Method and device for in vivo measuring the concentration of a substance in the blood

• US 5,452,716 A
• Filed: 09/24/1993
• Issued: 09/26/1995
• Est. Priority Date: 02/25/1992
• Status: Expired due to Fees

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Clift, Vaughan
• Primary Examiner(s): Sykes, Angela D.
• Application Number:
  US08/126,247
• Time in Patent Office: 732 Days
• Field of Search: 128/633-635, 128/664-667, 356/39-41
• US Class Current: 600/373
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence

Abstract

In vivo measurement of the concentration of a substance in the blood, e.g. glucose, despite varying concentrations of interfering components, e.g. protein and fat, by measuring the absorption of infra red light at a pair of selected wavelengths in the range 1-40 μm for each of the substance and the components one being a measuring wavelength at which the substance or component show a specific absorption and another being a reference wavelength at which the substance or component shows a low absorption, at least one wavelength being selected from the range 1-10 μm. The absorption is measured using a detector providing a computable electric signal corresponding to the absorbed amount of infra red radiation at the respective wavelengths. The electric signals are used to calculate the concentration of the substance taking into account the absorption caused by the interfering components.

Claims

1. A method for in vivo measurement of a substance'"'"'s concentration in blood, despite varying concentrations of interfering components, by measuring absorption of selected wavelengths of infrared light, the method comprising,

selecting for each of the substance and the components a pair of different wavelengths of infrared light from the range of 1-40 μ

m, one being a measuring wavelength at which the substance or component show a specific absorption and another being a reference wavelength at which the substance or component shows a low absorption, at least one wavelength being selected from a range of 3-10 μ

m;

transmitting the selected wavelengths of infrared light to a surface part covering vascularized tissue of a person whose blood is being tested for its concentration of the substance;

placing at said surface part a detector detecting for each selected wavelength the absorbed amount of infrared radiation and giving of a computable electric signal expressing the measured absorption;

calculating the concentrations of the interfering components, and calculating the concentration of the substance using the absorption measurement at the substance measuring and reference wavelengths taking into account the absorption caused by the interfering components at the measuring and reference wavelengths for this substance, the interfering absorption being calculated taking into account the measured concentrations of the interfering components and experimentally derived constants.

2. A method according to claim 1, wherein the substance the concentration of which is measured is glucose and the interfering components are fat, protein and water.

3. A method according to claim 1, wherein the substance the concentration of which is measured is CO₂ and the interfering components are glucose, fat, protein and water.

4. A method according to claim 1, wherein the substance the concentration of which is measured is ethanol and the interfering components are glucose, fat, protein and water.

5. A method according to claim 4, wherein the sample wavelength and the reference wavelength used for glucose are 9.5 ±

0.5 μ

m and 7.7 ±

0.5 μ

m, respectively.

6. A method according to claim 4, wherein the sample wavelength and the reference used for glucose are 3.47 ±

0.5 μ

m and 2.96 ±

0.5 μ

m, respectively.

7. A method according to 4, wherein the sample wavelength and the reference wavelength for fat are 5.74 ±

0.5 μ

m and 5.58 ±

0.5 μ

m, respectively.

8. A method according to claim 4, wherein the sample wavelength and the reference wavelength for fat are 3.513 ±

0.5 μ

m and 3.57 ±

0.5 μ

m, respectively.

9. A method according to claim 4, wherein the sample wavelength and the reference wavelength for protein are 6.5 ±

0.5 μ

m and 6.7 ±

0.5 μ

m, respectively.

10. A method according to claim 1, wherein the light is transmitted to the tissue and the light absorption is measured by attenuated total reflection transcutaneously, i.e. invasively or non-invasively.

11. A method according to claim 1, wherein the light is transmitted to the outer side of the surface part and the absorption is measured by detecting the heat generated in the tissue beneath the skin.

12. An apparatus for measurement of the concentration of a substance in blood despite varying concentrations of interfering components by measuring the absorption of selected wavelengths of infrared light, this apparatus comprising

a light aggregate able to provide selectable narrow bands of infrared light in the wavelength range of 1-40 μ

m;

light transmitting means for transmitting selected narrow bands of light to a measuring spot;

a detector detecting for each selected narrow band of infrared light the absorbed amount of infrared radiation at the measuring spot and giving of a computable electric signal expressing the measured absorption,

a calculating unit for calculating the concentration of the substance measuring and reference wavelengths taking into account the absorption caused by the interfering components at the measuring and reference wavelengths for this substance, the interfering absorption being calculated taking into account the measured concentrations of the interfering components and experimentally derived constants.

13. An apparatus according to claim 12 enclosed in a portable housing and comprising an ATR device with an external surface on which a sample may be placed, and focusing means for transmitting light into the device and from the device to a the detector.

14. An apparatus according to claim 13 where the light aggregate comprises a wide-banded light source and a number of filters each transmitting one of the selected narrow light bands.

15. An apparatus according to claim 13, wherein the light aggregate comprises a number of surface emitting light diodes each emitting infrared light of a chosen wavelength.

16. An apparatus according to claim 13, wherein the light aggregate comprises means for focusing the light on an optical coupling means for the light transmitting means.

17. An apparatus according to claim 16, wherein the chopper means is provided as an electronic circuit controlling the energizing of light diodes or semiconductor sources.

18. An apparatus according to claim 13, wherein the light aggregate comprises chopper means for chopping at preset chopping frequencies the light wave lengths transmitted from the light aggregate.

19. An apparatus according to claim 18, wherein the chopper means is a rotating diaphragm with cut-outs.

20. An apparatus according to claim 13, comprising an optical needle probe ATR cell having an input fibre and an output fibre, the detector being provided at the output fibre.

21. An apparatus according to claim 20, wherein the ATR needle probe cell is coated with a metal such that it acts as a surface plasma resonance device.

22. An apparatus according to claim 21, wherein the metal coated ATR needle probe is jacketed by a cellulose permeable membrane with a gap between the membrane and the probe.

23. An apparatus according to claim 22, wherein the membrane has a glucose specific enzyme or system of enzymes and the ATR prove is used to measure the product of enzymic reaction of the glucose molecule.

24. An apparatus according to claim 12, wherein the detector comprises a first and a second chamber each having an open side placed against the skin at the measuring spot, and a pressure transducer comprising a diaphragm and measuring the pressure difference between the chambers representing this differential pressure by an electric signal.

25. An apparatus according to claim 24, wherein the first chamber at a side opposite the open side has an inlet for infrared radiation transmitted from the light aggregate.

26. An apparatus according to claim 24, wherein both chambers have at a side opposite the open side inlets for infrared radiation transmitted for the light aggregate.

27. An apparatus according to claim 24, wherein a further transducer is added to each chamber at an end thereof and with a diaphragm lying in a plane parallel with the plane of the diaphragm of the transducer between the chambers.

28. An apparatus according to claim 27, wherein each chamber has an inlet for infrared radiation communicates with a compartment containing a desiccant.

29. An apparatus according to claim 27, wherein each chamber has an inlet for infrared radiation each chamber having a wall with a rigid water permeable membrane.