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Life-on-a-chip

Abstract

Mechanistic studies of cellular processes are usually carried out with large populations of cells. However, parameters that are measured as averages of large populations can be misleading. For instance, an apparently linear response to a signal could, in fact, reflect an increasing number of cells in the population that have switched from 'off' to 'on', rather than a graded increase in response by all the cells. At present, the study of single cells is challenging, but new technologies mean it might soon be a reality.

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Figure 1: Heterogeneity in cellular response systems.
Figure 2: Integrated microsystem schematic.
Figure 3: Heterogeneity in timing of infection events.
Figure 4: Expected MLSC outcomes.
Figure 5: MLSC technology development.

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Acknowledgements

The work described in this article has been supported by funding through the National Human Genome Research Institute (NHGRI) Centers of Excellence in Genomic Sciences programme. We wish to acknowledge the important contributions of other Microscale Life Sciences Center investigators to this work: K. Böhringer, L. Burgess, B. Cookson, N. Dovichi, M. Holl, B. Marquardt, J. Mittler, J. Mullins, V. Vogel and D. Wilson.

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Correspondence to Mary E. Lidstrom.

Supplementary information

41579_2003_BFnrmicro755_MOESM1_ESM.pdf

Online Figure | MLSC organizational pyramid. For the single-cell analysis group of the MLSC, application needs drive innovation in module and system-level development, and foundation technologies support system design and integration activities. The use of new technology creates new areas of experimental investigation. (PDF 24 kb)

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FURTHER INFORMATION

Mary E. Lidstrom laboratory

Deirdre R. Meldrum laboratory

Cell Systems Initiative

GOLD Genomes OnLine Database

MEMS

Microscale Life Sciences Center

Microarrays and microfluidics

Molecular Sciences Institute

Nanosystemes Biology Alliance

Glossary

DIELECTROPHORESIS

The induced motion of polarizable particles in non-uniform electric fields.

ELECTROIMPEDENCE SPECTROSCOPIC METHODS

An analytical technique that supplies frequency response information for a variety of conducting materials. A signature is obtained that can be related to specific changes in conducting properties.

MICROANALYTICAL SPECTROSCOPIC METHODS

Detection methods that are based on analysis of the energies and wavelengths of radiation emitted by atoms and molecules when particular physical conditions are applied to them, and which use small (sub-microlitre) volumes and low concentrations of analyte.

MICROFLUIDICS

Fluidics in structures on micron and smaller-length scales, resulting in low turbulence, with laminar flows.

MULTIANALYTE

Multiple chemicals to be analysed.

STOCHASTICITY

Describes a phenomenon that obeys the laws of probability.

SURFACE PLASMON RESONANCE

(SPR). A phenomenon that occurs when light is reflected off thin metal films. Although incident light is totally reflected, the electromagnetic field component penetrates a short (tens of nanometres) distance into a medium of a lower refractive index, thereby creating a type of wave that is known as an exponentially detenuating evanescent wave. If the interface between the media is coated with a thin layer of metal (gold), and light is monochromatic and p-polarized, the intensity of the reflected light is reduced at a specific incident angle producing a sharp shadow, called surface plasmon resonance.

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Lidstrom, M., Meldrum, D. Life-on-a-chip. Nat Rev Microbiol 1, 158–164 (2003). https://doi.org/10.1038/nrmicro755

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