CONDUCTIVITY MEASUREMENT CELL

• US 20110291670A1
• Filed: 12/24/2009
• Published: 12/01/2011
• Est. Priority Date: 12/31/2008
• Status: Active Grant

• Current Assignee: SPD Swiss Precision Diagnostics GmbH (Abbott Laboratories)
• Original Assignee: SPD Swiss Precision Diagnostics GmbH (Abbott Laboratories)
• Inventors: Jones, Malcolm R., Barnard, Jonathan D., Carlisle, Stephen J.
• Granted Patent: US 9,689,821 B2
• Time in Patent Office: Days
• US Class Current: 324/601
• CPC Class Codes: G01N 27/07 Construction of measuring vessels; Electrodes therefor
• CPC Class Codes: G01N 33/493 urine
• CPC Class Codes: H03K 3/0315 Ring oscillators

Abstract

The application relates to a conductivity measurement cell for measuring the concentration of a preselected biomarker or analyte in a body fluid, such as urine. In order to reduce the effect of sample dilution on measured concentration, the measured concentration can be normalised by a dilution factor, which can be determined from electrical conductivity. A test strip and measurement apparatus is disclosed for performing such normalised concentration measurement.

Claims

1. A method of deriving a temperature corrected measure of electrical conductivity of a sample, comprising:

obtaining a measure of a first, inherent conductance of a measurement arrangement having a first node and a second node;

electrically connecting a reference between the first and second nodes of the measurement arrangement to obtain a measure of a second conductance;

electrically connecting a sample to the measurement arrangement to obtain a measure of a third conductance; and

deriving the temperature corrected measure of electrical conductivity of the sample from the measures of the first, second and third conductances.

2. A method according to claim 1 wherein the reference and sample are connected in parallel between the first node and second node.

3. A method as claimed in claim 1 in which the reference and sample are provided on a conductivity measurement test strip.

4. A method according to claim 3 wherein the test strip is provided with first and second electrodes which are spaced apart and arranged to connect electrically in parallel respectively across the reference and sample applied to the test strip, and wherein the first and second electrodes are connected to the first and second nodes.

5. A method according to claim 1 in which the measure of inherent conductance is obtained by measurement.

6. A method according to claim 1 in which the measure of inherent conductance is obtained from a stored value.

7. A method according to claim 1 in which at least one of the reference and sample are connected electrically to the measurement arrangement by virtue of relative physical movement.

8. A method according to claim 1 in which at least one of the reference and sample are connected electrically to the measurement arrangement by virtue of electrical or electronic switching.

15. A method according to claim 1 wherein the sample is a bodily fluid.

16. The method according to claim 15 wherein the bodily fluid is urine or blood or saliva.

17. The method according to claim 1 wherein the reference comprises a liquid, gel or solid, or an electrical component.

18. The method according to claim 1 further comprising measurement of the concentration of an analyte in the sample and deriving a corrected concentration measurement from the temperature corrected measure of electrical conductivity of the sample.

9. A method of deriving a temperature corrected measure of electrical conductivity of a sample, comprising:

obtaining a measure of a first, inherent conductance of a measurement arrangement having a first node and a second node;

obtaining a measure at the measurement arrangement of a second conductance when a reference is connected between the first node and the second node;

obtaining a measure at the measurement arrangement of a third conductance when a sample is connected between a third node and the second node;

calculating a ratio derived from the measures of first, second and third conductances, repeating the steps of measuring a second conductance, measuring a third conductance and calculating a ratio until successive ratio calculations differ by less than an error amount; and

deriving the temperature corrected measure from the ratio.

10. A method as claimed in claim 9 in which the reference and sample are provided on a conductivity measurement test strip.

11. A method according to claim 10 wherein the test strip is provided with a reference portion and a sample container.

12. A method according to claim 11 wherein the test strip is provided with first, second and third electrodes which are spaced apart, and the first, second and third electrodes are connected to the first node, the second node and the third node, wherein the first and second electrodes are arranged to connect across the reference portion, and the second and third electrodes are arranged to connect across the sample.

13. A method according to claim 12 wherein the test strip is provided with a reference portion and a sample container, a sample is introduced into the sample container, the first and second electrodes are arranged to connect across the reference portion, and second and third electrodes are arranged to connect across the sample.

14. A method according to claim 13 wherein the sample is a liquid and is introduced into the sample container via a capillary channel.

19. A device for deriving a temperature corrected measure of electrical conductivity of a sample, the device having a measurement component, the measurement component having a first node and a second node, and the measurement component arranged to provide:

a measurement of a first, inherent conductance of the measurement component;

a measurement of a second conductance when a reference is connected electrically to the measurement component between the first node and the second node; and

a measurement of a third conductance when a sample is connected electrically to the measurement component, the device arranged to derive the temperature corrected measure by combining the first, second and third conductance measurements.

21. A device according to claim 19 wherein the measurement component represents each conductance as a frequency.

22. A device according to claim 19 further arranged for use with a conductance measurement test strip or a diagnostic test strip for the measurement of an analyte incorporating a conductance measurement test strip.

23. A device according to claim 22 in which the test strip is disposable.

24. A device according to claim 19 further incorporating display means by which a microprocessor is arranged to output instructions or an indication to a user.

25. A device according to claim 19 wherein the sample is a liquid.

26. The device according to claim 19 further incorporating a signal measurement means by which to measure a signal indicative of the amount of an analyte.

42. A conductivity measurement test strip having a body, a sample container and a reference portion, the sample container and the reference portion separated by a coincident membrane, wherein the test strip is configured for use with a device according to claim 19.

20. A device for deriving a temperature corrected measure of electrical conductivity of a sample, the device having a measurement component, the measurement component having a first node, a second node and a third node, and the measurement component arranged to provide:

a measurement of a first, inherent conductance of the measurement component;

a measurement of a second conductance when a reference is connected between the first node and the second node;

a measurement of a third conductance when a sample is connected between the first node and the second node; and

a calculation of a ratio derived from the first, second and third conductances, the device further arranged to provide successive measurements of the second conductance and the third conductance, and successive ratio calculations, until successive ratio calculations differ by less than an error amount and then to derive the temperature corrected measure from the ratio.

27. A conductivity measurement test strip having a body, a sample container and a reference portion, the sample container and the reference portion separated by a coincident membrane.

28. A test strip according to claim 27 in which the sample container and reference portion are arranged so as to maximize the ratio of membrane surface area to sample container volume.

29. A test strip according to claim 27 further incorporating a first electrode and a second electrode, wherein the first and second electrodes are spaced apart and arranged so that in use they connect electrically in parallel across the reference portion and the sample container.

30. A test strip according to claim 27 further incorporating a first electrode, a second electrode and a third electrode, the first and second electrodes spaced apart and arranged so that in use they connect across the reference portion, and the second and third electrodes arranged so that in use they connect across a sample contained in the sample container.

34. A test strip according to claim 27 comprising a sample application zone which fluidically connects the sample container via a capillary channel.

35. A test strip according to claim 27 wherein the reference portion is sealed and contains a reference liquid, gel or solid, or the reference portion comprises an electrical component.

36. The test strip according to claim 35 wherein the reference gel comprises potassium chloride.

37. A test strip according to claim 27 wherein the sample container surrounds the reference portion on more than one side.

38. The test strip according to claim 27 arranged, in use, for determining the amount or concentration of an analyte of interest.

39. The test strip according to claim 38 further comprising a binding reagent for the analyte of interest.

40. A test strip according to claim 27 wherein the electrodes have a chamfered edge in contact with the sample and/or reference, or the electrodes have surface features which increase their contact surface area with the reference and/or sample.

41. A test strip according to claim 27 wherein the electrodes are over-molded.

31. A conductivity measurement test strip having a body, a sample container, a reference portion, a first electrode and a second electrode, the first and second electrodes spaced apart, and the electrodes arranged so that in use they connect electrically in parallel across the reference portion and a sample contained in the sample container.

33. A test strip according to claim 31 wherein the sample container and the reference portion are separated by a coincident membrane, the sample container and reference portion arranged so as to maximize the ratio of membrane surface area to sample container volume.

32. A conductivity measurement test strip having a body, a sample container, a reference portion, a first electrode, a second electrode and a third electrode, the first and second electrodes spaced apart and arranged so that in use they connect across the reference portion, and the second and third electrodes arranged so that in use they connect across a sample contained in the sample container.

43. An electronic circuit for generating a frequency output which is related to a conductance between a first node and a second node, having first, second and third CMOS inverting gates arranged in series, the third inverting gate output connected by a conductance to the first inverting gate input, the third inverting gate output comprising the first node, the first inverting gate input comprising the second node, the second inverting gate output being connected to the first inverting gate input by a first capacitance, and the first inverting gate input connected towards ground potential by a second capacitance.

44. An electronic circuit according to claim 43 wherein the second capacitor connects the first inverting gate input to ground potential.

45. An electronic circuit according to claim 43 wherein the second capacitor connects the first inverting gate input towards ground potential via a network (N1).

46. An electronic circuit according to claim 45 wherein the network (N1) comprises a capacitor and resistor in parallel.

47. An electronic circuit according to claim 43 wherein the third inverting gate incorporates a tri-stateable output.

48. An electronic circuit according to claim 47 incorporating an additional inverting gate with tri-stateable output, the additional inverting gate input connected to the second inverting gate output, the additional inverting gate output connected to the first inverting gate input by an additional conductance, the additional inverting gate output comprising a third node (P3).

49. An assay device arranged to implement a method of deriving a temperature corrected measure of electrical conductivity of a sample, the method comprising:

obtaining a measure of a first, inherent conductance of a measurement arrangement having a first node and a second node;

electrically connecting a reference between the first and second nodes of the measurement arrangement to obtain a measure of a second conductance, electrically connecting a sample to the measurement arrangement to obtain a measure of a third conductance; and

deriving the temperature corrected measure of electrical conductivity of the sample from the measures of the first, second and third conductances.

50. Use of a device for deriving a temperature corrected measure of electrical conductivity of a sample for deriving a temperature corrected measure of electrical conductivity of a sample and/or measurement of the concentration of an analyte in the sample, the device having a measurement component, the measurement component having a first node and a second node, and the measurement component arranged to provide:

a measurement of a first, inherent conductance of the measurement component;

a measurement of a second conductance when a reference is connected electrically to the measurement component between the first node and the second node; and

a measurement of a third conductance when a sample is connected electrically to the measurement component,

the device arranged to derive the temperature corrected measure by combining the first, second and third conductance measurements.

51. (canceled)

52. An assay device arranged to incorporating a device for deriving a temperature corrected measure of electrical conductivity of a sample, the device having a measurement component, the measurement component having a first node and a second node, and the measurement component arranged to provide:

a measurement of a first, inherent conductance of the measurement component;

a measurement of a second conductance when a reference is connected electrically to the measurement component between the first node and the second node; and

a measurement of a third conductance when a sample is connected electrically to the measurement component,

the device arranged to derive the temperature corrected measure by combining the first, second and third conductance measurements.

53. An assay device arranged to incorporate an electronic circuit for generating a frequency output which is related to a conductance between a first node and a second node, the electronic circuit having first, second and third CMOS inverting gates arranged in series, the third inverting gate output connected by a conductance to the first inverting gate input, the third inverting gate output comprising the first node, the first inverting gate input comprising the second node, the second inverting gate output being connected to the first inverting gate input by a first capacitance, and the first inverting gate input connected towards ground potential by a second capacitance.

54. An assay device arranged for use with a conductivity measurement test strip having a body, a sample container and a reference portion, the sample container and the reference portion separated by a coincident membrane.

55. Use of an electronic circuit for generating a frequency output which is related to a conductance between a first node and a second node for deriving a temperature corrected measure of electrical conductivity of a sample and/or measurement of the concentration of an analyte in the sample, the electronic circuit having first, second and third CMOS inverting gates arranged in series, the third inverting gate output connected by a conductance to the first inverting gate input, the third inverting gate output comprising the first node, the first inverting gate input comprising the second node, the second inverting gate output being connected to the first inverting gate input by a first capacitance, and the first inverting gate input connected towards ground potential by a second capacitance.

56. Use of a conductivity measurement test strip for deriving a temperature corrected measure of electrical conductivity of a sample for deriving a temperature corrected measure of electrical conductivity of a sample and/or measurement of the concentration of an analyte in the sample, the test trip having a body, a sample container and a reference portion, the sample container and the reference portion separated by a coincident membrane.