Optical fiber apparatus for quantitative analysis

• US 4,399,099 A
• Filed: 09/14/1981
• Issued: 08/16/1983
• Est. Priority Date: 09/20/1979
• Status: Expired due to Term

• Current Assignee: Puritan Bennett Corp. (Medtronic Plc)
• Original Assignee: Richard G. Buckles
• Inventors: Buckles, Richard G.
• Primary Examiner(s): RICHMAN, BARRY
• Application Number:
  US06/302,242
• Time in Patent Office: 701 Days
• Field of Search: 422/55-60, 422/68, 422/73, 23/230 B, 23/230 R, 356/445, 356/448, 356/435, 435/7, 436/514, 436/535, 436/527, 436/531, 436/136, 436/138, 436/165, 436/805, 436/807
• US Class Current: 422/401
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 2021/4166 Methods effecting a waveguide mode enhancement through the property being measured
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/7716 in cladding
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/643 non-biological material
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 33/525 Multi-layer analytical elements
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10T 436/207497 Molecular oxygen
• CPC Class Codes: Y10T 436/209163 Dissolved or trace oxygen or oxygen content of a sealed environment

Abstract

This invention relates to a method and to apparatus for chemical and biochemical analyses which employ an energy-transmissive core and may employ one or more sheaths which selectively absorb, react with, and/or filter an analyte or a product of an analyte. The core is transmissive to a chosen energy carrier and it has an inlet end and an outlet end. Between these ends it has an extended length. The passage of energy through the core is modified by reason of events which occur in one or more of the sheaths or in the case where no sheath is employed, by reason of events which occur in an ambient fluid. The resulting modification of the transmitted energy is a measure of such events which in turn are a measure of the analyte. The energy may be any of several types of energy which can be transmitted through the core from end to end and which is susceptible to modification by reactions in the sheath or sheaths or ambient fluid. The energy may be electromagnetic, electrical or sonic. In the method aspect of the invention a permeable core may be used which is bare, i.e. without a sheath, and exposed directly to an environment, e.g. the air or an industrial fluid.

Claims

1. An optical fiber device for the quantitative analysis of oxygen in a fluid, said device comprising a fibersheath element including a fiber capable of transmitting electromagnetic energy in the visible and ultraviolet ranges and defining a path for the transmission of said energy, a first oxygen-permeable sheath surrounding said fiber, an oxygen-quenchable, fluorescent dye incorporated into the material forming said fiber or said sheath and means for reflecting said electromagnetic radiation from said sheath into said fiber, whereby the modification of the fluorescence caused by the quenching thereof by oxygen is cumulative along the length of said path.

2. The device of claim 1 wherein said fluorescent dye is fluoranthrene.

3. The device of claim 1 wherein said fluorescent dye is contained in said sheath.

4. The device of claim 1 comprising a plurality of said fiber-sheath elements, said elements containing said oxygen-quenchable fluorescent dye in different concentrations.

5. The device of claim 4 wherein said dye is contained in the sheaths of said elements.

6. An optical fiber-sheath element for the quantitative analysis of an analyte in a fluid containing said analyte species and a second species which reacts with said analyte species in the presence of a catalyst, said element comprising:

a fiber which transmits electromagnetic radiation;

a first sheath element covering said fiber and formed of a material which is permeable to at least one of said analyte species and said second species and which contains a reagent which reacts with one of said analyte species and said second species to modify, in a cumulative manner along the length of said fiber, an electromagnetic energy transmitting characteristic of the fiber; and

a second sheath element surrounding said first sheath element, said second sheath element being formed of a material which is permeable to both said analyte species and said second species and which contains a catalyst for causing a reaction between said analyte species and said second species.

7. The element of claim 6 wherein said analyte is glucose, said second species is oxygen, said catalyst is glucose oxidase, and said reagent is an oxygen-quenchable fluorescent dye.

8. An optical device for the quantitative analysis of an analyte in a fluid containing said analyte species and a second species which reacts with said analyte species in the presence of a catalyst, said device including a first fiber-sheath element comprising:

a fiber which transmits electromagnetic radiation;

a first sheath element covering said fiber and formed of a material which is permeable to at least one of said analyte species and said second species and which contains a reagent which reacts with one of said analyte species and said second species to modify, in a cumulative manner along the length of said fiber, an electromagnetic energy transmitting characteristic of the fiber; and

a second sheath element surrounding said first sheath element, said second sheath element being formed of a material which is permeable to both said analyte species and said second species and which contains a catalyst for causing a reaction between said analyte species and said second species; and

a second fiber-sheath element, like said first fiber-sheath element, but not containing said catalyst in its second sheath.

9. The device of claim 8 wherein said analyte is glucose, said second species is oxygen, said catalyst is glucose oxidase, and said reagent is an oxygen-quenchable fluorescent dye.

10. An optical fiber device for the quantitative analysis of an antigen A1 contained in a liquid, said device including a fiber-sheath element comprising a fiber element capable of transmitting electromagnetic energy and defining a path for the transmission of said energy, a first sheath surrounding said fiber element and containing a first complex A2 of an antigen and an energy-modifying compound, a second sheath surrounding said first sheath, said second sheath reflecting said electromagnetic radiation and being selectively permeable to said first complex when wet, and a third sheath, surrounding said second sheath, and an antibody Ab to A1 and A2 incorporated into the material forming said third sheath, whereby the modification to transmitted radiation resulting from the presence of said energy-modifying compound is cumulative along the length of said path.

11. The optical fiber device of claim 10 wherein said energy-modifying compound is a fluorescent compound.

12. The device of claim 10 comprising a plurality of said fiber-sheath elements, said elements containing said complex A2 of an antigen and an energy-modifying compound in different concentrations.

13. The optical fiber device of claim 12 wherein said energy-modifying compound is a fluorescent compound.

14. An optical fiber device for the quantitative analysis of an antigen A contained in a liquid, said device comprising a fiber-sheath element including a fiber which transmits electromagnetic radiation, said fiber having an index of refraction n_c and being permeable to the product Y of a reaction:

##EQU3## wherein E is an enzyme, X is a high molecular weight compound, and Y is a low molecular weight compound which absorbs said radiation;

a first sheath surrounding said fiber and being permeable to Y but not to X;

a second sheath surrounding said first sheath and having an index of refraction n_s lower than n_c, said second sheath being formed of a material containing (1) an antibody Ab immunobonded to a complex of an enzyme E and an antigen, said enzyme complex being inactive within the immunobonded complex but displaceable by A and thereby activated to catalyze said reaction, and (2) an excess of X, said second sheath being permeable to A, whereby the modification of the transmitted radiation resulting from the presence of said radiation-absorbant product Y is cumulative along the length of said fiber.

15. The device of claim 14 wherein Y is a dye which produces modification of the transmitted energy by absorption.

16. The device of claim 14 comprising a plurality of said fiber-sheath elements, said elements containing different amounts of X.

17. The device of claim 16 wherein Y is a dye which produces modification of the transmitted energy by absorption.

18. An optical fiber device for the quantitative analysis of an antigen contained in a liquid, said device comprising a fiber which transmits electromagnetic radiation, which is formed of a material containing an antibody Ab for the antigen bonded to a compound Y in the form of a complex Ab-Y and, said compound Y having an energy-modifying characteristic which changes upon immuno-bonding of the antigen to the antibody Ab, and a sheath, permeable to the antigen, surrounding said fiber, whereby the modification of transmitted radiation resulting from the presence of said energy-modifying compound Y is cumulative along the length of said fiber.

19. The device of claim 18 wherein Y is a dye which produces modification of the transmitted energy by absorption.

20. The device of claim 18 comprising a plurality of said fiber-sheath elements, said elements containing different amounts of Y.

21. The device of claim 18 wherein said fiber is selectively permeable to said antigen.

22. A device for the quantitative analysis of an enzyme in a liquid sample, said device comprising a fiber-sheath element including a fiber which transmits electromagnetic radiation, a sheath surrounding said fiber and formed of a hydrophilic polymer and an energy-modifying compound Y incorporated into and chemically bound to said polymer, said chemical bond being selectively degradable by the enzyme to be detected, said fiber being permeable to Y, whereby the modification of transmitted radiation resulting from the presence of energy-modifying compound Y is cumulative along the length of said fiber.

23. The device of claim 22 wherein Y is a dye which produces modification of the transmitted energy by absorption.

24. The device of claim 22 comprising a plurality of said fiber-sheath elements, said elements containing different amounts of Y.

25. An optical fiber device for the quantitative analysis of an analyte contained in a fluid, said device comprising a plurality of fiber-sheath elements, each of said elements including (1) an electromagnetic energy transmissive fiber defining a path for transmission of electromagnetic energy, at least a portion of said fiber being formed of a material having an electromagnetic energy transmitting characteristic capable of modification by the presence of an analyte contained in the fluid;

(2) a semipermeable sheath surrounding said fiber; and

(3) a reagent which modifies said transmitted energy responsive to the presence of an analyte or which reacts with the analyte to form a product which modifies said transmitted energy, said elements containing said reagent in different amounts, whereby the modification of transmitted energy resulting from the presence of said energy-modifying reagent or product is cumulative along the length of said path in each said fiber.