Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most prominent cause of dementia.In 2019,over 57.4million people were living with AD and other dementia subtypes,a number which is ex...Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most prominent cause of dementia.In 2019,over 57.4million people were living with AD and other dementia subtypes,a number which is expected to increase to over 152.8 million in the next 25years.This ever-increasing burden has resulted in AD and other neurodegenerative diseases rising to one of the top 10 causes of death globally (O'Connell et al.,2024).展开更多
The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel micr...The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.展开更多
Among various electrochemical imaging techniques,electrochemiluminescence microscopy(ECLM)stands out as a powerful approach to visualize electrochemical reactions by converting localized reactivity into optical signal...Among various electrochemical imaging techniques,electrochemiluminescence microscopy(ECLM)stands out as a powerful approach to visualize electrochemical reactions by converting localized reactivity into optical signals.This study investigates ECL light emission spatial distribution in a confined space by using microelectrode arrays(MEAs)fabricated on glassy carbon(GC)and gold(Au)substrates via thermal nanoimprint lithography(TNIL).With the Ru(bpy)32+/TPrA system,ECL imaging revealed distinct emission profiles,with Au exhibiting a broader spatial distribution compared to GC under identical geometric conditions.The estimated thickness of the ECL emitting layer(TEL)was significantly larger on Au(∼7μm)than on GC(∼4μm),attributed to the interplay between the electrode material and dominant ECL mechanism.Decreasing Ru(bpy)32+concentration resulted in minimal perturbation of the GC ECL profile,consistent with a predominant oxidative-reductive mechanism.In contrast,a significant narrowing of the ECL profile was observed on Au,indicative of a transition from a catalytic to an oxidative-reductive pathway.These observations were corroborated and rationalized by finite element simulations.Our findings demonstrate the capacity to fine-tune the Thickness of the Emission Layer(TEL)and modulate ECL emission through electrode material selection and luminophore concentration.Such precise control has significant implications for the development of highly sensitive and spatially resolved bioanalytical assays,particularly those employing bead-based detection methodologies.展开更多
The precise neural mechanisms by which general anesthetics induce unconsciousness remain undetermined,with ongoing debate over whether they primarily affect the cortex directly or act predominantly on the sleep–wake ...The precise neural mechanisms by which general anesthetics induce unconsciousness remain undetermined,with ongoing debate over whether they primarily affect the cortex directly or act predominantly on the sleep–wake brain regions.There is an urgent need for high-precision methodologies to detect and analyze neural information across cortical and subcortical regions.In this study,we designed and fabricated the microelectrode arrays to detect electrophysiological signals from nine brain regions,ranging from the secondary motor cortex to the preoptic area in mice under different concentrations of isoflurane anesthesia.The results demonstrate that isoflurane induces a synchronous inhibitory effect on neural activity in both cortical and subcortical regions of mice during the maintenance phase of anesthesia,which intensifies with increasing anesthesia concentration.Moreover,cortical neurons exhibit a more pronounced inhibitory response to isoflurane,as reflected by significant reductions in local field potential power and spike firing rates compared to subcortical neurons during the suppression phase.These findings suggest that isoflurane during the maintenance phase of anesthesia is more likely to align with the“top-down”paradigm by directly inhibiting cortical regions to maintain unconsciousness.In summary,these discoveries could further refine the study of the neural mechanisms of isoflurane-induced unconsciousness.展开更多
The globus pallidus internus(GPi)was considered a common target for stimulation in Parkinson’s disease(PD).Located deep in the brain and of small size,pinpointing it during surgery is challenging.Multi-channel microe...The globus pallidus internus(GPi)was considered a common target for stimulation in Parkinson’s disease(PD).Located deep in the brain and of small size,pinpointing it during surgery is challenging.Multi-channel microelectrode arrays(MEAs)can provide micrometer-level precision functional localization,which can maximize the surgical outcome.In this paper,a 64-channel MEA modified by platinum nanoparticles with a detection site impedance of 61.1 kΩ was designed and prepared,and multiple channels could be synchronized to cover the target brain region and its neighboring regions so that the GPi could be identified quickly and accurately.The results of the implant trajectory indicate that,compared to the control side,there is a reduction in local field potential(LFP)power in multiple subregions of the upper central thalamus on the PD-induced side,while the remaining brain regions exhibit an increasing trend.When the MEA tip was positioned at 8,700μm deep in the brain,the various characterizations of the spike signals,combined with the electrophysiological characteristics of the β-segmental oscillations in PD,enabled MEAs to localize the GPi at the single-cell level.More precise localization could be achieved by utilizing the distinct characteristics of the internal capsule(ic),the thalamic reticular nucleus(Rt),and the peduncular part of the lateral hypothalamus(PLH)brain regions,as well as the relative positions of these brain structures.The MEAs designed in this study provide a new detection method and tool for functional localization of PD targets and PD pathogenesis at the cellular level.展开更多
Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolat...Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolateral amygdala(BLA)is crucial in the cognitive and physiological processing and control of emotion.However,due to the lack of detection tools,the neural activity of the BLA during depression is not well understood.In this study,a microelectrode array(MEA)based on the shape and anatomical location of the BLA in the brain was designed and manufactured.Rats were injected with lipopolysaccharide(LPS)for 7 consecutive days to induce depressive behavior.We used the MEA to detect neural activity in the BLA before modeling,during modeling,and after LPS administration on 7 consecutive days.The results showed that after LPS treatment,the spike firing of neurons in the BLA region of rats gradually became more intense,and the local field potential power also increased progressively.Further analysis revealed that after LPS administration,the spike firing of BLA neurons was predominantly in the theta rhythm,with obvious periodic firing characteristics appearing after the 7 d of LPS administration,and the relative power of the local field potential in the theta band also significantly increased.In summary,our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats,providing valuable guidance for research into the neural mechanisms of depression.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
Based on the inhibition effect on the respiratory chain activity of microorganisms by toxicants, an electrochemical method has been developed to measure the current variation of a mediator in the presence of microorga...Based on the inhibition effect on the respiratory chain activity of microorganisms by toxicants, an electrochemical method has been developed to measure the current variation of a mediator in the presence of microorganisms contacted with a toxicant. Microelectrode arrays were adopted in this study, which can accelerate the mass transfer rate of an anaiyte to the electrode and also increase the total current signal, resulting in an improvement in detection sensitivity. We selected Escherichia coli as the testee and the standard glucose- glutamic acid as an exogenous material. Under oxygen restriction, the experiments in the presence of toxicant were performed at optimum conditions （solution pH 7.0, 37℃ and reaction for 3 hr）. The resulting solution was then separated from the suspended microorganisms and was measured by an electrochemical method, using ferricyanide as a mediator. The current signal obtained represents the reoxidation of ferrocyanide, which was transformed to inhibiting efficiency, IC50, as a quantitative measure of toxicity. The IC50 values measured were 410, 570 and 830 mg/L for sodium nitrite, borax and aluminum potassium sulfate, respectively. The results show that the toxicity sequence for these three food additives is consistent with the value reported by other methods. Furthermore, the order of damage degree to the microorganism was also observed to be： sodium nitrite 〉 borax 〉 aluminum potassium sulfate 〉 blank, according to the atomic force microscopy images of E. coli after being incubated for 3 hr with the toxic compound in buffer solutions. The electrochemical method is expected to be a sensitive and simple alternative to toxicity screening for chemical food additives.展开更多
Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action pot...Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action potentials(APs).Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings,but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored.Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes.In this study,we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments.We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation.Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios,while smaller electrodes exhibited higher perforation efficiency,AP duration,and single-cell signal ratios.This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings,rather than being limited to high-resolution designs.This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.展开更多
Increasing the proximity of microelectrode arrays(MEA)to targeted neural tissues can establish efficient neural interfaces for both recording and stimulation applications.This has been achieved by constructing protrud...Increasing the proximity of microelectrode arrays(MEA)to targeted neural tissues can establish efficient neural interfaces for both recording and stimulation applications.This has been achieved by constructing protruding three-dimensional(3D)structures on top of conventional planar microelectrodes via additional micromachining steps.However,this approach adds fabrication complexities and limits the 3D structures to certain shapes.We propose a one-step fabrication of MEAs with versatile microscopic 3D structures via“microelectrothermoforming(μETF)”of thermoplastics,by utilizing 3D-printed molds to locally deform planar MEAs into protruding and recessing shapes.Electromechanical optimization enabled a 3D MEA with 80μm protrusions and/or recession for 100μm diameter.Its simple and versatile shaping capabilities are demonstrated by diverse 3D structures on a single MEA.The benefits of 3D MEA are evaluated in retinal stimulation through numerical simulations and ex vivo experiments,confirming a threshold lowered by 1.7 times and spatial resolution enhanced by 2.2 times.展开更多
Neural representations arise from high-dimensional population activity,but current neuromodulation methods lack the precision to write information into the central nervous system at this complexity.In this perspective...Neural representations arise from high-dimensional population activity,but current neuromodulation methods lack the precision to write information into the central nervous system at this complexity.In this perspective,we propose high-dimensional stimulation as an approach to better approximate natural neural codes for brain-machine interfaces.Key advancements in resolution,coverage,and safety are essential,with flexible microelectrode arrays offering a promising path toward precise synthetic neural codes.展开更多
Biomolecules play important roles in physiological functions and pharmacological characteristics of human body.Uric acid(UA)is the end product of purine.Dopamine(DA)is a neurotransmitter of catecholamine group.L-trypt...Biomolecules play important roles in physiological functions and pharmacological characteristics of human body.Uric acid(UA)is the end product of purine.Dopamine(DA)is a neurotransmitter of catecholamine group.L-tryptophan is an essential amino acid that can be metabolized to neuroactive substances.Pyridoxine is a water-soluble vitamin playing an important role in nervous system.The abnormalities in their concentration levels led to a wide range of signifi cant mental and physical illnesses.Thus,electrochemical analysis of these analytes on an array system would be benefi cial from clinical or scientifi c points of view.This work was aimed at the development of practical sensor array for determination of multiple analytes on a single sensing platform using individually addressable microelectrodes.The occurrence of adsorption–desorption phenomenon on the surface of palladium microelectrode array(Pd MEA)printed on the silicon wafer through photolithography was exploited for electro-oxidation of UA,DA,L-tryptophan and pyridoxine.The sensing of electroactive UA was done using carbon nanotubes(CNTs)grown Pd MEA as a working electrode,while selectivity for other analytes was achieved by the modifi cation of CNTs/Pd MEA through electrodeposition of poly(L-lysine)(poly(L-lysine)/CNTs/Pd MEA)for DA sensing,poly(L-arginine)(poly(L-arginine)/CNTs/Pd MEA)for L-tryptophan sensing and reduced graphene oxide(rGO/CNTs/Pd MEA)for pyridoxine sensing.The electrochemical diff erential pulse voltammetry(DPV)analyses reveal excellent linearity in the concentration ranges of 50–6000μmol/L,2–8000μmol/L,20–15,000μmol/L,and 10–5000μmol/L with detection limits of 15.0,0.5,10.0,and 1.0μmol/L for UA,DA,L-tryptophan,and pyridoxine,respectively.The proposed multiple analytes sensor has shown very high sensitivities of 140,9580,2280,and 940μA·(μmol·L^(-1))^(-1)·cm^(-2)for UA,DA,L-tryptophan,and pyridoxine sensing,respectively.Further,accuracy and reliability of the fabricated sensor were also tested in real samples.展开更多
文摘Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most prominent cause of dementia.In 2019,over 57.4million people were living with AD and other dementia subtypes,a number which is expected to increase to over 152.8 million in the next 25years.This ever-increasing burden has resulted in AD and other neurodegenerative diseases rising to one of the top 10 causes of death globally (O'Connell et al.,2024).
基金funded by the National Natural Science Foundation of China(Nos.L2224042,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the Frontier Interdisciplinary Project of the Chinese Academy of Sciences(No.XK2022XXC003)+2 种基金the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of he Chinese Academy of Sciences(No.GJJSTD20210004).
文摘The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.
基金supported by the FSE-REACT-EU,PON Ricerca e Innovazione 2014−2020 DM 1062/202,Cod:19-G-12549−3funded by European Union−Next Generation EU,project MEET grant number 20225P4EJC,CUP J53D23014570001supported by ECLeptic project that has received funding from the European Union’s MSCA Doctoral network Horizon Europe programme Grant Agreement Number 101119951.
文摘Among various electrochemical imaging techniques,electrochemiluminescence microscopy(ECLM)stands out as a powerful approach to visualize electrochemical reactions by converting localized reactivity into optical signals.This study investigates ECL light emission spatial distribution in a confined space by using microelectrode arrays(MEAs)fabricated on glassy carbon(GC)and gold(Au)substrates via thermal nanoimprint lithography(TNIL).With the Ru(bpy)32+/TPrA system,ECL imaging revealed distinct emission profiles,with Au exhibiting a broader spatial distribution compared to GC under identical geometric conditions.The estimated thickness of the ECL emitting layer(TEL)was significantly larger on Au(∼7μm)than on GC(∼4μm),attributed to the interplay between the electrode material and dominant ECL mechanism.Decreasing Ru(bpy)32+concentration resulted in minimal perturbation of the GC ECL profile,consistent with a predominant oxidative-reductive mechanism.In contrast,a significant narrowing of the ECL profile was observed on Au,indicative of a transition from a catalytic to an oxidative-reductive pathway.These observations were corroborated and rationalized by finite element simulations.Our findings demonstrate the capacity to fine-tune the Thickness of the Emission Layer(TEL)and modulate ECL emission through electrode material selection and luminophore concentration.Such precise control has significant implications for the development of highly sensitive and spatially resolved bioanalytical assays,particularly those employing bead-based detection methodologies.
文摘The precise neural mechanisms by which general anesthetics induce unconsciousness remain undetermined,with ongoing debate over whether they primarily affect the cortex directly or act predominantly on the sleep–wake brain regions.There is an urgent need for high-precision methodologies to detect and analyze neural information across cortical and subcortical regions.In this study,we designed and fabricated the microelectrode arrays to detect electrophysiological signals from nine brain regions,ranging from the secondary motor cortex to the preoptic area in mice under different concentrations of isoflurane anesthesia.The results demonstrate that isoflurane induces a synchronous inhibitory effect on neural activity in both cortical and subcortical regions of mice during the maintenance phase of anesthesia,which intensifies with increasing anesthesia concentration.Moreover,cortical neurons exhibit a more pronounced inhibitory response to isoflurane,as reflected by significant reductions in local field potential power and spike firing rates compared to subcortical neurons during the suppression phase.These findings suggest that isoflurane during the maintenance phase of anesthesia is more likely to align with the“top-down”paradigm by directly inhibiting cortical regions to maintain unconsciousness.In summary,these discoveries could further refine the study of the neural mechanisms of isoflurane-induced unconsciousness.
基金funded by the National Natural Science Foundation of China(nos.61960206012,T2293731,T2293730,62121003,T2293731,T2293730,and 62121003)the National Key Research and Development Program of China(nos.2022YFC2402501 and 2022YFB3205602)Major Program of Scientific and Technical Innovation 2030(no.2021ZD02016030).
文摘The globus pallidus internus(GPi)was considered a common target for stimulation in Parkinson’s disease(PD).Located deep in the brain and of small size,pinpointing it during surgery is challenging.Multi-channel microelectrode arrays(MEAs)can provide micrometer-level precision functional localization,which can maximize the surgical outcome.In this paper,a 64-channel MEA modified by platinum nanoparticles with a detection site impedance of 61.1 kΩ was designed and prepared,and multiple channels could be synchronized to cover the target brain region and its neighboring regions so that the GPi could be identified quickly and accurately.The results of the implant trajectory indicate that,compared to the control side,there is a reduction in local field potential(LFP)power in multiple subregions of the upper central thalamus on the PD-induced side,while the remaining brain regions exhibit an increasing trend.When the MEA tip was positioned at 8,700μm deep in the brain,the various characterizations of the spike signals,combined with the electrophysiological characteristics of the β-segmental oscillations in PD,enabled MEAs to localize the GPi at the single-cell level.More precise localization could be achieved by utilizing the distinct characteristics of the internal capsule(ic),the thalamic reticular nucleus(Rt),and the peduncular part of the lateral hypothalamus(PLH)brain regions,as well as the relative positions of these brain structures.The MEAs designed in this study provide a new detection method and tool for functional localization of PD targets and PD pathogenesis at the cellular level.
基金sponsored by the National Natural Science Foundation of China(Nos.61960206012,T2293730,T2293731,62121003,62171434,62333020,62374004,81971348,and 61673024)the National Key Research and Development Program of China(Nos.2022YFB3205602 and 2022YFC2402501)Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030).
文摘Depression is a common and severely debilitating neuropsychiatric disorder.Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression.The basolateral amygdala(BLA)is crucial in the cognitive and physiological processing and control of emotion.However,due to the lack of detection tools,the neural activity of the BLA during depression is not well understood.In this study,a microelectrode array(MEA)based on the shape and anatomical location of the BLA in the brain was designed and manufactured.Rats were injected with lipopolysaccharide(LPS)for 7 consecutive days to induce depressive behavior.We used the MEA to detect neural activity in the BLA before modeling,during modeling,and after LPS administration on 7 consecutive days.The results showed that after LPS treatment,the spike firing of neurons in the BLA region of rats gradually became more intense,and the local field potential power also increased progressively.Further analysis revealed that after LPS administration,the spike firing of BLA neurons was predominantly in the theta rhythm,with obvious periodic firing characteristics appearing after the 7 d of LPS administration,and the relative power of the local field potential in the theta band also significantly increased.In summary,our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats,providing valuable guidance for research into the neural mechanisms of depression.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
基金supported by the National Natural Science Foundation of China (No. 20820102037,20935003)the National Basic Research Program (973) of China (No.2010CB933603)
文摘Based on the inhibition effect on the respiratory chain activity of microorganisms by toxicants, an electrochemical method has been developed to measure the current variation of a mediator in the presence of microorganisms contacted with a toxicant. Microelectrode arrays were adopted in this study, which can accelerate the mass transfer rate of an anaiyte to the electrode and also increase the total current signal, resulting in an improvement in detection sensitivity. We selected Escherichia coli as the testee and the standard glucose- glutamic acid as an exogenous material. Under oxygen restriction, the experiments in the presence of toxicant were performed at optimum conditions （solution pH 7.0, 37℃ and reaction for 3 hr）. The resulting solution was then separated from the suspended microorganisms and was measured by an electrochemical method, using ferricyanide as a mediator. The current signal obtained represents the reoxidation of ferrocyanide, which was transformed to inhibiting efficiency, IC50, as a quantitative measure of toxicity. The IC50 values measured were 410, 570 and 830 mg/L for sodium nitrite, borax and aluminum potassium sulfate, respectively. The results show that the toxicity sequence for these three food additives is consistent with the value reported by other methods. Furthermore, the order of damage degree to the microorganism was also observed to be： sodium nitrite 〉 borax 〉 aluminum potassium sulfate 〉 blank, according to the atomic force microscopy images of E. coli after being incubated for 3 hr with the toxic compound in buffer solutions. The electrochemical method is expected to be a sensitive and simple alternative to toxicity screening for chemical food additives.
基金financial support from the National Natural Science Foundation of China(Grant No.T2225010,32171399,32171456,62105380)Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515111139)+4 种基金Science and Technology Program of Guangzhou,China(Grant No.2024B03J0121,2024B03J1284)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.24xkjc011)the Independent Fund of the State Key Laboratory of Optoelectronic Materials and Technologies(Sun Yat-sen University)under grant No.OEMT-2022-ZRC-04Central Nervous System Drug Key Laboratory of Sichuan Province(Grant No.230036-01SZ)Fund of Key Laboratory of Advanced Materials of Ministry of Education(No.Advmat-2416).
文摘Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action potentials(APs).Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings,but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored.Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes.In this study,we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments.We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation.Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios,while smaller electrodes exhibited higher perforation efficiency,AP duration,and single-cell signal ratios.This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings,rather than being limited to high-resolution designs.This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(NRF-2022R1C1C1010422,RS-2023-00217893,and NRF 2020R1C1C1010505)。
文摘Increasing the proximity of microelectrode arrays(MEA)to targeted neural tissues can establish efficient neural interfaces for both recording and stimulation applications.This has been achieved by constructing protruding three-dimensional(3D)structures on top of conventional planar microelectrodes via additional micromachining steps.However,this approach adds fabrication complexities and limits the 3D structures to certain shapes.We propose a one-step fabrication of MEAs with versatile microscopic 3D structures via“microelectrothermoforming(μETF)”of thermoplastics,by utilizing 3D-printed molds to locally deform planar MEAs into protruding and recessing shapes.Electromechanical optimization enabled a 3D MEA with 80μm protrusions and/or recession for 100μm diameter.Its simple and versatile shaping capabilities are demonstrated by diverse 3D structures on a single MEA.The benefits of 3D MEA are evaluated in retinal stimulation through numerical simulations and ex vivo experiments,confirming a threshold lowered by 1.7 times and spatial resolution enhanced by 2.2 times.
基金funded by R01EY036094(L.L)R01NS102917(C.X)+1 种基金U01NS115588(C.X)U01NS131086(C.X&L.L.)。
文摘Neural representations arise from high-dimensional population activity,but current neuromodulation methods lack the precision to write information into the central nervous system at this complexity.In this perspective,we propose high-dimensional stimulation as an approach to better approximate natural neural codes for brain-machine interfaces.Key advancements in resolution,coverage,and safety are essential,with flexible microelectrode arrays offering a promising path toward precise synthetic neural codes.
基金The author AS(Chem./2018-19/RET/Sept.18term/1/4809),SA(Chem./2019-2020/RET-2/Sept.19-term/1/975)and SS(Chem.-22/RET-Ex./July-22-term/26/564)are grateful to UGC,New Delhi and IOE,BHU for funding their doctoral researchThe financial supports received from Scheme for Promotion of Academic and Research Collaboration(SPARC-6019)MHRD,India,UKIERI,UK and IOE incentive grant for faculty(Scheme Number-6031)。
文摘Biomolecules play important roles in physiological functions and pharmacological characteristics of human body.Uric acid(UA)is the end product of purine.Dopamine(DA)is a neurotransmitter of catecholamine group.L-tryptophan is an essential amino acid that can be metabolized to neuroactive substances.Pyridoxine is a water-soluble vitamin playing an important role in nervous system.The abnormalities in their concentration levels led to a wide range of signifi cant mental and physical illnesses.Thus,electrochemical analysis of these analytes on an array system would be benefi cial from clinical or scientifi c points of view.This work was aimed at the development of practical sensor array for determination of multiple analytes on a single sensing platform using individually addressable microelectrodes.The occurrence of adsorption–desorption phenomenon on the surface of palladium microelectrode array(Pd MEA)printed on the silicon wafer through photolithography was exploited for electro-oxidation of UA,DA,L-tryptophan and pyridoxine.The sensing of electroactive UA was done using carbon nanotubes(CNTs)grown Pd MEA as a working electrode,while selectivity for other analytes was achieved by the modifi cation of CNTs/Pd MEA through electrodeposition of poly(L-lysine)(poly(L-lysine)/CNTs/Pd MEA)for DA sensing,poly(L-arginine)(poly(L-arginine)/CNTs/Pd MEA)for L-tryptophan sensing and reduced graphene oxide(rGO/CNTs/Pd MEA)for pyridoxine sensing.The electrochemical diff erential pulse voltammetry(DPV)analyses reveal excellent linearity in the concentration ranges of 50–6000μmol/L,2–8000μmol/L,20–15,000μmol/L,and 10–5000μmol/L with detection limits of 15.0,0.5,10.0,and 1.0μmol/L for UA,DA,L-tryptophan,and pyridoxine,respectively.The proposed multiple analytes sensor has shown very high sensitivities of 140,9580,2280,and 940μA·(μmol·L^(-1))^(-1)·cm^(-2)for UA,DA,L-tryptophan,and pyridoxine sensing,respectively.Further,accuracy and reliability of the fabricated sensor were also tested in real samples.
