Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this tec...Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this technology provides in-depth insight into the underlying neural mechanisms for their movement and cognition in real-world scenarios.However,the application of implanted devices in freely moving animals is limited by restrictions on their behavioral freedom and physiologic impact.In this paper,four technological directions for ideal implantable neural interface devices are analyzed:higher spatial density,improved biocompatibility,enhanced multimodal detection of electrical/neurotransmitter signals,and more effective neural modulation.Finally,we discuss how these technological developments have been applied to freely moving animals to provide better insight into neuroscience and clinical medicine.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
Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Adv...Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.展开更多
To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip...To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.展开更多
In this study, a 60-channel microelectrode array(MEA) was fabricated and used to monitor the neural spikes and local field potentials(LFPs) of neurons differentiated from rat neural stem cells in vitro. The neurons we...In this study, a 60-channel microelectrode array(MEA) was fabricated and used to monitor the neural spikes and local field potentials(LFPs) of neurons differentiated from rat neural stem cells in vitro. The neurons were grown on the MEA surface to detect neural signals. Glutamate(Glu) was used to modulate neural activity during experiments. To enhance detection performance, platinum nanoparticles were modified onto the microelectrode site surface. Glutamate stimulated neural spikes and LFPs were recorded using the MEA. The average spike amplitude was approximately 70 μV in the normal state. The spike amplitude increased by 29% from 70 μV to 90 μV with Glu modulation. The firing rate increased by 69% from 4.01 Hz to 6.8 Hz with Glu modulation. The LFP power increased from 326 μW in the normal state to 617 μW with Glu modulation in the 0–10 Hz frequency band. Data analysis shows that neural activity stimulated by Glu modulation was recorded experimentally at high temporal-spatial resolution. These results may provide a new neuron detection method, as well as further understanding of neural stem cell spike firing and associated mechanisms.展开更多
A new type of disposable thin-film amperometric biosensor has been developed for measurement ofβ-hydroxybutyrate and total cholesterol in serum.The biosensor consists of two plain gold electrodes mounted on a Polyeth...A new type of disposable thin-film amperometric biosensor has been developed for measurement ofβ-hydroxybutyrate and total cholesterol in serum.The biosensor consists of two plain gold electrodes mounted on a Polyethylene terephthalate (PET) substrate.The reagent solution contains bienzymes (cholesterol oxidase and cholesterol esterase for total cholesterol,β-hydroxybutyrate dehydrogenase and diaphorase forβ-hydroxybutyrate respectively) with mediator (ferricyanide) were absorption at the surface of electrodes coated by electrodepositing platinum black.The presence of the mediator lowers the applied potential and eliminates the interference from other oxidizable species enhancing the sensitivity and selectivity of the biosensor without modifying the dynamic parameters of the response.The enzymes stably retains in the matrices of platinum black film improving the performance of the mediated sensor.The linearity is observed in the concentration range from 1.0×10^(-4) to 1.0×10^(-2) mM and 1.0×10^(-4) mM to 4.99×10^(-3) mM with sensitivity of 1.958μA/mM and 2.447μA/mM respectively.The optimized biosensor exhibits excellent reproducibility and stability retaining more than 90% of its original activity over a period of one month.The simple operation of the biosensor mass-produced at low cost is expected to find clinical application and homecare.展开更多
An enzyme biosensor for amperometric measurement of aspartate aminotransferase has been developed.The working electrode was modified with a thin-film of redox polymer,then glutamate oxidase,with the immobilized reagen...An enzyme biosensor for amperometric measurement of aspartate aminotransferase has been developed.The working electrode was modified with a thin-film of redox polymer,then glutamate oxidase,with the immobilized reagent cast and dried on the electrode.The biosensor responses to AST by detecting hydrogen peroxide were produced by enzymical reaction at-0.1 V with a response time of 120 seconds.The electrode gave a detection limit of 32.5 U/L with a linear concentration range of 32.5 U/L～2000 U/L in serum.Due to more sensitive and lower detection limit,the biosensor is expected mainly to be used for physiological identification and physical performance of athletes in the future.Extended application will also affect the practice of clinical medicine for the diagnosis of heart and liver disease.展开更多
<正>Amperometric biosensor applied to the determination of high concentration lactate in serum and whole blood was described.The biosensor was constructed by gold electrode modified with nanoplatinum particles.L...<正>Amperometric biosensor applied to the determination of high concentration lactate in serum and whole blood was described.The biosensor was constructed by gold electrode modified with nanoplatinum particles.Lactate oxidase (E.C.1.1.3.2) was immobilized at platinized activated gold electrode which was used for the determination of high concentration lactate at low potential (+0.2 V).The linear calibration graphs were obtained from 1 to 21 mmol·L~ (-1) lactate in serum and from 0.9 to 13.2 mmol.L~ (-1) lactate in whole blood.The correlation coefficients were 0.99 and 0.97,respectively at a steady-state response time of 50 s.展开更多
A point-of-care test system has been studied in this paper.It was used to determine substances in blood such as Hemoglobin (HB),Aspartate Aminotransferase (AST),Creatine Kinase (CK) and so on.Based on the principle ...A point-of-care test system has been studied in this paper.It was used to determine substances in blood such as Hemoglobin (HB),Aspartate Aminotransferase (AST),Creatine Kinase (CK) and so on.Based on the principle of amperometric determination,the research on detecting weak current signals was carried on.At the same time as to the weak signals (nA level),magnifying,sampling and processing the signals were also studied.Controlled by ADUC824 and assisted by other units, every substance could be determined automatically and rapidly integrated with the corresponding biosensor.In the experiment, the minimum detectable current of the instrument (YT2005-1) is 0.2 nA.With regard to the 1 nA which the experiment demanded,it could be up to the mustard.And the system can provide results in 180 s with a long term stability.展开更多
A new rapid,specific and sensitive method for assay of recombinant CFP10-ESAT6 amalgamation proteins from Mycobacterium tuberculosis was proposed.The method used streptavidincoated magnetic beads to enrich the specifi...A new rapid,specific and sensitive method for assay of recombinant CFP10-ESAT6 amalgamation proteins from Mycobacterium tuberculosis was proposed.The method used streptavidincoated magnetic beads to enrich the specific biotinylated anti-CFP10 antibody,then adopted a sandwich-type enzyme linked immunosorbent assay technology with two kinds of monoclonal antibodies:biotinylated anti-CFP10 antibody and HRP-labeled anti-CFP10 antibody to identify the target CFP10-ESAT6 proteins,and finally detected chemiluminescence intensity by a small home-made optical sensor.It was shown that,the corresponding chemiluminescence intensity had a good logarithmic linear response to the concentration of CFP10-ESAT6 proteins when ranging at 1~1000 ng/mL,and the correlation coefficient is 0.9937.The proposed method could detect the CFP10-ESAT6 proteins with low detection limit(1 ng/mL)and the detection time could be controlled within 45 min.Compared with commonly used detection methods of M.tuberculosis,this method was easy to operate,faster,and of higher sensitivity.The achievement of the quantitative detection of CFP10-ESAT6 proteins has important scientific significance and wide application prospects in tuberculosis control.展开更多
Timely monitoring of anesthesia status during surgery is important to prevent an overdose of isoflurane anesthesia.Therefore,in-depth studies of the neural mechanisms of anesthetics are warranted.Hippocampal CA1 plays...Timely monitoring of anesthesia status during surgery is important to prevent an overdose of isoflurane anesthesia.Therefore,in-depth studies of the neural mechanisms of anesthetics are warranted.Hippocampal CA1 plays an important role during anesthesia.Currently,a high spatiotemporal resolution microdevice technology for the accurate detection of deep brain nuclei is lacking.In this research,four-shank 32-channel implantable microelectrode arrays(MEAs)were developed for the real-time recording of single-cell level neural information in rat hippocampal CA1.Platinum nanoparticles were modified onto the microelectrodes to substantially enhance the electrical properties of the microelectrode arrays.The modified MEAs exhibited low impedance(11.5±1 kΩ)and small phase delay(-18.5°±2.54°),which enabled the MEAs to record single-cell level neural information with a high signal-to-noise ratio.The MEAs were implanted into the CA1 nuclei of the anesthetized rats,and the electrophysiological signals were recorded under different degrees of anesthesia mediated by low-dose concentrations of isoflurane.The recorded signals were analyzed in depth.Isoflurane caused an inhibition of spike firing rate in hippocampal CA1 neurons,while inducing low-frequency oscillations in CA1,thus enhancing the low-frequency power of local field potentials.In this manner,the spike firing rate and the power of local field potentials in CA1 could characterize the degree of isoflurane anesthesia.The present study provides a technical tool to study the neural mechanisms of isoflurane anesthesia and a research method for monitoring the depth of isoflurane anesthesia in clinical practice.展开更多
Neural information transmission between deep brain nuclei and the cortex is essential for brain function.Currently,high-resolution simultaneous detection of neural information between the deep brain nuclei and the lar...Neural information transmission between deep brain nuclei and the cortex is essential for brain function.Currently,high-resolution simultaneous detection of neural information between the deep brain nuclei and the large-scale cortex still poses challenges.We have developed the microelectrode arrays based on the Micro-Electro-Mechanical System technology,and modified the electrode surface with nanomaterials to improve the electrode performance.This study combined microelectrode arrays and extended-field-of-view microscopy to achieve simultaneous recording of claustrum(CLA)electrophysiology and wide-field cortical calcium imaging at single-cell resolution.This work investigated the synchronous changes of neural information in CLA and cortex of mice during the whole process from wakefulness to anesthesia and then to wakefulness,and summarized the characteristics of the CLA electrophysiology and cortical calcium signaling under different inhalation anesthesia concentrations.We found the synergy between microscopic spike and local field potential of CLA neurons under deep anesthesia,and the law that high inhalation anesthesia concentration enhanced the synchronization between neurons in CLA and cortex.The combination of microelectrode arrays and extended-field-of-view microscopy also gives a new method for synchronous detection of multimodal and multi-brain region neural information.展开更多
Epilepsy severely impairs the cognitive behavior of patients.It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex(MEC),a region known ...Epilepsy severely impairs the cognitive behavior of patients.It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex(MEC),a region known for its involvement in spatial cognition.To explore this neural mechanism,we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays.Through the open field test,we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy.Meanwhile,we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons.Furthermore,we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats.After the epilepsy modeling,the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period(1 to 5 d).Subsequently,the firing characteristics and theta oscillations were impaired.In the chronic period(>10 d),the performance in the novel object experiment deteriorated.In conclusion,our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency,suggesting the potential use of these changes as a"functional biomarker"for predicting cognitive impairment caused by epilepsy.展开更多
Navigating toward destinations with rewards is a common behavior among animals.The ventral tegmental area(VTA)has been shown to be responsible for reward coding and reward cue learning,and its response to other variab...Navigating toward destinations with rewards is a common behavior among animals.The ventral tegmental area(VTA)has been shown to be responsible for reward coding and reward cue learning,and its response to other variables,such as kinematics,has also been increasingly studied.These findings suggest a potential relationship between animal navigation behavior and VTA activity.However,the deep location and small volume of the VTA pose significant challenges to the precision of electrode implantation,increasing the uncertainty of measurement results during animal navigation and thus limiting research on the role of the VTA in goal-directed navigation.To address this gap,we innovatively designed and fabricated low-curvature microelectrode arrays(MEAs)via a novel backside dry etching technique to release residual stress.Histological verification confrmed that low-curvature MEAs indeed improved electrode implantation precision.These low-curvature MEAs were subsequently implanted into the VTA of the rats to observe their electrophysiological activity in a freely chosen modified T-maze.The results of the behavioral experiments revealed that the rats could quickly learn the reward probability corresponding to the left and right paths and that VTA neurons were deeply involved in goal-directed navigation.Compared with those in no-reward trials,VTA neurons in reward trials presented a significantly greater fring rate and larger local feld potential(LFP)amplitude during the reward-consuming period.Notably,we discovered place felds mapped by VTA neurons,which disappeared or were reconstructed with changes in the path-outcome relationship.These results provide new insights into the VTA and its role in goal-directed navigation.Our designed and fabricated low-curvature microelectrode arrays can serve as a new device for precise deep brain implantation in the future.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
L-glutamate,the most common excitatory neurotransmitter in the mammalian central nervous system(CNS),is associated with a wide range of neurological diseases.Because neurons in CNS communicate with each other both ele...L-glutamate,the most common excitatory neurotransmitter in the mammalian central nervous system(CNS),is associated with a wide range of neurological diseases.Because neurons in CNS communicate with each other both electrically and chemically,dualmode(electric and chemical)analytical techniques with high spatiotemporal resolution are required to better understand glutamate function in vivo.In the present study,a silicon-based implantable microelectrode array(MEA)composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical system.In the MEA probe,the electrophysiological electrodes have a low impedance of 0.018 MΩat 1 kHz,and the electrochemical electrodes show a sensitivity of 56 pAμM^(−1) to glutamate and have a detection limit of 0.5μM.The MEA probe was used to monitor extracellular glutamate levels,spikes and local field potentials(LFPs)in the striatum of anaesthetised rats.To explore the potential of the MEA probe,the rats were administered to KCl via intraperitoneal injection.K+significantly increases extracellular glutamate levels,LFP low-beta range(12–18 Hz)power and spike firing rates with a similar temporal profile,indicating that the MEA probe is capable of detecting dual-mode neuronal signals.It was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo.展开更多
Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons.The precise mechanisms are still unknown.Since the neuronal communications are inherently electrical and che...Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons.The precise mechanisms are still unknown.Since the neuronal communications are inherently electrical and chemical in nature,dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research.Subthalamic nucleus(STN)highfrequency stimulation(HFS)can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs.The mechanism of STN-HFS for PD still remains elusive.In this study,a silicon-based dual-mode microelectrode array(MEA)probe was designed and fabricated,and systematic dual-mode detection methods were established.The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise(SNR)ratio.To evaluate its applicability to PD research,in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models,respectively.Through comparison of the dual-mode signals,we demonstrated the following in a PD monkey:(1)the maximum dopamine concentration in the striatum decreased by 90%;(2)the spike firing frequency increased significantly,especially in the region of the cortex;(3)the spectrogram analysis showed that much power existed in the 0–10 Hz frequency band;and(4)following repeated subthalamic nucleus high-frequency stimulation trials,the level of DA in the striatum increased by 16.5μM,which led to a better elucidation of the mechanism of HFS.The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.展开更多
In this work,an electrochemical paper-based aptasensor was fabricated for label-free and ultrasensitive detection of epidermal growth factor receptor(EGFR)by employing anti-EGFR aptamers as the bio-recognition element...In this work,an electrochemical paper-based aptasensor was fabricated for label-free and ultrasensitive detection of epidermal growth factor receptor(EGFR)by employing anti-EGFR aptamers as the bio-recognition element.The device used the concept of paper-folding,or origami,to serve as a valve between sample introduction and detection,so reducing sampling volumes and improving operation convenience.Amino-functionalized graphene(NH 2-GO)/thionine(THI)/gold particle(AuNP)nanocomposites were used to modify the working electrode not only to generate the electrochemical signals,but also to provide an environment conducive to aptamer immobilization.Electrochemical characterization revealed that the formation of an insulating aptamer–antigen immunocomplex would hinder electron transfer from the sample medium to the working electrode,thus resulting in a lower signal.The experimental results showed that the proposed aptasensor exhibited a linear range from 0.05 to 200 ngmL^(−1)(R^(2)=0.989)and a detection limit of 5pgmL^(−1) for EGFR.The analytical reliability of the proposed paper-based aptasensor was further investigated by analyzing serum samples,showing good agreement with the gold-standard enzyme-linked immunosorbent assay.展开更多
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金sponsored by the National Natural Science Foundation of China(62121003,T2293730,T2293731,61960206012,62333020,and 62171434)the National Key Research and Development Program of China(2022YFC2402501 and 2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(2021ZD02016030)。
文摘Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this technology provides in-depth insight into the underlying neural mechanisms for their movement and cognition in real-world scenarios.However,the application of implanted devices in freely moving animals is limited by restrictions on their behavioral freedom and physiologic impact.In this paper,four technological directions for ideal implantable neural interface devices are analyzed:higher spatial density,improved biocompatibility,enhanced multimodal detection of electrical/neurotransmitter signals,and more effective neural modulation.Finally,we discuss how these technological developments have been applied to freely moving animals to provide better insight into neuroscience and clinical medicine.
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 National Natural Science Foundation of China(Nos.T2293730,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)+1 种基金the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.GJJSTD20210004).
文摘Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.
基金sponsored by the National Natural Science Foundation of China (Grant Nos.61960206012,62121003,T2293731,62171434,61975206,61971400,and 61973292)the National Key Research and Development Program of China (Grant Nos.2022YFB3205602 and 2022YFC2402501)+1 种基金Major Program of Scientific and Technical Innovation 2030 (Grant No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences (Grant No.GJJSTD20210004).
文摘To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.
基金supported by the NSFC (No. 61960206012, No. 61527815, No. 61775216, No. 61975206, No. 61971400, No.61973292)the National Key R&D Program of nano science and technology of China (2017YFA0205902)the Key Research Programs of Frontier Sciences, CAS (QYZDJ-SSW-SYS015, XDA16020902)。
文摘In this study, a 60-channel microelectrode array(MEA) was fabricated and used to monitor the neural spikes and local field potentials(LFPs) of neurons differentiated from rat neural stem cells in vitro. The neurons were grown on the MEA surface to detect neural signals. Glutamate(Glu) was used to modulate neural activity during experiments. To enhance detection performance, platinum nanoparticles were modified onto the microelectrode site surface. Glutamate stimulated neural spikes and LFPs were recorded using the MEA. The average spike amplitude was approximately 70 μV in the normal state. The spike amplitude increased by 29% from 70 μV to 90 μV with Glu modulation. The firing rate increased by 69% from 4.01 Hz to 6.8 Hz with Glu modulation. The LFP power increased from 326 μW in the normal state to 617 μW with Glu modulation in the 0–10 Hz frequency band. Data analysis shows that neural activity stimulated by Glu modulation was recorded experimentally at high temporal-spatial resolution. These results may provide a new neuron detection method, as well as further understanding of neural stem cell spike firing and associated mechanisms.
文摘A new type of disposable thin-film amperometric biosensor has been developed for measurement ofβ-hydroxybutyrate and total cholesterol in serum.The biosensor consists of two plain gold electrodes mounted on a Polyethylene terephthalate (PET) substrate.The reagent solution contains bienzymes (cholesterol oxidase and cholesterol esterase for total cholesterol,β-hydroxybutyrate dehydrogenase and diaphorase forβ-hydroxybutyrate respectively) with mediator (ferricyanide) were absorption at the surface of electrodes coated by electrodepositing platinum black.The presence of the mediator lowers the applied potential and eliminates the interference from other oxidizable species enhancing the sensitivity and selectivity of the biosensor without modifying the dynamic parameters of the response.The enzymes stably retains in the matrices of platinum black film improving the performance of the mediated sensor.The linearity is observed in the concentration range from 1.0×10^(-4) to 1.0×10^(-2) mM and 1.0×10^(-4) mM to 4.99×10^(-3) mM with sensitivity of 1.958μA/mM and 2.447μA/mM respectively.The optimized biosensor exhibits excellent reproducibility and stability retaining more than 90% of its original activity over a period of one month.The simple operation of the biosensor mass-produced at low cost is expected to find clinical application and homecare.
文摘An enzyme biosensor for amperometric measurement of aspartate aminotransferase has been developed.The working electrode was modified with a thin-film of redox polymer,then glutamate oxidase,with the immobilized reagent cast and dried on the electrode.The biosensor responses to AST by detecting hydrogen peroxide were produced by enzymical reaction at-0.1 V with a response time of 120 seconds.The electrode gave a detection limit of 32.5 U/L with a linear concentration range of 32.5 U/L～2000 U/L in serum.Due to more sensitive and lower detection limit,the biosensor is expected mainly to be used for physiological identification and physical performance of athletes in the future.Extended application will also affect the practice of clinical medicine for the diagnosis of heart and liver disease.
文摘<正>Amperometric biosensor applied to the determination of high concentration lactate in serum and whole blood was described.The biosensor was constructed by gold electrode modified with nanoplatinum particles.Lactate oxidase (E.C.1.1.3.2) was immobilized at platinized activated gold electrode which was used for the determination of high concentration lactate at low potential (+0.2 V).The linear calibration graphs were obtained from 1 to 21 mmol·L~ (-1) lactate in serum and from 0.9 to 13.2 mmol.L~ (-1) lactate in whole blood.The correlation coefficients were 0.99 and 0.97,respectively at a steady-state response time of 50 s.
文摘A point-of-care test system has been studied in this paper.It was used to determine substances in blood such as Hemoglobin (HB),Aspartate Aminotransferase (AST),Creatine Kinase (CK) and so on.Based on the principle of amperometric determination,the research on detecting weak current signals was carried on.At the same time as to the weak signals (nA level),magnifying,sampling and processing the signals were also studied.Controlled by ADUC824 and assisted by other units, every substance could be determined automatically and rapidly integrated with the corresponding biosensor.In the experiment, the minimum detectable current of the instrument (YT2005-1) is 0.2 nA.With regard to the 1 nA which the experiment demanded,it could be up to the mustard.And the system can provide results in 180 s with a long term stability.
基金This project is supported by National Major Scientific Research Program of China(No.2011CB933202)National High Technology Research and Development Program of China(No.2009AA03Z411)+1 种基金National Natural Science Foundation of China(No.61002037,61101048)Knowledge Innovation Program of The Chinese Academy of Sciences(CXJJ-10-M31,KGCX2-YW-916).
文摘A new rapid,specific and sensitive method for assay of recombinant CFP10-ESAT6 amalgamation proteins from Mycobacterium tuberculosis was proposed.The method used streptavidincoated magnetic beads to enrich the specific biotinylated anti-CFP10 antibody,then adopted a sandwich-type enzyme linked immunosorbent assay technology with two kinds of monoclonal antibodies:biotinylated anti-CFP10 antibody and HRP-labeled anti-CFP10 antibody to identify the target CFP10-ESAT6 proteins,and finally detected chemiluminescence intensity by a small home-made optical sensor.It was shown that,the corresponding chemiluminescence intensity had a good logarithmic linear response to the concentration of CFP10-ESAT6 proteins when ranging at 1~1000 ng/mL,and the correlation coefficient is 0.9937.The proposed method could detect the CFP10-ESAT6 proteins with low detection limit(1 ng/mL)and the detection time could be controlled within 45 min.Compared with commonly used detection methods of M.tuberculosis,this method was easy to operate,faster,and of higher sensitivity.The achievement of the quantitative detection of CFP10-ESAT6 proteins has important scientific significance and wide application prospects in tuberculosis control.
基金sponsored by the National Natural Science Foundation of China(T2293731,61960206012,62121003,62171434,61971400,61975206,and 61973292)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(GJJSTD20210004)+1 种基金the National Key Research and Development Program(2022YFC2402501,2022YFB3205602)Major Program of Scientific and Technical Innovation 2030(2021ZD0201603).
文摘Timely monitoring of anesthesia status during surgery is important to prevent an overdose of isoflurane anesthesia.Therefore,in-depth studies of the neural mechanisms of anesthetics are warranted.Hippocampal CA1 plays an important role during anesthesia.Currently,a high spatiotemporal resolution microdevice technology for the accurate detection of deep brain nuclei is lacking.In this research,four-shank 32-channel implantable microelectrode arrays(MEAs)were developed for the real-time recording of single-cell level neural information in rat hippocampal CA1.Platinum nanoparticles were modified onto the microelectrodes to substantially enhance the electrical properties of the microelectrode arrays.The modified MEAs exhibited low impedance(11.5±1 kΩ)and small phase delay(-18.5°±2.54°),which enabled the MEAs to record single-cell level neural information with a high signal-to-noise ratio.The MEAs were implanted into the CA1 nuclei of the anesthetized rats,and the electrophysiological signals were recorded under different degrees of anesthesia mediated by low-dose concentrations of isoflurane.The recorded signals were analyzed in depth.Isoflurane caused an inhibition of spike firing rate in hippocampal CA1 neurons,while inducing low-frequency oscillations in CA1,thus enhancing the low-frequency power of local field potentials.In this manner,the spike firing rate and the power of local field potentials in CA1 could characterize the degree of isoflurane anesthesia.The present study provides a technical tool to study the neural mechanisms of isoflurane anesthesia and a research method for monitoring the depth of isoflurane anesthesia in clinical practice.
基金sponsored by the National Natural Science Foundation of China(T2293730,T2293731,62121003,61960206012,62333020 and 62171434)the National Key Research and Development Program of China(2022YFC2402501,2022YFB3205602)Major Program of Scientific and Technical Innovation 2030(2021ZD02016030).
文摘Neural information transmission between deep brain nuclei and the cortex is essential for brain function.Currently,high-resolution simultaneous detection of neural information between the deep brain nuclei and the large-scale cortex still poses challenges.We have developed the microelectrode arrays based on the Micro-Electro-Mechanical System technology,and modified the electrode surface with nanomaterials to improve the electrode performance.This study combined microelectrode arrays and extended-field-of-view microscopy to achieve simultaneous recording of claustrum(CLA)electrophysiology and wide-field cortical calcium imaging at single-cell resolution.This work investigated the synchronous changes of neural information in CLA and cortex of mice during the whole process from wakefulness to anesthesia and then to wakefulness,and summarized the characteristics of the CLA electrophysiology and cortical calcium signaling under different inhalation anesthesia concentrations.We found the synergy between microscopic spike and local field potential of CLA neurons under deep anesthesia,and the law that high inhalation anesthesia concentration enhanced the synchronization between neurons in CLA and cortex.The combination of microelectrode arrays and extended-field-of-view microscopy also gives a new method for synchronous detection of multimodal and multi-brain region neural information.
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)Major Program of Scientific and Technical Innovation 2030(no.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(no.GJJSTD20210004).
文摘Epilepsy severely impairs the cognitive behavior of patients.It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex(MEC),a region known for its involvement in spatial cognition.To explore this neural mechanism,we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays.Through the open field test,we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy.Meanwhile,we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons.Furthermore,we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats.After the epilepsy modeling,the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period(1 to 5 d).Subsequently,the firing characteristics and theta oscillations were impaired.In the chronic period(>10 d),the performance in the novel object experiment deteriorated.In conclusion,our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency,suggesting the potential use of these changes as a"functional biomarker"for predicting cognitive impairment caused by epilepsy.
基金This work was sponsored by the National Natural Science Foundation of China(No.62121003,T2293730,T2293731,61960206012,62333020,and 62171434)the National Key Research and Development Program of China(2022YFC2402501,2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(2021ZD02016030).
文摘Navigating toward destinations with rewards is a common behavior among animals.The ventral tegmental area(VTA)has been shown to be responsible for reward coding and reward cue learning,and its response to other variables,such as kinematics,has also been increasingly studied.These findings suggest a potential relationship between animal navigation behavior and VTA activity.However,the deep location and small volume of the VTA pose significant challenges to the precision of electrode implantation,increasing the uncertainty of measurement results during animal navigation and thus limiting research on the role of the VTA in goal-directed navigation.To address this gap,we innovatively designed and fabricated low-curvature microelectrode arrays(MEAs)via a novel backside dry etching technique to release residual stress.Histological verification confrmed that low-curvature MEAs indeed improved electrode implantation precision.These low-curvature MEAs were subsequently implanted into the VTA of the rats to observe their electrophysiological activity in a freely chosen modified T-maze.The results of the behavioral experiments revealed that the rats could quickly learn the reward probability corresponding to the left and right paths and that VTA neurons were deeply involved in goal-directed navigation.Compared with those in no-reward trials,VTA neurons in reward trials presented a significantly greater fring rate and larger local feld potential(LFP)amplitude during the reward-consuming period.Notably,we discovered place felds mapped by VTA neurons,which disappeared or were reconstructed with changes in the path-outcome relationship.These results provide new insights into the VTA and its role in goal-directed navigation.Our designed and fabricated low-curvature microelectrode arrays can serve as a new device for precise deep brain implantation in the future.
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.
基金This work was sponsored by the Major National Scientific Research Plan(Grant Nos.2011CB933202 and 2014CB744605)the NSFC(Grant Nos.61125105 and 61471342)+1 种基金the Beijing Science and Technology Plan(Grant Nos.Z141100000214002 and Z141102003414014)the Key Programs of the Chinese Academy of Sciences(Grant No.KJZD-EW-L11-2).
文摘L-glutamate,the most common excitatory neurotransmitter in the mammalian central nervous system(CNS),is associated with a wide range of neurological diseases.Because neurons in CNS communicate with each other both electrically and chemically,dualmode(electric and chemical)analytical techniques with high spatiotemporal resolution are required to better understand glutamate function in vivo.In the present study,a silicon-based implantable microelectrode array(MEA)composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical system.In the MEA probe,the electrophysiological electrodes have a low impedance of 0.018 MΩat 1 kHz,and the electrochemical electrodes show a sensitivity of 56 pAμM^(−1) to glutamate and have a detection limit of 0.5μM.The MEA probe was used to monitor extracellular glutamate levels,spikes and local field potentials(LFPs)in the striatum of anaesthetised rats.To explore the potential of the MEA probe,the rats were administered to KCl via intraperitoneal injection.K+significantly increases extracellular glutamate levels,LFP low-beta range(12–18 Hz)power and spike firing rates with a similar temporal profile,indicating that the MEA probe is capable of detecting dual-mode neuronal signals.It was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo.
基金This work was sponsored by the NSFC(Grant Nos.61527815,31500800,61501426,61471342)the National Key Research and Development Program(Grant No.2017YFA0205900)+2 种基金the Beijing Science and Technology Plan(Grant Nos.Z141100000214002,Z1161100004916001)the National Science and Technology Major Project(2014CB744600)the Key Programs of the Chinese Academy of Sciences(Grant Nos.KJZD-EW-L11-2,QYZDJ-SSW-SYS015).
文摘Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons.The precise mechanisms are still unknown.Since the neuronal communications are inherently electrical and chemical in nature,dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research.Subthalamic nucleus(STN)highfrequency stimulation(HFS)can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs.The mechanism of STN-HFS for PD still remains elusive.In this study,a silicon-based dual-mode microelectrode array(MEA)probe was designed and fabricated,and systematic dual-mode detection methods were established.The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise(SNR)ratio.To evaluate its applicability to PD research,in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models,respectively.Through comparison of the dual-mode signals,we demonstrated the following in a PD monkey:(1)the maximum dopamine concentration in the striatum decreased by 90%;(2)the spike firing frequency increased significantly,especially in the region of the cortex;(3)the spectrogram analysis showed that much power existed in the 0–10 Hz frequency band;and(4)following repeated subthalamic nucleus high-frequency stimulation trials,the level of DA in the striatum increased by 16.5μM,which led to a better elucidation of the mechanism of HFS.The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.
基金This work was sponsored by the National Key Research and Development Program(2017YFA0205902)the NSFC(6196020612,61527815,61775216,61673024,and 61771452)+3 种基金the Key Research Programs(QYZDJ-SSW-SYS015)of Frontier Sciences,CASthe China Scholarship Councilthe UK Global Challenges Research Fund,the Scottish Funding Council,Engineering and Physical Sciences Research Council(EPSRC)Institutional Support Fund(Grant EP/R512813/1)as well by EPSRC(grants EP/K027611/1 and EP/R01437X/1 also supported by the National Institute for Health Research).
文摘In this work,an electrochemical paper-based aptasensor was fabricated for label-free and ultrasensitive detection of epidermal growth factor receptor(EGFR)by employing anti-EGFR aptamers as the bio-recognition element.The device used the concept of paper-folding,or origami,to serve as a valve between sample introduction and detection,so reducing sampling volumes and improving operation convenience.Amino-functionalized graphene(NH 2-GO)/thionine(THI)/gold particle(AuNP)nanocomposites were used to modify the working electrode not only to generate the electrochemical signals,but also to provide an environment conducive to aptamer immobilization.Electrochemical characterization revealed that the formation of an insulating aptamer–antigen immunocomplex would hinder electron transfer from the sample medium to the working electrode,thus resulting in a lower signal.The experimental results showed that the proposed aptasensor exhibited a linear range from 0.05 to 200 ngmL^(−1)(R^(2)=0.989)and a detection limit of 5pgmL^(−1) for EGFR.The analytical reliability of the proposed paper-based aptasensor was further investigated by analyzing serum samples,showing good agreement with the gold-standard enzyme-linked immunosorbent assay.
