Methods for evaluating cell membrane properties

• US 20060105321A1
• Filed: 07/28/2005
• Published: 05/18/2006
• Est. Priority Date: 07/28/2004
• Status: Abandoned Application

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: Bai, Er-Wei, Bodmer, James E., English, Anthony, Moy, Alan B.
• Application Number:
  US11/192,322
• Publication Number:
  US 20060105321A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/5076 involving cell organelles, e.g. Golgi complex, endoplasmic reticulum

Abstract

Methods for measuring cell membrane property are disclosed. A computer readable medium includes instructions for deriving from transcellular impedance a measurement of a cell membrane property and provides the stability and error of the measurement. The derivation from the transcellular impedance includes the real and imaginary components of the transcellular impedance and also uses a geometric shape to model the shape of the cell. Alternatively, the derivation from the transcellular impedance includes magnitude and complex components. The measurements include the membrane capacitance, membrane resistance, and/or cell adhesion.

Claims

1. A method comprising:

(a) determining a cell membrane property derived from a transcellular impedance measurement;

(b) determining a stability of the measurement; and

(c) determining an error of the measurement.

2. The method claim 1, where the cell membrane property comprises cell adhesion and where determining the cell adhesion comprises measuring a cell-cell adhesion.

3. The method of claim 2, where determining the cell adhesion comprises measuring a cell-matrix adhesion.

4. The method of claim 1, where the cell membrane property comprises cell membrane capacitance and cell membrane resistance.

5. The method of claim 1, where determining the stability comprises performing a statistical calculation.

6. The method of claim 1, where determining an error comprises a performing a Chi² calculation.

7. The method of claim 1, further comprising determining a precision of the measurement.

8. The method of claim 1, where the transcellular impedance comprises transcellular impedance of cultured cells.

9. The method of claim 8, where the cultured cells comprise cells grown on a microsensor.

10. The method of claim 9, where the microsensor comprises a microscopic biosensor.

11. The method of claim 9, where the microsensor comprises a microelectrode.

12. The method of claim 1, where (a) comprises utilizing a non-linear optimization algorithm.

13. The method of claim 12, where the non-linear optimization algorithm comprises a Levenberg-Maquardt non-linear optimization algorithm.

14. The method of claim 12, where the non-linear optimization algorithm comprises a least-squared non-linear optimization algorithm.

15. The method of claim 1, where (a) comprises utilizing real and imaginary data pertaining to the transcellular impedance.

16. The method of claim 1, where (a) comprises utilizing complex and magnitude data pertaining to the transcellular impedance.

17. The method of claim 1, where (a) comprises modeling a cell using a geometric shape, the geometric shape being selected from the group consisting of a disk, a square, a rectangle, a parallelogram, and an ellipsoid.

18. The method of claim 1, where (a) further comprises eliminating low frequency data pertaining to the transcellular impedance.

19. The method of claim 1, where (a) further comprises statistically weighting low frequency data pertaining to the transcellular impedance.

20. The method of claim 1, where (a) further comprises modeling an accumulating error in an electrode property over time.

21. A program storage device readable by a machine, tangibly embodying a program of instructions executable by the machine to perform the method steps of claim 1.

22. A method comprising:

determining a cell membrane property from a transcellular impedance measurement, where determining the cell membrane property comprises;

(a) modeling real and imaginary data pertaining to the transcellular impedance; and

(b) using a geometric shape to model the shape of the cell.

23. The method of claim 22, further comprising utilizing a Levenberg-Maquardt non-linear optimization algorithm.

24. The method of claim 22, further determining a stability of the transcellular impedance.

25. The method of claim 22, further determining an error of the transcellular impedance.

26. The method of claim 25, where determining an error comprises a performing a Chi² calculation.

27. The method of claim 22, where the geometric shape is selected from the group consisting of a disk, a square, a rectangle, a parallelogram, and a ellipsoids.

28. A method comprising:

(a) determining membrane capacitance and membrane resistance of a cell from a transcellular impedance measurement.

29. The method of claim 28, where (a) comprises utilizing a Levenberg-Maquardt non-linear optimization algorithm.

30. The method of claim 28, where (a) further comprises modeling the cell using a geometric shape, the geometric shape being selected from a group consisting of a disk, a square, a rectangle, a parallelogram, and a ellipsoids.