Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or...
Patent
1997-06-23
2000-01-04
Weber, Jon P.
Chemistry: molecular biology and microbiology
Treatment of micro-organisms or enzymes with electrical or...
435 29, 204403, C12N 1300, C12Q 102, G01N 2726
Patent
active
060108894
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a method and apparatus for the monitoring of electrochemical signals which reflect the metabolic and behavioural activities of living cells.
All cells utilise metabolic pathways based on chemical processes, for example, the oxidation-reduction reactions of energy metabolism. In addition there are hundreds of other chemical processes, especially the electrochemical reactions and ionic pumps' that cross the cell surface, all of which provide the molecular basis for the cell's behavioural activities.
It is well known that cells are electrochemically active, and that changes in energy metabolism often relate to modified cell behaviour. For example, the article "The Cytosensor Microphysiometer: Biological Applications of Silicon Technology" by H M Mcconnell, J C Owicki, J W Parce, D L Miller, G T Baxter, H G Wada and S Pitchford in the Journal "Science", Volume 257, Sep. 25, 1992 describes a device which is capable of measuring the rate of proton excretion by cells in response to chemical/ligand stimulation. The Cytosensor device is based upon the fact that some cells acidify their surrounding environment because of acidic products of energy metabolism, especially glycolysis. The device measures changes in pH (acidification) that occur as cells release acidic metabolites into their immediate environment, this being related to rates of energy, metabolism. The Cytosensor may be used for two functions, that is as a detector for specific molecules (e.g. ligands) whereby responsive, viable cells in the instrument serve as detectors and amplifiers, and for the investigation of cell function and biochemistry. Thus the Cytosensor is a useful device for monitoring extra cellular pH which generally relates to changes in he energy metabolism of cells. However, there are many other electrochemical processes that cross the cell surface, some of which may contribute to the rate of acidification of the surrounding environment, but many others of which will not. Accordingly, it may be that in some circumstances a significant change in electrochemical activity within a cell does not result in significant change in the rate of acidification of the cell's environment.
The present invention provides a different method and device for assessing cell behaviour and metabolic activity. The present invention is based upon the realisation that the many chemical processes taking place at the cell surface produce electrochemical signals. The "signals" include, for example, potential noise and current noise, the term "noise" being used to indicate the sum of those signals resulting from cellular electrochemical activity. Techniques developed to assess the progress of electrical or electrochemical processes can be applied to the analysis of signals generated by the electrochemical activity of cells.
The present invention provides a method for assessing the metabolic and behavioural activities of cells, wherein electrochemical signals generated by the cells are detected and analysed to provide data representative of cell behaviour.
The term "behavioural activities" is used herein to include ionic transport and all those biological activities recognised as metabolic, proliferative, and locomotory, and cellular responses to exogenous factors.
The invention also provides an apparatus for assessing the metabolic and behavioural activities of cells, comprising a means for the detection of electrochemical signals generated by the cells, and means for analysing the detected signals to provide data reflecting cell behaviour and changes therein.
Cells maintained in vitro under defined culture conditions produce a characteristic electrochemical signal, this being modified upon exposure to one or more chemicals/ligands/biological factors know to affect cell activity. The electrochemical signals generated by cells with or without stimulation, upon analysis, provides a different set of data representative of the behavioural characteristics of those cells. Thus it is believed that a high degree of discrimination is afforded
REFERENCES:
patent: 5489515 (1996-02-01), Hatschek et al.
patent: 5507936 (1996-04-01), Hatschek et al.
Kandel et al. (1981) Principles of Neural Science, Elsevier/North-Holland, New York, p. 74.
Stryer (1988) Biochemistry, 3rd Ed., W.H. Freeman and Co., New York, pp. 1018-1019.
Eden Robert David
Gearey David
Woolley David Edward
The University of Manchester Institute of Science and Technology
Weber Jon P.
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