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
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
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
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
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
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
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
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
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
Flexible deep brain neural interfaces,as an important research direction in the field of neural engineering,have broad application prospects in areas such as neural signal detection,treatment of neurological diseases,...Flexible deep brain neural interfaces,as an important research direction in the field of neural engineering,have broad application prospects in areas such as neural signal detection,treatment of neurological diseases,and intelligent control systems.However,chronic inflammatory responses caused by longterm implantation and the resulting electrode failure seriously hinder the clinical development of this technology.This review systematically explores the long-term stability issues of flexible deep brain neural interfaces,with a focus on analyzing the synergistic optimization of electrode geometric morphology and implantation strategies in regulating inflammatory responses.Additionally,this paper delves into innovative strategies,such as passive enhancement of biocompatibility through electrode surface functionalization and active inhibition of inflammation through drug-controlled release systems,offering new technical paths to extend electrode lifespan.By integrating and reviewing existing innovative methods for deep brain flexible electrodes,this study provides an important theoretical foundation and technical guidance for the development of high-stability neural interface devices.展开更多
Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefront...Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.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
Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial inform...Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.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.
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.
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.
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.
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.
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supported by the National Key Research and Development Program of China(2022YFC2402501,2022YFB3205602)the National Natural Science Foundation of China(Nos.62121003,T2293730,T2293731,62333020,62171434,and 62471291)+3 种基金the Major Program of Scientific and Technical Innovation 2030(2021ZD02016030)the Joint Foundation Program of the Chinese Academy of Sciences(No.8091A170201)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.PTYQ2024BJ0009)the National Natural Science Foundation of Beijing(F252069)。
文摘Flexible deep brain neural interfaces,as an important research direction in the field of neural engineering,have broad application prospects in areas such as neural signal detection,treatment of neurological diseases,and intelligent control systems.However,chronic inflammatory responses caused by longterm implantation and the resulting electrode failure seriously hinder the clinical development of this technology.This review systematically explores the long-term stability issues of flexible deep brain neural interfaces,with a focus on analyzing the synergistic optimization of electrode geometric morphology and implantation strategies in regulating inflammatory responses.Additionally,this paper delves into innovative strategies,such as passive enhancement of biocompatibility through electrode surface functionalization and active inhibition of inflammation through drug-controlled release systems,offering new technical paths to extend electrode lifespan.By integrating and reviewing existing innovative methods for deep brain flexible electrodes,this study provides an important theoretical foundation and technical guidance for the development of high-stability neural interface devices.
基金sponsored by the National Key R&D Program of China(Grant Nos.2022YFC2402500 and 2022YFB3205602)the National Natural Science Foundation of China(Grant Nos.62121003,T2293730,T2293731,62333020,62171434,62471291)+2 种基金the Major Program of Scientific and Technical Innovation 2030(Grant No.2021ZD02016030)the Joint Foundation Program of the Chinese Academy of Sciences(Grant No.8091A170201)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.PTYQ2024BJ0009).
文摘Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.
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.
基金sponsored by the National Key R&D Program(Grant No.2017YFA0205902)the National Natural Science Foundation of China(Grant No.62121003,61960206012,61973292,61975206,61971400,and 62171434)+1 种基金the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.GJJSTD20210004)the Major Program of Scientific and Technical Innovation 2030(No.2021ZD0201603).
文摘Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.
