Microelectrode array

Definition

Microelectrode arrays (MEAs) are devices that contain multiple shanks through which neural signals are obtained or delivered, essentially serving as neural interfaces that connect neurons to electronic circuitry for interpretation or therapy. There are two general classes of MEAs: implantable MEAs, used in vivo, and non-implantable MEAs, used in vitro.

Types

Microelectrode arrays can be divided up into subcategories based on their potential use: in vitro and in vivo arrays.

Types of 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 um. These arrays are normally used for single-cell cultures or acute brain slices (Book chapter 2).

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 um allowing them to be used with high-power lenses (Book chapter 2; Eytan et al, 2004).

In another special design, 60 electrodes are split into 6 x 5 arrays separated by 500 um. Electrodes within a group are separated by 30 um with diameters of 10 um. Arrays such as this are used to examine local responses of neurons while also studying functional connectivity of organotypic slices (Book chapter 12; Segev and Berry, 2003).

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 (book chapter 2).

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 (book chapter 2).

The MEA60 System by MULTI CHANNEL SYSTEMS (MCS) is used for a variety of application. It includes a 60-channel amplifier reduces noise level in the retrieved signal so that lower range voltages can be recorded (book chapter 2; Granados-Fuentes et al, 2004).

Types of 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 3D, 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 (Cheung, 2007).

Advantages

In general, the major strengths of in vitro arrays when compared to more traditional methods such as patch clamping include (Whitson J):

1.Allowing the placement of multiple electrodes at once rather than individually 2.The ability to set up controls within the same experimental setup (by using one electrode as a control and others as experimental) 3.The ability to select different recordings sites within the array 4.The ability to simultaneously receive data from multiple sites

Furthermore, in vitro arrays are relatively non-invasive when compared to patch clamping because they do not require breeching of the cell membrane.

With respect to in vivo arrays however, the major advantage over patch clamping is the high special resolution. Implantable arrays allow signals to be obtained from individual neurons enabling information such as position or velocity of motor movement that can be used to control a prosthetic device.

Disadvantages

In vitro MEAs are relatively ill-suited for recording and stimulating single cells due to their low spatial resolution compared to patch clamp and dynamic clamp systems. The complexity of signals an MEA electrode could effectively transmit to other cells is limited compared to the capabilities of dynamic clamps.

There are also several biological responses to implantation of a microelectrode array, particularly in regards to chronic implantation. Most notable among these effects are neuronal cell loss, glial scarring, and a drop in the number of functioning electrodes (Biran, 2005). The tissue response to implantation is dependent among many factors including size of the MEA shanks, distance between the shanks, MEA material composition, and time period of insertion. The tissue response is typically divided into short term and long term response. The short term response occurs within hours of implantation and begins with an increased population of astrocytes and glial cells surrounding the device. The recruited microglia then initiate inflammation and a process of phagocytosis of the foreign material begins. Over time, the astrocytes and microglia recruited to the device begin to accumulate, forming a sheath surrounding the array that extends tens of microns around the device. This not only increases the space between electrode probes, but also insulates the electrodes and increases impedance measurements. Problems with chronic implantation of arrays have been a driving force in the research of these devices. One novel study examined the neurodegenerative effects of inflammation caused by chronic implantation (McConnell, 2007). Immunohistochemical markers showed a surprising presence of hyperphosphorylated tau, an indicator of Alzheimer’s disease, near the electrode recording site. The phagocytosis of electrode material also brings to question the issue of a biocompatibility response, which research suggests has been minor and becomes almost nonexistent after 12 weeks in vivo. Research to minimize the negative effects of device insertion include surface coating of the devices as well as coating with drug eluting substances (He, 2006).

Applications

In vivo Applications

There are several implantable interfaces that are currently available for consumer use including deep brain stimulators, cochlear implants, and cardiac pacemakers. Deep brain stimulation (DBS) has been effective at treating movement disorders such as Parkinson’s disease ((Breit et al., 2004), and cochlear implants have helped many to improve their hearing by assisting stimulation of the auditory nerve. Because of their remarkable potential, MEAs are a prominent area of neuroscience research. Research suggests that MEAs may provide insight into processes such as memory formation and perception and may also hold therapeutic value for conditions such as epilepsy, depression, and obsessive-compulsive disorder. Clinical trials using interface devices for restoring motor control after spinal cord injury or as treatment for ALS have been initiated by CyberKinetics Neurotechnology Systems in a project entitled BrainGate (see video demo: http://www.cyberkineticsinc.com/video.htm). MEAs provide the high resolution necessary to record time varying signals, giving them the potential to be used to control prosthetic devices (Nicolelis, 2001, Schwartz, 2004, Nicolelis and Chapin, 2002). Research suggests that MEA use may be able to assist in the restoration of vision by stimulating the optic pathway (Cheung, 2007).