Oligodendrocytes are the myelinating glia of the central nervous system (CNS), essential for rapid signal propagation, metabolic support, and neuronal health. While rodent-based cultures and organoid systems have provided insights into oligodendrocyte biology, they fall short of capturing human-specific features of myelination or integrating structural and functional readouts. Here, we present MyeliMAP (Myelination MAPping), a human pluripotent stem cell (hPSC) -derived microphysiological and electrophysiological platform that enables robust modeling of CNS myelination. The system combines inducible hPSC-derived neurons and oligodendrocytes in a custom-engineered microfluidic microstructure designed to mimic the developing brain microenvironment, promoting spatially organized axon-glia interactions and controlled myelin sheath formation. Within six weeks, we demonstrate myelin formation and maturation by immunofluorescence and ultrastructural validation using transmission electron microscopy (TEM), confirming compact multilayered wrapping of human axons. Importantly, the microstructure is directly integrated with a high-density microelectrode array (HD-MEA), enabling real-time, long-term functional assessment of network activity and myelin-dependent changes in signal conduction. This allowed us to demonstrate that oligodendrocyte-based myelinated neurons display enhanced conduction velocity of action potentials compared to neuron monocultures. Moreover, the presence of oligodendrocytes stabilized the temporal neuronal network activity by reducing variability in firing patterns and enhancing synchrony across the culture. This dual structure-function approach surpasses static end-point analyses by coupling morphological validation with dynamic, quantitative measurements of maturing circuit physiology. MyeliMAP provides a reproducible, human-relevant platform to dissect neuron-glia interactions and accelerate discovery of remyelination-promoting strategies for CNS disease.
{"title":"MyeliMAP: A Microfluidic-Multielectrode Array Hybrid Platform to Investigate Oligodendrocyte Function in Human iPSC derived Brain-Like Networks","authors":"Karan Ahuja, Blandine Françoise Clément, Giulia Amos, Joël Küchler, Keimpe Wierda, Yoke C Chai, Lieve Moons, Catherine Verfaillie","doi":"10.1039/d5lc01062d","DOIUrl":"https://doi.org/10.1039/d5lc01062d","url":null,"abstract":"Oligodendrocytes are the myelinating glia of the central nervous system (CNS), essential for rapid signal propagation, metabolic support, and neuronal health. While rodent-based cultures and organoid systems have provided insights into oligodendrocyte biology, they fall short of capturing human-specific features of myelination or integrating structural and functional readouts. Here, we present MyeliMAP (Myelination MAPping), a human pluripotent stem cell (hPSC) -derived microphysiological and electrophysiological platform that enables robust modeling of CNS myelination. The system combines inducible hPSC-derived neurons and oligodendrocytes in a custom-engineered microfluidic microstructure designed to mimic the developing brain microenvironment, promoting spatially organized axon-glia interactions and controlled myelin sheath formation. Within six weeks, we demonstrate myelin formation and maturation by immunofluorescence and ultrastructural validation using transmission electron microscopy (TEM), confirming compact multilayered wrapping of human axons. Importantly, the microstructure is directly integrated with a high-density microelectrode array (HD-MEA), enabling real-time, long-term functional assessment of network activity and myelin-dependent changes in signal conduction. This allowed us to demonstrate that oligodendrocyte-based myelinated neurons display enhanced conduction velocity of action potentials compared to neuron monocultures. Moreover, the presence of oligodendrocytes stabilized the temporal neuronal network activity by reducing variability in firing patterns and enhancing synchrony across the culture. This dual structure-function approach surpasses static end-point analyses by coupling morphological validation with dynamic, quantitative measurements of maturing circuit physiology. MyeliMAP provides a reproducible, human-relevant platform to dissect neuron-glia interactions and accelerate discovery of remyelination-promoting strategies for CNS disease.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"79 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089611","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}
Cameron Boggon, Jeremy P Wong, Arpita Sahoo, Annelies Zinkernagel, Markus A Seeger, Eleonora Secchi, Lucio Isa
Bacteria in surface-attached communities often engage in social interactions with neighbouring microbes and spatial structure within these communities is thought to strongly influence community development. However, there is a significant lack of experimental platforms which allow for the tight spatial control of microbial communities at the microscale, severely limiting our ability to investigate the relationship between spatial structure and community development. Here, we demonstrate a workflow for patterning two or more bacterial species on a template with high throughput (∼ 10 5 patterned cells per template) and micron-scale precision. We leverage bio-orthogonal and highly specific binding reactions to construct two-species bacterial communities by depositing nanobodyfunctionalised colloidal particles into tailored arrays of shape-asymmetric cavities via directional sequential capillary assembly. Using Staphyloccocus aureus and Escherichia coli as model systems, we demonstrate how these organisms can be patterned in any desired spatial configuration before culturing under the microscope. This technique paves the way for careful investigations into the role of initial spatial structure on microbial interactions at low cell density, which is crucial to understanding and manipulating microbial community development.
{"title":"Controlling Spatial Structure in Minimal Microbial Communities by Sequential Capillary Assembly","authors":"Cameron Boggon, Jeremy P Wong, Arpita Sahoo, Annelies Zinkernagel, Markus A Seeger, Eleonora Secchi, Lucio Isa","doi":"10.1039/d6lc00040a","DOIUrl":"https://doi.org/10.1039/d6lc00040a","url":null,"abstract":"Bacteria in surface-attached communities often engage in social interactions with neighbouring microbes and spatial structure within these communities is thought to strongly influence community development. However, there is a significant lack of experimental platforms which allow for the tight spatial control of microbial communities at the microscale, severely limiting our ability to investigate the relationship between spatial structure and community development. Here, we demonstrate a workflow for patterning two or more bacterial species on a template with high throughput (∼ 10 5 patterned cells per template) and micron-scale precision. We leverage bio-orthogonal and highly specific binding reactions to construct two-species bacterial communities by depositing nanobodyfunctionalised colloidal particles into tailored arrays of shape-asymmetric cavities via directional sequential capillary assembly. Using Staphyloccocus aureus and Escherichia coli as model systems, we demonstrate how these organisms can be patterned in any desired spatial configuration before culturing under the microscope. This technique paves the way for careful investigations into the role of initial spatial structure on microbial interactions at low cell density, which is crucial to understanding and manipulating microbial community development.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"117 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089615","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}
Jiayi Yan,Jingyan Gao,Xinyi Jin,Jiacheng Cheng,Wentao Su,Chunqing Ai,Fanhua Kong,Shuang Song
The study of human intestinal diseases, particularly those involving oxidative stress-induced barrier dysfunction, has attracted increasing attention. Traditional studies have relied heavily on animal models and static 2D cell cultures, and recently, intestinal organ-on-a-chip models have emerged as a promising alternative for modeling intestinal pathophysiology in a human-relevant context. In this study, a high-throughput intestinal chip model was developed using double-sided pressure-sensitive adhesive tape and commercial polycarbonate materials. The model was employed to culture the Caco-2 barrier under continuous fluid flow and cyclic mechanical strain which are crucial for mature barrier formation and function. Bright-field and dark-field microscopy showed that the cells formed a tight, continuous barrier layer within the system. Sodium fluorescein permeation experiments demonstrated good permeability, while polymerase chain reaction (PCR) experiments and laser confocal microscopy imaging further confirmed a high degree of epithelial polarization. Additionally, an oxidative damage model was constructed using hydrogen peroxide. Immunofluorescence staining and metabolomics analysis verified that the model exhibited characteristics consistent with oxidative damage in intestinal cells, indicating the successful construction of the oxidative damage model.
{"title":"A dynamically cultured intestinal epithelial barrier model with metabolomics assessment for evaluating oxidative injury.","authors":"Jiayi Yan,Jingyan Gao,Xinyi Jin,Jiacheng Cheng,Wentao Su,Chunqing Ai,Fanhua Kong,Shuang Song","doi":"10.1039/d5lc01070e","DOIUrl":"https://doi.org/10.1039/d5lc01070e","url":null,"abstract":"The study of human intestinal diseases, particularly those involving oxidative stress-induced barrier dysfunction, has attracted increasing attention. Traditional studies have relied heavily on animal models and static 2D cell cultures, and recently, intestinal organ-on-a-chip models have emerged as a promising alternative for modeling intestinal pathophysiology in a human-relevant context. In this study, a high-throughput intestinal chip model was developed using double-sided pressure-sensitive adhesive tape and commercial polycarbonate materials. The model was employed to culture the Caco-2 barrier under continuous fluid flow and cyclic mechanical strain which are crucial for mature barrier formation and function. Bright-field and dark-field microscopy showed that the cells formed a tight, continuous barrier layer within the system. Sodium fluorescein permeation experiments demonstrated good permeability, while polymerase chain reaction (PCR) experiments and laser confocal microscopy imaging further confirmed a high degree of epithelial polarization. Additionally, an oxidative damage model was constructed using hydrogen peroxide. Immunofluorescence staining and metabolomics analysis verified that the model exhibited characteristics consistent with oxidative damage in intestinal cells, indicating the successful construction of the oxidative damage model.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"41 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056366","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}
The SlipChip is a versatile microfluidic platform that enables precise control of fluidic connections through the relative sliding of two microstructured plates, without requiring external pumps or valves. SlipChip facilitates fluid aliquoting, mixing, and partitioning via a simple sliding operation induced microfluidic reconfiguration. Various designs have been developed and applied to nucleic acid assays, protein crystallization, protein analysis, single-cell analysis, and materials synthesis. Compared with conventional microfluidics, SlipChip offers advantages such as simple fluidic manipulation, on-chip reagent preloading, portability, and cost-effective fabrication in diverse materials (glass, PDMS, plastic, paper). This review summarizes the fluidic principles, device fabrication, and applications of SlipChip, highlighting representative architectures, driving mechanisms, and material considerations. We also address current limitations of SlipChip technology, particularly in terms of assembly precision and dependence on manual operation. Looking forward, advances in materials engineering, device automation, and artificial intelligence are anticipated to enhance assembly reliability and support increasingly autonomous workflows. These developments are poised to significantly broaden the role of SlipChip in systems biology, clinical diagnostics, and personalized medicine. Overall, SlipChip represents a simple, robust, and accessible microfluidic platform suitable for diverse research applications as well as clinical diagnostics.
{"title":"SlipChip: From Principle to Applications","authors":"Yang Luo, Weijie Yuan, Sujin Jung, Feng Shen","doi":"10.1039/d5lc01069a","DOIUrl":"https://doi.org/10.1039/d5lc01069a","url":null,"abstract":"The SlipChip is a versatile microfluidic platform that enables precise control of fluidic connections through the relative sliding of two microstructured plates, without requiring external pumps or valves. SlipChip facilitates fluid aliquoting, mixing, and partitioning via a simple sliding operation induced microfluidic reconfiguration. Various designs have been developed and applied to nucleic acid assays, protein crystallization, protein analysis, single-cell analysis, and materials synthesis. Compared with conventional microfluidics, SlipChip offers advantages such as simple fluidic manipulation, on-chip reagent preloading, portability, and cost-effective fabrication in diverse materials (glass, PDMS, plastic, paper). This review summarizes the fluidic principles, device fabrication, and applications of SlipChip, highlighting representative architectures, driving mechanisms, and material considerations. We also address current limitations of SlipChip technology, particularly in terms of assembly precision and dependence on manual operation. Looking forward, advances in materials engineering, device automation, and artificial intelligence are anticipated to enhance assembly reliability and support increasingly autonomous workflows. These developments are poised to significantly broaden the role of SlipChip in systems biology, clinical diagnostics, and personalized medicine. Overall, SlipChip represents a simple, robust, and accessible microfluidic platform suitable for diverse research applications as well as clinical diagnostics.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146057106","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}
Khurshed Akabirov,Hanna Nguyen,Shakila Peli Thanthri,Sheila M Barros,Maximillian Chibuike,Sunggook Park,Steven A Soper
Nanopore sensing provides an ideal strategy for the label-free detection of single molecules in a variety of application scenarios. Working under the principle of resistive pulse sensing (RPS), nanopores consist of constrictions with sub-100 nm dimensions to enable single-molecule resolution by matching pore size to target dimensions (scaling); the optimal signal-to-noise ratio (SNR) results when the electrically biased pore is comparable in size to the molecule to be analyzed. When single molecules are electrokinetically transported through such remarkably small pores, they temporarily disturb the flux of ions moving through them, generating unique signals. These signals vary based upon the molecules' shape, size, orientation, and other physicochemical properties. Nanopores are generally divided into two main categories owing to their fabrication approach and material: biological and solid state. While biological nanopores have been the dominant sensor format due to their exceptionally small size, solid-state nanopores can demonstrate high performance characteristics attributed to their rigidity, stability, and high versatility in shape, material, and configuration. This review will explore the state-of-the-art in biological and solid-state nanopores and their abilities to detect and identify single biomolecules in a label-free manner. We will also review two topographical configurations of nanopore sensors; in-plane and out-of-plane sensors. The evolution of nanopore sensing will be reviewed, starting with out-of-plane biological sensors and progressing to in-plane sensors fabricated in plastics via replication technologies.
{"title":"The evolution of nanopore measurements: from biological out-of-plane pores to plastic in-plane pores.","authors":"Khurshed Akabirov,Hanna Nguyen,Shakila Peli Thanthri,Sheila M Barros,Maximillian Chibuike,Sunggook Park,Steven A Soper","doi":"10.1039/d5lc00885a","DOIUrl":"https://doi.org/10.1039/d5lc00885a","url":null,"abstract":"Nanopore sensing provides an ideal strategy for the label-free detection of single molecules in a variety of application scenarios. Working under the principle of resistive pulse sensing (RPS), nanopores consist of constrictions with sub-100 nm dimensions to enable single-molecule resolution by matching pore size to target dimensions (scaling); the optimal signal-to-noise ratio (SNR) results when the electrically biased pore is comparable in size to the molecule to be analyzed. When single molecules are electrokinetically transported through such remarkably small pores, they temporarily disturb the flux of ions moving through them, generating unique signals. These signals vary based upon the molecules' shape, size, orientation, and other physicochemical properties. Nanopores are generally divided into two main categories owing to their fabrication approach and material: biological and solid state. While biological nanopores have been the dominant sensor format due to their exceptionally small size, solid-state nanopores can demonstrate high performance characteristics attributed to their rigidity, stability, and high versatility in shape, material, and configuration. This review will explore the state-of-the-art in biological and solid-state nanopores and their abilities to detect and identify single biomolecules in a label-free manner. We will also review two topographical configurations of nanopore sensors; in-plane and out-of-plane sensors. The evolution of nanopore sensing will be reviewed, starting with out-of-plane biological sensors and progressing to in-plane sensors fabricated in plastics via replication technologies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"52 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056940","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}
Jaehyun Kim, Eunseok Seo, Na Yeon Kim, Bong Geun Chung, Jungchul Lee, Taesung Kim, Seung-Woo Cho, Gun Ho Kim, Sung Soo Kim, Jungyul Park
Low-temperature stimulation is recognized as a promising approach for neuromodulation, with the potential to suppress or slow neural activity. However, its impact on the spatial and electrophysiological properties of axonal conduction remains poorly understood. Conventional methods have lacked the spatial resolution necessary to isolate axon-specific responses to localized cooling. To overcome these limitations, we developed a microfluidic platform that integrates a microelectrode array (MEA) with a rapid and spatially confined cooling module. This platform enables real-time, phase-resolved monitoring of cooling-induced signal propagation between neuronal populations via unidirectionally guided axons, while maintaining structural integrity and enabling targeted thermal modulation. Using the microfluidic-MEA platform, we observed that one-minute cooling induced reversible suppression of both neuronal and axonal activity, followed by complete functional recovery. In contrast, five-minute cooling resulted in full recovery of neural network activity but persistent conduction delays in axons after rewarming, indicating selective vulnerability of axonal pathways and incomplete restoration of conduction dynamics. These outcomes were quantitatively validated through high-resolution electrophysiological recordings. Our findings demonstrate that localized cooling significantly modulates axonal conduction by altering ion channel kinetics and membrane excitability. The proposed platform offers a robust in vitro platform for dissecting cold-induced neuromodulation with axonal resolution, and lays the groundwork for precision-targeted neuromodulatory strategies in neuroengineering, brain-on-a-chip systems, and potential therapeutic applications for neurodegenerative disorders.
{"title":"Microfluidics-Guided Localized Low-Temperature Modulation of Axonal Signal Propagation","authors":"Jaehyun Kim, Eunseok Seo, Na Yeon Kim, Bong Geun Chung, Jungchul Lee, Taesung Kim, Seung-Woo Cho, Gun Ho Kim, Sung Soo Kim, Jungyul Park","doi":"10.1039/d5lc01103e","DOIUrl":"https://doi.org/10.1039/d5lc01103e","url":null,"abstract":"Low-temperature stimulation is recognized as a promising approach for neuromodulation, with the potential to suppress or slow neural activity. However, its impact on the spatial and electrophysiological properties of axonal conduction remains poorly understood. Conventional methods have lacked the spatial resolution necessary to isolate axon-specific responses to localized cooling. To overcome these limitations, we developed a microfluidic platform that integrates a microelectrode array (MEA) with a rapid and spatially confined cooling module. This platform enables real-time, phase-resolved monitoring of cooling-induced signal propagation between neuronal populations via unidirectionally guided axons, while maintaining structural integrity and enabling targeted thermal modulation. Using the microfluidic-MEA platform, we observed that one-minute cooling induced reversible suppression of both neuronal and axonal activity, followed by complete functional recovery. In contrast, five-minute cooling resulted in full recovery of neural network activity but persistent conduction delays in axons after rewarming, indicating selective vulnerability of axonal pathways and incomplete restoration of conduction dynamics. These outcomes were quantitatively validated through high-resolution electrophysiological recordings. Our findings demonstrate that localized cooling significantly modulates axonal conduction by altering ion channel kinetics and membrane excitability. The proposed platform offers a robust in vitro platform for dissecting cold-induced neuromodulation with axonal resolution, and lays the groundwork for precision-targeted neuromodulatory strategies in neuroengineering, brain-on-a-chip systems, and potential therapeutic applications for neurodegenerative disorders.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"184 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095751","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}
Aniruddha Paul, Eric R. Safai, Laura E. de Heus, Anke R. Vollertsen, Kevin Weijgertse, Bjorn de Wagenaar, Hossein E. Amirabadi, Evita van de Steeg, Mathieu Odijk, Andries D. van der Meer and Joshua Loessberg-Zahl
Organ-on-chips (OoC) have the potential to revolutionize drug testing. However, the fragmented landscape of existing OoC systems leads to wasted resources and collaboration barriers, slowing broader adoption. To unite the ecosystem, there is an urgent need for generic OoC platforms based on interoperability and modularity. Technology platforms based on open designs would enable seamless integration of diverse OoC models and components, facilitating translation. Our study introduces a modular microfluidic platform that integrates swappable modules for pumping, sensing, and OoCs, all within the ANSI/SLAS microplate footprint. Sub-components operate as microfluidic building blocks (MFBBs) and can interface with the demonstrated fluidic circuit board (FCB) universally as long as the designs adhere to ISO standards. The platform architecture allows tube-less inter-module interactions via arbitrary and reconfigurable fluidic circuits. We demonstrate two possible fluidic configurations which include in-line sensors and furthermore demonstrate biological functionality by running both in vitro and ex vivo OoC models for multiple days. This platform is designed to support automated multi-organ experiments, independent of the OoC type or material. All designs shown are made open source to encourage broader compatibility and collaboration.
{"title":"STARTER: a stand-alone reconfigurable and translational organ-on-chip platform based on modularity and open design principles","authors":"Aniruddha Paul, Eric R. Safai, Laura E. de Heus, Anke R. Vollertsen, Kevin Weijgertse, Bjorn de Wagenaar, Hossein E. Amirabadi, Evita van de Steeg, Mathieu Odijk, Andries D. van der Meer and Joshua Loessberg-Zahl","doi":"10.1039/D5LC00756A","DOIUrl":"10.1039/D5LC00756A","url":null,"abstract":"<p >Organ-on-chips (OoC) have the potential to revolutionize drug testing. However, the fragmented landscape of existing OoC systems leads to wasted resources and collaboration barriers, slowing broader adoption. To unite the ecosystem, there is an urgent need for generic OoC platforms based on interoperability and modularity. Technology platforms based on open designs would enable seamless integration of diverse OoC models and components, facilitating translation. Our study introduces a modular microfluidic platform that integrates swappable modules for pumping, sensing, and OoCs, all within the ANSI/SLAS microplate footprint. Sub-components operate as microfluidic building blocks (MFBBs) and can interface with the demonstrated fluidic circuit board (FCB) universally as long as the designs adhere to ISO standards. The platform architecture allows tube-less inter-module interactions <em>via</em> arbitrary and reconfigurable fluidic circuits. We demonstrate two possible fluidic configurations which include in-line sensors and furthermore demonstrate biological functionality by running both <em>in vitro</em> and <em>ex vivo</em> OoC models for multiple days. This platform is designed to support automated multi-organ experiments, independent of the OoC type or material. All designs shown are made open source to encourage broader compatibility and collaboration.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 604-617"},"PeriodicalIF":5.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/lc/d5lc00756a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044774","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}
The development of effective cancer therapies remains constrained by the complex and dynamic nature of the tumor microenvironment (TME), with tumor vasculature representing a critical barrier and modulator of treatment response. This review critically examines recent advances in the generation of vascularized tumor models using organ-on-a-chip (OoC) microfluidic technologies, emphasizing their capacity to recapitulate key interactions between tumor cells, stroma, and vasculature in vitro. We outline the mechanistic roles of tumor vasculature in therapy resistance, metastatic dissemination, and immune modulation, and highlight current strategies targeting vasculature for improved therapeutic outcomes. State-of-the-art biomaterials and engineering approaches, including template-based fabrication, self-organization, and the integration of patient-derived organoids, are discussed regarding their efficacy in constructing physiologically relevant vasculature. The review critically assesses findings from drug testing studies and discusses the translational potential of microfluidic platform capabilities, such as real-time monitoring, precise flow control, and functional assessment of vessel permeability and drug delivery, while identifying key limitations for clinical implementation. Challenges in standardization, scalability, and clinical translation are discussed, and recommendations are proposed to enhance the human-relevance and impact of vascularized OoC models in preclinical oncology research. These advanced platforms represent a transformative approach for bridging the translational gap between preclinical research and clinical oncology, offering opportunities to advance personalized cancer therapeutics and improve patient outcomes.
{"title":"Engineering perfusion to meet tumor biology: are vascularized tumor-on-a-chip models ready to drive therapy innovation?","authors":"Ines Poljak, Ciro Chiappini, Giulia Adriani","doi":"10.1039/d5lc01060h","DOIUrl":"https://doi.org/10.1039/d5lc01060h","url":null,"abstract":"The development of effective cancer therapies remains constrained by the complex and dynamic nature of the tumor microenvironment (TME), with tumor vasculature representing a critical barrier and modulator of treatment response. This review critically examines recent advances in the generation of vascularized tumor models using organ-on-a-chip (OoC) microfluidic technologies, emphasizing their capacity to recapitulate key interactions between tumor cells, stroma, and vasculature <em>in vitro</em>. We outline the mechanistic roles of tumor vasculature in therapy resistance, metastatic dissemination, and immune modulation, and highlight current strategies targeting vasculature for improved therapeutic outcomes. State-of-the-art biomaterials and engineering approaches, including template-based fabrication, self-organization, and the integration of patient-derived organoids, are discussed regarding their efficacy in constructing physiologically relevant vasculature. The review critically assesses findings from drug testing studies and discusses the translational potential of microfluidic platform capabilities, such as real-time monitoring, precise flow control, and functional assessment of vessel permeability and drug delivery, while identifying key limitations for clinical implementation. Challenges in standardization, scalability, and clinical translation are discussed, and recommendations are proposed to enhance the human-relevance and impact of vascularized OoC models in preclinical oncology research. These advanced platforms represent a transformative approach for bridging the translational gap between preclinical research and clinical oncology, offering opportunities to advance personalized cancer therapeutics and improve patient outcomes.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"51 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044737","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}
Peilong Li, Yunfan Li, Jiajie Zhan, Deng Wang, Ruyu Zhang, Feng Liu
Microfluidic lab-on-a-chip technology has shown great potential in various fields such as bioscience, medical diagnostics, and environmental monitoring. However, its widespread adoption has been hindered by challenges in functional integration, operational autonomy, and manufacturing scalability. To address these limitations, we present a 3D-printed self-sensing magnetically actuated microfluidic (SMAM) chip designed for autonomous bioanalysis. This innovative device utilizes stereolithography apparatus (SLA) 3D printing to rapidly prototype and integrate microchannel networks alongside with a magnetically driven functional module. The chip employs magnetic actuation for precise, wireless manipulation of fluids within the microchannels, eliminating the need for bulky external pumps. Additionally, the system features an integrated self-sensing mechanism, enabling flow monitoring and on-chip analyte detection. The SMAM chip demonstrates exceptional dual-function performance, achieving a high pumping flow rate of up to 972 µL/min and a good piezoresistive sensitivity of 43.1 MPa⁻¹. We first demonstrate its system-level utility by assembling the chip into a modular, wirelessly monitored microfluidic platform with an integrated flow rectifier. Furthermore, its potential for therapeutic interventions is validated through a proof-of-concept of an untethered device for magnetically guided, on-demand drug release. This work provides a novel approach for developing intelligent analytical devices, promising to enable new paradigms in automated biological research and diagnostics.
{"title":"3D-printed self-sensing magnetically actuated microfluidic chip for closed-loop drug delivery","authors":"Peilong Li, Yunfan Li, Jiajie Zhan, Deng Wang, Ruyu Zhang, Feng Liu","doi":"10.1039/d5lc01006c","DOIUrl":"https://doi.org/10.1039/d5lc01006c","url":null,"abstract":"Microfluidic lab-on-a-chip technology has shown great potential in various fields such as bioscience, medical diagnostics, and environmental monitoring. However, its widespread adoption has been hindered by challenges in functional integration, operational autonomy, and manufacturing scalability. To address these limitations, we present a 3D-printed self-sensing magnetically actuated microfluidic (SMAM) chip designed for autonomous bioanalysis. This innovative device utilizes stereolithography apparatus (SLA) 3D printing to rapidly prototype and integrate microchannel networks alongside with a magnetically driven functional module. The chip employs magnetic actuation for precise, wireless manipulation of fluids within the microchannels, eliminating the need for bulky external pumps. Additionally, the system features an integrated self-sensing mechanism, enabling flow monitoring and on-chip analyte detection. The SMAM chip demonstrates exceptional dual-function performance, achieving a high pumping flow rate of up to 972 µL/min and a good piezoresistive sensitivity of 43.1 MPa⁻¹. We first demonstrate its system-level utility by assembling the chip into a modular, wirelessly monitored microfluidic platform with an integrated flow rectifier. Furthermore, its potential for therapeutic interventions is validated through a proof-of-concept of an untethered device for magnetically guided, on-demand drug release. This work provides a novel approach for developing intelligent analytical devices, promising to enable new paradigms in automated biological research and diagnostics.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034221","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}
Guohao Yang, Seonghun Shin, Seongsu Cho, Jinkee Lee, Ryungeun Song
Three-dimensional (3D) printing has emerged as a promising method for fabricating microfluidic devices due to its rapid prototyping, adaptability, and cost-effectiveness. However, the intrinsic hydrophobicity of commercial photocurable resins limits their ability to generate stable oil-in-water (O/W) emulsions droplets. In this study, we addressed this limitation by introducing a simple yet effective surface modification technique, photochemical grafting, which covalently attaches hydrophilic methacrylic acid group onto the surfaces of 3D-printed channels, enabling reliable monodisperse O/W droplets formation. Integrating two modules with contrasting wettabilities yields a modular platform for single-step production of double emulsions (W/O/W and O/W/O). The result is a versatile system with precise control over droplet formation and exceptional monodispersity with tunable shell-to-core ratios. The grafted surfaces retained wettability and dropletgeneration performance after three months of storage and 15 hours of continuous shear. Collectively, this work presents a robust and scalable strategy to bridge rapid 3D printing with durable surface functionalization, expanding the potential of customizable emulsion generation in lab-on-a-chip applications.
{"title":"Surface modification of 3D printed microfluidic device by photochemical grafting","authors":"Guohao Yang, Seonghun Shin, Seongsu Cho, Jinkee Lee, Ryungeun Song","doi":"10.1039/d5lc00994d","DOIUrl":"https://doi.org/10.1039/d5lc00994d","url":null,"abstract":"Three-dimensional (3D) printing has emerged as a promising method for fabricating microfluidic devices due to its rapid prototyping, adaptability, and cost-effectiveness. However, the intrinsic hydrophobicity of commercial photocurable resins limits their ability to generate stable oil-in-water (O/W) emulsions droplets. In this study, we addressed this limitation by introducing a simple yet effective surface modification technique, photochemical grafting, which covalently attaches hydrophilic methacrylic acid group onto the surfaces of 3D-printed channels, enabling reliable monodisperse O/W droplets formation. Integrating two modules with contrasting wettabilities yields a modular platform for single-step production of double emulsions (W/O/W and O/W/O). The result is a versatile system with precise control over droplet formation and exceptional monodispersity with tunable shell-to-core ratios. The grafted surfaces retained wettability and dropletgeneration performance after three months of storage and 15 hours of continuous shear. Collectively, this work presents a robust and scalable strategy to bridge rapid 3D printing with durable surface functionalization, expanding the potential of customizable emulsion generation in lab-on-a-chip applications.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"288 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044775","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}
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