Real-time impedance assay to follow the invasive activities of metastatic cells in culture

• US 20050130119A1
• Filed: 09/10/2004
• Published: 06/16/2005
• Est. Priority Date: 09/10/2003
• Status: Active Grant

• Current Assignee: Applied BioPhysics, Inc.
• Original Assignee: Applied BioPhysics, Inc.
• Inventors: Keese, Charles R., Giaever, Ivar
• Granted Patent: US 7,399,631 B2
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5044 involving specific cell types
• CPC Class Codes: G01N 33/5064 Endothelial cells

Abstract

The present invention provides methods for the assessment of the metastatic potential of cells by measuring the effect of the cells on the impedance of an electrode. Accordingly, the present invention similarly provides methods for testing the efficacy of anti-cancer therapies and for establishing indicators of metastatic potential based on a cell'"'"'s effect on impedance. Such methods may be employed in vitro or in vivo. In some embodiments, the electrode is coated with endothelial or epithelial cells. A first aspect of the invention provides a method of assessing a metastatic potential of a cell comprising the steps of providing an electrode coated with a plurality of substrate cells, obtaining a first measurement of at least one electrical property of the coated electrode, contacting the electrode with at least one test cell, obtaining a second measurement of at least one electrical property of the coated electrode, and comparing the first and second measurements.

Claims

1. A method of assessing a metastatic potential of a cell comprising the steps of:

providing an electrode coated with a plurality of substrate cells;

obtaining a first measurement of at least one electrical property of the coated electrode;

contacting the electrode with at least one test cell;

obtaining a second measurement of at least one electrical property of the coated electrode; and

comparing the first and second measurements.

2. The method of claim 1, wherein the substrate cells are at least one of endothelial cells and epithelial cells.

3. The method of claim 1, wherein the electrical property is impedance.

4. The method of claim 3, wherein the test cell is considered potentially metastatic if the second impedance is less than the first impedance.

5. The method of claim 1, wherein the test cell is contacted in vivo.

6. The method of claim 1, wherein at least one of the obtaining and contacting steps are carried out under flow conditions.

7. The method of claim 1, further comprising the step of comparing the first and second measurements to a first and a second measurement of an electrical property of a cell known to be non-metastatic.

8. A method of assessing the efficacy of an anti-cancer therapy comprising the steps of:

assessing a first metastatic potential of a test cell;

providing an anti-cancer therapy to the test cell;

assessing a second metastatic potential of the test cell; and

comparing the first and second metastatic potentials.

9. The method of claim 8, wherein the anti-cancer therapy is considered efficacious if the second metastatic potential is less than the first metastatic potential.

10. The method of claim 8, wherein the assessing steps comprise:

providing an electrode coated with a plurality of substrate cells;

obtaining a first measurement of at least one electrical property of the coated electrode;

contacting the electrode with at least one test cell;

obtaining a second measurement of at least one electrical property of the coated electrode; and

comparing the first and second measurements.

11. The method of claim 10, wherein the substrate cells are at least one of endothelial cells and epithelial cells.

12. The method of claim 10, wherein the electrical property is impedance.

13. The method of claim 12, wherein the anti-cancer therapy is considered efficacious if the reduction in impedance from the first measurement and the second measurement of the second assessment is less than the reduction in impedance from the first measurement and the second measurement of the first assessment.

14. The method of claim 10, wherein the test cell is contacted in vivo.

15. The method of claim 10, wherein at least one of the obtaining and contacting steps are carried out under flow conditions.

16. The method of claim 8, wherein the anti-cancer therapy is at least one of chemical treatment and radiological treatment.

17. A method of developing an indicator of metastatic potential comprising the steps of:

providing a plurality of sets of index cells of known metastatic potentials;

providing an electrode coated with a plurality of substrate cells;

obtaining a first measurement of at least one electrical property of the coated electrode;

contacting the electrode with a first set of index cells;

obtaining a second measurement of at least one electrical property of the coated electrode;

repeating the contacting step and the obtaining a second measurement step for each of the sets of index cells; and

comparing the first and second measurements for each of the sets of index cells to the known metastatic potential of each of the sets of index cells,

wherein the difference in the first and second measurements is predictive of metastatic potential.

18. The method of claim 17, wherein the substrate cells are at least one of endothelial cells and epithelial cells.

19. The method of claim 17, wherein the electrical property is impedance.

20. The method of claim 17, wherein at least one of the obtaining and contacting steps are carried out under flow conditions.