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Journal of Semiconductors 2018年第7期39卷 104-109页

作者： Tongqiang Gao Zhenxiong Chen Siqi Zhao Haigang Yang xinxia cai Institute of Electronics Chinese Academy of Sciences Beijing 100190 China University of Chinese Academy of Sciences Beijing 100049 China

A BFSK and OOK IF base-band circuit is provided to implement the low-IF RF receivers for a dualband MICS/BCC network controller. In order to transfer the massive vital data immediately, the IF circuit is comprised of the fast-settling feed-forward programmable gain amplifier（PGA）, a Gm-C complex filter, the fixed gain amplifier（FGA） and a 4-input ＂quadratic sum＂ demodulator. A novel auto-switched coarse gain-setting method is adopted in the PGA to enhance the reaction speed and narrow the output signal range. Also the PGA does not suffer the same stability constraint as open-loop topologies. The complex filter fulfills the function of image rejection,in which the center frequency and bandwidth can be adjusted individually. The FGA is used to ameliorate the linearity and the ＇quadratic sum＇ demodulator can reduce the overall power consumption. The designed IF circuit is fabricated with SMIC 0.18 μm CMOS process. The chip area is about 5.36 mm^2. Measurement results are given to verify the design goals.

关键词： low-IF receiver VGA complex filter MICS BCC

Rapid detection of Cyfra 21-1 by optical-biosensing based on chemiluminescence immunoassay using bio-functionlized magnetic nanocomposites

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Chinese Science Bulletin 2013年第21期58卷 2567-2569页

作者： LUO JinPing QU ShuXue LIU JunTao WANG Bin cai xinxia State Key Laboratory of Transducer Technology Institute of Electronics Chinese Academy of Sciences Graduate School of Chinese Academy of Sciences

This letter reports a chemiluminescene immunoassay method combined with immunomagnetic separation to rapidly detect Cyfra 21-1, in which bio-functionlized magnetic nanocomposites were used as mobile substrate for capturing and isolating the cyfra 21-1 proteins. After the captured Cyfra 21-1 further reacted with horseradish peroxidase-conjugated anti-Cyfra 21-1 antibody to form a sandwich immunocomplex, the chemiluminescence would be produced as a result of addition of the chemiluminescent substrate. A home-made optical biosensor was designed to detect the chemiluminescence instead of other large instruments. There is a good linear response between the chemiluminescence intensity and the concentration of Cyfra 21-1 in the range from 0.2 to 50 ng/mL. The whole detection process including incubation, washing and detection could be performed within 45 min. The proposed method offers a simple, noninvasive and reliable tool for detecting non-small cell lung cancer and has potential application for clinical testing.

关键词：化学发光免疫分析纳米复合材料光学传感器快速检测生物传感磁性辣根过氧化物酶非小细胞肺癌

Recent advances and research progress on microsystems and bioeffects of terahertz neuromodulation

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Microsystems & Nanoengineering 2023年第6期9卷 25-41页

作者： Meiting Liu Juntao Liu Wei Liang Botao Lu Penghui Fan Yilin Song Mixia Wang Yirong Wu xinxia cai State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing100049China

Terahertz waves can interact with the nervous system of organisms under certain *** to common optical modulation methods,terahertz waves have the advantages of low photon energy and low risk;therefore,the use of terahertz waves to regulate the nervous system is a promising new method of ***,most of the research has focused on the use of terahertz technology for biodetection,while relatively little research has been carried out on the biological effects of terahertz radiation on the nervous system,and there are almost no review papers on this *** the present article,we begin by reviewing principles and objects of research regarding the biological effects of terahertz radiation and summarizing the current state of related research from a variety of aspects,including the bioeffects of terahertz radiation on neurons in vivo and in vitro,novel regulation and detection methods with terahertz radiation devices and neural microelectrode arrays,and theoretical simulations of neural information encoding and *** addition,we discuss the main problems and their possible causes and give some recommendations on possible future *** paper will provide insight and assistance to researchers in the fields of neuroscience,terahertz technology and biomedicine.

关键词： breakthrough neural microelectrode

Nanomaterial-based microelectrode arrays for in vitro bidirectional brain–computer interfaces:a review

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Microsystems & Nanoengineering 2023年第1期9卷 55-72页

作者： Yaoyao Liu Shihong Xu Yan Yang Kui Zhang Enhui He Wei Liang Jinping Luo Yirong Wu xinxia cai State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing100049PR China

A bidirectional in vitro brain–computer interface(BCI)directly connects isolated brain cells with the surrounding environment,reads neural signals and inputs modulatory *** a noninvasive BCI,it has clear advantages in understanding and exploiting advanced brain function due to the simplified structure and high controllability of ex vivo neural ***,the core of ex vivo BCIs,microelectrode arrays(MEAs),urgently need improvements in the strength of signal detection,precision of neural modulation and ***,nanomaterial-based MEAs cater to all the requirements by converging the multilevel neural signals and simultaneously applying stimuli at an excellent spatiotemporal resolution,as well as supporting long-term cultivation of *** is enabled by the advantageous electrochemical characteristics of nanomaterials,such as their active atomic reactivity and outstanding charge conduction efficiency,improving the performance of ***,we review the fabrication of nanomaterial-based MEAs applied to bidirectional in vitro BCIs from an interdisciplinary *** also consider the decoding and coding of neural activity through the interface and highlight the various usages of MEAs coupled with the dissociated neural cultures to benefit future developments of BCIs.

关键词： modulator neural computer

An implantable microelectrode array for simultaneous L-glutamate and electrophysiological recordings in vivo

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Microsystems & Nanoengineering 2015年第1期1卷 159-164页

作者： Wenjing Wei Yilin Song Li Wang Song Zhang Jinping Luo Shengwei Xu xinxia cai State Key Laboratory of Transducer Technology Institute of ElectronicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

L-glutamate,the most common excitatory neurotransmitter in the mammalian central nervous system(CNS),is associated with a wide range of neurological *** 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 *** the present study,a silicon-based implantable microelectrode array(MEA)composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical *** 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 0.5μ*** MEA probe was used to monitor extracellular glutamate levels,spikes and local field potentials(LFPs)in the striatum of anaesthetised *** 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 *** was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo.

关键词： MEMS implantable microelectrode array glutamate electrophysiological detection in vivo

Wireless closed-loop deep brain stimulation using microelectrode array probes

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第10期25卷 803-823页

作者： Qianli JIA Yaoyao LIU Shiya LV Yiding WANG Peiyao JIAO Wei XU Zhaojie XU Mixia WANG xinxia cai State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China

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 *** in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in *** 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 *** the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently *** this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this *** technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

关键词： Deep brain stimulation(DBS) Wireless closed-loop deep brain stimulation(CL-DBS)microsystem Microelectrode array(MEA)probe Optical stimulation Electrical stimulation

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

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Nanotechnology and Precision Engineering 2024年第2期7卷 1-10页

作者： Yan Yang Shihong Xu Yu Deng Yaoyao Liu Kui Zhang Shiya Lv Longze Sha Qi Xu xinxia cai Jinping Luo State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

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 *** chip was designed based on the specific structure of neurons and the requirements for detection and ***-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 *** employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated *** hippocampal neurons were cultured on the chip,forming a well-defined neural *** 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 *** 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.

关键词： Microfluidic Microelectrode array In vitro Neural chip

Nanoliposome-encapsulated caged-GABA for modulating neural electrophysiological activity with simultaneous detection by microelectrode arrays

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Nano Research 2020年第6期13卷 1756-1763页

作者： Jingyu Xie Yilin Song Yuchuan Dai Ziyue Li Fei Gao Xuanyu Li Guihua Xiao Yu Zhang Hao Wang Zeying Lu Xingyu Jiang Wenfu Zheng xinxia cai State Key Laboratory of Transducer Technology Institute of ElectronicsChinese Academy of SciencesBeijing100190China University of Chinese Academy of Sciences Beijing100049China Beijing Engineering Research Center for BioNanotechnology CAS Key Laboratory for Biological Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for NanoScience and TechnologyBeijing100190China Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen518055China

Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant ***-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution,delayed drug clearance,and restricted drug biodistribution for neural *** this study,we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds(Nanolipo-Ru)to modulate neural activity and allow for real-time monitoring using the microelectrode arrays(MEAs).The Nanolipo-Ru nanoparticles had an average size of 134.10±4.30 nm and exhibited excellent stability for seven *** the in vivo experiment in the rat,release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4%and 81.6%,***,the average power of local field potentials in the 0–15 Hz range degraded from 4.34 to 0.85 *** addition,the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the *** results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal ***,nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.

关键词： neural modulation nanoliposome microelectrode array light-sensitive drug

Real-time simultaneous recording of electrophysiological activities and dopamine overflow in the deep brain nuclei of a non-human primate with Parkinson’s disease using nano-based microelectrode arrays

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Microsystems & Nanoengineering 2018年第1期4卷 541-549页

作者： Song Zhang Yilin Song Mixia Wang Guihua Xiao Fei Gao Ziyue Li Guoxian Tao Ping Zhuang Feng Yue Piu Chan xinxia cai State Key Laboratory of Transducer Technology Institute of ElectronicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100190China Wincon TheraCells Biotechnologies Co. Ltd.Nanning 530002China Department of Neurobiology Xuanwu HospitalCapital Medical UniversityThe Beijing Key Laboratory of Parkinson's DiseaseBeijing 100053China

Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic *** precise mechanisms are still *** the neuronal communications are inherently electrical and chemical in nature,dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD *** nucleus(STN)highfrequency stimulation(HFS)can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian *** mechanism of STN-HFS for PD still remains *** this study,a silicon-based dual-mode microelectrode array(MEA)probe was designed and fabricated,and systematic dual-mode detection methods were *** recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise(SNR)*** evaluate its applicability to PD research,in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models,*** 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 *** dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.

关键词： dual mode implantable MEA non-human primate Parkinson's disease STN-HFS

Impaired Spatial Firing Representations of Neurons in the Medial Entorhinal Cortex of the Epileptic Rat Using Microelectrode Arrays

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Research 2024年第2期2023卷 541-552页

作者： Zhaojie Xu Fan Mo Gucheng Yang Penghui Fan Botao Lu Wei Liang Fanli Kong Luyi Jing Wei Xu Juntao Liu Mixia Wang Yirong Wu xinxia cai State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Epilepsy severely impairs the cognitive behavior of *** 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 *** 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 *** the open field test,we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of ***,we analyzed theta oscillations and theta modulation in both excitatory and inhibitory ***,we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic *** 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 *** the chronic period(>10 d),the performance in the novel object experiment *** 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.

关键词： epilepsy impaired involvement