Multielectrode array

Microelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes 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. Microelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes 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. Neurons and muscle cells create ion currents through their membranes when excited, causing a change in voltage between the inside and the outside of the cell. When recording, the electrodes on an MEA transduce the change in voltage from the environment carried by ions into currents carried by electrons (electronic currents). When stimulating, electrodes transduce electronic currents into ionic currents through the media. This triggers the voltage-gated ion channels on the membranes of the excitable cells, causing the cell to depolarize and trigger an action potential if it is a neuron or a twitch if it is a muscle cell. The size and shape of a recorded signal depend upon several factors: the nature of the medium in which the cell or cells are located (e.g. the medium's electrical conductivity, capacitance, and homogeneity); the nature of contact between the cells and the MEA electrode (e.g. area of contact and tightness); the nature of the MEA electrode itself (e.g. its geometry, impedance, and noise); the analog signal processing (e.g. the system's gain, bandwidth, and behavior outside of cutoff frequencies); and the data sampling properties (e.g. sampling rate and digital signal processing). For the recording of a single cell that partially covers a planar electrode, the voltage at the contact pad is approximately equal to the voltage of the overlapping region of the cell and electrode multiplied by the ratio the surface area of the overlapping region to the area of the entire electrode, or: V p a d = V o v e r l a p × A o v e r l a p A e l e c t r o d e {displaystyle V_{pad}=V_{overlap} imes {frac {A_{overlap}}{A_{electrode}}}} assuming the area around an electrode is well-insulated and has a very small capacitance associated with it. The equation above, however, relies on modeling the electrode, cells, and their surroundings as an equivalent circuit diagram. An alternative means of predicting cell-electrode behavior is by modeling the system using a geometry-based finite element analysis in an attempt to circumvent the limitations of oversimplifying the system in a lumped circuit element diagram. An MEA can be used to perform electrophysiological experiments on tissue slices or dissociated cell cultures. With acute tissue slices, the connections between the cells within the tissue slices prior to extraction and plating are more or less preserved, while the intercellular connections in dissociated cultures are destroyed prior to plating. With dissociated neuronal cultures, the neurons spontaneously form networks. It can be seen that the voltage amplitude an electrode experiences is inversely related to the distance from which a cell depolarizes. Thus, it may be necessary for the cells to be cultured or otherwise placed as close to the electrodes as possible. With tissue slices, a layer of electrically passive dead cells form around the site of incision due to edema. A way to deal with this is by fabricating an MEA with three-dimensional electrodes fabricated by masking and chemical etching. These 3-D electrodes penetrate the dead cell layer of the slice tissue, decreasing the distance between live cells and the electrodes. In dissociated cultures, proper adherence of the cells to the MEA substrate is important for getting robust signals. 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 Guenter Gross and his colleagues at the Center for Network Neuroscience 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. This non-invasive electrophysiology laboratory technique can be more efficient than the patch clamp method.