Biomedical Engineering Reference
In-Depth Information
M and 600 nM,
respectively. Applying the rat oral LD
50
for cadmium chloride of 88 mg/kg for a 70-kg
human, a molecular weight of 183 g/mol, and a conservative estimate of 10 l of water con-
sumption, the LD
50
for cadmium corresponds to 4.8 mM. For similar calculations for strych-
nine, the LD
50
corresponds to 190
induce significant alterations in NNBS behavior at approximately 1
M. The fact that the NNBS shows profound responses
well below these levels suggests potential utility for function-based environmental threat
detection. Similar relationships can be observed for a wide range of toxicants.
6.5
Development of Multinetwork Platforms for High Throughput
A major limitation of present techniques for laboratory-based analyte screening is the low
throughput and lack of data analysis automation. Although the CNNS at UNT has recently
moved to simultaneous recording from two separate networks (32 electrodes each), this
approach is still far from what is needed for efficient applications of network dynamics.
Statistical evaluations of interculture repeatability, of multiple drug and multiple concentra-
tion applications, and of the temporal evolution of toxic responses, are tedious and far too
slow for present industrial and even research utility. The eight-network module under devel-
opment is an important step to increasing the throughput of this approach (Figure 6.22).
6.6
Summary
There are substantial advantages provided by the NNBS approach: (1) the cultured networks
provide both electrophysiological and morphological data; (2) the chemical environment of
the networks and the concentrations of the toxicants can be controlled with high precision; (3)
the simplicity of the tissue allows repeatable measurements resulting in reproducible EC
50
and dissociation constants where major shifts from these constants imply changes in receptor
densities, properties, or linkages to chemical pathways; (4) large, stable SNR allow wave-
shape analysis for voltage-gated ion channel toxicology and pharmacology; (5) the robustness
of the cultures enables shipping of nonfrozen networks to provide high-quality cell cultures
(a)
(b)
FIGURE 6.22
Emerging system for parallel recording from multiple networks. (a) Two-network open chamber served by a liq-
uid handling robot in an environmental chamber. (b) Eight-network module with experimental preamplifier (256
channels; Plexon Inc., Dallas) on microscope stage.
