Multi-electrode arrays (MEAs ) or microelectrode arrays are devices that contain multiple plates or needles, can be taken up or released by the neural signals. They serve as a neural interface that can connect neurons with electronic circuits. There are two classes of MEAs: implantable MEAs used in vivo and non- implantable MEAs used in vitro.
- 7.1 In vitro applications
- 7.2 In vivo applications
If neurons or muscle cells are stimulated ion currents flowing through their membranes. Characterized charge potentials change inside and outside the cell. In recording, the electrodes of the MEA convert the potential change, which is caused by the flow of ions ( which corresponds to a voltage change due to a displacement of the charge carrier ions equivalent ) in a current flow to ( which corresponds to a displacement of the charge carriers are electrons ). If the electrodes of the MEAs used for stimulation, they convert electricity flow from the outside into ion flow in the medium. This causes the voltage-activated sodium ion channels in the membrane of an excitable cell is depolarized. Thereby, in a neuron action potential, caused a reduction in a muscle cell.
Size and shape of the recorded signal depends on several factors:
- From the nature of the medium in which the cell or cells are located (eg, conductivity, capacity and homogeneity ).
- The type of contact between the cell and the MEA (such as area of contact, and its density).
- From the nature of the MEA electrode itself (eg geometry, impedance).
- Of the analog signal processing (such as gain, bandwidth ).
- Of the digital signal processing (for example sampling rate, the type of processing).
When recording of a single cell, a planar electrode partially covers the voltage at the contact surface is approximately equal to the voltage of the overlapping region of the cell with the electrode, multiplied by the ratio of the surface area of the overlapped region with the total surface area of the electrode, and:
Provided that the region around the electrode is well insulated and has a small capacity. The formula is based on the electrode, the cell and the environment is modeled as a circuit. An alternative tool to predict the behavior of cell - electrode is a modeling based on a geometry-based finite element method, which tries to circumvent the limitations of a too simplified representation of the system in a compact circuit diagram.
A MEA can also be used to perform electrophysiological testing of tissue samples or cell cultures. In tissue samples, the connections between the cells within the sample remain more or less preserved, while they are absent in cell cultures. In cell cultures of neuronal cells spontaneously form neural networks.
It turns out that the voltage level which gives an electrode is inversely proportional to the distance of a cell from its depolarization. Therefore, it may be necessary to grow the cells to the electrode as close as possible to place or otherwise. In tissue samples due to edema forms around a location electrically passive dead cells around the cut. One way to deal with it, are MEAs with three-dimensional electrodes, which are made fotolitografisch. These three-dimensional electrodes penetrate the layer of dead cells of the tissue sample, and reduce the distance between the living cells and the electrode. A good adhesion of the cells on the MEA substrate is important for stable signals in cell cultures.
The first implantable arrays were fine wire arrays that were developed in the 1950s. The first experiment, which took place with flat electrodes to record signals from cell cultures, was founded in 1972 by CA Thomas, Jr. and his colleagues carried out. The structure consisted of an array of 2 × 15 gold electrodes coated with platinum, each 100 microns apart. A cell culture derived from embryonic chicken muscle, which was cultured on the MEA provided in the recording signals with an amplitude up to 1 mV. MEAs were built and used to investigate the electrophysiology of snails ganglia independently of the work of Thomas G. Gross and his colleagues in 1977. In 1982, large spontaneous electrophysiological activity in cell cultures of spinal cord cells and found that the activity was very temperature dependent. Below 30 ˚ C, the amplitude decreases rapidly to very small values at room temperature.
Before the 1990s, passed for laboratories who wanted to do research on MEAs, significant barriers to entry through the customized production of MEAs and the software that had to develop them. However, as a cheaper computer and commercial MEA was always hardware and software available, many other labs were also able to conduct research with MEAs.
Microelectrode arrays can be divided over their potential utility in catagories: in vitro and in vivo arrays.
Types of arrays, in vitro
The default type of in vitro MEA has a grid of 8 × 8 or 6 × 10 electrodes. The electrodes are typically made of indium tin oxide or titanium and have diameters of 10 to 30 microns. These arrays are used for cell culture or tissue sample from the brain.
One challenge with in vitro MEAs was imaging with microscopes that use high-resolution lenses and need a small working distance in the range of micrometers. To avoid this problem, "thin" MEAs were fabricated using the a covering glass. These arrays have a diameter of about 180 microns, allowing them to be used with high-resolution lenses.
In another particular type electrodes 60 are divided into a 6 × 5 array, which have 500 micron spacing. The electrodes within a group at a distance of 30 microns and have a diameter of 10 microns. Arrays such as these are used to study local neuronal responses and at the same time functional relationships of the organic tissue.
The spatial resolution is one of the special advantages of the MEAs. It makes it possible to record signals which are transmitted over long distances, and so with high accuracy, a high resolution when MEA is used. These arrays usually have a square grid of 256 electrodes, which covers an area of 2.8 × 2.8 mm.
A much better resolution is CMOS-based high-density microelectrode arrays allows the exhibit to compact chips with the size of a fingernail thousands of electrodes with integrated readout and stimulation circuits. Even the signal propagation along individual axons could be demonstrated. To record signals good quality fabric and electrodes must be in close contact with each other. Perforated MEAs create a vacuum at the openings of the substrate so that the fabric can be positioned on the electrodes, in order to improve the contact and thus the signals.
Types of arrays in vivo
The three main categories of implantable MEAs are: fine wire, silicon -based and flexible microelectrode arrays.
- The fine wire MEAs are made mainly of stainless steel or tungsten and can be used to determine the location of individual neurons recorded by triangulation.
- Silicon -based microelectrode arrays contain two special models: Michigan and Utah arrays. Allow Michigan array both a higher density of sensors at the implantation and a higher spatial resolution than the fine wire array. Among them, the measurement of the signals along the needles is possible not just at the end.
- Utah arrays are three-dimensional and consist of 100 type silicon needles. At Utah array, the signals can be received but only the tips of the needles, which limits the amount of information that can be recorded at a time. They are also manufactured in fixed quantities and parameters, while larger degrees of freedom are given in the production at the Michigan arrays.
Methods of data processing
The ' base unit ' of communication between nerve cells is, at least in electrical terms, the action potential. There we assumed that this " all-or- nothing " phenomenon has its origin at the axon hillock and a depolarization of the cellular environment with the result that propagates through the axon. The flow of ions through the cellular membrane causes a significant voltage change in the extracellular environment, which the electrodes of the MEA detect eventually. Therefore, the count of spikes and their order are often used in studies on the classification of network activities.
Basically, the great advantage of in vitro array is compared with more traditional methods such as the patch -clamp technique:
- Any number of electrodes at the same time, they must not be set individually.
- It is possible to set both the experimental electrodes and control electrodes in the same experiment.
- It is possible to select different locations for recording within an array.
- It is possible to simultaneously record information of different location.
- Use may be referred to as non-invasive, since the membrane does not have to be penetrated, as in most configurations of the patch clamp technique.
In in vivo arrays, the high spatial resolution is a big advantage over the patch -clamp technique. With implantable array signals of individual nerve fibers can be detected, which information can be added to position or speed of a motor movement, which for example a prosthesis can be controlled.
Compared with patch-clamp or Dynamic- clamp techniques have in vitro MEAs a lower spatial resolution. Therefore, they are less well suited to stimulate individual cells. The complexity of the signals can send a MEA electrode to other cells is small compared with the capabilities of the dynamic clamp technique.
There are a number of biological responses to the implantation of microelectrode arrays is known, in particular for permanent implantation. The main effects are: loss of neuronal cells, gliosis and loss of electrodes. The response of the tissue to the implant is dependent on inter alia the size of the MEA needles, the distance, the material composition and the duration of implantation. The reaction of the tissue is typically divided into a short term and a long-term reaction. The short-term response occurs within hours after implantation and begins with an increased number of astrocytes and glial cells in the vicinity of the array. The attacking microglia cause inflammation and phagocytosis of foreign material begins. Over time, accumulate around the array astrocytes and microglia and form a shell around the array, which can extend over several 10 microns. This not only increases the distance between the needles but also those isolated which has a higher impedance is measured. The problems with the permanent implantation of the arrays was the driving force for research on them. A new study examined the neurodegenerative effects of inflammation, resulting in permanent implantations. Immunohistochemical markers demonstrated the surprising presence of hyperphosphorylated Tau protein, an indicator for Alzheimer 's disease, in the vicinity of the recording electrodes. The phagocytosis of the electrode material also raises the question of the biological reaction. Research indicates that this is low and is at 12 weeks in vivo virtually disappeared. Research to reduce the negative effects of the implant have been carried out for the surface coating with polymers such as laminin or ausschwemmbaren drugs.
In vitro applications
In cultures of neural cells, the pharmacological response does not seem to change or decrease compared with in vivo models, so that it can be assumed that constitute MEAs for studies of such cultures, a simple controlled environment. There was previously a number of pharmacological studies using MEAs, eg Studies with ethanol.
MEAs have been used as an interface for the control of non-biological systems by neural cell cultures. MEAs can be used as an interface of a neural computer. Thus, cell cultures were used by brain nerve cells of rats in a closed loop to control stimulus-response feedback of an animat in a virtual environment.
A system used for a control loop for a stimulus-response model, the MEAs was performed by Dr. Potter, Dr. Mandhavan, Dr. DeMarse and Mark Hammond, Kevin Warwick and Ben Whalley built in the University of Reading. Approximately 300,000 nerve cells of rats were placed on MEAs, which were connected to the motors and the ultrasonic sensors of a robot, which was trained to avoid obstacles.
MEAs with the firing of the nerve impulses in tissue samples from the hippocampus was examined.
In vivo applications
There are several implantable interfaces for the " end users " currently available:
- Brain pacemaker
- Cochlear implants
Brain pacemakers have been proven in the treatment of movement disorders such as in Parkinson 's disease. Cochlear implants have helped many people to hear better by the auditory nerve is stimulated. Due to their remarkable capabilities are MEAs an important field of research in the neurosciences. Studies suggest that MEAs can provide deeper insights into the processes of memory formation and perception and may be of therapeutic value for conditions such as epilepsy, depression or obsessive-compulsive disorder. In a project with the name Braingate (see video at web links) were clinical trials carried out in which interfaces to restore motor control with spinal injuries or treatment of ALS were used. MEAs have high resolution, which is necessary to record time-varying signals, which are suitable for both the controller and the feedback of prostheses, have as Kevin Warwick, Mark Gasson and Peter Kyberd shown. Studies also suggest that MEAs can help in the restoration of vision by the optic nerve is excited with them.