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Multielectrode arrays (MEAs) or microelectrode arrays are devices that contain multiple plates or shanks through which neural signals are obtained or delivered, essentially serving as neural interfaces that connect neurons to electronic circuitry. There are two general classes of MEAs: implantable MEAs, used in vivo, and non-implantable MEAs, used in vitro.
The first implantable arrays were microwire arrays developed in the 1950s. The first experiment involving the use of an array of planar electrodes to record from cultured cells was conducted in 1972 by C.A. Thomas, Jr. and his colleagues. The experimental setup used a 2 x 15 array of gold electrodes plated with platinum black, each spaced 100 µm apart from each other. Myocytes harvested from embryonic chicks were dissociated and cultured onto the MEAs, and signals up to 1 mV high in amplitude were recorded. MEAs were constructed and used to explore the electrophysiology of snail ganglia independently by G. Gross and his colleagues in 1977 without prior knowledge of Thomas and his colleagues' work. In 1982, Gross observed spontaneous electrophysiological activity from dissociated spinal cord neurons, and found that activity was very dependent on temperature. Below about 30˚C signal amplitudes decrease rapidly to relatively small value at room temperature.
Before the 1990s, significant entry barriers existed for new laboratories that sought to conduct MEA research due to the custom MEA fabrication and software they had to develop. However, with the advent of affordable computing power and commercial MEA hardware and software, many other laboratories were able to undertake research using MEAs.
Microelectrode arrays can be divided up into subcategories based on their potential use: in vitro and in vivo arrays.
In vitro arrays
The standard type of in vitro MEA comes in a pattern of 8 x 8 or 6 x 10 electrodes. Electrodes are typically composed of indium tin oxide or titanium and have diameters between 10 and 30 μm. These arrays are normally used for single-cell cultures or acute brain slices.
One challenge among in vitro MEAs has been imaging them with microscopes that use high power lenses, requiring low working distances on the order of micrometers. In order to avoid this problem, "thin"-MEAs have been created using cover slip glass. These arrays are approximately 180 μm allowing them to be used with high-power lenses.
In another special design, 60 electrodes are split into 6 x 5 arrays separated by 500 μm. Electrodes within a group are separated by 30 um with diameters of 10 μm. Arrays such as this are used to examine local responses of neurons while also studying functional connectivity of organotypic slices.
Spatial resolution is one of the key advantages of MEAs and allows signals sent over a long distance to be taken with higher precision when a high-density MEA is used. These arrays usually have a square grid pattern of 256 electrodes that cover an area of 2.8 by 2.8 mm.
Increased spatial resolution is provided by CMOS-based high-density microelectrode arrays featuring thousands of electrodes along with integrated readout and stimulation circuits on compact chips of the size of a thumbnail. Even the resolution of signals propagating along single axons has been demonstrated.
In order to obtain quality signals electrodes and tissue must be in close contact with one another. The perforated MEA design applies negative pressure to openings in the substrate so that tissue slices can be positioned on the electrodes to enhance contact and recorded signals.
A different approach to lower the electrode impedance is by modification of the interface material, for example by using carbon nanotubes, or by modification of the structure of the electrodes, with for example gold nanopillars or nanocavities.
In vivo arrays
The three major categories of implantable MEAs are microwire, silicon- based, and flexible microelectrode arrays. Microwire MEAs are largely made of stainless steel or tungsten and they can be used to estimate the position of individual recorded neurons by triangulation. Silicon-based microelectrode arrays include two specific models: the Michigan and Utah arrays. Michigan arrays allow a higher density of sensors for implantation as well as a higher spatial resolution than microwire MEAs. They also allow signals to be obtained along the length of the shank, rather than just at the ends of the shanks. In contrast to Michigan arrays, Utah arrays are 3-D, consisting of 100 conductive silicon needles. However, in a Utah array signals are only received from the tips of each electrode, which limits the amount of information that can be obtained at one time. Furthermore, Utah arrays are manufactured with set dimensions and parameters while the Michigan array allows for more design freedom. Flexible arrays, made with polyimide, parylene, or benzocyclobutene, provide an advantage over rigid microelectrode arrays because they provide a closer mechanical match, as the Young's modulus of silicon is much larger than that of brain tissue, contributing to shear-induced inflammation.
Data processing methods
The fundamental unit of communication of neurons is, electrically, at least, the action potential. This all-or-nothing phenomenon originates at the axon hillock, resulting in a depolarization of the intracellular environment which propagates down the axon. This ion flux through the cellular membrane generates a sharp change in voltage in the extracellular environment, which is what the MEA electrodes ultimately detect. Thus, voltage spike counting and sorting is often used in research to characterize network activity.