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Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
Department of Chemistry, Vanderbilt University, VU Station B. Nashville, TN 37235, USA
Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, VU Station B. Nashville, TN 37235. USA
Edgewood Chemical and Biological Center, Aberdeen Proving Ground, MD 21010. USA
* Author to whom correspondence should be addressed.
Received: 7 January 2009; in revised form: 15 March 2009 / Accepted: 17 March 2009 / Published: 23 March 2009
Abstract: Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP) that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production) in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.
Keywords: toxin; biotoxin; biosensors; microphysiometry
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Eklund, S.E.; Thompson, R.G.; Snider, R.M.; Carney, C.K.; Wright, D.W.; Wikswo, J.; Cliffel, D.E. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer. Sensors 2009, 9, 2117-2133.
Eklund SE, Thompson RG, Snider RM, Carney CK, Wright DW, Wikswo J, Cliffel DE. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer. Sensors. 2009; 9(3):2117-2133.
Eklund, Sven E.; Thompson, Roy G.; Snider, Rachel M.; Carney, Clare K.; Wright, David W.; Wikswo, John; Cliffel, David E. 2009. "Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer." Sensors 9, no. 3: 2117-2133.