Biomedical Engineering Reference
In-Depth Information
to the treatment of neurodegenerative diseases by the substitution of lost
neurons via cell therapy.
Many challenges remain that must be overcome with respect to the detection
strategies presented thus far for MEAs. For instance, the low signal-to-noise
ratio due to the resistance between the neurons and the FET or microelectrode
requires improvement in terms of acquisition and processing of multiple noisy
signals. This is thought to be possibly remedied through the use of low-noise
transistors and CMOS technology.
39,40
With regard to optimizing neur-
onelectrode coupling, patterning with aminosilanes or adhesion proteins such
as laminin or fibronectin can be utilized. Another challenge to consider is the
fact that the number of total active microelectrodes is usually low. Fabrication
of smaller electrodes will only worsen the signal-to-noise ratio. Alternative
technologies such as CMOS and APS-MEAs that increase the number of
measuring sites are currently under development. The data obtained from all
the electrodes are usually overwhelmingly large and dicult to analyze.
However, computational approaches for pattern recognition in neural response
and data mining strategies can be utilized to enhance the high specificity of
neural receptor interaction without reducing sensitivity.
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New bioinformatics and system biology methods to interpret, classify and
link the measured data to neurophysiologic responses are also being explored.
As single neurons possess the intrinsic ability to resonate and oscillate at
particular frequencies, probing their activity at cellular levels using transistor
and microelectrode arrays may reveal the mechanisms responsible for patterns
connected to neural signaling.
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3.6 Microelectronic Interfaces for In Vitro Study of
Neurons
MEAs can be designed in a variety of ways to achieve specific experimental
aims or to enable and assist in a particular experimental aim. One example is
the linear multielectrode, which is a class of one-dimensional array, where an
electrode site is mounted on a needle or incorporated in a glass or silicon tip-
shaped carrier. The needle can be a hollow metal shaft in which a side-window
perforation houses the tips of a number of leads threaded through the shaft.
Lithographic patterning and deposition of thin-film metal can also be used to
design electrode sites onto glass, silicon, or polyimide carriers.
Another example is a two-dimensional (2D) array. The 2D array consists of
electrodes, which may be designed as above, with the tips arranged in the same plane
(Figure 3.7). These electrodes can be configured and manufactured as a simple
bundle of wires or they may be galvanically or lithographically grown needles.
A third example is the 3D structure of microelectrode arrays. This structure
can be achieved if the plane of the arrays is not constant or the electrodes
extend to different heights above the substrate (Figure 3.8) and are often
employed when spatial selectivity of interaction with neuronal cultures requires
height resolutions.
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