Biomedical Engineering Reference
In-Depth Information
for end users; (6) noncytotoxic, but functionally toxic compounds are often reversible and
allow repeated studies with the same networks; (7) on glass plates with transparent ITO con-
ductors high-power microscopy, access can be achieved making simultaneous electrophysio-
logical, optical, and fluorescent studies possible; (8) one pregnant mouse can seed over 400
MEAs, thus reducing the number of experimental animals, at least, in the compound screen-
ing stages; and (9) the networks can serve as the biological component for a portable record-
ing system for environmental threat detection.
Current sensor paradigms for environmental threats are incapable of detecting unantici-
pated threats, raising the need for a broad-spectrum detection capability. The number of
novel chemical compounds that have been or can be synthesized to be toxic to mammals is
large and is continually growing. Unknown compounds will most likely not be detected by
conventional in-line scanning with existing instruments unless they appear in such large
concentrations as to trigger a follow-up testing in animals or cellular systems. As instru-
ments cannot measure toxicity, living tissues must be used for broadband scanning.
However, it is difficult to use living tissue in a similar manner as electronic monitoring
instruments. In-line water monitoring, a relatively simple task for instruments, becomes a
major technical problem when using cell-based systems. However, if it is considered vital
to have a broadband monitoring capability, then it is technically possible to route supply
water in such a manner that only tested supply water enters a secure central holding tank.
Such testing can be accomplished with high confidence using neuronal networks on MEAs.
With the development of multinetwork systems, a larger number of tests can be performed
in parallel, providing greater reliability, accuracy, and throughput. The eight-network plat-
form described in this chapter takes a step in that direction. The automated use of multiple
eight-network modules is anticipated and a further increase of networks per plate is feasi-
ble. However, water-testing stations using such networks require a reliable supply of func-
tional living tissue on MEAs. Thus, the first step has been taken with the shipment of living
networks to end users. Yet, such a supply service would be greatly simplified by an ability
to freeze networks, with network thawing and activation at the water-testing stations. This
has not yet been accomplished and will require further research.
Acknowledgments
This research effort was supported by the Defense Advanced Research Projects Agency
(DARPA) Tissue-Based Biosensor and Activities Detection Technology Programs, by two
grants from the Texas Advanced Technology Program, and by the Charles Bowen
Memorial Endowment to the CNNS. The authors recognize the intellectual and funding
support by Dr. Alan S. Rudolph in his role as a Program Manager at the DARPA. The opin-
ions and assertions contained herein are the private ones of the authors and are not to be
construed as official or reflecting the view of the National Institutes of Health (NIH).
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