By simply triggering the microjets, we can reliably and repeatedly generate cell-sized liposomes, thereby enabling on-demand liposome production. We employed a high-speed camera to capture and analyze the penetration behavior of microjets. Additionally, we confirmed the unilamellarity of the liposomes using melittin, confirming their suitability for various biochemical applications. Furthermore, we conducted a numerical analysis to investigate potential factors influencing liposome formation in detail. These findings hold promise for advancing on-demand liposome production and contributing to the development of biochemical research.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"104 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893518","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}

{"title":"Microdevice for confinement of T-cells on functionalized bio-interfaces.","authors":"Christoph Trenzinger,Caroline Kopittke,Barbora Kalousková,Nemanja Šikanić,Marina Bishara,Gerhard J Schütz,Mario Brameshuber","doi":"10.1039/d5lc00248f","DOIUrl":"https://doi.org/10.1039/d5lc00248f","url":null,"abstract":"Mechanical stimuli are an integral part of the natural cellular microenvironment, influencing cell growth, differentiation, and survival, particularly in mechanically challenging environments like tumors. These stimuli are also crucial in the T-cell microenvironment, where they play a role in antigen recognition and pathogen detection. To study T-cell mechanobiology effectively, in vitro methods must replicate these mechanical stimuli induced by compression, tension or shear flow, in the presence of antigen-presenting cells (APCs). While custom-made microdevices and microfluidic chips have successfully observed bulk cell behavior under mechanical strain, no existing device fully replicated the T-cell mechanoenvironment comprehensively. In this study, we developed a microdevice that integrates the mechanoenvironmental aspects of an APC mimicry with compression under live-cell imaging conditions. This device allows for precise confinement of cells between two glass surfaces, which can be individually coated with functional bio-interfaces. The microdevice is reusable and enables presetting of confinement heights, manual seeding of cells and the assembly of components directly at the microscope. To validate our microdevice we confined primary mouse T-cells on different APC-mimicking supported lipid bilayers while monitoring their morphology and migratory behaviour over time. To study the effect of confinement on TCR signalling, we tracked intracellular calcium levels and quantified Erk1/2 phosphorylation by immunostaining. We observed that T-cell morphology and motility are affected by confinement but also by bilayer composition. Moreover our findings suggest that confinement, despite not interfering with T-cell activation, might increase TCR background signalling in resting T-cells. Importantly, our microdevice is not limited to T-cell research; it can also serve as a platform for studying mechanical stimulation in other cell types, cell aggregates like spheroids and organoids, or even tissue samples in the presence of various bio-interfaces.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"18 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893315","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}

{"title":"A membrane-based immunosensor enabling high antifouling performance and sensitive molecular recognition.","authors":"Hiroki Yamashita,Hiroto Okuyama,Takeo Yamaguchi","doi":"10.1039/d5lc00031a","DOIUrl":"https://doi.org/10.1039/d5lc00031a","url":null,"abstract":"The fouling of non-targeted biomolecules on sensing surfaces, which can cause a reduction in sensing performance, is a severe problem in immunosensing platforms. The incorporation of hydrophilic polymers on sensing surfaces is effective against antifouling. However, such an approach can reduce the density of the capture antibody, resulting in a decrease in sensitivity and signal output. Here, both high sensitivity and antifouling properties were achieved using a porous-membrane-based immunosensor. This sensor can drastically mitigate the signal reduction due to the introduction of an antifouling moiety by antibody densification in submicron-scaled pores. The ideal ratio of the receptor/antifouling moiety was estimated from numerical modeling. The high sensitivity and antifouling properties of the designed sensor were demonstrated via the detection test of interleukin-6 (IL-6). The proposed sensor exhibited excellent antifouling and high sensitivity with limits of detection of 4.8 and 1.2 pg mL-1 in artificial saliva and serum, respectively. The study findings highlight the potential of membrane-based sensors for practical diagnoses.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889223","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}

{"title":"A high-throughput microfluidic platform for functional hiPSC-derived liver organoids with bile duct- and lobule-like structures.","authors":"Xiuxiu Zhang,Zixian Wang,Jianwei Chen,Tao Xu","doi":"10.1039/d5lc00154d","DOIUrl":"https://doi.org/10.1039/d5lc00154d","url":null,"abstract":"HiPSC-derived organoids have attracted significant attention in stem cell research and regenerative medicine. However, obtaining functional organoids in sufficient quantities, consistent sizes, and reproducible formats remains a significant challenge. Here, we present an innovative microfluidic platform for the high-throughput production of HAMA core-shell microspheres (HCSM) for the encapsulation and differentiation of hiPSCs. Fish gelatin and HAMA were employed as the core and shell materials, respectively. Using this platform, we successfully fabricated HCSM with uniform and controllable sizes in a high-throughput manner. Single-cell hiPSC suspensions self-organized into spheroids within HCSM, leading to the formation of EBs exhibiting cavitation. These EBs effectively differentiated into brain organoids, beating cardiac organoids, and liver organoids. Detailed structural and functional analyses of the liver organoids revealed a heterogeneous cellular composition including hepatocyte-, bile duct epithelial-, epithelial-, and stellate-like cells. Structurally, they exhibited bile duct- and hepatic lobule-like formations. Functionally, liver organoids displayed lipid and glycogen accumulation, ICG uptake and release, albumin and urea secretion, as well as metabolic responses to APAP and rifampin. Consequently, our study introduces a high-throughput manufacturing platform for hiPSC-derived organoids, with the potential to generate functional organoids for therapeutic applications and drug screening.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"9 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889245","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}

{"title":"Vascularized tumor-on-a-chip to investigate immunosuppression of CAR-T cells.","authors":"Rajul S Bains,Tara G Raju,Layla C Semaan,Anton Block,Yukiko Yamaguchi,Saul J Priceman,Steven C George,Venktesh S Shirure","doi":"10.1039/d4lc01089b","DOIUrl":"https://doi.org/10.1039/d4lc01089b","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell immunotherapy, effective in blood cancers, shows limited success in solid tumors, such as prostate, pancreatic, and brain cancers due, in part, to an immunosuppressive tumor microenvironment (TME). Immunosuppression affects various cell types, including tumor cells, macrophages, and endothelial cells. Conventional murine-based models offer limited concordance with human immunology and cancer biology. Therefore, we have developed a human \"tumor-on-a-chip\" (TOC) platform to model elements of immunosuppression at high spatiotemporal resolution. Our TOC features an endothelial cell-lined channel that mimics features of an in vivo capillary, such as cell attachment and extravasation across the endothelium and into the TME. Using 70 kDa dextran and fluorescence-recovery-after-photobleaching (FRAP), we confirmed physiologic interstitial flow velocities (0.1-1 μm s-1). Our device demonstrates that tumor-derived factors can diffuse in the opposite direction of interstitial flow to reach the endothelium up to 200 μm away, and at concentrations as high as 20% of those at the tumor margin. M2-like immunosuppressive macrophages and endothelial cells affect prostate tumor cell growth, clustering, and migration. M2-like macrophages also induce PD-L1 and inhibit ICAM-1 gene expression on the adjacent endothelium in a pattern that limits CAR-T cell extravasation and effector function. This observation is abrogated in the presence of the anti-PD-L1 drug atezolizumab. These results provide mechanistic insight for in vivo observations showing limited CAR-T cell extravasation and effector function in solid tumors. Furthermore, they point to a specific role of M2 macrophages in driving CAR-T cell migration into and within the TME and could prove useful in the development of novel therapies to improve solid tumor CAR-T cell therapies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"67 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885535","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}

{"title":"Micro elastofluidics for tuneable droplet splitting.","authors":"Uditha Roshan,Amith Mudugamuwa,Xiaoyue Kang,Jun Zhang,Nam-Trung Nguyen","doi":"10.1039/d5lc00100e","DOIUrl":"https://doi.org/10.1039/d5lc00100e","url":null,"abstract":"Droplet microfluidics is a transformative technology for generating and manipulating droplets in an immiscible carrier fluid. This technology spans many application areas, including biomedicine, food and beverage processing, as well as material synthesis. Droplet splitting is a key task in droplet microfluidics, which is essential for metering fluid samples between multiple assays in lab-on-a-chip applications. Passive droplet splitting with a T-junction is a straightforward and simple method. However, achieving variable droplet sizes typically requires numerous devices with different channel dimensions and complex channel arrangements. To address this limitation, we proposed a fully flexible and stretchable microfluidic technology for tunable droplet splitting. By externally stretching the T-junction, the dimensions of the channel arms can be dynamically altered in real time, allowing precise control over daughter droplet volumes and ratios. We investigated the effects of stretching on channel dimensions, hydraulic resistance, and droplet-splitting behaviour by theoretical analysis, numerical modelling, and experimental evaluations. The results revealed symmetric splitting at zero stretching and a tunable daughter droplet volume ratio up to approximately 4 with up to 4 mm device stretching (∼16% strain). Furthermore, we demonstrated the suitability of this technology for particle sorting, where particle-encapsulating mother droplets were asymmetrically split by adjusting device stretching. Finally, we demonstrated the encapsulation of microalgae within mother droplets and the tuning of microalgae concentration in the daughter droplets with stretching. This innovative approach provides a versatile and straightforward method for tunable droplet splitting, offering real-time control over droplet sizes without complex or multiple microfluidic designs. This advancement in micro elastofluidic technology opens up new possibilities for high-throughput and customisable droplet-based assays.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"3 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876480","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}

{"title":"Integrated microfluidic colorimetric patch with auto-framing APP for multiplex temporal detection of ketone bodies in sweat.","authors":"Tianhao Xue,Jianing Shen,Wanting Lin,Jiahui Zhou,Xiaofang Zhang,Ching-Jung Chen,Jen-Tsai Liu,Guixian Zhu","doi":"10.1039/d5lc00189g","DOIUrl":"https://doi.org/10.1039/d5lc00189g","url":null,"abstract":"Ketone bodies are key products of fat metabolism, primarily consisting of acetoacetate (AcAc), β-hydroxybutyrate (BHB), and acetone (acetone). Monitoring the concentration of ketone bodies in sweat can reflect the metabolic status of the body; it is also particularly significant in areas such as diabetes management, exercise monitoring, and the evaluation of the ketogenic diet. This paper presents a microfluidic patch for sweat collection and multiplex detection of AcAc, BHB and glucose. The microfluidic patch can achieve time-sequential sensing through Tesla valves, hydrophilic coatings, and unique chamber structural design. The concentrations of the three substances are quantified using colorimetric methods. Additionally, this study has designed a colorimetric app which can achieve automatic framing and detect the grayscale value of the colored area. Experimental results show that the patch can accurately detect changes in the concentrations of the three substances within specific ranges. The linear detection range for AcAc is 0.25 mM to 8 mM, the limit of detection (LOD) is 0.08 mM; for BHB, the linear detection range is 0.05 mM to 0.80 mM, the LOD is 0.02 mM; and for glucose, the linear detection range is 62.50 μM to 1000 μM, the LOD is 20.83 μM. In the future, this technology is expected to be applied to portable metabolic monitoring devices, offering a convenient solution for personal health management.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"219 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876485","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}