Sensors and methods for sensing

• US 5,498,549 A
• Filed: 01/18/1995
• Issued: 03/12/1996
• Est. Priority Date: 08/08/1991
• Status: Expired due to Term

• Current Assignee: Terumo Cardiovascular Systems Corporation (Terumo Corporation)
• Original Assignee: 3M Company
• Inventors: Nagel, Colleen C., Kipke, Cary A., Bentsen, James G., Katritzky, Alan R., Yafuso, Masao, Dektar, John L.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Le, Long V.
• Application Number:
  US08/373,855
• Time in Patent Office: 419 Days
• Field of Search: 436/172, 436/68, 436/136, 436/138, 436/178, 422/82.05, 422/82.11, 422/86, 422/55, 422/58
• US Class Current: 436/172
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: C07F 7/0838 Compounds with one or more Si-O-Si sequences compounds with a ring containing only alternating Si and O atoms, i.e. cyclosilanes C07F7/21
• CPC Class Codes: C08G 77/38 Polysiloxanes modified by chemical after-treatment C08G77/045 takes precedence
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 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
• 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 31/225 for oxygen, e.g. including dissolved oxygen
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A sensor for measuring the concentration of an analyte in a medium is disclosed. In one embodiment, the sensor comprises a sensing element including a matrix material and, covalently bonded thereto, one or more monomeric indicator components each of which is capable of providing a first emitted signal of a given wavelength in response to being exposed to an excitation signal. The sensing element is capable of providing a second emitted signal having a longer wavelength than the first emitted signal or signals in response to being exposed to the excitation signal, the second emitted signal being provided by an excimer component produced in the sensing element from the monomeric indicator component(s) and being dependent on the concentration of the analyte in the medium to a greater extent than the first emitted signal or signals. In another embodiment, the sensor comprises a sensing element including two or more different monomeric components at least one or which is a monomeric indicator component capable of providing a first emitted signal in response to being exposed to a first excitation signal. The sensing element is capable of providing a second emitted signal in response to being exposed to a second excitation signal. This second emitted signal is provided by an exciplex produced from the monomeric components. This second emitted signal is preferably dependent on the concentration of the analyte in the medium. An excitation assembly is positioned and adapted to provide the excitation signal to the sensing element. A detector assembly is positioned and adapted to detect the second emitted signal. Preferably, a processor assembly is positioned and adapted to analyze the second emitted signal in determining the concentration of the analyte in the medium.

Claims

1. A method for sensing the concentration of an analyte in a medium comprising the steps of:

exposing a sensing element to said medium, said sensing element comprising an analyte permeable matrix material and an indicator component in said matrix material comprising at least two monomeric components in enforced association, at least one of which is a monomeric indicator component which provides a first emitted signal or signals in response to being exposed to a first excitation signal, said sensing element further comprising, when exposed to said first excitation signal, an excited state complex produced from said at least two monomeric components, said excited state complex providing a second emitted signal which is dependent on the concentration of said analyte in said medium;

causing said sensing element to provide said first emitted signal or signals and said second emitted signal; and

analyzing said second emitted signal in determining the concentration of said analyte in said medium.

2. The method of claim 1, wherein said analyzing step includes determining an intensity ratio of said second emitted signal to said first emitted signal or at least one of said first emitted signals, said intensity ratio being dependent on the concentration of said analyte in said medium.

3. The method of claim 1, wherein said first emitted signal or at least one of said first emitted signals and said second emitted signal are modulated, and at least one of:

an extent of a phase shift between a modulated second excitation signal and said modulated second emitted signal;

or an extent of a phase shift between said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or an extent of a phase shift between a combined modulated first and second emitted signals and said first excitation signal or signals;

or a magnitude of relative demodulation between said modulated second excitation signal and said modulated second emitted signal;

or a ratio of demodulation factors of said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or a magnitude of relative demodulation between a combined modulated first emitted signal or signals and the modulated second emitted signal;

or a excitation frequency necessary to maintain a fixed phase shift between said modulated first and second emitted signals is dependent on the concentration of said analyte in said medium and wherein a processor assembly is adapted to determine at least one of said phase shift, said demodulation factor, or said excitation frequency.

15. The method of claim 1, wherein said at least two monomeric components are covalently bonded together.

16. The method of claim 1, wherein said at least two monomeric components are different and said produced excited state complex is an exciplex component.

17. The method of claim 1, wherein said indicator component is covalently bonded to said solid matrix material.

18. The method of claim 1, wherein said monomeric components in enforced association are selected from the group consisting of intramolecular excited state complex forming molecules dispersed in a matrix material, intramolecular excited state complex forming molecules covalently attached, adsorbed or otherwise attached to the surface of a matrix material, intramolecular excited state complex forming molecules covalently attached to a matrix material, monomeric component aggregates covalently attached to a matrix material, monomeric component aggregates adsorbed to the surface of a matrix material, an inclusion complex comprising a supra-molecule, and ionically bound monomeric components.

26. The method of claim 1, wherein said analyte comprises oxygen, said medium comprises blood, and said matrix comprises a silicone material.

27. The method of claim 1, wherein said indicator component comprises a polynuclear aromatic compound.

28. The method of claim 1, wherein said indicator component comprises a polynuclear aromatic compound selected from the group consisting of perylene, decacyclene, benzoperylene, coronene, pyrene, porphycine, porphyrin, chlorin, phthalocyanine and derivatives and mixtures thereof.

4. A method for sensing the concentration of an analyte in a medium comprising the steps of:

exposing a sensing element to said medium, said sensing element comprising an analyte permeable matrix material and at least two different monomeric components at least one of which is a monomeric indicator component which provides a first emitted signal or signals in response to being exposed to a first excitation signal, said sensing element further comprising, when exposed to said first excitation signal, an exciplex component produced from said at least two monomeric components, said exciplex component providing a second emitted signal which is dependent on the concentration of said analyte in said medium wherein at least one of said monomeric components is covalently bonded to said matrix material;

causing said sensing element to provide said first emitted signal or signals and said second emitted signal; and

analyzing said first emitted signal or signals and said second emitted signal in determining the concentration of said analyte in said medium.

5. The method of claim 4, wherein said analyzing step includes determining an intensity ratio of said second emitted signal to said first emitted signal or at least one of said first emitted signals, said intensity ratio being dependent on the concentration of said analyte in said medium.

6. The method of claim 4, wherein said first emitted signal or at least one of said first emitted signals and said second emitted signal are modulated, and at least one of:

an extent of a phase shift between a modulated second excitation signal and said modulated second emitted signal;

or an extent of a phase shift between said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or an extent of a phase shift between a combined modulated first and second emitted signals and said first excitation signal or signals;

or a magnitude of relative demodulation between said modulated second excitation signal and said modulated second emitted signal;

or a ratio of demodulation factors of said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or a magnitude of relative demodulation between a combined modulated first emitted signal or signals and the modulated second emitted signal;

or an excitation frequency necessary to maintain a fixed phase shift between said modulated first and second emitted signals is dependent on the concentration of said analyte in said medium and wherein a processor assembly is adapted to determine at least one of said phase shift, said demodulation factor, or said excitation frequency.

19. The method of claim 4, wherein at least two of said monomeric components are covalently bonded to said matrix material.

20. The method of claim 4, wherein said at least two different monomeric components are covalently bonded together.

7. A method for sensing the concentration of an analyte in a medium comprising the steps of:

exposing a sensing element to said medium, said sensing element comprising an analyte permeable matrix material and at least two different monomeric components at least one of which is a monomeric indicator component which provides a first emitted signal or signals in response to being exposed to a first excitation signal, said sensing element further comprising, when exposed to said first excitation signal, an exciplex component produced from said at least two monomeric components, said exciplex component providing a second emitted signal which is dependent on the concentration of said analyte in said medium, and wherein a total integrated intensity at the wavelength of the second emitted signal has less than ten percent contribution due to monomer emission;

causing said sensing element to provide said first emitted signal or signals and said second emitted signal; and

analyzing said first emitted signal or signals and said second emitted signal in determining the concentration of said analyte in said medium.

8. The method of claim 7, wherein said analyzing step includes determining an intensity ratio of said second emitted signal to said first emitted signal or at least one of said first emitted signals, said intensity ratio being dependent on the concentration of said analyte in said medium.

9. The method of claim 7, wherein said first emitted signal or at least one of said first emitted signals and said second emitted signal are modulated, and at least one of:

an extent of a phase shift between a modulated second excitation signal and said modulated second emitted signal;

or an extent of a phase shift between said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or an extent of a phase shift between a combined modulated first and second emitted signals and said first excitation signal or signals;

or a magnitude of relative demodulation between said modulated second excitation signal and said modulated second emitted signal;

or a ratio of demodulation factors of said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or a magnitude of relative demodulation between a combined modulated first emitted signal or signals and the modulated second emitted signal;

or an excitation frequency necessary to maintain a fixed phase shift between said modulated first and second emitted signals is dependent on the concentration of said analyte in said medium and wherein a processor assembly is adapted to determine at least one of said phase shift, said demodulation factor, or said excitation frequency.

21. The method of claim 7, wherein said at least two different monomeric components are linked by less than 20 atoms.

29. The method of claim 7, wherein said exciplex component comprises at least one polynuclear aromatic monomeric component selected from the group consisting of biphenyl, naphthalene, phenanthrene, p-terphenyl, chrysene, benzpyrene, pyrene, dibenzanthrene, benzanthrene, anthracene, perylene, benzperylene, fluoranthene, coronene, quinoline, phenylquinoline, benzquinoline, quinoxaline, dibenzquinoxaline, benzquinoxaline, phthalimide, pyridine, phenazine, dibenzphenzine, acridine, benzacridine and derivatives of these compounds and at least one monomeric component selected from the group consisting of tetramethyl-p-phenylenediamine, dimethoxydimethylaniline, methoxydimethylaniline, diethylaniline, diphenylmethylamine, triethylamine, indole, dimethyltoluidine, tri-p-anisylamine, ditolylmethylamine, tritolylamine, triphenylamine, ethylcarbazole, trimethoxybenzene, tetramethoxybenzene and derivatives of these compounds.

30. The method of claim 7, wherein said exciplex component comprises at least one polynuclear aromatic monomeric component and at least one aliphatic or aromatic amine-containing or aromatic ether-containing monomeric component.

31. The method of claim 7, wherein said exciplex component comprises at least one aromatic nitrite monomeric component and at least one monomeric component selected from the group consisting of polynuclear aromatic monomeric components, aliphatic or aromatic amine-containing or aromatic ether-containing monomeric components.

10. A method for sensing the concentration of an analyte in a medium comprising the steps of:

exposing a sensing element to said medium, said sensing element comprising an analyte permeable matrix material and at least two monomeric components at least one of which is a monomeric indicator component which provides a first emitted signal or signals in response to being exposed to a first excitation signal, said sensing element further comprising, when exposed to said first excitation signal, an excited state complex produced from said at least two monomeric components, said excited state complex providing a second emitted signal having a longer wavelength than said first emitted signal and being dependent on the concentration of said analyte in said medium wherein at least one of said monomeric components is covalently bonded to said matrix material;

causing said sensing element to provide said first emitted signal or signals and said second emitted signal; and

analyzing said first emitted signal or signals and said second emitted signal in determining the concentration of said analyte in said medium.

11. The method of claim 10, wherein said analyzing step includes determining an intensity ratio of said second emitted signal to said first emitted signal or at least one of said first emitted signals, said intensity ratio being dependent on the concentration of said analyte in said medium.

12. The method of claim 10, wherein said first emitted signal or at least one of said first emitted signals and said second emitted signal are modulated, and at least one of:

an extent of a phase shift between a modulated second excitation signal and said modulated second emitted signal;

or an extent of a phase shift between said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or an extent of a phase shift between a combined modulated first and second emitted signals and said first excitation signal or signals;

or a magnitude of relative demodulation between said modulated second excitation signal and said modulated second emitted signal;

or a ratio of demodulation factors of said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or a magnitude of relative demodulation between a combined modulated first emitted signal or signals and the modulated second emitted signal;

or an excitation frequency necessary to maintain a fixed phase shift between said modulated first and second emitted signals is dependent on the concentration of said analyte in said medium and wherein a processor assembly is adapted to determine at least one of said phase shift, said demodulation factor, or said excitation frequency.

22. The method of claim 10, wherein said at least two monomeric components are covalently bonded together or to said matrix material.

23. The method of claim 10, wherein said at least two monomeric components are different and said produced excited state complex is an exciplex component.

13. A method for sensing the concentration of an analyte in a medium comprising the steps of:

exposing a sensing element to said medium, said sensing element comprising at least two monomeric components, at least one of which is a monomeric indicator component which provides a first emitted signal or signals in response to being exposed to a first excitation signal, said sensing element further comprising, when exposed to said first excitation signal, an excited state complex produced from said at least two monomeric components, said excited state complex providing a second emitted signal;

causing said sensing element to provide said first emitted signal or signals and said second emitted signal; and

analyzing said first emitted signal or signals and said second emitted signal in determining the concentration of said analyte in said medium, wherein said first emitted signal or at least one of said first emitted signals and said second emitted signal are modulated, and at least one of;

an extent of a phase shift between a modulated second excitation signal and said modulated second emitted signal;

or an extent of a phase shift between said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or an extent of a phase shift between a combined modulated first and second emitted signals and said first excitation signal or signals;

or a magnitude of relative demodulation between said modulated second excitation signal and said modulated second emitted signal;

or a ratio of demodulation factors of said modulated first emitted signal or at least one of said modulated first emitted signals and said modulated second emitted signal;

or a magnitude of relative demodulation between a combined modulated first emitted signal or signals and the modulated second emitted signal;

or an excitation frequency necessary to maintain a fixed phase shift between said modulated first and second emitted signals is dependent on the concentration of said analyte in said medium and wherein a processor assembly is adapted to determine at least one of said phase shift, said demodulation factor, or said excitation frequency.

14. The method of claim 13, wherein said monomeric components are covalently bonded together.

24. The method of claim 13, wherein said at least two monomeric components are covalently bonded together.

25. The method of claim 13, wherein said at least two monomeric components are different and said produced excited state complex is an exciplex component.