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
Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in bio...Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.展开更多
Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including ...Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of “Semi-implantable bioelectronics”, summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.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
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
Nanomaterials with low-dimensional morphology have been explored for enhancing the performance of strain sensors,but it remains difficult to achieve high stretchability and sensitivity simultaneously.In this work,a co...Nanomaterials with low-dimensional morphology have been explored for enhancing the performance of strain sensors,but it remains difficult to achieve high stretchability and sensitivity simultaneously.In this work,a composite structure strain sensor based on nanomaterials and conductive liquid is designed,demonstrated,and engineered.The nanowire-microfluidic hybrid(NMH)strain sensor responds to multiscale strains from 4%to over 400%,with a high sensitivity and durability under small strain.Metal nanowires and carbon nanotubes are used to fabricate the NMH strain sensors,which simultaneously exhibit record-high average gauge factors and stretchability,far better than the conventional nanowire devices.Quantitative modeling of the electrical characteristics reveals that the effective conductivity percolation through the hybrid structures is the key to achieving high gauge factors for multiscale sensing.The sensors can operate at low voltages and are capable of responding to various mechanical deformations.When fixed on human skin,the sensors can monitor large-scale deformations(skeleton motion)and small-scale deformations(facial expressions and pulses).The sensors are also employed in multichannel,interactive electronic system for wireless control of robotics.Such demonstrations indicate the potential of the sensors as wearable detectors for human motion or as bionic ligaments in soft robotics.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 authors would like to acknowledge financial support from the National Key R&D Program of China(Nos.2021YFF1200700 and 2021YFA0911100)the National Natural Science Foundation of China(Nos.T2225010,32171399,and 32171456)+4 种基金the Fundamental Research Funds for the Central Universities,Sun Yat-Sen University(No.22dfx02)Pazhou Lab,Guangzhou(No.PZL2021KF0003)The authors also would like to thank the funding support from the Opening Project of Key Laboratory of Microelectronic Devices&Integrated Technology,Institute of Microelectronics,Chinese Academy of Sciences,and State Key Laboratory of Precision Measuring Technology and Instruments(No.pilab2211)QQOY would like to thank the China Postdoctoral Science Foundation(No.2022M713645)JL would like to thank the National Natural Science Foundation of China(No.62105380)and the China Postdoctoral Science Foundation(No.2021M693686).
文摘Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.
基金financial support from the National Natural Science Foundation of China(Grant Nos.32171399)the National Key R&D Program of China(Grant Nos.2021YFF1200700,2021YFA0911100)+1 种基金the National Natural Science Foundation of China(Grant Nos.32171456,32171335,61901535,31900954,62104264)。
文摘Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of “Semi-implantable bioelectronics”, summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.
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.
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The authors gratefully acknowledge thefinancial support of the Guangdong Natural Science Funds for Distinguished Young Scholars under Grant 2016A030306046the Guangdong Youth Top-notch Talent Support Program(No.2016TQ03X648)the“985”Project(30000-31101200).
文摘Nanomaterials with low-dimensional morphology have been explored for enhancing the performance of strain sensors,but it remains difficult to achieve high stretchability and sensitivity simultaneously.In this work,a composite structure strain sensor based on nanomaterials and conductive liquid is designed,demonstrated,and engineered.The nanowire-microfluidic hybrid(NMH)strain sensor responds to multiscale strains from 4%to over 400%,with a high sensitivity and durability under small strain.Metal nanowires and carbon nanotubes are used to fabricate the NMH strain sensors,which simultaneously exhibit record-high average gauge factors and stretchability,far better than the conventional nanowire devices.Quantitative modeling of the electrical characteristics reveals that the effective conductivity percolation through the hybrid structures is the key to achieving high gauge factors for multiscale sensing.The sensors can operate at low voltages and are capable of responding to various mechanical deformations.When fixed on human skin,the sensors can monitor large-scale deformations(skeleton motion)and small-scale deformations(facial expressions and pulses).The sensors are also employed in multichannel,interactive electronic system for wireless control of robotics.Such demonstrations indicate the potential of the sensors as wearable detectors for human motion or as bionic ligaments in soft robotics.
