The development of biomimetic chloroplasts offers significant potential in addressing global energy and environmental challenges.Traditional droplet-based models are limited by transmembrane transport inefficiencies,l...The development of biomimetic chloroplasts offers significant potential in addressing global energy and environmental challenges.Traditional droplet-based models are limited by transmembrane transport inefficiencies,leading to the accumulation of aqueous products that severely hinder reaction performance.In this work,we present a biomimetic chloroplast system that integrates light-dependent and lightindependent reactions,reaction compartments,and selectively permeable interfaces,fabricated using a biphasic microfluidic platform.The permeable interface facilitates continuous substrate–product exchange,mitigating product inhibition and side reactions,thus enhancing reaction efficiency.Furthermore,a quartz spiral tube was engineered to amplify Dean vortex effects,improving mass transfer.This system exhibited a nicotinamide adenine dinucleotide regeneration efficiency during lightdependent reactions that was 5.52 times higher than that of conventional slurry reactors.In the light-independent reaction,the energy conversion efficiency for the transformation ofα-ketoglutaric acid to L-glutamic acid reached 1.45 times that of natural photosynthesis.As the first comprehensive integration of photosynthetic processes within artificial chloroplasts,this work combines biological mechanisms with engineered components to establish a transformative platform for efficient energy conversion and directional biosynthesis.This breakthrough advances the field of photocatalysis and bioinspired technologies,with wide-reaching implications for sustainable energy and synthetic biology applications.展开更多
Cardiovascular diseases account for ~40% of global deaths annually. This situation has revealed the urgent need forthe investigation and development of corresponding drugs for pathogenesis due to the complexity of res...Cardiovascular diseases account for ~40% of global deaths annually. This situation has revealed the urgent need forthe investigation and development of corresponding drugs for pathogenesis due to the complexity of researchmethods and detection techniques. An in vitro cardiomyocyte model is commonly used for cardiac drug screeningand disease modeling since it can respond to microphysiological environmental variations through mechanoelectricfeedback. Microfluidic platforms are capable of accurate fluid control and integration with analysis and detectiontechniques. Therefore, various microfluidic platforms (i.e., heart-on-a-chip) have been applied for the reconstruction ofthe physiological environment and detection of signals from cardiomyocytes. They have demonstrated advantages inmimicking the cardiovascular structure and function in vitro and in monitoring electromechanical signals. This reviewpresents a summary of the methods and technologies used to monitor the contractility and electrophysiologicalsignals of cardiomyocytes within microfluidic platforms. Then, applications in common cardiac drug screening andcardiovascular disease modeling are presented, followed by design strategies for enhancing physiology studies. Finally,we discuss prospects in the tissue engineering and sensing techniques of microfluidic platforms.展开更多
Developing precise extracellular vesicles(EVs)labelling techniques with minimal disturbance is of great importance to the follow-up EVs detection and analysis.However,currently available methods such as using probes t...Developing precise extracellular vesicles(EVs)labelling techniques with minimal disturbance is of great importance to the follow-up EVs detection and analysis.However,currently available methods such as using probes to conjugate phospholipids or membrane proteins have certain limitations due to EV steric hindrance,dye aggregation,etc.Here,we present a microfluidic platform to enhance EVs’labelling efficiency and improve their detection.This platform provides excellent sample throughput and high-efficiency EV labelling at lower label concentrations with an optimized flowing rate.Flow cytometry analysis(FCM)and cellular uptake results show that EV labelling by utilizing this platform possesses the merits of a higher labelling efficiency with 64.1%relative improvement than conventional co-incubation method and a lower background noise.Moreover,this technique maintains EVs’size,morphology and biological activities.After the recipient cells uptake the EVs treated by the microfluidic platform,the spatial and temporal distribution of EVs in the cells are clearly observed.These results demonstrate that our method holds great potential in efficient labelling of EVs,which is essential to subsequent EV quantification and analysis.展开更多
Centrifugal microfluidic platforms are highly regarded for their potential in multiplexing and automation,as well as their wide range of applications,especially in separating blood plasma and manipulating two-phase fl...Centrifugal microfluidic platforms are highly regarded for their potential in multiplexing and automation,as well as their wide range of applications,especially in separating blood plasma and manipulating two-phase flows.However,the need to use stroboscopes or high-speed cameras for monitoring these tasks hinders the extensive use of these platforms in research and commercial settings.In this study,we introduce an innovative and cost-effective strategy for using an array of light-dependent resistors(LDRs)as optical sensors in microfluidic devices,particularly centrifugal platforms.While LDRs are attractive for their potential use as photodetectors,their bulky size frequently restricts their ability to provide high-resolution detection in microfluidic systems.Here,we use specific waveguides to direct light beams from narrow apertures onto the surface of LDRs.We integrated these LDRs into electrified Lab-on-a-Disc(eLOD)devices,with wireless connectivity to smartphones and laptops.This enables many applications,such as droplet/particle counting and velocity measurement,concentration analysis,fluidic interface detection in multiphase flows,real-time monitoring of sample volume on centrifugal platforms,and detection of blood plasma separation as an alternative to costly stroboscope devices,microscopes,and high-speed imaging.We used numerical simulations to evaluate various fluids and scenarios,which include rotation speeds of up to 50 rad/s and a range of droplet sizes.For the testbed,we used the developed eLOD device to analyze red blood cell(RBC)deformability and improve the automated detection of sickle cell anemia by monitoring differences in RBC deformability during centrifugation using the sensors’signals.In addition to sickle cell anemia,this device has the potential to facilitate low-cost automated detection of other medical conditions characterized by altered RBC deformability,such as thalassemia,malaria,and diabetes.展开更多
The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent intera...The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.展开更多
Carbon dots(CDs)have been extensively studied owing to their fascinating optical properties and wide potential applications.Here,we report an easy-to-perform and organic-solvent-free synthesis strategy for green-emiss...Carbon dots(CDs)have been extensively studied owing to their fascinating optical properties and wide potential applications.Here,we report an easy-to-perform and organic-solvent-free synthesis strategy for green-emissive CDs(G-CDs)possessing high photoluminescence(PL)quantum yield(QY).The G-CDs are synthesized by heating the homogeneous precursors of citric acid and cyanamide in an open vessel,circumventing the use of organic solvents,complex operations,high-pressure reactors,and expensive instruments in the synthesis process.The effect of various reaction variables on the formation and the optical properties of G-CDs are systematically investigated.The resultant G-CDs show bright PL emission at 521 nm with PL QY up to 73%.Then a white light-emitting diode(LED)with Commission Internationable de L'Eclairage(CIE)coordinates of(0.33,0.34)and color rendering index(CRI)of 92 is constructed based on G-CDs/thermoplastic polyurethane(TPU)composite.Moreover,a visual microfluidic detection platform is designed by using G-CDs as fluorescent probes for rapid quantitative detection of Fe^(3+),Cu^(2+),and Mn^(2+)metal ions,which can realize synchronized testing of multiple samples.This study might promote the development and preparation methods of high-performance CDs with various optical applications.展开更多
Rapid,high-throughput,timely,multiplex diagnosis of respiratory-tract infections still relies on laboratory infrastructure,sequential assays,and trained personnel,thereby delaying targeted therapy and outbreak contain...Rapid,high-throughput,timely,multiplex diagnosis of respiratory-tract infections still relies on laboratory infrastructure,sequential assays,and trained personnel,thereby delaying targeted therapy and outbreak containment.In this study,a Fully Automated rotary microfluidic platform(FA-RMP)for high-throughput multiplex respiratory tract pathogens detection was presented.FA-RMP enables a true“sample-in,result-out”workflow through the integration of swab lysis,reagent partitioning,lyophilized reverse transcription loop-mediated isothermal amplification(RT-LAMP),and movingprobe fluorescence read-out,all encapsulated with a disposable microfluidic cartridge and paired with a 9 kg,fourchannel benchtop reader.The FA-RMP enables parallel processing of 16 independent reactions within 30 min,supporting simultaneous detection of up to 4 distinct clinical samples.Analytical validation using serially diluted Mycoplasma pneumoniae(MP)DNA established a limit of detection(LoD)of 50 copies μL^(-1) and a log-linear correlation between threshold time and template load(R^(2)=0.9528).Testing with eight non-target respiratory pathogens yielded no amplification,confirming high analytical specificity.FA-RMP successfully detected the clinical samples with influenza A,influenza B,and MP,further demonstrating its robust multiplex detection capability.By integrating automated sample preparation,multiplex isothermal amplification and quantitative detection into a portable,high-throughput system,the platform delivers laboratory-grade performance at the point of care,serving as a scalable tool for routine respiratory pathogens screening and rapid epidemic response.展开更多
Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabricat...Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.展开更多
In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often ba...In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models,where cell sedimentation on the target tissue can occur.The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions.The realization of continuous medium flow helps to better recapitulate physiological conditions and cell-tissue interactions.To tackle current limitations of perfused organ-on-chip approaches,we developed a microfluidic chip and operation concept,which prevents undesired sedimentation and accumulation of suspended cells during multiple days by relying on gravity-driven perfusion.Our platform,which we termed“human immune flow(hiFlow)chip”,enables to co-culture cells in suspension with up to 7 preformed microtissue models.Here,we present the design principle and operation of the platform,and we validate its performance by culturing cells and microtissues of a variety of different origins.Cells and tissues could be monitored on chip via high-resolution microscopy,while cell suspensions and microtissues could be easily retrieved for off-chip analysis.Our results demonstrate that primary immune cells and a range of different spheroid models of healthy and diseased tissues can be maintained for over 6 days on chip.As proof-of-concept cell-tissue interaction assay,we used an antibody treatment against diffuse midline glioma,a highly aggressive pediatric tumor.We are confident that our platform will help to increase the prediction power of in vitro preclinical testing of novel therapeutics that rely on the interaction of circulating cells with organ tissues.展开更多
Electrocatalytic nitrogen reduction reaction(NRR)is regarded as a potential routine to achieve environment-friendly ammonia production,because of its abundant nitrogen resources,clean energy utilization and flexible o...Electrocatalytic nitrogen reduction reaction(NRR)is regarded as a potential routine to achieve environment-friendly ammonia production,because of its abundant nitrogen resources,clean energy utilization and flexible operation.However,it is hindered by low activity and selectivity,in which con-dition well-designed catalysts are urgently in need.In this work,a binary Mo/Ir nanodots/carbon(Mo/Ir/C)hetero-material is efficiently constructed via microfluidic strategy,of which the nanodots are ho-mogeneously distributed on the carbon skeleton and the average size is approximately 1 nm.Excellent performance for NRR is obtained in 1 mol L^(-1) KOH,of which the optimized ammonia yield and faradic efficiency are 7.27μg h^(-1) cm^(-2) and 2.31%respectively.Moreover,the optimized ammonia yield of 6.20μg h-1 cm-2 and faradic efficiency of 10.59%are also obtained in 0.005 mol L^(-1) H_(2)SO_(4).This work achieves the continuous-flow synthesis and controllable adjustment of hetero-materials for favorable morphologies,which provides an innovative pathway for catalyst design and further promotes the development of ammonia production field.展开更多
Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified catio...Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan.The hydrogel microsphere,consisting of photocurable GelMA and ChSMA,were fabricated using a microfluidic platform for cargo delivery.The cationic targeting nanoparticle-hydrogel microsphere@-fucoidan(CTNM@FU)possess three-step programmable characteristics that enable responsive transport toward injured cartilage,effective penetration of the cartilage matrix and selective entry into chondrocytes,escape from lysosomes,and release of bio-activators.The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU.Intraarticular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited de novo cartilage formation.Mechanistically,CTNM@FU protected cartilage by activating SIRT3,enhancing mitochondrial energy and countering aging.Collectively,a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.展开更多
Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into infl...Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into inflam-mation,fibrosis,cirrhosis and liver cancer in severe cases.However,due to the lack of appropriate in vitro drug testing platforms,an in-depth understanding of the therapeutic activity of ginsenoside Rb_(1) in NAFLD remains challenging.Here,we proposed a NAFLD model on a liver organoids(LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb_(1) in a dynamic,multi-condition and high-throughput manner.This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver.Free fatty acids(FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression,including steatosis,oxidative stress,lipid peroxidation,inflammation and fibrosis.With ginsenoside Rb_(1) intervention,these pathological features can be significantly improved,which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans.The proposed system enables the formation,differentiation,and function of LOs to serve as a scalable,high-throughput and sensitive drug testing model,to potentially expedite the NAFLD drug discovery.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:31901057General Science ProgramofWuxi Healthcare Commission,Grant/Award Number:M202347+5 种基金Fundamental Research Funds for the Central Universities,Grant/Award Numbers:2682016CX101,2682025ZTPY047Foundation for Outstanding Young Scientist in Shandong Province,Grant/Award Number:ZR2024YQ064Shandong Province Science and Technology Small and Medium Enterprises Innovation Capacity Improvement Project,Grant/Award Number:2024TSGC008Shandong Provincial Key Research and Development Project,Grant/Award Numbers:2020CXGC011304,2022CXGC020206TaiShan Scholars,Grant/Award Number:tsqn202408256Qilu University of Technology(Shandong Academy of Sciences),Grant/Award Number:2023JBZ03。
文摘The development of biomimetic chloroplasts offers significant potential in addressing global energy and environmental challenges.Traditional droplet-based models are limited by transmembrane transport inefficiencies,leading to the accumulation of aqueous products that severely hinder reaction performance.In this work,we present a biomimetic chloroplast system that integrates light-dependent and lightindependent reactions,reaction compartments,and selectively permeable interfaces,fabricated using a biphasic microfluidic platform.The permeable interface facilitates continuous substrate–product exchange,mitigating product inhibition and side reactions,thus enhancing reaction efficiency.Furthermore,a quartz spiral tube was engineered to amplify Dean vortex effects,improving mass transfer.This system exhibited a nicotinamide adenine dinucleotide regeneration efficiency during lightdependent reactions that was 5.52 times higher than that of conventional slurry reactors.In the light-independent reaction,the energy conversion efficiency for the transformation ofα-ketoglutaric acid to L-glutamic acid reached 1.45 times that of natural photosynthesis.As the first comprehensive integration of photosynthetic processes within artificial chloroplasts,this work combines biological mechanisms with engineered components to establish a transformative platform for efficient energy conversion and directional biosynthesis.This breakthrough advances the field of photocatalysis and bioinspired technologies,with wide-reaching implications for sustainable energy and synthetic biology applications.
基金supported by the National Natural Science Foundation of China(NO.62371267,62121003)Key R&D Program of Shandong Province(Major innovation project)(2022CXGC020501)+4 种基金Science,Education and Industry Integration Innovation Pilot Project from Qilu University of Technology(Shandong Academy of Sciences)(NO.2022JBZ02-01)Research Leader Studio in Colleges and Universities of Jinan(NO.2021GXRC083)Innovation Team of Organ-on-a-Chip Manufacturing Key Technologies(NO.202333015,Funded by Jinan Science and Technology Bureau)Young Innovative Talents Introduction&Cultivation Program for Colleges and Universities of Shandong Province(Granted by Department of Education of Shandong Province,Sub-Title 1:Innovative Research Team of High-Performance Integrated Device,Sub-Title 2:Innovative Research Team of Advanced Energy Equipment)Shandong Provincial Natural Science Foundation(ZR2023QH405)。
文摘Cardiovascular diseases account for ~40% of global deaths annually. This situation has revealed the urgent need forthe investigation and development of corresponding drugs for pathogenesis due to the complexity of researchmethods and detection techniques. An in vitro cardiomyocyte model is commonly used for cardiac drug screeningand disease modeling since it can respond to microphysiological environmental variations through mechanoelectricfeedback. Microfluidic platforms are capable of accurate fluid control and integration with analysis and detectiontechniques. Therefore, various microfluidic platforms (i.e., heart-on-a-chip) have been applied for the reconstruction ofthe physiological environment and detection of signals from cardiomyocytes. They have demonstrated advantages inmimicking the cardiovascular structure and function in vitro and in monitoring electromechanical signals. This reviewpresents a summary of the methods and technologies used to monitor the contractility and electrophysiologicalsignals of cardiomyocytes within microfluidic platforms. Then, applications in common cardiac drug screening andcardiovascular disease modeling are presented, followed by design strategies for enhancing physiology studies. Finally,we discuss prospects in the tissue engineering and sensing techniques of microfluidic platforms.
基金supported by the National Natural Science Foundation of China(Nos.62074155,62204253 and 62205366)Guangdong Program(No.2016ZT06D631)+1 种基金Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515110938 and 2020A1515110142)Shenzhen Science and Technology Innovation Committee(Nos.KCXFZ202002011008124 and JCYJ20210324101405016)。
文摘Developing precise extracellular vesicles(EVs)labelling techniques with minimal disturbance is of great importance to the follow-up EVs detection and analysis.However,currently available methods such as using probes to conjugate phospholipids or membrane proteins have certain limitations due to EV steric hindrance,dye aggregation,etc.Here,we present a microfluidic platform to enhance EVs’labelling efficiency and improve their detection.This platform provides excellent sample throughput and high-efficiency EV labelling at lower label concentrations with an optimized flowing rate.Flow cytometry analysis(FCM)and cellular uptake results show that EV labelling by utilizing this platform possesses the merits of a higher labelling efficiency with 64.1%relative improvement than conventional co-incubation method and a lower background noise.Moreover,this technique maintains EVs’size,morphology and biological activities.After the recipient cells uptake the EVs treated by the microfluidic platform,the spatial and temporal distribution of EVs in the cells are clearly observed.These results demonstrate that our method holds great potential in efficient labelling of EVs,which is essential to subsequent EV quantification and analysis.
基金funding from CONAHCYT in the form of a scholarship as a member of the National System of Researchers(CVU:969467)the financial support of the FEMSA foundation.
文摘Centrifugal microfluidic platforms are highly regarded for their potential in multiplexing and automation,as well as their wide range of applications,especially in separating blood plasma and manipulating two-phase flows.However,the need to use stroboscopes or high-speed cameras for monitoring these tasks hinders the extensive use of these platforms in research and commercial settings.In this study,we introduce an innovative and cost-effective strategy for using an array of light-dependent resistors(LDRs)as optical sensors in microfluidic devices,particularly centrifugal platforms.While LDRs are attractive for their potential use as photodetectors,their bulky size frequently restricts their ability to provide high-resolution detection in microfluidic systems.Here,we use specific waveguides to direct light beams from narrow apertures onto the surface of LDRs.We integrated these LDRs into electrified Lab-on-a-Disc(eLOD)devices,with wireless connectivity to smartphones and laptops.This enables many applications,such as droplet/particle counting and velocity measurement,concentration analysis,fluidic interface detection in multiphase flows,real-time monitoring of sample volume on centrifugal platforms,and detection of blood plasma separation as an alternative to costly stroboscope devices,microscopes,and high-speed imaging.We used numerical simulations to evaluate various fluids and scenarios,which include rotation speeds of up to 50 rad/s and a range of droplet sizes.For the testbed,we used the developed eLOD device to analyze red blood cell(RBC)deformability and improve the automated detection of sickle cell anemia by monitoring differences in RBC deformability during centrifugation using the sensors’signals.In addition to sickle cell anemia,this device has the potential to facilitate low-cost automated detection of other medical conditions characterized by altered RBC deformability,such as thalassemia,malaria,and diabetes.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutes of China(PAPD)the Science and Technology Plan Project of Nantong of China,No.JC2020026(to JW)the National Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)。
文摘The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.
基金supported by National Natural Science Foundation of China(Nos.21736006 and 21978132)National Key Research and Development Program of China(No.2022YFC2104600)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Carbon dots(CDs)have been extensively studied owing to their fascinating optical properties and wide potential applications.Here,we report an easy-to-perform and organic-solvent-free synthesis strategy for green-emissive CDs(G-CDs)possessing high photoluminescence(PL)quantum yield(QY).The G-CDs are synthesized by heating the homogeneous precursors of citric acid and cyanamide in an open vessel,circumventing the use of organic solvents,complex operations,high-pressure reactors,and expensive instruments in the synthesis process.The effect of various reaction variables on the formation and the optical properties of G-CDs are systematically investigated.The resultant G-CDs show bright PL emission at 521 nm with PL QY up to 73%.Then a white light-emitting diode(LED)with Commission Internationable de L'Eclairage(CIE)coordinates of(0.33,0.34)and color rendering index(CRI)of 92 is constructed based on G-CDs/thermoplastic polyurethane(TPU)composite.Moreover,a visual microfluidic detection platform is designed by using G-CDs as fluorescent probes for rapid quantitative detection of Fe^(3+),Cu^(2+),and Mn^(2+)metal ions,which can realize synchronized testing of multiple samples.This study might promote the development and preparation methods of high-performance CDs with various optical applications.
文摘Rapid,high-throughput,timely,multiplex diagnosis of respiratory-tract infections still relies on laboratory infrastructure,sequential assays,and trained personnel,thereby delaying targeted therapy and outbreak containment.In this study,a Fully Automated rotary microfluidic platform(FA-RMP)for high-throughput multiplex respiratory tract pathogens detection was presented.FA-RMP enables a true“sample-in,result-out”workflow through the integration of swab lysis,reagent partitioning,lyophilized reverse transcription loop-mediated isothermal amplification(RT-LAMP),and movingprobe fluorescence read-out,all encapsulated with a disposable microfluidic cartridge and paired with a 9 kg,fourchannel benchtop reader.The FA-RMP enables parallel processing of 16 independent reactions within 30 min,supporting simultaneous detection of up to 4 distinct clinical samples.Analytical validation using serially diluted Mycoplasma pneumoniae(MP)DNA established a limit of detection(LoD)of 50 copies μL^(-1) and a log-linear correlation between threshold time and template load(R^(2)=0.9528).Testing with eight non-target respiratory pathogens yielded no amplification,confirming high analytical specificity.FA-RMP successfully detected the clinical samples with influenza A,influenza B,and MP,further demonstrating its robust multiplex detection capability.By integrating automated sample preparation,multiplex isothermal amplification and quantitative detection into a portable,high-throughput system,the platform delivers laboratory-grade performance at the point of care,serving as a scalable tool for routine respiratory pathogens screening and rapid epidemic response.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFB3208200)the equipment research and development projects of the Chinese Academy of Sciences(PTYQ2024YZ0010)+3 种基金the Science and Technology Commission of Shanghai Municipality Project(XTCX-KJ-2024-038)National Natural Science Foundation of China(62401555)Shanghai Science and Technology Development Funds(23J21900100)supported by the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20232838.
文摘Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.
基金the support for flow cytometry and microscopy by the single cell facility(SCF)at the Department of Biosystems Science and Engineering at ETH Zurichfinancially supported by the Innosuisse grant 38880.1 IP-LS.by the“Personalized Health and Related Technologies(PHRT)”of the ETH Domain(Project#2021-351).
文摘In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models,where cell sedimentation on the target tissue can occur.The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions.The realization of continuous medium flow helps to better recapitulate physiological conditions and cell-tissue interactions.To tackle current limitations of perfused organ-on-chip approaches,we developed a microfluidic chip and operation concept,which prevents undesired sedimentation and accumulation of suspended cells during multiple days by relying on gravity-driven perfusion.Our platform,which we termed“human immune flow(hiFlow)chip”,enables to co-culture cells in suspension with up to 7 preformed microtissue models.Here,we present the design principle and operation of the platform,and we validate its performance by culturing cells and microtissues of a variety of different origins.Cells and tissues could be monitored on chip via high-resolution microscopy,while cell suspensions and microtissues could be easily retrieved for off-chip analysis.Our results demonstrate that primary immune cells and a range of different spheroid models of healthy and diseased tissues can be maintained for over 6 days on chip.As proof-of-concept cell-tissue interaction assay,we used an antibody treatment against diffuse midline glioma,a highly aggressive pediatric tumor.We are confident that our platform will help to increase the prediction power of in vitro preclinical testing of novel therapeutics that rely on the interaction of circulating cells with organ tissues.
基金supported by the National Natural Science Foundation of China(grant Nos.22025801 and 22208190)National Postdoctoral Program for Innovative Talents(grant No.BX2021146)Shuimu Tsinghua Scholar Program(grant No.2021SM055).
文摘Electrocatalytic nitrogen reduction reaction(NRR)is regarded as a potential routine to achieve environment-friendly ammonia production,because of its abundant nitrogen resources,clean energy utilization and flexible operation.However,it is hindered by low activity and selectivity,in which con-dition well-designed catalysts are urgently in need.In this work,a binary Mo/Ir nanodots/carbon(Mo/Ir/C)hetero-material is efficiently constructed via microfluidic strategy,of which the nanodots are ho-mogeneously distributed on the carbon skeleton and the average size is approximately 1 nm.Excellent performance for NRR is obtained in 1 mol L^(-1) KOH,of which the optimized ammonia yield and faradic efficiency are 7.27μg h^(-1) cm^(-2) and 2.31%respectively.Moreover,the optimized ammonia yield of 6.20μg h-1 cm-2 and faradic efficiency of 10.59%are also obtained in 0.005 mol L^(-1) H_(2)SO_(4).This work achieves the continuous-flow synthesis and controllable adjustment of hetero-materials for favorable morphologies,which provides an innovative pathway for catalyst design and further promotes the development of ammonia production field.
基金supported by grants from the National Nature Science Foundation of China(82272494,82472452,82402864)the National Key R&D Program of China(2022YFC2502902)+5 种基金the Key Project of Jiangsu Health Commission(K2023079)the Natural Science Foundation of Jiangsu Province(BK20240368)the Basic Research Pilot Project Suzhou(SSD2024062)the China Postdoctoral Science Foundation(2024M762313)Boxi Youth Natural Science Foundation(BXQN2023014)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan.The hydrogel microsphere,consisting of photocurable GelMA and ChSMA,were fabricated using a microfluidic platform for cargo delivery.The cationic targeting nanoparticle-hydrogel microsphere@-fucoidan(CTNM@FU)possess three-step programmable characteristics that enable responsive transport toward injured cartilage,effective penetration of the cartilage matrix and selective entry into chondrocytes,escape from lysosomes,and release of bio-activators.The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU.Intraarticular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited de novo cartilage formation.Mechanistically,CTNM@FU protected cartilage by activating SIRT3,enhancing mitochondrial energy and countering aging.Collectively,a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.
基金supported by the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Projects(TSBICIP-CXRC-008)Major Project of Haihe Laboratory of Synthetic Biology(E2M9560201)+1 种基金National Natural Science Foundation of China(32301210&31200035)the China Postdoctoral Science Foundation(No.2022M713330).
文摘Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into inflam-mation,fibrosis,cirrhosis and liver cancer in severe cases.However,due to the lack of appropriate in vitro drug testing platforms,an in-depth understanding of the therapeutic activity of ginsenoside Rb_(1) in NAFLD remains challenging.Here,we proposed a NAFLD model on a liver organoids(LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb_(1) in a dynamic,multi-condition and high-throughput manner.This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver.Free fatty acids(FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression,including steatosis,oxidative stress,lipid peroxidation,inflammation and fibrosis.With ginsenoside Rb_(1) intervention,these pathological features can be significantly improved,which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans.The proposed system enables the formation,differentiation,and function of LOs to serve as a scalable,high-throughput and sensitive drug testing model,to potentially expedite the NAFLD drug discovery.
