Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

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 simul...

Full description

Bibliographic Details
Main Authors: John Wikswo, David E. Cliffel, David W. Wright, Clare K. Carney, Roy G. Thompson, Rachel M. Snider, Sven E. Eklund
Format: Article
Language:English
Published: MDPI AG 2009-03-01
Series:Sensors
Subjects:
Online Access:http://www.mdpi.com/1424-8220/9/3/2117/
_version_ 1811185257731325952
author John Wikswo
David E. Cliffel
David W. Wright
Clare K. Carney
Roy G. Thompson
Rachel M. Snider
Sven E. Eklund
author_facet John Wikswo
David E. Cliffel
David W. Wright
Clare K. Carney
Roy G. Thompson
Rachel M. Snider
Sven E. Eklund
author_sort John Wikswo
collection DOAJ
description 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.
first_indexed 2024-04-11T13:27:28Z
format Article
id doaj.art-18bc5dbb615d45d2a20b75e558ee91e2
institution Directory Open Access Journal
issn 1424-8220
language English
last_indexed 2024-04-11T13:27:28Z
publishDate 2009-03-01
publisher MDPI AG
record_format Article
series Sensors
spelling doaj.art-18bc5dbb615d45d2a20b75e558ee91e22022-12-22T04:22:00ZengMDPI AGSensors1424-82202009-03-01932117213310.3390/s90302117Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte MicrophysiometerJohn WikswoDavid E. CliffelDavid W. WrightClare K. CarneyRoy G. ThompsonRachel M. SniderSven E. EklundHarnessing 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.http://www.mdpi.com/1424-8220/9/3/2117/toxinbiotoxinbiosensorsmicrophysiometry
spellingShingle John Wikswo
David E. Cliffel
David W. Wright
Clare K. Carney
Roy G. Thompson
Rachel M. Snider
Sven E. Eklund
Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
Sensors
toxin
biotoxin
biosensors
microphysiometry
title Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
title_full Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
title_fullStr Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
title_full_unstemmed Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
title_short Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
title_sort metabolic discrimination of select list agents by monitoring cellular responses in a multianalyte microphysiometer
topic toxin
biotoxin
biosensors
microphysiometry
url http://www.mdpi.com/1424-8220/9/3/2117/
work_keys_str_mv AT johnwikswo metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT davidecliffel metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT davidwwright metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT clarekcarney metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT roygthompson metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT rachelmsnider metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer
AT sveneeklund metabolicdiscriminationofselectlistagentsbymonitoringcellularresponsesinamultianalytemicrophysiometer