Analytical or monitoring apparatus and method

• US 5,569,591 A
• Filed: 07/21/1994
• Issued: 10/29/1996
• Est. Priority Date: 08/30/1990
• Status: Expired due to Term

• Current Assignee: University College of Wales Aberystwyth
• Original Assignee: University College of Wales Aberystwyth
• Inventors: Kell, Douglas B., Woodward, Andrew M.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US08/278,725
• Time in Patent Office: 831 Days
• Field of Search: 435/14, 435/29, 436/63, 436/149-151, 422/82.01, 422/82.02, 204/153.1, 204/400, 204/403, 324/692, 324/71.1
• US Class Current: 435/29
• CPC Class Codes: G01N 33/48735 Investigating suspensions of cells, e.g. measuring microbe concentration by chemical means C12Q1/04; colony counters C12M1/34; concentration of particle suspensions in general G01N15/06

Abstract

Cellular biological material (such as living tissue) is analysed or monitored by applying an AC electrical potential across the biological material so as to produce a nonlinear dielectric spectrum, and obtaining a detectable signal corresponding to the resulting spectrum. The potential is of a first frequency and the measured response at one or more second frequency substantially not overlapping with the first frequency.

Claims

1. A method of analysing a metabolic state of cellular biological material, said method comprising applying an AC electric potential at one or more discrete frequencies to a sample of the cellular biological material, and determining a response at one or more response frequencies which were substantially absent from the applied AC potential, said one or more response frequencies resulting from a combination of the applied frequency or frequencies.

2. A method according to claim 1, wherein the applied electric potential comprises a first field applied to excite the system, and a second field comprising a probing AC voltage effective to register the field-dependent dielectric properties of the cellular biological material, said first field being of higher magnitude than the second field.

3. A method according to claim 1, wherein said applied AC potential is sinusoidal, and the response frequency or frequencies are observed by performing a translation to ascertain the extent to which the non-linearities of the material are manifest by the generation of harmonics.

4. A method according to claim 1, wherein said material comprises a cell suspension.

5. A method according to claim 1, wherein said material comprises living tissue.

6. A method according to claim 4, wherein said AC electric potential at one or more discrete frequencies is applied to a supernatant of a dispersion or suspension of said cellular biological material suspension, the conductivity of said supernatant being adjusted to be substantially identical to that of said biological material.

7. A method according to claim 1, which method further comprises observing the third harmonic of said response.

8. A method according to claim 1, which method comprises observing even-numbered harmonics of said response.

18. A method according to claim 1, wherein the metabolic state of the cellular biological material is analyzed in the presence of a substrate for the cellular biological materials.

19. A method according to claim 1, wherein the metabolic state of the cellular biological material is analyzed in the presence of an inhibitor of cell metabolism for said cellular biological material.

20. A method according to claim 1, wherein the electric potential is applied using a plurality of electrodes immersed in a suspension of the biological material.

21. A method according to claim 1, wherein the electric potential is applied using a plurality of electrodes affixed to an exterior surface of a living organism.

9. In a method of analysing a metabolic state of cellular biological material, which method comprises applying an electric potential of one or more initial frequencies to the cellular biological material, and measuring a response of the material at at least one response frequency, wherein the improvement comprises that at least one response frequency is substantially not overlapping with the initial frequency or frequencies and results from a combination of the initial frequency or frequencies.

22. A method according to claim 9, wherein the electric potential is applied using a plurality of electrodes immersed in a suspension of the biological material.

23. A method according to claim 9, wherein the electric potential is applied using a plurality of electrodes affixed to an exterior surface of a living organism.

10. A method of analysing or monitoring a determinand associated with cellular biological material, which comprises applying an AC electrical potential at at least one discrete initial frequency to a sample of said material;

measuring a response of said material at at least one response frequency substantially not overlapping with said applied potential; and

comparing said response with a stored characteristic of said determinand.

11. A method according to claim 10, wherein said determinand is a glucose concentration.

12. Apparatus for analysing a metabolic state of cellular biological material, which apparatus comprises:

a) retaining means for retaining a sample of said cellular biological material;

b) means for applying an AC electric potential at one or more discrete frequencies to said sample; and

c) means for determining a response at one or more response frequencies which were substantially absent from the applied AC potential, said one or more response frequencies resulting from a combination of the applied frequency or frequencies.

13. Apparatus according to claim 12, wherein the means for applying an AC electric potential comprises means for applying a first field effective to excite the biological cell material, and means for applying a probing AC voltage effective to register the field-dependent dielectric properties of the cellular biological material.

14. Apparatus for monitoring or analysing a determinand associated with cellular biological material, which apparatus comprises:

(a) means for applying an AC electrical potential at one or more discrete frequencies to said material;

(b) means for determining a response of said material at one or more frequencies which were substantially absent from the applied AC potential; and

(c) means for comparing said response to a stored characteristic of said determinand.

15. Apparatus according to claim 14, which further comprises means for retaining said biological material in proximity to said electric potential applying means.

16. Apparatus according to claim 14, wherein said means for retaining the biological material comprises adhesive provided on a patch for retention of an electrode to the skin of a subject.

17. Apparatus according to claim 14, wherein the means for applying an AC electric potential comprises means for applying a field field effective to excite the cellular biological material, and means for applying a probing AC voltage effective to register the field-dependent dielectric properties of the cellular biological material.