Method for measuring the concentration of a substance in a living body and device for measuring the same concentration

• US 7,248,908 B2
• Filed: 06/03/2004
• Issued: 07/24/2007
• Est. Priority Date: 06/06/2003
• Status: Expired due to Fees

• Current Assignee: University of Tokyo
• Original Assignee: University of Tokyo
• Inventors: Shimoyama, Isao, Matsumoto, Kiyoshi, Nagasawa, Sumito
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/859,127
• Publication Number:
  US 20050013779A1
• Time in Patent Office: 1,146 Days
• Field of Search: 600/309, 600/310, 600/317, 600/329
• US Class Current: 600/317
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53

Abstract

A fluorescence indicator is injected into a living body from a container via an injecting inlet to be chemically reacted with a substance in the living body. Then, an excitation light is irradiated to the living body from an excitation light source. Then, the thus obtained reflected light is reflected multiply at an reflective film formed on the inner wall of the container, and introduced into a detecting section, where a fluorescence response originated from the chemical bond between the substance and the fluorescence indicator and contained in the reflected light is detected.

Claims

1. A method for measuring a concentration of a substance in a living body, comprising the steps of:

injecting a fluorescence indicator into a given living body at an injecting outlet;

irradiating and reflecting an excitation light to and from said living body to obtain a reflected light;

detecting a fluorescence response originated from a chemical bond between said fluorescence indicator and a substance to be measured in concentration and contained in said reflected light to measure a concentration of said substance in said living body; and

indicating the measured concentration;

wherein said reflected light is collected through an optical waveguide having an opening placed coaxial with said injecting outlet.

2. The measuring method as defined in claim 1, wherein said fluorescence indicator is injected as an ion flow or an electric infiltration flow which is formed by a difference in potential between said fluorescence indicator and said living body.

3. The measuring method as defined in claim 2, further comprising the step of measuring an electric current originated from said ion flow or said electric infiltration flow of said fluorescence indicator to monitor an injecting amount of said fluorescence indicator into said living body.

4. The measuring method as defined in claim 1, wherein said fluorescence indicator is injected into the living body by means of pressurization.

5. The measuring method as defined in claim 1, wherein said fluorescence indicator is retained in a solution of which a hydrophilic and hydrophobic are controlled by applying a voltage to said solution, and said fluorescence indicator is injected into said living body by a volume expansion of said solution through hydrophilic-hydrophobic control.

6. The measuring method as defined in claim 1, further comprising the step of monitoring an injecting amount of said fluorescence indicator into said living body.

7. The measuring method as defined in claim 6, wherein said monitoring comprises the steps of:

preparing an additional fluorescence indicator;

injecting said additional fluorescence indicator into said living body with said fluorescence indicator; and

measuring a fluorescence response from said additional fluorescence indicator to monitor said injecting amount of said fluorescence indicator.

8. The measuring method as defined in claim 1, further comprising the step of controlling an injecting amount of said fluorescence indicator into said living body.

9. The measuring method as defined in claim 8, wherein said injecting amount of said fluorescence indicator is controlled mechanically.

10. The measuring method as defined in claim 9, wherein said injecting amount of said fluorescence indicator is controlled with a shatter.

11. The measuring method as defined in claim 8, wherein said injecting amount of said fluorescence indicator is controlled electrically.

12. The measuring method as defined in claim 11, wherein said injecting amount of said fluorescence indicator is controlled by means of electrostatic force.

13. The measuring method as defined in claim 1, wherein said fluorescence indicator is retained in a container constituting said optical waveguide with said injecting outlet formed at a forefront thereof which is configured to penetrate said living body, and said reflected light is reflected multiply at an inner wall of said container prior to said detecting step.

14. The measuring method as defined in claim 13, wherein said excitation light is passed through a second optical waveguide formed at a periphery of said container, and introduced into an optical scattering instrument mounted at a forefront of said second optical waveguide to be irradiated to said living body.

15. The measuring method as defined in claim 1, wherein said excitation light is irradiated to said living body through an optical fiber constituting said optical waveguide, and said reflected light is reflected multiply at an interface between a clad and a core of said optical fiber prior to said detecting step.

16. The measuring method as defined in claim 15, wherein said fluorescence indicator is injected into said living body through a guide so formed as to penetrate said optical fiber.

17. The measuring method as defined in claim 1, wherein said injecting step is synchronized with said irradiation step.

18. The measuring method as defined in claim 17, wherein said irradiating step is performed when a concentration of said fluorescence indicator becomes uniform in a measuring region in said living body.

19. The measuring method as defined in claim 1, wherein at least one of said injecting and said irradiating is modulated by a given frequency.

20. The measuring method as defined in claim 1, wherein when said concentration of said substance is changed through an action of said substance, said method further comprising detecting a pre-fluorescence response in said living body at non-activity of said substance in advance, and during a subsequent measurement subtracting said pre-fluorescence response at said non-activity from said fluorescence response contained in said reflected light to detect a fluorescence response at activity of said substance.

21. A device for measuring a concentration of a substance in a living body, comprising:

a container with an injecting outlet at a forefront thereof which is configured to penetrate a living body and to retain a fluorescence indicator to be injected into said living body;

an excitation light source to irradiate an excitation light to said living body; and

a detecting section to detect a reflected light from said living body;

wherein said detecting section is disposed on a line passing through a center of said injecting outlet of said container, and said reflected light is collected through said injecting outlet of said container.

22. The measuring device as defined in claim 21, further comprising an electrode outside said container.

23. The measuring device as defined in claim 22, wherein a difference in potential is generated between said electrode and said living body to generate an ion flow or an electric infiltration flow of said fluorescence indicator, and said fluorescence indicator is injected as said ion flow or said electric infiltration flow into said living body.

24. The measuring device as defined in claim 22, wherein a difference in potential is generated between said electrode and said fluorescence indicator to control an injecting amount of said fluorescence indicator into said living body.

25. The measuring device as defined in claim 22, wherein said fluorescence indicator is retained in a solution of which a hydrophilic and hydrophobic properties are controlled by a difference in potential between said electrode and said solution, and said fluorescence indicator is injected into said living body by a volume expansion of said solution through hydrophilic-hydrophobic control.

26. The measuring device as defined in claim 21, further comprising a pressure source to inject said fluorescence indicator into said living body through pressurization.

27. The measuring device as defined in claim 21, further comprising a shatter at a forefront of said container, wherein an injecting amount of said fluorescence indicator into said living body is controlled with said shatter.

28. The measuring device as defined in claim 21, further comprising an optical waveguide with an optical scattering instrument at a forefront thereof outside said container.

29. A device for measuring a concentration of a substance in a living body, comprising:

an excitation light source to irradiate an excitation light to a living body;

an optical fiber to transmit said excitation light;

a detecting section to detect a reflected light from said living body; and

a storage container to retain a fluorescence indicator to be injected into said living body;

wherein a guide to introduce said fluorescence indicator to a forefront of said optical fiber is formed in said optical fiber; and

said detecting section is disposed on a line passing through a center of said guide, and said reflected light is collected through said forefront of said guide when positioned within said living body.