High‐Density Stretchable Electrode Grids for Chronic Neural Recording

Electrical interfacing with neural tissue is key to advancing diagnosis and therapies for neurological disorders, as well as providing detailed information about neural signals. A challenge for creating long‐term stable interfaces between electronics and neural tissue is the huge mechanical mismatch between the systems. So far, materials and fabrication processes have restricted the development of soft electrode grids able to combine high performance, long‐term stability, and high electrode density, aspects all essential for neural interfacing. Here, this challenge is addressed by developing a soft, high‐density, stretchable electrode grid based on an inert, high‐performance composite material comprising gold‐coated titanium dioxide nanowires embedded in a silicone matrix. The developed grid can resolve high spatiotemporal neural signals from the surface of the cortex in freely moving rats with stable neural recording quality and preserved electrode signal coherence during 3 months of implantation. Due to its flexible and stretchable nature, it is possible to minimize the size of the craniotomy required for placement, further reducing the level of invasiveness. The material and device technology presented herein have potential for a wide range of emerging biomedical applications.     

Nanocapsules for Programmed Neurotransmitter Release: Toward Artificial Extracellular Synaptic Vesicles

Nanocapsules present a promising platform for delivering chemicals and biomolecules to a site of action in a living organism. Because the biological action of the encapsulated molecules is blocked until they are released from the nanocapsules, the encapsulation structure enables triggering of the topical and timely action of the molecules at the target site. A similar mechanism seems promising for the spatiotemporal control of signal transduction triggered by the release of signal molecules in neuronal, metabolic, and immune systems. From this perspective, nanocapsules can be regarded as practical tools to apply signal molecules such as neurotransmitters to intervene in signal transduction. However, spatiotemporal control of the payload release from nanocapsules persists as a key technical issue. Stimulus‐responsive nanocapsules that release payloads in response to external input of physical stimuli are promising platforms to enable programmed payload release. These programmable nanocapsules encapsulating neurotransmitters are expected to lead to new insights and perspectives related to artificial extracellular synaptic vesicles that might provide an experimental and therapeutic strategy for neuromodulation and nervous system disorders.     

A Review of Organic and Inorganic Biomaterials for Neural Interfaces

Recent advances in nanotechnology have generated wide interest in applying nanomaterials for neural prostheses. An ideal neural interface should create seamless integration into the nervous system and performs reliably for long periods of time. As a result, many nanoscale materials not originally developed for neural interfaces become attractive candidates to detect neural signals and stimulate neurons. In this comprehensive review, an overview of state‐of‐the‐art microelectrode technologies provided first, with focus on the material properties of these microdevices. The advancements in electro­active nanomaterials are then reviewed, including conducting polymers, carbon nanotubes, graphene, silicon nanowires, and hybrid organic‐inorganic nanomaterials, for neural recording, stimulation, and growth. Finally, technical and scientific challenges are discussed regarding biocompatibility, mechanical mismatch, and electrical properties faced by these nanomaterials for the development of long‐lasting functional neural interfaces.     

Improving performance of neurons by adding colour noise

Noise is not always an interfering signal which perturbs the system. On the contrary, noise signals can enhance the performance of some non‐linear systems such as stochastic resonance (SR). These systems can detect the weak input signal when it is added to the noise signal. According to this property, SR models play a significant role in the functioning of the brain for detecting weak input signals and synchronisation of neural connections. In this study, the authors model neurons as SR systems where different types of noise, i.e. white noise and pink noise, are employed to amplify the weak nervous signals. They demonstrate colour noise, in particular, pink noise enhances the performance of the SR system to amplify the input signal. Furthermore, pink noise has a wider range of optimum values in comparison to white noise. Therefore, they can conclude that neurons are more sensitive to detect the signals that carry pink noise than signals with white noise or without noise. Hence, the retrieving ability of neurons can be improved by adding pink noise.Inspec keywords: stochastic processes, white noise, neural nets, brain, noise, neurophysiologyOther keywords: interfering signal, particular noise, colour noise, weak nervous signals, pink noise, white noise, SR system, authors model neurons, SR models, noise signal, weak input signal, nonlinear systems     

Graphene in the Design and Engineering of Next‐Generation Neural Interfaces

Neural interfaces are becoming a powerful toolkit for clinical interventions requiring stimulation and/or recording of the electrical activity of the nervous system. Active implantable devices offer a promising approach for the treatment of various diseases affecting the central or peripheral nervous systems by electrically stimulating different neuronal structures. All currently used neural interface devices are designed to perform a single function: either record activity or electrically stimulate tissue. Because of their electrical and electrochemical performance and their suitability for integration into flexible devices, graphene‐based materials constitute a versatile platform that could help address many of the current challenges in neural interface design. Here, how graphene and other 2D materials possess an array of properties that can enable enhanced functional capabilities for neural interfaces is illustrated. It is emphasized that the technological challenges are similar for all alternative types of materials used in the engineering of neural interface devices, each offering a unique set of advantages and limitations. Graphene and 2D materials can indeed play a commanding role in the efforts toward wider clinical adoption of bioelectronics and electroceuticals.     

Single-beam data encoding using a holographic angular multiplexing technique

We propose a novel configuration for angular multiplexing holographic encoding in which the signal beam and the reference beam are combined into a single beam. By using a spatial light modulator based on twisted nematic liquid crystals, the signal and the reference beams are modulated in amplitude mode and phase mode, respectively. The multiplexed interference patterns with the reference beams of different incident angles are recorded near the Fourier transform plane, and then the signals are selectively reconstructed by the corresponding reference beam. Both the simulation and the experiment of single-beam angular multiplexed holography are performed with consistent results. Compared with the traditional angular multiplexing holographic recording system, the single-beam configuration is more compact, easier to adjust, and less sensitive to the vibration of the environment. Therefore, it will be more attractive for potential applications in many fields, such as high-density signal recording and data encryption.     

外置式非标准视频同步信号发生器的设计

采用TMS320F206作为USB接口芯片PDIUSBD12的控制器,实现对高速数据采集卡的同步控制。主机从荻得的非标准视频数据中提取同步信号参数,通过USB接口及时传输给DSP,DSP对分频系数实行模糊控制,产生精度可达7ps的视频同步信号,实现非标准视频信号的采集和稳定显示。分别对行频为15．625kHz、场频为50Hz的CCD视频信号,及行频为48．656kHz、场频为60Hz的计算机显示器视频泄漏信号进行了采集与显示,证实了此方案的可行性。     

System integration design in MEMS — A case study of micromachined load cell

One of the critical issues in large scale commercial exploitation of MEMS technology is its system integration. In MEMS, a system design approach requires integration of varied and disparate subsystems with one of a kind interface. The physical scales as well as the magnitude of signals of various subsystems vary widely. Known and proven integration techniques often lead to considerable loss in advantages the tiny MEMS sensors have to offer. Therefore, it becomes imperative to think of the entire system at the outset, at least in terms of the concept design. Such design entails various aspects of the system ranging from selection of material, transduction mechanism, structural configuration, interface electronics, and packaging. One way of handling this problem is the system-in-package approach that uses optimized technology for each function using the concurrent hybrid engineering approach. The main strength of this design approach is the fast time to prototype development. In the present work, we pursue this approach for a MEMS load cell to complete the process of system integration for high capacity load sensing. The system includes; a micromachined sensing gauge, interface electronics and a packaging module representing a system-in-package ready for end characterization. The various subsystems are presented in a modular stacked form using hybrid technologies. The micromachined sensing subsystem works on principles of piezo-resistive sensing and is fabricated using CMOS compatible processes. The structural configuration of the sensing layer is designed to reduce the offset, temperature drift, and residual stress effects of the piezo-resistive sensor. ANSYS simulations are carried out to study the effect of substrate coupling on sensor structure and its sensitivity. The load cell system has built-in electronics for signal conditioning, processing, and communication, taking into consideration the issues associated with resolution of minimum detectable signal. The packaged system represents a compact and low cost solution for high capacity load sensing in the category of compressive type load sensor.     

Intracellular recording of action potentials by nanopillar electroporation

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.     

Imperceptible Epidermal–Iontronic Interface for Wearable Sensing

Recent development of epidermal electronics provides an enabling means to continuous monitoring of physiological signals and close tracking of physical activities without affecting quality of life. Such devices require high sensitivity for low‐magnitude signal detection, noise reduction for motion artifacts, imperceptible wearability with long‐term comfortableness, and low‐cost production for scalable manufacturing. However, the existing epidermal pressure sensing devices, usually involving complex multilayer structures, have not fully addressed the aforementioned challenges. Here, the first epidermal–iontronic interface (EII) is successfully introduced incorporating both single‐sided iontronic devices and the skin itself as the pressure sensing architectures, allowing an ultrathin, flexible, and imperceptible packaging with conformal epidermal contact. Notably, utilizing skin as part of the EII sensor, high pressure sensitivity and high signal‐to‐noise ratios are achieved, along with ultralow motion artifacts for both internal (body) and external (environmental) mechanical stimuli. Monitoring of various vital signals, such as blood pressure waveforms, respiration waveforms, muscle activities and artificial tactile sensation, is successfully demonstrated, implicating a broad applicability of the EII devices for emerging wearable applications.     

PDE信号修补方法及在EMD端点效应处理中的应用

根据信号的连续性、光滑性等特性,可以利用已有相邻信号实现对缺陷信号的修补。分析了热传导方程的物理特性;提出了基于偏微分方程（PDE）的信号修补方法。分析了线性PDE修补和非线性PDE修补方法的基本原理。经验模态分解（EMD）过程中因存在着端点效应问题,使得EMD分解结果产生失真,从而导致分解无效。利用PDE信号修补的基本原理,实现了基于PDE的端点扩展方法。实验表明,PDE信号修补方法具有较好的修补效果,基于这一方法的端点扩展,可处理较长时间信号,且处理之后的信号畸变少     

Carbon nanotube coating improves neuronal recordings

Implanting electrical devices in the nervous system to treat neural diseases is becoming very common. The success of these brain-machine interfaces depends on the electrodes that come into contact with the neural tissue. Here we show that conventional tungsten and stainless steel wire electrodes can be coated with carbon nanotubes using electrochemical techniques under ambient conditions. The carbon nanotube coating enhanced both recording and electrical stimulation of neurons in culture, rats and monkeys by decreasing the electrode impedance and increasing charge transfer. Carbon nanotube-coated electrodes are expected to improve current electrophysiological techniques and to facilitate the development of long-lasting brain-machine interface devices.     

一种集成纳米金柱结构的神经薄膜微电极阵列

在神经假体系统中,神经微电极是实现信号检测以及激励任务的重要组成部分.然而,神经微电极由于尺寸微小,往往具有很高的电极/组织界面阻抗.本文提出了一种在电极位点表面处集成纳米结构来增大电极有效表面积的方法.这种方法结合了光刻、局部氧化铝以及电子束蒸发等技术,在薄膜微电极的表面集成了纳米金柱结构.最后,本文测试和评价了此微电极的表面形貌以及电学性能.实验结果表明,这种集成有纳米金柱结构的微电极其界面阻抗降低了约25倍,促进了这种微电极在神经工程领域的广泛应用.     

Cyber–Physiochemical Interfaces

Living things rely on various physical, chemical, and biological interfaces, e.g., somatosensation, olfactory/gustatory perception, and nervous system response. They help organisms to perceive the world, adapt to their surroundings, and maintain internal and external balance. Interfacial information exchanges are complicated but efficient, delicate but precise, and multimodal but unisonous, which has driven researchers to study the science of such interfaces and develop techniques with potential applications in health monitoring, smart robotics, future wearable devices, and cyber physical/human systems. To understand better the issues in these interfaces, a cyber–physiochemical interface (CPI) that is capable of extracting biophysical and biochemical signals, and closely relating them to electronic, communication, and computing technology, to provide the core for aforementioned applications, is proposed. The scientific and technical progress in CPI is summarized, and the challenges to and strategies for building stable interfaces, including materials, sensor development, system integration, and data processing techniques are discussed. It is hoped that this will result in an unprecedented multi-disciplinary network of scientific collaboration in CPI to explore much uncharted territory for progress, providing technical inspiration—to the development of the next-generation personal healthcare technology, smart sports-technology, adaptive prosthetics and augmentation of human capability, etc.     

Hydrophilic modification of neural microelectrode arrays based on multi-walled carbon nanotubes

To decrease the impedance of microelectrode arrays, for neuroscience applications we have fabricated and tested MEA based on multi-walled carbon nanotubes. With decreasing physical size of a microelectrode, its impedance increases and charge-transfer capability decreases. To decrease the impedance, the effective surface area of the electrode must generally be increased. We explored the effect of plasma treatment on the surface wettability of MWCNT. With a steam-plasma treatment the surface of MWCNT becomes converted from superhydrophobic to superhydrophilic; this hydrophilic property is attributed to?-OH bonding on the surface of MWCNT. We reported the synthesis at 400?°C of MWCNT on nickel-titanium multilayered metal catalysts by thermal chemical vapor deposition. Applying plasma with a power less than 25?W for 10?s improved the electrochemical and biological properties, and circumvented the limitation of the surface reverting to a hydrophobic condition; a hydrophilic state is maintained for at least one month. The MEA was used to record neural signals of a lateral giant cell from an American crayfish. The response amplitude of the action potential was about 275?μV with 1?ms period; the recorded data had a ratio of signal to noise up to 40.12?dB. The improved performance of the electrode makes feasible the separation of neural signals and the recognition of their distinct shapes. With further development the rapid treatment will be useful for long-term recording applications.     

基于Parylene的柔性生物微电极阵列的制作

在神经工程中,微电极阵列是神经系统与外界电子电路的接口,其性能决定了整个神经系统的信号采集和刺激的效果.提出了一种基于Parylene的半球形柔性生物微电极阵列.在微电极的制备过程中,使用了光刻胶热熔技术和MEMS技术.半球形形貌的微电极有利于形成和神经组织的良好接触,并且相比同底面积的平板电极,表面积增加为2倍,这有利于降低界面阻抗,降低系统功耗.使用化学气相沉积法沉积Parylene C薄膜作为微电极的封装材料,它具有良好的生物相容性和柔性,可以降低对神经组织的损害.实验结果表明,与此半球形微电极底面积大1.3倍的平板电极相比,半球形微电极的界面阻抗下降了55%,并且界面阻抗随着微电极顶部开口直径的变化而变化.使用Comsol有限元软件进行了电极/组织液液面流出电流密度仿真,仿真结果也表明,微电极的流出电流密度也随着微电极顶部开口直径的变化而变化,因此可以通过调整微电极顶部开口直径来调节电流密度,从而满足不同部位需要不同电流密度刺激的要求.     

Flexible Nanoarchitectonics for Biosensing and Physiological Monitoring Applications

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm⁻² µM⁻¹, which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.     

5.25 inch floppy disk drive using perpendicular magnetic recording

5.25 inch high density perpendicular magnetic recording floppy disk drive has beer developed by employing new types of high saturation magnetization ring head, Co-Cr single layer medium with Ge underlayer, head slider with ellipsoidal surface configuration to assure intimate head to medium contact, and signal equalization. By these combination, recording density D50 of 145 kFCI, peakshift of 28 % at 100 kFCI, signal to noise ratio of 40.4 dB for cut-off frequency 4.25 MHz, overwrite signal to noise ratio of 27 dB, measured by writing signals at 48 kFCI over previously written 100 kFCI signals were obtained as typical recording characteristics. These results would indicate that floppy disk drive with 100 kFCI recording density has enough system margin by above-mentioned combination. In this paper, design and performance of newly developed floppy disk drive are described.     

Modeling of direction-dependent Processes using Wiener models and neural networks with nonlinear output error structure

The modeling of direction-dependent dynamic processes using Wiener models and recurrent neural network models with nonlinear output error structure is considered. The results obtained are compared for several simulated first-order and second-order processes and using three different types of input signals: a pseudorandom binary signal, an inverse-repeat pseudorandom binary signal and a multisine (sum of harmonics) signal. Experimental results on a real system, namely an electronic nose system, are also presented to illustrate the applicability of the techniques discussed.     

Detection of airway obstructions and sleep apnea by analyzing the phase relation of respiration movement signals

This paper presents a novel computer-aided diagnostic method of sleep apnea syndrome, a very common respiration disorder. Apnea diagnostics require long-term, multichannel vital signal recording called polysomnography. Although various methods already exist for the computer-aided analysis of the polysomnograms, only some of them can detect the type of apnea precisely enough (i.e., central versus obstructive episodes). The system introduced in this paper processes only the thoracic and abdominal excursion signals and can distinguish between obstructive and central episodes of apnea. The main novelty is that the phase difference between the two respiration signals is considered in order to determine the presence and grade of obstructive apnea. Central apnea is recognized if no or only very small respiration movements occur. Unlike many existing systems, the presented signal processing allows on-line implementation, which plays an important role in many clinical applications.