Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain an...Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.展开更多
Introduction Despite the numerous breakthroughs made in medical and biomedical technologies,biosensing underneath the skin without any associated pain still sounds like a dream yet to be realized.Minimally invasive bi...Introduction Despite the numerous breakthroughs made in medical and biomedical technologies,biosensing underneath the skin without any associated pain still sounds like a dream yet to be realized.Minimally invasive biosensors refer to functional or electronic sensors that can contact the interior environment of living organisms and their biological tissues,while the connected bulk devices remain on the surface of the biological objects[1].Minimally invasive biosensors are currently a key research area because they can not only meet the increasing technical demands to precisely detect biological activities inside biological objects,but also provide an ideal platform to externally incorporate complicated functionalities and electronic integration[2].The current development level of minimally invasive sensing still necessitates solving the constraints and bottlenecks in the three aspects of functionalities,sensitivity and biocompatibility[3].In this perspective,we select minimally invasive sensors as a representative research object with the aim to solve the limitations of current diabetes diagnosis and treatment approaches.展开更多
Application of weathering and cold-formed steel in transmission lines can reduce steel consumption and environmental pollution. Some advances in the studies on the weathering and cold-formed steel in transmission towe...Application of weathering and cold-formed steel in transmission lines can reduce steel consumption and environmental pollution. Some advances in the studies on the weathering and cold-formed steel in transmission tower are introduced. Firstly, corrosion-resistant tests of weathering steel samples under different simulating technical atmospheres were carried out separately for 240 hours. It shows that the corrosion degree of joint samples is higher than that of single chip samples, and the corrosion-resistant performance of weathering steel is superior to common carbon steel. The corrosion-resistance of weathering steel meets with the requirement of transmission tower. Secondly, experiments and finite element analysis for cold-formed angles and a 220kV prototype tower were completed, and the stability coeffi-cient fitting curves as well as the modification formulas of slenderness ratio for cold-formed members were determined. According to the structural characteristics of transmission towers, four sections of cold-formed angles with different sections and slenderness ratios were selected in this study. The finite element model well predicted the buckling behav-iour of the cold-formed members. Ultimate loads calculating by the fitting curve were well agreed to the experimental values, especially for the members with small slenderness ratios. Weight of the cold-formed steel tower can be reduced by more than 5 percent after considering the strength enhancement. Cost of the weathering and cold-formed steel transmission tower is nearly equivalent to that of hot-rolled steel tower with hot galvanizing.展开更多
Needles,as some of the most widely used medical devices,have been effectively applied in human disease prevention,diagnosis,treatment,and rehabilitation.Thin 1D needle can easily penetrate cells/organs by generating h...Needles,as some of the most widely used medical devices,have been effectively applied in human disease prevention,diagnosis,treatment,and rehabilitation.Thin 1D needle can easily penetrate cells/organs by generating highly localized stress with their sharp tips to achieve bioliquid sampling,biosensing,drug delivery,surgery,and other such applications.In this review,we provide an overview of multiscale needle fabrication techniques and their biomedical applications.Needles are classified as nanoneedles,microneedles and millineedles based on the needle diameter,and their fabrication techniques are highlighted.Nanoneedles bridge the inside and outside of cells,achieving intracellular electrical recording,biochemical sensing,and drug delivery.Microneedles penetrate the stratum corneum layer to detect biomarkers/bioelectricity in interstitial fluid and deliver drugs through the skin into the human circulatory system.Millineedles,including puncture,syringe,acupuncture and suture needles,are presented.Finally,conclusions and future perspectives for next-generation nano/micro/milli needles are discussed.展开更多
Monitoring human health is of considerable significance in biomedicine.In particular,the ion concentrations in blood are important reference indicators related to many diseases.Microneedle array-based sensors have ena...Monitoring human health is of considerable significance in biomedicine.In particular,the ion concentrations in blood are important reference indicators related to many diseases.Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature.In this study,we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays.The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining;the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided.The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca^(2+),K^(+),and Na^(+) concentrations,and it exhibited good detection performance.The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca^(2+),k^(+),and Na^(+) in the interstitial fluids of rats in real time.By using an integrated circuit design,we constructed the proposed microneedle sensor into a wearable integrated monitoring system.The integrated system could potentially provide information feedback for diseases related to physiological ion changes.展开更多
COVID-19 has seriously threatened public health,and transdermal vaccination is an effective way to prevent pathogen infection.Microneedles(MNs)can damage the stratum corneum to allow passive diffusion of vaccine macro...COVID-19 has seriously threatened public health,and transdermal vaccination is an effective way to prevent pathogen infection.Microneedles(MNs)can damage the stratum corneum to allow passive diffusion of vaccine macromolecules,but the delivery effciency is low,while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum.Herein,we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and effcient transdermal vaccine macromolecule delivery.Polyacrylamide/chitosan hydrogels with good biocompatibility,excellent conductivity,high elasticity,and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis.The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is“press and poke,iontophoresis-driven delivery,and immune response”.We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery effciency.In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current.In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection.Moreover,there was little concern about the biosafety of the iontophoresis-driven MN patch.This delivery system has a low cost,is user-friendly,and displays active delivery,showing great potential for vaccine self-administration at home.展开更多
The incidence rate of diabetes has been increasing every year in nearly all nations and regions.The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain...The incidence rate of diabetes has been increasing every year in nearly all nations and regions.The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections.While microneedle arrays(MAs)have emerged as painless delivery techniques,the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized.In this study,we developed an iontophoresis-microneedle array patch(IMAP)powered by a portable smartphone for the active and controllable transdermal delivery of insulin.The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch,achieving a one-step drug administration strategy of“penetration,diffusion and iontophoresis”.The MA of the IMAP is first pressed on the skin to create microholes and then is retracted,followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner.This method has synergistically and remarkably enhanced controlled insulin delivery.The amount of insulin can be effectively regulated by the IMAP by applying different current intensities.This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model,with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis.The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care.展开更多
基金This work was financially supported by the National Key R&D Program of China(Nos.2021YFF1200700 and 2021YFA0911100)the National Natural Science Foundation of China(Nos.32171399,32171456,and T2225010)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515012261)the Science and Technology Program of Guangzhou,China(No.202103000076)the Fundamental Research Funds for the Central Universities,Sun Yat-Sen University(No.22dfx02),and Pazhou Lab,Guangzhou(No.PZL2021KF0003)FML would like to thank the National Natural Science Foundation of China(Nos.32171335 and 31900954)JL would like to thank the National Natural Science Foundation of China(No.62105380)the China Postdoctoral Science Foundation(No.2021M693686)QQOY would like to thank the China Postdoctoral Science Foundation(No.2022M713645).
文摘Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.
基金the National Natural Science Foundation of China(Nos.61771498,61901535 and 81970778)Science and Technology Planning Project of Guangdong Province for Industrial Applications(No.2017B090917001)+3 种基金Guangdong Province Key Area R&D Program(No.2018B030332001)Science and Technology Program of GuangzhouChina(No.202102080192)Guangdong Basic and Applied Basic Research Foundation(Nos.2021A1515012261,2019A1515012087,2020A1515010987 and 2020A1515110424)and Key Program of Sun Yat-Sen University(No.20lgzd14).
文摘Introduction Despite the numerous breakthroughs made in medical and biomedical technologies,biosensing underneath the skin without any associated pain still sounds like a dream yet to be realized.Minimally invasive biosensors refer to functional or electronic sensors that can contact the interior environment of living organisms and their biological tissues,while the connected bulk devices remain on the surface of the biological objects[1].Minimally invasive biosensors are currently a key research area because they can not only meet the increasing technical demands to precisely detect biological activities inside biological objects,but also provide an ideal platform to externally incorporate complicated functionalities and electronic integration[2].The current development level of minimally invasive sensing still necessitates solving the constraints and bottlenecks in the three aspects of functionalities,sensitivity and biocompatibility[3].In this perspective,we select minimally invasive sensors as a representative research object with the aim to solve the limitations of current diabetes diagnosis and treatment approaches.
文摘Application of weathering and cold-formed steel in transmission lines can reduce steel consumption and environmental pollution. Some advances in the studies on the weathering and cold-formed steel in transmission tower are introduced. Firstly, corrosion-resistant tests of weathering steel samples under different simulating technical atmospheres were carried out separately for 240 hours. It shows that the corrosion degree of joint samples is higher than that of single chip samples, and the corrosion-resistant performance of weathering steel is superior to common carbon steel. The corrosion-resistance of weathering steel meets with the requirement of transmission tower. Secondly, experiments and finite element analysis for cold-formed angles and a 220kV prototype tower were completed, and the stability coeffi-cient fitting curves as well as the modification formulas of slenderness ratio for cold-formed members were determined. According to the structural characteristics of transmission towers, four sections of cold-formed angles with different sections and slenderness ratios were selected in this study. The finite element model well predicted the buckling behav-iour of the cold-formed members. Ultimate loads calculating by the fitting curve were well agreed to the experimental values, especially for the members with small slenderness ratios. Weight of the cold-formed steel tower can be reduced by more than 5 percent after considering the strength enhancement. Cost of the weathering and cold-formed steel transmission tower is nearly equivalent to that of hot-rolled steel tower with hot galvanizing.
基金National Natural Science Foundation of China(Grant Nos.52175446,51975133,51975597)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2021A1515011740,2019A1515011011)Shenzhen Fundamental Research Program(Grant No.JCYJ20170818163426597).
文摘Needles,as some of the most widely used medical devices,have been effectively applied in human disease prevention,diagnosis,treatment,and rehabilitation.Thin 1D needle can easily penetrate cells/organs by generating highly localized stress with their sharp tips to achieve bioliquid sampling,biosensing,drug delivery,surgery,and other such applications.In this review,we provide an overview of multiscale needle fabrication techniques and their biomedical applications.Needles are classified as nanoneedles,microneedles and millineedles based on the needle diameter,and their fabrication techniques are highlighted.Nanoneedles bridge the inside and outside of cells,achieving intracellular electrical recording,biochemical sensing,and drug delivery.Microneedles penetrate the stratum corneum layer to detect biomarkers/bioelectricity in interstitial fluid and deliver drugs through the skin into the human circulatory system.Millineedles,including puncture,syringe,acupuncture and suture needles,are presented.Finally,conclusions and future perspectives for next-generation nano/micro/milli needles are discussed.
基金support from the National Key R&D Program of China(Grant No.2021YFF1200700,2021YFA0911100)National Natural Science Foundation of China(Grant No.32171399,32171456,T2225010)+6 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2021A1515012261)Science and Technology Program of Guangzhou,China(Grant No.202103000076)Fundamental Research Funds for the Central Universities,Sun Yat-Sen University(Grant No.22dfx02)Pazhou Lab,Guangzhou(Grant No.PZL2021KF0003)Opening Project of Key Laboratory of Microelectronic Devices&Integrated Technology,Institute of Microelectronics,Chinese Academy of Sciences,Tianjin Key Laboratory of Imaging and Sensing Microelectronic Technology,Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province,Second Affliated Hospital of Zhejang University,School of Medicine(Grant.2022K02)State Key Laboratory Of Precision Measuring Technology And Instruments(Grant No.pilab2211)Open Funds of State Key Laboratory of Oncology in South China(Grant No.HN2022-01).
文摘Monitoring human health is of considerable significance in biomedicine.In particular,the ion concentrations in blood are important reference indicators related to many diseases.Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature.In this study,we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays.The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining;the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided.The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca^(2+),K^(+),and Na^(+) concentrations,and it exhibited good detection performance.The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca^(2+),k^(+),and Na^(+) in the interstitial fluids of rats in real time.By using an integrated circuit design,we constructed the proposed microneedle sensor into a wearable integrated monitoring system.The integrated system could potentially provide information feedback for diseases related to physiological ion changes.
基金supported by the National Natural Science Foundation of China(Project No.51975597 and 52175446)the Natural Science Foundation of Guangdong Province(Project Nos.2022B1515020011 and 2021A1515011740)+1 种基金the Shenzhen Science and Technology Program(Project No.JCYJ20220818102201003)the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument(Project No.2020B1212060077).
文摘COVID-19 has seriously threatened public health,and transdermal vaccination is an effective way to prevent pathogen infection.Microneedles(MNs)can damage the stratum corneum to allow passive diffusion of vaccine macromolecules,but the delivery effciency is low,while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum.Herein,we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and effcient transdermal vaccine macromolecule delivery.Polyacrylamide/chitosan hydrogels with good biocompatibility,excellent conductivity,high elasticity,and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis.The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is“press and poke,iontophoresis-driven delivery,and immune response”.We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery effciency.In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current.In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection.Moreover,there was little concern about the biosafety of the iontophoresis-driven MN patch.This delivery system has a low cost,is user-friendly,and displays active delivery,showing great potential for vaccine self-administration at home.
基金This research is financially supported by the National Natural Science Foundation of China(Grant Nos.51575543,51975597,61771498,61901535,51805556,and 31900954)the Natural Science Foundation of Guangdong Province(Grant No.2019A1515011011 and 2018A030313698)+7 种基金the General Program of Shenzhen Innovation Funding(Grant No.JCYJ20170818164246179)the Special Support Plan for High Level Talents in Guangdong Province(Grant No.2017TQ04X674)The authors also would like to acknowledge financial support from the National Natural Science Foundation of China(Grant Nos.61901535,31900954,81970778)Guangdong Province Key Area R&D Program(Grant No.2018B030332001)Natural Science Foundation of Guangdong Province(2019A1515012087,2020A1515010665)Science and Technology Program of Guangzhou,China(Grant No.201803010097,201907010038)This work is also supported by the Open Research Fund of State Key Laboratory of Ophthalmology,Sun Yat-sen University(Grant No.303060202400358)the Youth Teacher Training Program of Sun Yat-Sen University(Grant No.20lgpy47,18lgpy18,and 20lgzd14).
文摘The incidence rate of diabetes has been increasing every year in nearly all nations and regions.The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections.While microneedle arrays(MAs)have emerged as painless delivery techniques,the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized.In this study,we developed an iontophoresis-microneedle array patch(IMAP)powered by a portable smartphone for the active and controllable transdermal delivery of insulin.The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch,achieving a one-step drug administration strategy of“penetration,diffusion and iontophoresis”.The MA of the IMAP is first pressed on the skin to create microholes and then is retracted,followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner.This method has synergistically and remarkably enhanced controlled insulin delivery.The amount of insulin can be effectively regulated by the IMAP by applying different current intensities.This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model,with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis.The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care.
