Biomedical Engineering Reference
In-Depth Information
4.5
Neural Network, Neural, or Brain Analyses:
Measurements of Neural Activity and Their
Application for Analyses of the Neural Network
System in the Living Body
4.5.1
Ultra-Microglutamate Sensors for Brain Analyses
Chemical neurotransmitters play an important role in the brain, since they
are the key link in communication between neurons. Glutamate is one of
the neurotransmitters that carry nerve signals across the synapse from one
neuron to another. Released by the presynaptic neuron, glutamate binds to
specific receptors on the postsynaptic neuron. Interactions between glutamate
and the glutamate receptor are involved in memory-storage phenomena in
the hippocampus, known as long-term potentiation (LTP), and long-term
depression (LTD) in the cerebellum [73]. Quantitative analyses of released
glutamate are required to further investigate the biomolecular mechanisms
of neuron function and the etiology of neural diseases.
Possible approaches to monitoring the glutamate concentration in such
small environments are to use the microdialysis (MD) probe sampling system
[74] and to develop an “ultra-”microglutamate sensor.
Monitoring of the glutamate concentration released from cultured nerve
cells by using an MD probe and an enzyme sensor system was reported by
Niwa et al. [75]. The sensor consisted of an MD probe fixed at the manipula-
tor, a small-volume glutamate oxidase enzymatic reactor (0.75 mm i.d. and
2.5 cm long), and an electrochemical reactor in a thin-layer radial flow cell
with an active volume of 70-340 nl. The overall eciency of the glutamate de-
tector with the sensor is 94%. They achieved a sensitivity of 24.3 nA/mM and
a detection limit of 7.2 nM. By using this sensor system, they could monitor
glutamate concentration changes at the submicromolar level caused by KCl
stimulation of a single nerve cell and micromolar glutamate concentration
increases caused by electrical stimulation of a brain slice. The combination of
the MD probe and the enzyme sensors is useful for not only neural and brain
analyses, but also for small-scale bioprocess monitoring. We have reported
simultaneous monitoring of glucose and lactate in lactic acid fermentation
by using integrated miniature enzyme electrodes and an MD probe sampling
system [76].
Recent studies have demonstrated that the in vivo electrochemical sensor
is a powerful tool for clinical and neurochemical monitoring [77]. A smaller
electrode causes less damage to tissue during its insertion into the brain
or nerve tissue. To examine such small environments, a very small electrode
with a diameter of the order of micrometers is required. Since microbiosensors
based on semiconductor fabrication technology are of the order of millimeters
in size [78], novel ultra-microbiosensors should be developed for this purpose.
The carbon-fiber electrode is considered to be one of the most useful
transducers for in vivo biosensors, because it can be designed for use as
