Xu Du, Masaru Tsujii, Nobuyuki Uozumi, Fumihito Arai
How cells mechanically respond to rapid stimulation in the extracellular microenvironment is a key question for understanding the physiological functions of mechanosensitive (MS) channels. In this study, we investigated the single Synechocystis sp. PCC 6803 cell transient mechanical response under osmotic downshock using a microfluidic system that assembles a robot-integrated microfluidic chip with a synchronized injection-aspiration liquid switching module. Through theoretical analysis and system optimization, we achieved high-speed, localized liquid switching on the millisecond scale while simultaneously measuring cell deformation and reactive force. Using this system, we compared the Young's modulus of wild-type (WT) and MS channel-deficient mutant (ΔmscL) cells in hypoosmotic and hyperosmotic conditions, and quantified their transient mechanical responses under millisecond-scale liquid switching times. In particular, we compared the response time and key deformation parameters (expansion and shrinkage rates) of the two strains when the cells were compressed under osmotic downshock. Multi-parameter analysis suggested that MscL transiently gates to buffer membrane tension during osmotic downshock, thereby delaying deformation and preventing excessive swelling or rupture. These findings advance the understanding of cellular mechanical adaptation under rapid environmental transitions and demonstrate the broad applicability of this integrated microfluidic system for high-speed liquid switching and synchronous force sensing in single-cell mechanobiological studies.
{"title":"High-Speed Liquid Switching and On-Chip Force Sensing Reveal the Transient Mechanical Response of MscL in Synechocystis sp. PCC 6803","authors":"Xu Du, Masaru Tsujii, Nobuyuki Uozumi, Fumihito Arai","doi":"10.1039/d6lc00004e","DOIUrl":"https://doi.org/10.1039/d6lc00004e","url":null,"abstract":"How cells mechanically respond to rapid stimulation in the extracellular microenvironment is a key question for understanding the physiological functions of mechanosensitive (MS) channels. In this study, we investigated the single Synechocystis sp. PCC 6803 cell transient mechanical response under osmotic downshock using a microfluidic system that assembles a robot-integrated microfluidic chip with a synchronized injection-aspiration liquid switching module. Through theoretical analysis and system optimization, we achieved high-speed, localized liquid switching on the millisecond scale while simultaneously measuring cell deformation and reactive force. Using this system, we compared the Young's modulus of wild-type (WT) and MS channel-deficient mutant (ΔmscL) cells in hypoosmotic and hyperosmotic conditions, and quantified their transient mechanical responses under millisecond-scale liquid switching times. In particular, we compared the response time and key deformation parameters (expansion and shrinkage rates) of the two strains when the cells were compressed under osmotic downshock. Multi-parameter analysis suggested that MscL transiently gates to buffer membrane tension during osmotic downshock, thereby delaying deformation and preventing excessive swelling or rupture. These findings advance the understanding of cellular mechanical adaptation under rapid environmental transitions and demonstrate the broad applicability of this integrated microfluidic system for high-speed liquid switching and synchronous force sensing in single-cell mechanobiological studies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447864","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}
Alexander Bevacqua, Fuguo Liu, Jianzhu Chen, Jongyoon Han
Scalable production of cell therapy doses relies on inexpensive, efficient production of gene delivery vectors, such as lentiviral vectors, in HEK293 cell culture. Intensified perfusion processes improve the volumetric productivity of cell culture by continuously supplying nutrients, oxygen, and media to cells while removing harmful metabolites, thereby enabling higher producer cell densities. Membrane filter-based cell retention devices commonly used in perfusion bioprocessing can experience significant clogging and fouling over long-term processes, which leads to the undesired retention of lentiviral vectors in the filter matrix. In this work, we used spiral microfluidic technology as a cell retention device to continuously harvest lentiviral vectors and remove metabolic waste from HEK293 cells in a bioreactor running high cell density perfusion cultures. With the spiral microfluidic device, we performed four perfusion culture runs with maximum cell densities between 15×106 and 25×106 cells/mL, achieving up to seven days of continuous LV production and lossless harvesting with maximum, unconcentrated, functional titers on the order of 108 transducing units (TU) per mL. These production titers are competitive with other bioprocessing approaches in industry and academia. The highest cell-specific productivity (over 50 TU cell−1 day−1) and cell-specific yields of our study (over 80 TU cell−1) were achieved when using spiral device-mediated perfusion bioprocessing to cultivate cells and then transferring the cells to a shake flask environment with daily media replacement to generate lentiviral vectors.
{"title":"Intensified lentiviral vector perfusion bioprocessing with a spiral inertial microfluidic cell retention device","authors":"Alexander Bevacqua, Fuguo Liu, Jianzhu Chen, Jongyoon Han","doi":"10.1039/d6lc00029k","DOIUrl":"https://doi.org/10.1039/d6lc00029k","url":null,"abstract":"Scalable production of cell therapy doses relies on inexpensive, efficient production of gene delivery vectors, such as lentiviral vectors, in HEK293 cell culture. Intensified perfusion processes improve the volumetric productivity of cell culture by continuously supplying nutrients, oxygen, and media to cells while removing harmful metabolites, thereby enabling higher producer cell densities. Membrane filter-based cell retention devices commonly used in perfusion bioprocessing can experience significant clogging and fouling over long-term processes, which leads to the undesired retention of lentiviral vectors in the filter matrix. In this work, we used spiral microfluidic technology as a cell retention device to continuously harvest lentiviral vectors and remove metabolic waste from HEK293 cells in a bioreactor running high cell density perfusion cultures. With the spiral microfluidic device, we performed four perfusion culture runs with maximum cell densities between 15×10<small><sup>6</sup></small> and 25×10<small><sup>6</sup></small> cells/mL, achieving up to seven days of continuous LV production and lossless harvesting with maximum, unconcentrated, functional titers on the order of 10<small><sup>8</sup></small> transducing units (TU) per mL. These production titers are competitive with other bioprocessing approaches in industry and academia. The highest cell-specific productivity (over 50 TU cell<small><sup>−1</sup></small> day<small><sup>−1</sup></small>) and cell-specific yields of our study (over 80 TU cell<small><sup>−1</sup></small>) were achieved when using spiral device-mediated perfusion bioprocessing to cultivate cells and then transferring the cells to a shake flask environment with daily media replacement to generate lentiviral vectors.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393525","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}
Emma Kals, Morten Kals, Viola Introini, Boyko Vodenicharski, Jurij Kotar, Julian C Rayner, Pietro Cicuta
Understanding the impact of forces generated by blood flow on biological processes in the circulatory system, such as the growth of malaria parasites, is currently limited by the lack of experimental systems that integrate them. Recent systematic quantification of the growth of Plasmodium falciparum -the species that causes the majority of malaria mortality -under a range of shaking conditions has shown that parasite invasion of erythrocytes is affected by the shear stress to which the interacting cells are exposed. Blood flow could similarly impact shear stress and therefore invasion in vivo, but there is currently no method to precisely test the impact of flow-induced forces on parasite invasion. We have developed a microfluidic device with four channels, each with dimensions similar to those of a post-capillary venule, but with different flow velocities. Highly synchronised P. falciparum parasites are injected into the device, and parasite egress and invasion are quantified using newly developed custom video analysis, which fully automates cell type identification and trajectory tracking. The device was tested with both wild-type P. falciparum lines and lines where genes encoding proteins involved in parasite attachment had been deleted. Deletion of Erythrocyte Binding Antigen 175 (PfEBA175) has a significant impact on invasion under flow, but not in static culture. These findings establish for the first time that flow conditions may have a critical effect on parasite invasion. The method can be applied to other biological processes affected by fluid motion, such as cell adhesion, migration, and mechanotransduction.
{"title":"Microfluidic Platform for Automatic Quantification of Malaria Parasite Invasion Under Physiological Flow Conditions","authors":"Emma Kals, Morten Kals, Viola Introini, Boyko Vodenicharski, Jurij Kotar, Julian C Rayner, Pietro Cicuta","doi":"10.1039/d5lc00748h","DOIUrl":"https://doi.org/10.1039/d5lc00748h","url":null,"abstract":"Understanding the impact of forces generated by blood flow on biological processes in the circulatory system, such as the growth of malaria parasites, is currently limited by the lack of experimental systems that integrate them. Recent systematic quantification of the growth of Plasmodium falciparum -the species that causes the majority of malaria mortality -under a range of shaking conditions has shown that parasite invasion of erythrocytes is affected by the shear stress to which the interacting cells are exposed. Blood flow could similarly impact shear stress and therefore invasion in vivo, but there is currently no method to precisely test the impact of flow-induced forces on parasite invasion. We have developed a microfluidic device with four channels, each with dimensions similar to those of a post-capillary venule, but with different flow velocities. Highly synchronised P. falciparum parasites are injected into the device, and parasite egress and invasion are quantified using newly developed custom video analysis, which fully automates cell type identification and trajectory tracking. The device was tested with both wild-type P. falciparum lines and lines where genes encoding proteins involved in parasite attachment had been deleted. Deletion of Erythrocyte Binding Antigen 175 (PfEBA175) has a significant impact on invasion under flow, but not in static culture. These findings establish for the first time that flow conditions may have a critical effect on parasite invasion. The method can be applied to other biological processes affected by fluid motion, such as cell adhesion, migration, and mechanotransduction.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"8 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383925","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}
Surface topography is a key regulator of cell behavior, and high-throughput screening enables the systematic identification of patterns that direct specific cell fates. Hydroxyapatite (HA) is widely used as a bone substitute, yet precise fabrication of micropatterned HA surfaces and their role in contact guidance remain largely unexplored. Here, we report an HA-coated micropatterned TopoChip incorporating groove and pillar arrays with feature sizes ranging from 3 µm to 50 µm. Using bone marrow-derived mesenchymal stem cells (BMSCs), we screened cellular responses to these topographies and identified geometries that strongly promoted osteogenic differentiation. Grooves induced more pronounced contact guidance than pillars, with narrow ridges and small inter-pillar spacing driving cell elongation and alignment. These micropatterns enhanced focal adhesion formation and cytoskeletal tension, leading to upregulated osteogenesis. Importantly, the selected patterns accelerated bone regeneration in rat cranial defect models. This work establishes a facile strategy for fabricating HA micropattern libraries, elucidates the mechanisms by which topography directs osteogenesis, and provides design principles for orthopedic and dental biomaterials aimed at improving bone regeneration.
{"title":"TopoChip-Based High-Throughput Screening of Micropatterned Hydroxyapatite to Guide Stem Cell Behavior and Accelerate Bone Regeneration","authors":"Yada Li, Chuanxin Zhong, Mingyu Zhu, Junqin Wang, Qiming Zhuang, Yuqi Tang, Jianfeng Yan, Xiang Ge, Ju Fang, Fuzeng Ren","doi":"10.1039/d5lc01166c","DOIUrl":"https://doi.org/10.1039/d5lc01166c","url":null,"abstract":"Surface topography is a key regulator of cell behavior, and high-throughput screening enables the systematic identification of patterns that direct specific cell fates. Hydroxyapatite (HA) is widely used as a bone substitute, yet precise fabrication of micropatterned HA surfaces and their role in contact guidance remain largely unexplored. Here, we report an HA-coated micropatterned TopoChip incorporating groove and pillar arrays with feature sizes ranging from 3 µm to 50 µm. Using bone marrow-derived mesenchymal stem cells (BMSCs), we screened cellular responses to these topographies and identified geometries that strongly promoted osteogenic differentiation. Grooves induced more pronounced contact guidance than pillars, with narrow ridges and small inter-pillar spacing driving cell elongation and alignment. These micropatterns enhanced focal adhesion formation and cytoskeletal tension, leading to upregulated osteogenesis. Importantly, the selected patterns accelerated bone regeneration in rat cranial defect models. This work establishes a facile strategy for fabricating HA micropattern libraries, elucidates the mechanisms by which topography directs osteogenesis, and provides design principles for orthopedic and dental biomaterials aimed at improving bone regeneration.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454529","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}
Lu Zhong, Hang Chen, Hong-Lei Chen, Jun Peng, Zhi-Ling Zhang
The demand for efficient detection of tumor biomarkers in clinical settings is growing. Traditional immunohistochemistry (IHC) is time-consuming and labor-intensive, making rapid IHC technologies essential for improving efficiency in pathological diagnosis. Microfluidic technology, characterized by miniaturization, high throughput, and automation, has emerged as one of the most promising approaches for advancing rapid tissue diagnostics. This study designed a fluid distribution channel with excellent uniformity and developed a microfluidic chip featuring an upper V-groove structure, based on a passive mixing strategy in microfluidic systems. This chip effectively enhances the mixing efficiency of antigens and antibodies without relying on external field-driven mechanisms. Furthermore, a novel, automated, and integrated microfluidic platform was constructed to achieve rapid, reliable, and automated immunohistochemical staining. Experimental results demonstrated that the immunohistochemical staining performance obtained with this chip is comparable to that of conventional methods, exhibiting excellent uniformity and reproducibility. The staining time for markers such as CK and Ki-67 in tissue samples can be reduced to 11 minutes, representing a 90% time saving compared to traditional methods.
{"title":"An automated microfluidic system based on V-groove chip for rapid immunohistochemistry","authors":"Lu Zhong, Hang Chen, Hong-Lei Chen, Jun Peng, Zhi-Ling Zhang","doi":"10.1039/d6lc00089d","DOIUrl":"https://doi.org/10.1039/d6lc00089d","url":null,"abstract":"The demand for efficient detection of tumor biomarkers in clinical settings is growing. Traditional immunohistochemistry (IHC) is time-consuming and labor-intensive, making rapid IHC technologies essential for improving efficiency in pathological diagnosis. Microfluidic technology, characterized by miniaturization, high throughput, and automation, has emerged as one of the most promising approaches for advancing rapid tissue diagnostics. This study designed a fluid distribution channel with excellent uniformity and developed a microfluidic chip featuring an upper V-groove structure, based on a passive mixing strategy in microfluidic systems. This chip effectively enhances the mixing efficiency of antigens and antibodies without relying on external field-driven mechanisms. Furthermore, a novel, automated, and integrated microfluidic platform was constructed to achieve rapid, reliable, and automated immunohistochemical staining. Experimental results demonstrated that the immunohistochemical staining performance obtained with this chip is comparable to that of conventional methods, exhibiting excellent uniformity and reproducibility. The staining time for markers such as CK and Ki-67 in tissue samples can be reduced to 11 minutes, representing a 90% time saving compared to traditional methods.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"82 7 SC 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383931","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}
Linda Marriott, Ana Martinez Lopez, Antonio Liga, Kazuhiro Horiba, Amanda Warr, Jacob N Phulusa, Radhe Shantha Kumar, Laura Carey, Nicholas R. Leslie, Yoshinori Ito, Benjamin J Parcell, Nicholas A Feasey, Shevin T Jacob, Jamie Rylance, Maïwenn Kersaudy-Kerhoas
The prompt identification of pathogens in human circulation in a clinically deployable format remains an unmet clinical need. The established test for infection diagnostics remains blood culture, which typically takes 2-4 days and is positive in less than 15% of cases, with many prevalent pathogens difficult or impossible to culture. While microbial cfDNA in blood could facilitate the diagnosis of sepsis and febrile and infectious conditions, sample preparation for cell-free DNA (cfDNA) analysis in decentralised settings presents challenges due to its complexity and the low concentration and fragmented nature of cfDNA in blood plasma. We developed a portable and automated platform (CNASafe) for cfDNA isolation from human plasma samples. Device performance was evaluated by comparing cfDNA yield against a reference (QIAGEN QIAamp Circulating Nucleic Acid Kit). cfDNA eluates from ten non-cultured blood samples from hospital patients were sequenced on a nanopore sequencer, and results compared to blood cultures. Extraction of cfDNA using the CNASafe device was completed in 40 minutes, compared to the 2-hour reference protocol. The device achieved an average relative cfDNA recovery of 100.5% over 333 unique extractions encompassing all parameter variations, demonstrating a performance equivalent to the reference kit. From the patient samples, a sufficient quantity of microbial cfDNA was extracted to either identify pathogens missed by blood cultures or confirm negative cultures. The CNASafe platform and real-time nanopore sequencing offer a promising solution for the rapid deployment of metagenomic diagnostics, enabling pathogen identification within a few hours in decentralised clinical environments.
{"title":"An Automated and Portable Platform for Rapid Cell-Free DNA Isolation and Its Application in Microbial DNA metagenomic Sequencing from Human Blood Samples","authors":"Linda Marriott, Ana Martinez Lopez, Antonio Liga, Kazuhiro Horiba, Amanda Warr, Jacob N Phulusa, Radhe Shantha Kumar, Laura Carey, Nicholas R. Leslie, Yoshinori Ito, Benjamin J Parcell, Nicholas A Feasey, Shevin T Jacob, Jamie Rylance, Maïwenn Kersaudy-Kerhoas","doi":"10.1039/d5lc00876j","DOIUrl":"https://doi.org/10.1039/d5lc00876j","url":null,"abstract":"The prompt identification of pathogens in human circulation in a clinically deployable format remains an unmet clinical need. The established test for infection diagnostics remains blood culture, which typically takes 2-4 days and is positive in less than 15% of cases, with many prevalent pathogens difficult or impossible to culture. While microbial cfDNA in blood could facilitate the diagnosis of sepsis and febrile and infectious conditions, sample preparation for cell-free DNA (cfDNA) analysis in decentralised settings presents challenges due to its complexity and the low concentration and fragmented nature of cfDNA in blood plasma. We developed a portable and automated platform (CNASafe) for cfDNA isolation from human plasma samples. Device performance was evaluated by comparing cfDNA yield against a reference (QIAGEN QIAamp Circulating Nucleic Acid Kit). cfDNA eluates from ten non-cultured blood samples from hospital patients were sequenced on a nanopore sequencer, and results compared to blood cultures. Extraction of cfDNA using the CNASafe device was completed in 40 minutes, compared to the 2-hour reference protocol. The device achieved an average relative cfDNA recovery of 100.5% over 333 unique extractions encompassing all parameter variations, demonstrating a performance equivalent to the reference kit. From the patient samples, a sufficient quantity of microbial cfDNA was extracted to either identify pathogens missed by blood cultures or confirm negative cultures. The CNASafe platform and real-time nanopore sequencing offer a promising solution for the rapid deployment of metagenomic diagnostics, enabling pathogen identification within a few hours in decentralised clinical environments.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"52 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383926","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}
Particulate matter (PM) is a major component of urban air pollution and is strongly associated with respiratory diseases. However, the mechanisms of PM-induced inflammation remain poorly understood due to a lack of physiologically relevant airway models which can incorporate PM exposure.To address this, we used our nasal airway-on-chip platform to establish a co-culture model of human nasal epithelial cells and human pulmonary microvascular endothelial cells and used this model to investigate the effects of PM exposure on the nasal airway. In particular, we sought to understand the PM-induced reactive oxygen species (ROS)-mediated inflammatory response of the co-culture. Upon PM exposure, we observed a significant increase in ROS production consistent with oxidative stress-mediated injury. Additionally, treatment with the ROS scavenger N-acetyl-cysteine attenuated ROS levels and showed a trend toward reduced inflammation, suggesting a protective effect. These findings support the utility of our model for studying PM-induced airway inflammation in a more physiologically-relevant environment.
{"title":"Development of a nasal airway-on-chip co-culture model to study particulate matter exposure","authors":"Amanda Walls, Adrienne Vaughan, Kartik Balachandran","doi":"10.1039/d5lc00978b","DOIUrl":"https://doi.org/10.1039/d5lc00978b","url":null,"abstract":"Particulate matter (PM) is a major component of urban air pollution and is strongly associated with respiratory diseases. However, the mechanisms of PM-induced inflammation remain poorly understood due to a lack of physiologically relevant airway models which can incorporate PM exposure.To address this, we used our nasal airway-on-chip platform to establish a co-culture model of human nasal epithelial cells and human pulmonary microvascular endothelial cells and used this model to investigate the effects of PM exposure on the nasal airway. In particular, we sought to understand the PM-induced reactive oxygen species (ROS)-mediated inflammatory response of the co-culture. Upon PM exposure, we observed a significant increase in ROS production consistent with oxidative stress-mediated injury. Additionally, treatment with the ROS scavenger N-acetyl-cysteine attenuated ROS levels and showed a trend toward reduced inflammation, suggesting a protective effect. These findings support the utility of our model for studying PM-induced airway inflammation in a more physiologically-relevant environment.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"405 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371148","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}
Gabrielle Saint-Girons,Kaustav A Gopinathan,Sajad Razavi Bazaz,Li Zhan,Jon F Edd,Mehmet Toner
Although several contact-free trapping techniques exist in microfluidics - such as optical, acoustic, and dielectrophoretic - these approaches often face tradeoffs including: limited area, fine tuning, or special buffers. Here, we introduce the microfluidic oscillatory asymmetrical trap (MOAT), an oscillatory Reynolds number-dependent phenomenon that overcomes these limitations. The MOAT enables stable, contact-free trapping under a bias flow through pressure oscillations, but only in devices with streamwise geometric asymmetry. Our investigation of this phenomenon involves experiments conducted on a 3D-printed plane expansion chip and associated numerical simulations. We measure trapping efficiency and strength, propose a physical explanation, and outline a parameter space in which this phenomenon occurs. Notably, trapping behavior manifests across diverse devices and particle types, spanning from plastic beads to cell lines. Trapping efficiency is highest when particle streamlines intersect the trap regions, meaning that upstream pre-focusing-by e.g. inertial focusing, as employed here, enhances contactless trapping.
{"title":"Oscillatory flow for contactless particle trapping.","authors":"Gabrielle Saint-Girons,Kaustav A Gopinathan,Sajad Razavi Bazaz,Li Zhan,Jon F Edd,Mehmet Toner","doi":"10.1039/d5lc00813a","DOIUrl":"https://doi.org/10.1039/d5lc00813a","url":null,"abstract":"Although several contact-free trapping techniques exist in microfluidics - such as optical, acoustic, and dielectrophoretic - these approaches often face tradeoffs including: limited area, fine tuning, or special buffers. Here, we introduce the microfluidic oscillatory asymmetrical trap (MOAT), an oscillatory Reynolds number-dependent phenomenon that overcomes these limitations. The MOAT enables stable, contact-free trapping under a bias flow through pressure oscillations, but only in devices with streamwise geometric asymmetry. Our investigation of this phenomenon involves experiments conducted on a 3D-printed plane expansion chip and associated numerical simulations. We measure trapping efficiency and strength, propose a physical explanation, and outline a parameter space in which this phenomenon occurs. Notably, trapping behavior manifests across diverse devices and particle types, spanning from plastic beads to cell lines. Trapping efficiency is highest when particle streamlines intersect the trap regions, meaning that upstream pre-focusing-by e.g. inertial focusing, as employed here, enhances contactless trapping.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"53 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350811","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}
Qikai Wang,Wenwen Shi,Qihang Yang,Feng Teng,Qiuhong Cui
To address the low light-harvesting efficiency, rapid charge recombination, and restricted mass transport in conventional photocatalysts, this study proposes a bio-inspired SiO2@TiO2 photocatalytic microsphere reactor (ST-PCMR), rapidly fabricated via microfluidic technology and confined self-assembly. This reactor employs an ordered macroporous SiO2 framework as a mechanical support and a rapid mass transfer channel, while a high-surface-area interconnected mesoporous TiO2 catalytic network is constructed under spatial confinement. By tuning the size of the SiO2 nanoparticles, the photonic band-gap was precisely matched with the absorption edge of TiO2, significantly enhancing light absorption via the slow-photon effect. The confinement effect further induced the formation of Ti-O-Si bonded interfaces and high-density grain boundaries, which effectively accelerated the separation and suppressed the recombination of photogenerated charge carriers, leading to a significant increase in photocurrent density and a notable reduction in charge-transfer resistance compared to non-confined TiO2. Under identical illumination conditions, the ST-PCMR exhibited excellent hydrogen production performance, showing an activity 8 times higher than that of single-component TiO2, with 86% retention of its initial activity after five cycles. This study provides a new material paradigm for synergistically optimizing light harvesting, charge separation, and reaction transport, offering a promising pathway for highly efficient solar-to-hydrogen conversion.
{"title":"Macroporous transport - mesoporous catalysis: a rapid microfluidic-fabricated biomimetic sponge photocatalytic microsphere reactor.","authors":"Qikai Wang,Wenwen Shi,Qihang Yang,Feng Teng,Qiuhong Cui","doi":"10.1039/d6lc00078a","DOIUrl":"https://doi.org/10.1039/d6lc00078a","url":null,"abstract":"To address the low light-harvesting efficiency, rapid charge recombination, and restricted mass transport in conventional photocatalysts, this study proposes a bio-inspired SiO2@TiO2 photocatalytic microsphere reactor (ST-PCMR), rapidly fabricated via microfluidic technology and confined self-assembly. This reactor employs an ordered macroporous SiO2 framework as a mechanical support and a rapid mass transfer channel, while a high-surface-area interconnected mesoporous TiO2 catalytic network is constructed under spatial confinement. By tuning the size of the SiO2 nanoparticles, the photonic band-gap was precisely matched with the absorption edge of TiO2, significantly enhancing light absorption via the slow-photon effect. The confinement effect further induced the formation of Ti-O-Si bonded interfaces and high-density grain boundaries, which effectively accelerated the separation and suppressed the recombination of photogenerated charge carriers, leading to a significant increase in photocurrent density and a notable reduction in charge-transfer resistance compared to non-confined TiO2. Under identical illumination conditions, the ST-PCMR exhibited excellent hydrogen production performance, showing an activity 8 times higher than that of single-component TiO2, with 86% retention of its initial activity after five cycles. This study provides a new material paradigm for synergistically optimizing light harvesting, charge separation, and reaction transport, offering a promising pathway for highly efficient solar-to-hydrogen conversion.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"43 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346467","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}
Darragh G Kennedy,Wenting Zhao,Terry L Chern,Michael Yang,Nicolas Acosta,Siddarth Arumugam,Pavan Upadhyayula,Julia Furnari,Athanassios Dovas,Jeffrey N Bruce,Peter Canoll,Samuel K Sia,Peter A Sims
New approaches are needed to screen anti-cancer drugs that can target specific subpopulations of tumor cells. This study presents a microfluidic chip that enables parallel culture and drug perturbation of five thick tissue slices from human GBM resections, and removes the slices non-destructively for downstream single-cell RNA sequencing (scRNA-seq). Importantly, in contrast to methods relying on chemical attachment of tissue to chip, mechanical clamping of layers allows for positive-pressure perfusion of 3D slices and nondisruptive dissociation of tissue slices from the microfluidic chip. We ran the dissociable perfusion chip (DPC) on slice cultures freshly resected from human glioblastoma (within 1 h of surgery), one of the deadliest forms of malignant brain tumor which exhibits profound intra-tumoral heterogeneity that is challenging to recapitulate even with patient-derived models. DPC maintained similar fluidic conditions between channels and high cell viability in slices, and enabled downstream scRNA-seq to confirm that a topoisomerase inhibitor targets a subpopulation of proliferating tumor cells. Tissues run on DPC showed oxidative stress levels more similar to uncultured GBM slices compared to Transwell culture, as demonstrated by scRNA-seq, fluorometric assessment on a separate human patient sample, and assessment of long-term viability in mouse GBM samples under low and high oxygen tension. Overall, this proof-of-concept work suggests that combining DPC with off-chip scRNA-seq enables rapid, high-resolution identification of cell type-specific drug responses directly in GBM tissue from individual patients. Future work will aim to use this approach for screening of multiple drugs and further validation on additional fresh human GBM slices.
{"title":"Dissociable perfusion chip (DPC): perfusable microfluidic chip for single-cell screening of anti-cancer drugs in live glioblastoma explants.","authors":"Darragh G Kennedy,Wenting Zhao,Terry L Chern,Michael Yang,Nicolas Acosta,Siddarth Arumugam,Pavan Upadhyayula,Julia Furnari,Athanassios Dovas,Jeffrey N Bruce,Peter Canoll,Samuel K Sia,Peter A Sims","doi":"10.1039/d5lc01105a","DOIUrl":"https://doi.org/10.1039/d5lc01105a","url":null,"abstract":"New approaches are needed to screen anti-cancer drugs that can target specific subpopulations of tumor cells. This study presents a microfluidic chip that enables parallel culture and drug perturbation of five thick tissue slices from human GBM resections, and removes the slices non-destructively for downstream single-cell RNA sequencing (scRNA-seq). Importantly, in contrast to methods relying on chemical attachment of tissue to chip, mechanical clamping of layers allows for positive-pressure perfusion of 3D slices and nondisruptive dissociation of tissue slices from the microfluidic chip. We ran the dissociable perfusion chip (DPC) on slice cultures freshly resected from human glioblastoma (within 1 h of surgery), one of the deadliest forms of malignant brain tumor which exhibits profound intra-tumoral heterogeneity that is challenging to recapitulate even with patient-derived models. DPC maintained similar fluidic conditions between channels and high cell viability in slices, and enabled downstream scRNA-seq to confirm that a topoisomerase inhibitor targets a subpopulation of proliferating tumor cells. Tissues run on DPC showed oxidative stress levels more similar to uncultured GBM slices compared to Transwell culture, as demonstrated by scRNA-seq, fluorometric assessment on a separate human patient sample, and assessment of long-term viability in mouse GBM samples under low and high oxygen tension. Overall, this proof-of-concept work suggests that combining DPC with off-chip scRNA-seq enables rapid, high-resolution identification of cell type-specific drug responses directly in GBM tissue from individual patients. Future work will aim to use this approach for screening of multiple drugs and further validation on additional fresh human GBM slices.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"25 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346466","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}