神经信号检测和功能激励微电极

多学科交叉研究神经功能重建已经成为神经科学和微电子学的一个新的研究热点,主要介绍神经功能重建系统的重要部件——神经微电极。阐述神经电极与神经细胞的耦合原理,从不同角度介绍神经微电极的分类和发展并描述了其具体的微机电工艺实例,对神经微电极的生物相容性也做了介绍。     

神经信号检测和功能激励微电极

多学科交叉研究神经功能重建已经成为神经科学和微电子学的一个新的研究热点，主要介绍神经功能重建系统的重要部件——神经微电极。阐述神经电极与神经细胞的耦合原理，从不同角度介绍神经微电极的分类和发展并描述了其具体的微机电工艺实例，对神经微电极的生物相容性也做了介绍。     

柔性衬底微电极在视网膜修复上的应用

介绍了柔性神经微电极最新研究进展及其在视网膜修复上的应用价值.报道了目前柔性神经微电极主要采用的基底材料性能、微结构以及表征方法.     

神经束内微电极提取大鼠坐骨神经信号的实验研究

基于已设计完成的植入式筛型微电极和神经信号调理电路,组成一个完整的系统,用于提取大鼠坐骨神经信号,以探索获取周围神经信息的方法.用显微外科技术将微电极植入于大鼠坐骨神经束中,通过微电极传导出神经束电信号,经信号调理电路处理后记录.已成功稳定导出的电信号波形经分析具有神经动作电位特征,验证了神经束内微电极可以获取大鼠坐骨神经信号.     

DWF-2微电极放大器前放电路的设计和噪声指标的探讨

一、微电极实验系统生物电信号如:心电、脑电、肌电神经电位等目前已成为临床诊断和生理、药理研究的重要指标和依据.从微观来看,所有这些生物电信号都来源于细胞电位的总和.对细胞兴奋性的深入研究促进了细胞生理学、微量药理学以及相应的微电极实验技术的迅速发展,使某些领域为之面貌一新,许多难解之谜得到了较好的解释.     

神经芯片研究新进展：微接触印刷将神经元和硅片融为一体

神经芯片是一种利用微电极阵列实现神经细胞与电子器件信息传导的生物芯片,是人工神经代偿器件的接口.它通过把活的神经元和硅电路有机地连接在一起.实现对细胞无损伤的长时程记录,并且可以施加人为刺激.目前这一领域的关键问题在于如何使神经细胞在芯片上按照电极点的位置黏附生长,建立通讯联系并提高芯片材料的信噪比.利用微加工工艺有望达到这一目的 .微接触印刷技术在其中应用最为广泛.它应用聚二甲基硅氧烷为印章,以生物大分子或有机聚合物为"墨水",把主模板上的精细图案转印到硅片材料上,从而实现对材料表面黏附底物的改性和结构的微加工.本综述简要介绍了神经芯片的研究进展,详细阐述了微接触印刷技术的研究现状,并且初步探讨了这一工艺在神经芯片领域中的最新应用.     

双绞微电极制作装置设计与验证

微电极作为外部电子设备与内部神经核团之间的接口,在动物机器人、深度脑刺激、神经假体等方面都起着重要的作用。针对现有微电极制作装置价格高昂且制作工艺复杂等问题,本文提出了一种基于开源电子原型平台(Arduino)和三维打印技术的双绞微电极制作装置,并验证了其电极制作性能及神经刺激性能。实验结果表明,在微电极制作过程中,电极丝的正向绞合圈数一般应设置为其长度的1.8倍左右较适宜,逆向绞合圈数与长度无关,一般为5左右。与同类产品相比,本文所提装置不仅价格低廉、制作简单并具有较好的扩展性,对于微电极制作的个性化、普及化以及降低实验成本都有着积极的促进意义。     

一种磁性耦合的多微电极系统

在所描述的多微电极系统中,微电极分别被磁化并一个一个地被对每个微电极起作用的磁力耦合。这种排列增加了纤细微电极的机械力,而且还约束着每根微电极电线的弯曲。这种多微电极结构允许许多纤细微电极在局部的神经组织区域内,独立地,并平行地穿透。这些特点使得每个电极均以良好的信噪比对神经电位加以记录。此外,微电极尖端间的距离在实验操作期间能清楚地识别和保持。本文描述了这种多微电极结构的制作和特性,它的实用性由从几个局部神经区域的神经细胞的神经电位的同时记录说明。前言解剖学上的、生理学上的和关于行为的     

清醒活动树鼩(Treeshrew)上丘神经元单位活动的观察(摘要)

有关上丘深浅层细胞在视觉信息处理中的不同作用,近年已有大量研究工作。被研究的动物包括猴、猫、大鼠、小鼠等。1978年·J·E·Albano应用急性微电极技术研究了树鼩上丘神经元的某些生理特性,而采用慢性微电极技术的研究迄今未见报导,本文报告这方面的某些结果。实验用云南产树鼩11只,体重120—150克,雌雄兼用。依树鼩慢性微电极技术(孙公铎等1982)记录单位放电,实验结果由TQ—19医用数据处理机,117—Ⅰ型或Ⅱ型神经脉冲分析仪处理,实验结束后进行厚片定位。实验分二部分进行:     

微电极阵列细胞传感器芯片技术的研究进展

综述了目前国际上基于微电极阵列技术的细胞传感器芯片的研究状况。介绍了微电极阵列的工艺设计、界面模型以及在细胞电生理研究中的应用,同时分析了细胞胞外记录技术在实现组织-细胞以及细胞间信号传导过程的实时动态检测的特点和目前存在的问题。在此基础上,介绍了单细胞以及细胞传感器网络芯片技术的发展。最后,提出微电极阵列细胞传感器研究的发展方向。     

An inexpensive drivable cannulated microelectrode array for simultaneous unit recording and drug infusion in the same brain nucleus of behaving rats

Neurons are functionally segregated into discrete populations that perform specific computations. These computations, mediated by neuron-neuron electrochemical signaling, form the neural basis of behavior. Thus fundamental to a brain-based understanding of behavior is the precise determination of the contribution made by specific neurotransmitters to behaviorally relevant neural activity. To facilitate this understanding, we have developed a cannulated microelectrode array for use in behaving rats that enables simultaneous neural ensemble recordings and local infusion of drugs in the same brain nucleus. The system is inexpensive, easy to use, and produces robust and quantitatively reproducible drug effects on recorded neurons.     

Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation

The function and longevity of implantable microelectrodes for chronic neural stimulation depends heavily on the electrode materials, which need to present high charge injection capability and high stability. While conducting polymers have been coated on neural microelectrodes and shown promising properties for chronic stimulation, their practical applications have been limited due to unsatisfying stability. Here, poly(3,4-ethylenedioxythiophene) (PEDOT) doped with pure carbon nanotubes (CNTs) was electrochemically deposited on Pt microelectrodes to evaluate its properties for chronic stimulation. The PEDOT/CNT coated microelectrodes demonstrated much lower impedance than the bare Pt, and the PEDOT/CNT film exhibited excellent stability. For both acute and chronic stimulation tests, there is no significant increase in the impedance of the PEDOT/CNT coated microelectrodes, and none of the PEDOT/CNT films show any cracks or delamination, which have been the limitation for many conducting polymer coatings on neural electrodes. The charge injection limit of the Pt microelectrode was significantly increased to 2.5 mC/cm(2) with the PEDOT/CNT coating. Further in vitro experiments also showed that the PEDOT/CNT coatings are non-toxic and support the growth of neurons. It is expected that this highly stable PEDOT/CNT composite may serve as excellent new material for neural electrodes.     

In vitro microelectrode array technology and neural recordings

In vitro microelectrode array (MEA) technology has evolved into a widely used and effective methodology to study cultured neural networks. An MEA forms a unique electrical interface with the cultured neurons in that neurons are directly grown on top of the electrode (neuron-on-electrode configuration). Theoretical models and experimental results suggest that physical configuration and biological environments of the cell-electrode interface play a key role in the outcome of neural recordings, such as yield of recordings, signal shape, and signal-to-noise ratio. Recent interdisciplinary approaches have shown that MEA performance can be enhanced through novel nanomaterials, structures, surface chemistry, and biotechnology. In vitro and in vivo neural interfaces share some common factors, and in vitro neural interface issues can be extended to solve in vivo neural interface problems of brain-machine interface or neuromodulation techniques.     

Fabrication of an inexpensive, implantable cooling device for reversible brain deactivation in animals ranging from rodents to primates

We have developed a compact and lightweight microfluidic cooling device to reversibly deactivate one or more areas of the neocortex to examine its functional macrocircuitry as well as behavioral and cortical plasticity. The device, which we term the "cooling chip," consists of thin silicone tubing (through which chilled ethanol is circulated) embedded in mechanically compliant polydimethylsiloxane (PDMS). PDMS is tailored to compact device dimensions (as small as 21 mm(3)) that precisely accommodate the geometry of the targeted cortical area. The biocompatible design makes it suitable for both acute preparations and chronic implantation for long-term behavioral studies. The cooling chip accommodates an in-cortex microthermocouple measuring local cortical temperature. A microelectrode may be used to record simultaneous neural responses at the same location. Cortex temperature is controlled by computer regulation of the coolant flow, which can achieve a localized cortical temperature drop from 37 to 20°C in less than 3 min and maintain target temperature to within ±0.3°C indefinitely. Here we describe cooling chip fabrication and performance in mediating cessation of neural signaling in acute preparations of rodents, ferrets, and primates.     

Glial cell and fibroblast cytotoxicity study on plasma-deposited diamond-like carbon coatings

Diamond-like carbon films have been evaluated as coatings to improve biocompatibility of orthopedic and cardiovascular implants. This study initiates a series of investigations that will evaluate diamond-like carbon (DLC) as a coating for improved biocompatibility in chronic neuroprosthetic implants. Studies in this report assess the cytotoxicity and cell adhesion behavior of DLC coatings exposed to glial and fibroblast cell lines in vitro. It can be concluded from these studies that DLC coatings do not adversely affect 3T3 fibroblast and T98-G glial cell function in vitro. We also successfully rendered DLC coatings non-adhesive (no significant fibroblast or glial cell adhesion) with surface immobilized dextran using methods developed for other biomaterials and applications. Future work will further develop DLC coatings on prototype microelectrode devices for chronic neural implant applications.     

High-resolution three-dimensional microelectrode brain mapping using stereo microfocal X-ray imaging

Much of our knowledge of brain function has been gleaned from studies using microelectrodes to characterize the response properties of individual neurons in vivo. However, because it is difficult to accurately determine the location of a microelectrode tip within the brain, it is impossible to systematically map the fine three-dimensional spatial organization of many brain areas, especially in deep structures. Here, we present a practical method based on digital stereo microfocal X-ray imaging that makes it possible to estimate the three-dimensional position of each and every microelectrode recording site in "real time" during experimental sessions. We determined the system's ex vivo localization accuracy to be better than 50 microm, and we show how we have used this method to coregister hundreds of deep-brain microelectrode recordings in monkeys to a common frame of reference with median error of <150 microm. We further show how we can coregister those sites with magnetic resonance images (MRIs), allowing for comparison with anatomy, and laying the groundwork for more detailed electrophysiology/functional MRI comparison. Minimally, this method allows one to marry the single-cell specificity of microelectrode recording with the spatial mapping abilities of imaging techniques; furthermore, it has the potential of yielding fundamentally new kinds of high-resolution maps of brain function.     

Electrophysiological Mapping of Cat Primary Auditory Cortex with Multielectrode Arrays

The present study employs simultaneous multielectrode recording techniques to study the feline primary auditory cortex (AI) to characterize its functional architecture. High electrode-count microelectrode arrays provide a high spatial and temporal view of AI, but at the potential cost of significant cortical insult. However, the number of electrodes that record single- and multiunit action potentials shown in this study suggest that the implantation of high electrode-count microelectrode arrays allows for reliable recordings from the cortex and that the neurons abutting the electrode tips appear to be spared from significant insult. Using these recordings, we have constructed a functional model of AI that best specifies the distribution of characteristic frequencies (CF's), and have reaffirmed that CF is logarithmically distributed across the cortical surface with a principal CF axis perpendicular to generally straight isofrequency contours. In four cats, we found that the average CF gradient was 0.53 ± 0.08 octave per millimeter. This study demonstrates the use of high electrode count, microelectrode array recordings in characterizing the spatial distribution of acoustic information in the feline AI.     

BBB leakage,astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance

The clinical usefulness of brain machine interfaces that employ penetrating silicon microelectrode arrays is limited by inconsistent performance at chronic time points. While it is widely believed that elements of the foreign body response (FBR) contribute to inconsistent single unit recording performance, the relationships between the FBR and recording performance have not been well established. To address this shortfall, we implanted 4X4 Utah Electrode Arrays into the cortex of 28 young adult rats, acquired electrophysiological recordings weekly for up to 12 weeks, used quantitative immunohistochemical methods to examine the intensity and spatial distribution of neural and FBR biomarkers, and examined whether relationships existed between biomarker distribution and recording performance. We observed that the FBR was characterized by persistent inflammation and consisted of typical biomarkers, including presumptive activated macrophages and activated microglia, astrogliosis, and plasma proteins indicative of blood-brain-barrier disruption, as well as general decreases in neuronal process distribution. However, unlike what has been described for recording electrodes that create only a single penetrating injury, substantial brain tissue loss generally in the shape of a pyramidal lesion cavity was observed at the implantation site. Such lesions were also observed in stab wounded animals indicating that the damage was caused by vascular disruption at the time of implantation. Using statistical approaches, we found that blood–brain barrier leakiness and astrogliosis were both associated with reduced recording performance, and that tissue loss was negatively correlated with recording performance. Taken together, our data suggest that a reduction of vascular damage at the time of implantation either by design changes or use of hemostatic coatings coupled to a reduction of chronic inflammatory sequela will likely improve the recording performance of high density intracortical silicon microelectrode arrays over long indwelling periods and lead to enhanced clinical use of this promising technology.