Method and apparatus for rapid quantification of an analyte in breath

• US 9,689,864 B2
• Filed: 02/10/2016
• Issued: 06/27/2017
• Est. Priority Date: 02/01/2012
• Status: Active Grant

• Current Assignee: Invoy Holdings, Inc.
• Original Assignee: Invoy Technologies, LLC
• Inventors: Ahmad, Lubna M., Smith, Zachary, Satterfield, Brent C., Martineau, Rhett L., Ahmad, Salman A.
• Primary Examiner(s): WEARE, MEREDITH H
• Application Number:
  US15/040,790
• Publication Number:
  US 20160245797A1
• Time in Patent Office: 503 Days
• CPC Class Codes: A61B 2560/0443 Modular apparatus
• CPC Class Codes: A61B 5/082 Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath A61B5/083, A61B5/091 take precedence
• CPC Class Codes: A61B 5/087 Measuring breath flow
• CPC Class Codes: A61B 5/097 Devices for facilitating collection of breath or for directing breath into or through measuring devices
• CPC Class Codes: A61B 5/201 Assessing renal or kidney functions
• CPC Class Codes: A61B 5/4244 liver
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72

Abstract

A method of determining the concentration of an analyte of interest in breath. The method includes obtaining a disposable cartridge comprising a reaction chamber, a liquid chamber, and a window to permit determination of a color intensity in the reaction chamber, directing a volume of breath into the cartridge, and initiating a sequence whereby liquid is released from the liquid container into the reaction chamber to cause a reaction which produces a change in the intensity of a color viewable through the window. The intensity of the color corresponds to the concentration of the analyte of interest. The reaction progresses through a kinetic phase and eventually reaches equilibrium. The sequence additionally includes measuring the intensity of the color at a point in the kinetic phase, to determine the concentration of the analyte of interest in breath.

Claims

1. A method of determining the concentration of an analyte of interest in breath, comprising the steps of:

obtaining a disposable cartridge comprising a reaction chamber, and a window to permit determination of a color intensity in the reaction chamber, the reaction chamber comprising a dry reagent;

directing a volume of breath into the cartridge such that the volume of breath comes into contact with the dry reagent;

subsequently, initiating a sequence, under control of a processor, whereby liquid is released from a liquid container into the reaction chamber to cause a reaction which produces a change in the intensity of a color viewable through the window, the intensity of the color corresponding to the concentration of the analyte of interest, the reaction progressing through a kinetic phase and eventually reaching equilibrium;

wherein the sequence additionally comprises the step of measuring the intensity of the color at a point in the kinetic phase, to determine the concentration of the analyte of interest in breath.

2. A method of determining the concentration of an analyte as in claim 1, wherein the reaction is with an amine.

3. A method of determining the concentration of an analyte as in claim 2, wherein the amine is bound to a surface.

4. A method of determining the concentration of an analyte as in claim 3, wherein the amine is bound to a silica gel surface.

5. A method of determining the concentration of an analyte as in claim 4, wherein the amine is bound to the surface of a plurality of silica gel beads.

6. A method of determining the concentration of an analyte as in claim 5, wherein the silica gel beads have a size distribution between 270 and 100 mesh.

7. A method of determining the concentration of an analyte as in claim 5, wherein the silica gel beads have a volume of no more than 1.0 ml.

8. A method of determining the concentration of an analyte as in claim 1, wherein the liquid released from the liquid container comprises a nitroprusside solution.

9. A method of determining the concentration of an analyte as in claim 8, wherein no more than 1 ml of liquid is released from the liquid container.

10. A method of determining the concentration of an analyte as in claim 9, wherein no more than 0.5 ml of liquid is released from the liquid container.

11. A method of determining the concentration of an analyte as in claim 1, wherein prior to the release of liquid step the reaction chamber comprises an alkaline environment.

12. A method of determining the concentration of an analyte as in claim 1, further comprising the step of removing water vapor from the volume of breath.

13. A method of determining the concentration of an analyte as in claim 1, wherein the step of measuring the intensity of the color is accomplished within six minutes following the initiating step.

14. A method of determining the concentration of an analyte as in claim 13, wherein the step of measuring the intensity of the color is accomplished using a camera.

15. A method of determining the concentration of an analyte as in claim 14, comprising using the camera to view information carried by the cartridge in addition to the color intensity.

16. A method of determining the concentration of an analyte as in claim 15, comprising using the camera to view both color intensity as well as a barcode.

17. A method of determining the concentration of an analyte as in claim 15, comprising using the camera to view both color intensity as well as an indication of expiration date.

18. A method of determining the concentration of an analyte as in claim 1, wherein the step of measuring the intensity of the color is accomplished within four minutes following the initiating step.

19. A method of determining the concentration of an analyte as in claim 1, wherein the analyte comprises acetone.

20. A method of determining the concentration of an analyte as in claim 1, wherein the analyte comprises ammonia.

21. A portable breath analysis system, comprising:

a disposable cartridge comprising a reaction chamber that holds a dry reactant material, the disposable cartridge including a window that enables a color change in the reaction chamber to be sensed from outside the disposable cartridge, the reaction chamber fluidly coupled to a breath input port such that a breath sample received through the breath input port is exposed to the dry reactant material; and

a base unit comprising an optical sensor and a processor, the base unit configured to receive the disposable cartridge and to initiate a chemical reaction in which a liquid reagent is released into the reaction chamber after the breath sample is exposed to the dry reactant material, the chemical reaction having a kinetic phase in which a color changes at a rate that depends upon a concentration of an analyte in the breath sample, the optical sensor positioned to sense the color change through the window;

wherein the processor is programmed to use the optical sensor to measure a color intensity during the kinetic phase of the chemical reaction, and to use the measured color intensity to estimate the concentration of the analyte in the breath sample.

22. The portable breath analysis system of claim 21, wherein the disposable cartridge further comprises a liquid container that holds the liquid reagent prior to its release into the reaction chamber.

23. The portable breath analysis system of claim 22, wherein the liquid container holds no more than 1 ml of the liquid reagent.

24. The portable breath analysis system of claim 22, wherein the liquid container holds no more than 0.5 ml of the liquid reagent.

25. The portable breath analysis system of claim 21, wherein the optical sensor comprises a camera.

26. The portable breath analysis system of claim 21, wherein the processor is programmed to measure the color intensity with the optical sensor at a predetermined time after the liquid reagent is released into the reaction chamber, the predetermined time selected to fall within the kinetic phase.

27. The portable breath analysis system of claim 21, wherein the processor is programmed to measure the color intensity at multiple points in time during the kinetic phase.

28. A process for measuring an analyte concentration in a breath sample, the process comprising:

initiating a chemical reaction in which a liquid reagent is brought into contact with a dry reactant exposed to the breath sample, wherein the chemical reaction causes a color to be produced at a rate that is dependent upon a concentration of the analyte in the breath sample;

generating, with an optical sensor during a kinetic phase of the chemical reaction, a measurement representing a rate of change of color production resulting from the chemical reaction; and

estimating the analyte concentration in the breath sample based on the measurement;

wherein the process is performed under control of a processor.

29. The process of claim 28, wherein the dry reactant comprises interactant beads.

30. The process of claim 29, wherein the processor additionally regulates a flow rate at which the breath sample is exposed to the interactant beads.

31. The process of claim 28, wherein generating the measurement comprises taking multiple color measurements.

32. The process of claim 28, wherein estimating the analyte concentration comprises using a calibration curve of color production rate versus analyte concentration.

33. The process of claim 28, wherein the optical sensor comprises a camera.

34. The process of claim 28, wherein the optical sensor comprises a semiconductor photodetector.

35. The process of claim 28, wherein the chemical reaction occurs inside a reaction chamber of a disposable cartridge, and the measurement is generated by a base unit that receives the disposable cartridge.

36. A breath analysis device, comprising:

a breath input port coupled to a flow path;

a dry interactant material housed within a reactive region of the flow path such that a breath sample that passes along the flow path is exposed to the dry interactant material;

an optical sensor configured to measure a color change produced by a chemical reaction in which a liquid reactant is brought into contact with the dry interactant material after the interactant material is exposed to the breath sample; and

a processor programmed to estimate a concentration of an analyte in the breath sample by using the optical sensor to generate a measurement reflective of a rate of color change produced by the chemical reaction, said rate of color change being dependent upon the analyte concentration, wherein the chemical reaction is initiated under control of the processor.

37. The breath analysis device of claim 36, wherein the processor is programmed to use the optical sensor to generate the measurement during a kinetic phase of the chemical reaction.

38. The breath analysis device of claim 36, wherein the processor is programmed to use the optical sensor to measure a color intensity at multiple points in time during a kinetic phase of the chemical reaction.