Detection of physiologically active compounds using cell-based biosensors

doi:10.1016/S0167-7799(01)01690-0

Trends in Biotechnology

Volume 19, Issue 8, 1 August 2001, Pages 304-309

https://doi.org/10.1016/S0167-7799(01)01690-0 Get rights and content

Abstract

Cell-based biosensors are portable devices that contain living biological cells that monitor physiological changes induced by exposure to environmental perturbations such as toxicants, pathogens or other agents. Methods of detecting physiological changes include extracellular electrical recordings, optical measurements, and, in the future, functional genomics and proteomics. Several technical developments are occurring that will increase the feasibility of cell-based biosensors for field applications; these developments include stem cell and 3D culture technologies. Possible scenarios for the use of cell-based biosensors include broad-range detectors of unknown threat agents and functional assessment of identified agents.

Section snippets

Detection of physiologically active compounds using excitable cells

Over the past 20 years, many laboratories have established the capability to perform non-invasive extracellular recordings from cultured cardiomyocytes, neurons and neuronal networks using microelectrode arrays ³. Extracellular recordings obtained from neuronal networks cultured on microelectrode arrays exhibit complex spatio-temporal spike and burst patterns that are highly sensitive to their chemical environment 4, 5, 6, 7. These extracellular recordings rely on close coupling of electrically

Use of stem cells for biosensor applications

In general, tumor-derived neuronal cells are poorly suited for extracellular recording owing to incomplete synapse formation and a lack of ion-channel expression necessary for robust membrane potentials ³; this results in action potentials with slow rise times that do not transfer well at the capacitive electrode–electrolyte interface. Typically, this has meant that animal dissection is required to obtain a source of cells for use in physiologically relevant assays. Stem cells (uncommitted

Stabilization of neural cells in 3D culture matrices

In vivo, neurons are situated in an extracellular matrix (ECM) that provides structural integrity, cell attachment and growth factors. Neurons form a highly diffuse synaptic network with other neurons and multiple point contacts with astrocytes within this space. Because these conditions are not satisfied in typical 2D cultures, neuronal survival and viability are often compromised and the system might be limited in its ability to accurately predict the behavior of the same cell types in vivo.

Devices for monitoring excitable cells

The ability to estimate physiological consequences of environmental threats in non-laboratory settings could significantly affect the manner of toxicant assessment in environmental and military scenarios. Multielectrode array technology amenable for conventional microelectronic fabrication has been described by several research groups 31, 32, 33, 34, 35, 36. More significantly, the feasibility of extracellular recording from excitable cells in outdoor environments using a portable device has

Conclusions

Today, CBBs are laboratory devices that are not yet fully amenable to field use. However, meaningful physiological information can be obtained using these devices that demonstrates the use of biological cells as detector elements. The most significant hurdle that remains relating to the eventual use of such sensors is that the cells themselves are not comparably ‘stable’ to other sensing elements such as antibodies or nucleic acid probes. Under laboratory standard cell culture conditions, the

Acknowledgements

Funding to the authors was provided by the Office of Naval Research, the Defense Advanced Research Projects Agency and the National Institutes of Health. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Dept of the Navy.

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Trends in Biotechnology

ReviewDetection of physiologically active compounds using cell-based biosensors

Abstract

Section snippets

Detection of physiologically active compounds using excitable cells

Use of stem cells for biosensor applications

Stabilization of neural cells in 3D culture matrices

Devices for monitoring excitable cells

Conclusions

Acknowledgements

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

J. Neurosci. Methods

Neurosci. Lett.

Neurosci. Lett.

J. Neurosci. Methods

Biosens. Bioelectron.

J. Neurosci. Methods

Biosens. Bioelectron.

Sens. Actuators B

Animals as sentinels of human health hazards of environmental chemicals

Environ. Health Perspect.

Development and application of cell-based biosensors

Ann. Biomed. Eng.

The dynamics of a neuronal culture of dissociated cortical neurons of neonatal rats

Biol. Cybern.

Multi-neuronal recordings reveal a differential effect of thapsigargin on bicuculline- or gabazine-induced epileptiform excitability in rat hippocampal neuronal networks

Neuropharmacology

Evaluation of shipboard formation of a neurotoxicant (trimethylolpropane phosphate) from thermal decomposition of synthetic aircraft engine lubricant

Am. Ind. Hyg. Assoc. J.

Inhibition of spontaneous GABAergic transmission by trimethylolpropane phosphate

Neurotoxicology

Quantitative monitoring of gene expression patterns with a complementary DNA microarray

Science

Application of DNA arrays to toxicology

Environ. Health Perspect.

Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells

Toxicol. Sci.

Applications of gene arrays in environmental toxicology: fingerprints of gene regulation associated with cadmium chloride, benzo(a)pyrene, and trichloroethylene

Environ. Health Perspect.

Review
Detection of physiologically active compounds using cell-based biosensors