Method for non-invasilvely determining the relative levels of two biological substances

• US 20050074810A1
• Filed: 06/17/2002
• Published: 04/07/2005
• Est. Priority Date: 06/22/2001
• Status: Active Grant

• Current Assignee: University of Bath
• Original Assignee: Maria Begona Delgado-Charro, Richard Henry Guy
• Inventors: Delgado-Charro, Maria Begona, Guy, Richard Henry
• Granted Patent: US 7,555,337 B2
• Time in Patent Office: Days
• US Class Current: 435/7.100
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

The method for non-invasively determining the relative levels of two substances present in a biological system includes the steps of extracting by reverse iontophoresis charged and uncharged substances from said biological system, and collecting said substances, analysing the collected amount of a first extracted substance and a second extracted substance and determining the extraction ratio of the first substance to the second substance to determine their relative levels in the biological system. When the first and second substances are both analytes susceptible to changes in their concentration in the biological system, this method provides information about the relative concentrations of the two substances in the biological system. When the first substance is an analyte susceptible to changes in its concentration in the biological system and the second substance has a substantially constant concentration in the biological system, the second subtance acts as an internal standard and the extraction ratio becomes a direct measurement of the physiological level of the first substance in the biological system. A iontophoretic sampling device for monitoring the relative levels of two substances present in a biological system is also disclosed.

Claims

1. A method for non-invasively determining the relative levels of two substances present in a biological system, said method comprising

contacting an anodal chamber and a cathodal chamber of an iontophoresis device comprising reversible electrodes with a biological system;

extracting by reverse iontophoresis charged and uncharged substances from said biological system, and collecting said charged and uncharged substances each independently into the anodal chamber or the cathodal chamber;

analysing the collected amount of at least a first extracted substance and a second extracted substance;

wherein said first and second substances are selected in such a way that the transport and/or transference number of the first substance is independent of the transport and/or transference number of the second substance;

subsequently, determining the extraction ratio of the first substance to the second substance to determine their relative levels in the biological system.

2. The method according to claim 1, characterised in that the electrodes of the iontophoretic device are silver/silver chloride electrodes.

3. The method according to claim 2, characterised in that the first substance analysed and the second substance analysed are contained in the same chamber.

4. The method according to claim 3, characterised in that the biological system is a human body.

5. The method according to claim 4, characterised in that the current density applied by the iontophoretic device during the iontophoretic extraction is not higher than 0.5 mA/cm².

6. The method according to claim 5, characterised in that the determination of the extraction ratio of the first substance to the second substance is made by calculating the ratio of the collected amount of the first extracted substance to the collected amount of the second extracted substance.

7. The method according to any claim 5, characterised in that the determination of the extraction ratio of the first substance to the second substance is made by first calculating the flux of the first extracted substance and the flux of the second substance, based on the extracted amount of the first substance and the extracted amount of the second substance, respectively, and then by calculating the ratio of the flux of the first extracted substance to the flux of the second extracted substance.

8. The method according to claim 7, characterised in that the analysis of the two selected substances is made by techniques involving specific enzymes or biosensors, ion-selective chemistry, measurement of conductivity, and all other known analytical chemistry techniques.

9. The method according to claim 8, characterised in that the first and second analysed substances are susceptible to changes in their concentration in the biological system.

10. The method according to claim 8, characterised in that the first analysed substance is susceptible to changes in its concentration in the biological system and the second analysed substance has a substantially constant concentration in the biological system.

11. The method according to claim 10, characterised in that the first substance is glucose.

12. The method according to claim 10, characterised in that the first substance is lithium.

13. The method according to claim 12, characterised in that the second substance is sodium.

14. The method according to claim 13, characterised in that electrode polarity is reversed subsequent to each extraction/analysis cycle.

15. A iontophoretic sampling device for non-invasively monitoring the relative levels of two substances present in a biological system, said device comprising:

an electrical power supply,

a collection assembly comprising a first collection chamber containing a first electroconductive medium in contact with a first electrode and a second collection chamber containing a second electroconductive medium in contact with a second electrode, said electrodes being reversible electrodes and being each in contact with the electrical power supply when the collection assembly is inserted in the iontophoretic device;

a means for analysing two or more selected charged and/or uncharged substances in either one or both of the collection chambers in order to determine their extracted amounts,

a means for converting the extracted amounts of a first substance and a second substance to the extraction ratio of the first substance to the second substance, wherein said first and second substances are selected in such a way that the transport and/or transference number of the first substance is independent of the transport and/or transference number of the second substance.

16. The iontophoretic sampling device according to claim 15, characterised in that the electrodes are silver/silver chloride electrodes.

17. The iontophoretic sampling device according to claim 16, characterised in that the means for converting the extracted amounts of a first substance and a second substance to the extraction ratio of the first substance to the second substance is a programmable means able to calculate the ratio of the collected amount of the first extracted substance to the collected amount of the second extracted substance.

18. The iontophoretic sampling device according to claim 16, characterised in that the means for converting the extracted amounts of a first substance and of a second substance to the extraction ratio of the first substance to the second substance is a programmable means able to first calculate the flux of the first extracted substance and the flux of the second substance, based on the extracted amount of the first substance and the extracted amount of the second substance, respectively, and then to calculate the ratio of the flux of the first extracted substance to the flux of the second extracted substance.

19. The iontophoretic sampling device according to claim 18, characterised in that the analysis of the selected substances is made by techniques involving biosensing techniques.

20. The iontophoretic sampling device according to claim 19, characterised in that the first and second substances for which the extraction ratio is to be determined are susceptible to changes in their concentration in the biological system, so that relative levels of the first substance to the second substance are determined.

21. The iontophoretic device according to claim 19, characterised in that the first substance is susceptible to changes in its concentration in the biological system and the second substance has a substantially constant concentration in the biological system, so that the physiological concentration of the first substance is determined based upon the constant physiological concentration of the second substance.

22. The iontophoretic device according to claim 21, characterised in that the first substance is glucose.

23. The iontophoretic device according to claim 21, characterised in that the first substance is lithium.

24. The iontophoretic device according to claim 23, characterised in that the second substance is sodium.

25. The iontophoretic device according to claim 24, characterised in that it further comprises a means to reverse the electrode polarity subsequent to each extractionlanalysis cycle.

26. The iontophoretic device according to claim 25, characterised in that it is miniaturised to be worn on a person'"'"'s body.