Spectroscopic breath analysis

• US 7,300,408 B2
• Filed: 08/16/2002
• Issued: 11/27/2007
• Est. Priority Date: 08/16/2001
• Status: Expired due to Fees

• Current Assignee: Oxford University Innovation Limited (University of Oxford)
• Original Assignee: Isis Innovation Limited
• Inventors: Hancock, Graham, Peverall, Robert, Ritchie, Grant Andrew Dedman
• Primary Examiner(s): Marmor, II; Charles A.
• Assistant Examiner(s): Mallari; Patricia C
• Application Number:
  US10/486,675
• Publication Number:
  US 20040211905A1
• Time in Patent Office: 1,929 Days
• Field of Search: 73/233, 600/532
• US Class Current: 600/532
• CPC Class Codes: A61B 5/083 Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
• CPC Class Codes: G01N 21/39 using tunable lasers
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: H01J 49/04 Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components

Abstract

Methods and apparatus for the analysis of exhaled breath by spectroscopy are disclosed. An optical cavity containing the exhaled breath, typically comprising a pair of opposing high reflectivity mirrors, is used to implement a cavity enhanced absorbtion technique. Pairs of ¹²CO₂ and ¹³CO₂ absorbtion lines suitable for use in spectroscopic breath analysis are also disclosed.

Claims

1. Exhaled breath analysis apparatus for quantifying the presence of one or more target substances in exhaled breath comprising:

a cavity enhanced absorption assembly comprising an optical cavity coupled to an optical source operable to emit radiation and an optical detector configured to generate a signal representative of the intensity of radiation in said optical cavity, wherein the optical cavity is arranged to allow radiation emitted from the optical source to be repeatedly reflected and retrace its path to excite a plurality of cavity modes;

a breath collection assembly arranged to pass at least a portion of said exhaled breath into said optical cavity for illumination by said radiation; and

a data processor connected to said optical detector and adapted to quantify the presence of said one or more target substances in said optical cavity by measuring a reduction in the intensity of radiation in said optical cavity caused by variations in cavity ringdown time caused by absorption of said radiation by said target substance.

2. The apparatus of claim 1 wherein said optical source is a tunable laser.

3. The apparatus of claim 2 further comprising a frequency controller connected to said tunable laser, the frequency controller being configured to cause the optical source to repeatedly change the frequency of said radiation within a predefined range comprising one or more absorption lines of said target substances.

4. The apparatus of claim 3 wherein the frequency controller is a sweep generator adapted to cause the optical source to repeatedly sweep the frequency of said radiation across a predefined range comprising one or more absorption lines of said target substances.

5. The apparatus of claim 3 wherein said absorption lines comprise at least a first line characteristic of ¹²CO₂ and at least a second line characteristic of ¹³CO₂.

6. The apparatus of claim 5 wherein said first line has a wavelength of about 1607.634 nm and said second line has a wavelength of about 1607.501 mm.

7. The apparatus of claim 1 further comprising a blind detector having substantially the same noise characteristics as said optical detector, said blind detector being optically isolated from said radiation and connected to said data processor.

8. The apparatus of claim 7 wherein said optical detector and said blind detector are connected to said data processor by a Dicke switch, and said data processor comprises a lock-in amplifier.

9. The apparatus of claim 1 wherein the optical cavity comprises at least two opposed mirrors.

10. The apparatus of claim 1 wherein said optical cavity is configured so as to yield an effective path length of said radiation within the optical cavity of at least 10 meters.

17. The apparatus of claim 1 wherein the data processor is adapted to determine the absorption of radiation by a breath sample at the wavelengths of a ¹³CO₂ absorption line and a ¹²CO₂ absorption line selected from the list of (¹³CO₂, ¹²CO₂) absorption lines comprising:

(1596.978 nm, 1596.869 nm) (1597.241 nm, 1597.361 nm) (1597.512 nm, 1587.361 nm) (1606.997 nm, 1607.142 nm) (1607.501 nm, 1607.634 nm) (1608.014 nm, 1608.057 nm).

11. A method of quantifying the presence of one or more target substances in breath exhaled by a subject, the method comprising the steps of:

collecting said exhaled breath;

passing at least a portion of said exhaled breath into an optical cavity of a cavity enhanced absorption assembly, wherein the optical cavity is arranged to allow radiation emitted from an optical source to be repeatedly reflected and retrace its path to excite a plurality of cavity modes;

illuminating said exhaled breath in said optical cavity with radiation emitted by the optical source;

generating a signal representative of the intensity of radiation in said optical cavity by means of an optical detector coupled to said optical cavity; and

analysing said signal to quantify therefrom the presence of said one or more target substances in said optical cavity by measuring a reduction in the intensity of radiation in said optical cavity caused by variations in cavity ringdown time caused by absorption of said radiation by said target substances.

12. The method of claim 11 further comprising the step of repeatedly changing the frequency of said radiation within a predefined range comprising one or more absorption lines of said target substances.

13. The method of claim 12 wherein the step of repeatedly changing the frequency of said radiation comprises the step of repeatedly sweeping the frequency of said radiation across a predefined range comprising one or more absorption lines of said target substances.

14. The method of claim 12 wherein said absorption lines comprise at least a first line characteristic of ¹²CO₂ and at least a second line characteristic of ¹³CO₂.

15. The method of claim 14 wherein said first line has a wavelength of about 1607.634 nm and said second line has a wavelength of about 1607.501 mm.

16. The method of claim 11 further comprising the step of generating a reference signal using a blind detector substantially identical to said optical detector, said blind detector being optically isolated from said optical cavity and connected to said data processor, and using said reference signal in said step of analysing.

18. The method of claim 11 including quantifying the presence of ¹³CO₂ and ¹²CO₂ in exhaled breath by determining the absorption of radiation by a breath sample at the wavelengths of a ¹³CO₂ absorption line and a ¹²CO₂ absorption line selected from the list of (¹³CO₂, ¹²CO₂) absorption lines comprising:

(1596.978 nm, 1596,869 nm) (1597.241 nm, 1597.361 nm) (1597.512 nm, 1587.361 nm) (1606.997 nm, 1607.142 nm) (1607.501 nm, 1607.634 nm) (1608.014 nm, 1608.057 nm).

19. A method for using cavity enhanced absorption to quantify one or more target components of exhaled breath the method comprising:

passing at least a portion of said exhaled breath into an optical cavity;

illuminating said exhaled breath in said optical cavity with radiation emitted by an optical source, wherein the optical cavity is arranged to allow radiation emitted from the optical source to be repeatedly reflected and retrace its path to excite a plurality of cavity modes; and

measuring a reduction in the intensity of radiation in said optical cavity caused by variations in cavity ringdown time caused by absorption of said radiation in said optical cavity by said one or more target components of exhaled breath, thereby to quantify said one or more target components of exhaled breath.

20. A method for using cavity enhanced absorption to detect human or animal disease comprising quantifying one or more target components in breath exhaled by a human or animal by the steps of:

passing at least a portion of said exhaled breath into an optical cavity;

illuminating said exhaled breath in said optical cavity with radiation emitted by an optical source, wherein the optical cavity is arranged to allow radiation emitted from the optical source to be repeatedly reflected and retrace its path to excite a plurality of cavity modes;

measuring a reduction in the intensity of radiation in said optical cavity caused by variations in cavity ringdown time caused by absorption of said radiation in said optical cavity by said one or more target components in said breath exhaled; and

detecting human or animal disease on the basis of the quantified one or more target components in said breath exhaled.