Biomedical Engineering Reference
In-Depth Information
neuromodulators such as strychnine).
36
Additionally, these compounds can
stop the propagation of action potentials. For example, tetrodotoxin (TTX)
blocks Na
1
channels and oubain causes a similar effect on the sodium pump,
preventing the maintenance of the membrane potential. Additionally, there are
generic membrane effects mediated by non-synaptic Ca
21
or K
1
channels. Both
neural biosensor systems presented above (cells cultured on FETs or micro-
electrodes) are able to detect the effects of such neurochemicals through the
changes in membrane potential during an action potential that directly effects
the gate of the FET or the electrical capacity of a microelectrode.
Interestingly in use, the built-in sensitivity of neurons enables identification
of neurotoxins, such as the Botulinum toxin (a potent neurotoxin produced by
toxigenic strains of Clostridium botulinum). The Botulinum toxin poses a
significant health threat to the public since it can be generated in any insuf-
ficiently processed food, or even used deliberately to poison food supplies. As a
result, rapid and reliable detection of such a toxin is necessary to reduce the
risks of food contamination. A biosensor employing living neural cultures
grown in vitro on microelectrode arrays can detect such neurotoxin threats with
high specificity.
The experimental setup to develop such sensitivity in neurons is discussed
further. First, the neurons are grown in a culture dish embedded with a grid of
electrodes on its surface. This enables the extracellular recording of action
potentials generated by the neural cells. After applying a toxin to the media
bath (surrounding the mature neurons), changes are observed. These changes
consist of both spontaneous spikes and bursts of activity, which differ relative
to control cultures. The application of the toxin also induces a unique
oscillatory behavior within each burst that is more reminiscent of early devel-
opmental activity patterns in neurons than the behavior of mature cultures as
was used in this experiment.
36,37
Once a mature culture is developed above the
electrode further research can be conducted.
MEAs are used in frontier stem cell research. For example, MEAs are being
used pharmaceutically to develop new novel methods to test active compounds
(hypothesized to have drug potential). Researchers have explored the temporal
development and pharmacological modulation of the activity in neural
networks derived from embryonic stem cells by simultaneously monitoring the
in vitro electrical activity exhibited by the entire network of neurons over
several months.
38
After 5-6 weeks in culture, oscillating and synchronous
activity was accompanied by an increase of presynaptic vesicles. The MEA
neurochip consisted of 60 planar Ti/TiN microelectrodes of 30 mm diameter
situated 200 mm apart. The spike and burst detection software examined the
effects of the sodium channel blocker tetrodotoxin, synaptic-acting agonists
g-aminobutyric acid (GABA), N-methyl-
D
-aspartate (NMDA) and combi-
nations with the latter respective antagonists bicuculline and 2-amino-
5-phosphonovalerate (APV) by calculating the changes in spike activity
compared with baseline activity in the absence of the drug. With this research,
the MEA method is evidenced to be a powerful tool with which to investigate
pharmaceutically active compounds. Furthermore, it presents a novel approach
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