Neuroelectronic interfacing with cultured multielectrode arrays toward a cultured probe

Efficient and selective electrical stimulation and recording of neural activity in peripheral, spinal, or central pathways requires multielectrode arrays at micrometer scale. ¿Cultured probe¿ devices are being developed, i.e., cell-cultured planar multielectrode arrays (MEAs). They may enhance efficiency and selectivity because neural cells have been grown over and around each electrode site as electrode-specific local networks. If, after implantation, collateral sprouts branch from a motor fiber (ventral horn area) and if they can be guided and contacted to each ¿host¿ network, a very selective and efficient interface will result. Four basic aspects of the design and development of a cultured probe, coated with rat cortical or dorsal root ganglion neurons, are described. First, the importance of optimization of the cell-electrode contact is presented. It turns out that impedance spectroscopy, and detailed modeling of the electrode-cell interface, is a very helpful technique, which shows whether a cell is covering an electrode and how strong the sealing is. Second, the dielectrophoretic trapping method directs cells efficiently to desired spots on the substrate, and cells remain viable after the treatment. The number of cells trapped is dependent on the electric field parameters and the occurrence of a secondary force, a fluid flow (as a result of field-induced heating). It was found that the viability of trapped cortical cells was not influenced by the electric field. Third, cells must adhere to the surface of the substrate and form networks, which are locally confined, to one electrode site. For that, chemical modification of the substrate and electrode areas with various coatings, such as polyethyleneimine (PEI) and fluorocarbon monolayers promotes or inhibits adhesion of cells. Finally, it is shown how PEI patterning, by a stamping technique, successfully guides outgrowth of collaterals from a neonatal rat lumbar spinal cord explant, after six days in cultur

Characterizing Self-Developing Biological Neural Networks: A First Step Towards their Application To Computing Systems

Carbon nanotubes are often seen as the only alternative technology to silicon transistors. While they are the most likely short-term one, other longer-term alternatives should be studied as well. While contemplating biological neurons as an alternative component may seem preposterous at first sight, significant recent progress in CMOS-neuron interface suggests this direction may not be unrealistic; moreover, biological neurons are known to self-assemble into very large networks capable of complex information processing tasks, something that has yet to be achieved with other emerging technologies. The first step to designing computing systems on top of biological neurons is to build an abstract model of self-assembled biological neural networks, much like computer architects manipulate abstract models of transistors and circuits. In this article, we propose a first model of the structure of biological neural networks. We provide empirical evidence that this model matches the biological neural networks found in living organisms, and exhibits the small-world graph structure properties commonly found in many large and self-organized systems, including biological neural networks. More importantly, we extract the simple local rules and characteristics governing the growth of such networks, enabling the development of potentially large but realistic biological neural networks, as would be needed for complex information processing/computing tasks. Based on this model, future work will be targeted to understanding the evolution and learning properties of such networks, and how they can be used to build computing systems

Multi-microelectrode devices for intrafascicular use in peripheral nerve

This minisymposium paper gives an overview of experimental, modeling, design and microfabrication steps which lead towards the University of Twente three-dimensional 128-fold silicon microelectrode device. The device is meant for implantation in peripheral nerve for neuromuscular control purposes and is estimated to be able to selectively control 10-20 motor fibres. Also, the potentialities of an alternative LIGA microfabrication technology are considered. A brief comparison is made with the two-dimensional sieve and flexible foil types of neuro electronic interfaces, under development elsewhere. Microfabrication technologies appear to be an important tool, but evidence is accumulating that for selective neuroelectronic interfacing the micro devices are not yet small/selective enough. More precision and selectivity is needed to contact individual axons intimately and selectively. Therefore, new lines of research develop towards in-vitro-neuron-cultured MEPs (Multi Electrode Plates) to be implanted in neural tissu

Cell patterning on photolithographically defined parylene-C:SiO2 substrates

Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO(2 )wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO(2) regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology

Massive open online-course "Abc finance": features of development and use

The description of massive open online course "ABC of Finance", the features of the design of massive open online course at Tomsk State University of Control Systems and Radio Electronics, features of the organization of the teacher's communication with the students of the course, describes tools improve motivation and retention of students

A versatile all-channel stimulator for electrode arrays, with real-time control

Over the last few decades, technology to record through ever increasing numbers of electrodes has become available to electrophysiologists. For the study of distributed neural processing, however, the ability to stimulate through equal numbers of electrodes, and thus to attain bidirectional communication, is of paramount importance. Here, we present a stimulation system for multi-electrode arrays which interfaces with existing commercial recording hardware, and allows stimulation through any electrode in the array, with rapid switching between channels. The system is controlled through real-time Linux, making it extremely flexible: stimulation sequences can be constructed on-the-fly, and arbitrary stimulus waveforms can be used if desired. A key feature of this design is that it can be readily and inexpensively reproduced in other labs, since it interfaces to standard PC parallel ports and uses only off-the-shelf components. Moreover, adaptation for use with in vivo multi-electrode probes would be straightforward. In combination with our freely available data-acquisition software, MeaBench, this system can provide feedback stimulation in response to recorded action potentials within 15 ms

Interfacing cultured neurons to microtransducers arrays: A review of the neuro-electronic junction models

Microtransducer arrays, both metal microelectrodes and silicon-based devices, are widely used as neural interfaces to measure, extracellularly, the electrophysiological activity of excitable cells. Starting from the pioneering works at the beginning of the 70's, improvements in manufacture methods, materials, and geometrical shape have been made. Nowadays, these devices are routinely used in different experimental conditions (both in vivo and in vitro), and for several applications ranging from basic research in neuroscience to more biomedical oriented applications. However, the use of these micro-devices deeply depends on the nature of the interface (coupling) between the cell membrane and the sensitive active surface of the microtransducer. Thus, many efforts have been oriented to improve coupling conditions. Particularly, in the latest years, two innovations related to the use of carbon nanotubes as interface material and to the development of micro-structures which can be engulfed by the cell membrane have been proposed. In this work, we review what can be simulated by using simple circuital models and what happens at the interface between the sensitive active surface of the microtransducer and the neuronal membrane of in vitro neurons. We finally focus our attention on these two novel technological solutions capable to improve the coupling between neuron and micro-nano transducer

Neuroelectronic interface. Of first experiments to the present days

Neuroelectronic interface - is a system designed to exchange information between the brain and an electronic device. Such an interface can give unlimited possibilities in the processing of information by a person. He is able to completely change the life of a person and greatly improve it. It is worth paying more attention to this direction

Extracellular electrical signals in a neuron-surface junction: model of heterogeneous membrane conductivity

Signals recorded from neurons with extracellular planar sensors have a wide range of waveforms and amplitudes. This variety is a result of different physical conditions affecting the ion currents through a cellular membrane. The transmembrane currents are often considered by macroscopic membrane models as essentially a homogeneous process. However, this assumption is doubtful, since ions move through ion channels, which are scattered within the membrane. Accounting for this fact, the present work proposes a theoretical model of heterogeneous membrane conductivity. The model is based on the hypothesis that both potential and charge are distributed inhomogeneously on the membrane surface, concentrated near channel pores, as the direct consequence of the inhomogeneous transmembrane current. A system of continuity equations having non-stationary and quasi-stationary forms expresses this fact mathematically. The present work performs mathematical analysis of the proposed equations, following by the synthesis of the equivalent electric element of a heterogeneous membrane current. This element is further used to construct a model of the cell-surface electric junction in a form of the equivalent electrical circuit. After that a study of how the heterogeneous membrane conductivity affects parameters of the extracellular electrical signal is performed. As the result it was found that variation of the passive characteristics of the cell-surface junction, conductivity of the cleft and the cleft height, could lead to different shapes of the extracellular signals

Polysaccarides-based gels and solid-state electronic devices with memresistive properties: Synergy between polyaniline electrochemistry and biology

A new architecture of organic memristive device is proposed with a double-layered polyelectrolyte, one of which is a biological system that alone drives the memristive behavior. In the device the Physarum polycephalum was used as living organism, the polyaniline as conducting polymer for the source-drain channel. The key choice for the device functioning was the interposition of a biocompatible solid layer between polyaniline and living organism, that must result both electrochemically inert and able to preserve a good electrical conductivity of the polyaniline, notwithstanding the alkaline pH environment required for the surviving of living being, by avoiding strong acids. Pectin with a high degree of methylation and chitosan were tested as interlayer, but only the first one satisfied the essential requirements. It was demonstrated that only when the living organism was integrated in the device, the current-voltage characteristics showed the hysteretic rectifying trends typical of the memristive devices, which however disappeared if the Physarum polycephalum switched to its sclerotic state. The mould resulted to survive a series of at least three cycles of voltage-current measurements carried out in sequence