Breath analysis systems and methods for asthma, tuberculosis and lung cancer diagnostics and disease management

• US 10,568,541 B2
• Filed: 11/30/2009
• Issued: 02/25/2020
• Est. Priority Date: 12/01/2008
• Status: Active Grant

• Current Assignee: Tricorntech Corp.
• Original Assignee: Tricorntech Taiwan
• Inventors: Wang, Li-Peng, Young, Chi-Lin, Huang, Chien-Lin, Chou, Tsung-Kuan A.
• Primary Examiner(s): Jang, Christian
• Assistant Examiner(s): Toth, Karen E
• Application Number:
  US12/628,126
• Publication Number:
  US 20100137733A1
• Time in Patent Office: 3,739 Days
• Field of Search: 600529-543
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 5/08 Detecting, measuring or recording devices for evaluating the respiratory organs A61B5/0205 takes precedence
• 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 5/097 Devices for facilitating collection of breath or for directing breath into or through measuring devices
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: G01N 2030/025 Gas chromatography
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: G01N 33/4975 other than oxygen, carbon dioxide or alcohol, e.g. organic vapours

Abstract

Methods and systems are disclosed for the detecting of whether a subject has a lung disorder such as asthma, tuberculosis or lung cancer. Monitoring the subject'"'"'s health and prognosis is also disclosed.

Claims

1. A method for detecting whether a subject has a respiratory disease or monitoring a subject with a respiratory disease said method comprising:

receiving, at a portable apparatus having a gas chromatograph coupled to a detector array, ambient air to be inhaled by said subject, wherein the portable apparatus includes the gas chromatograph and the detector array replaceably mounted to a substrate of the portable apparatus;

filtering, by a volatile organic compound (VOC) filter, the ambient air to remove at least a portion of background VOC content in the ambient air;

further filtering, by a nitric oxide (NO) filter, the ambient air to remove at least a portion of background NO content from the ambient air;

providing, at the portable apparatus, at least a portion of the ambient air to said subject to be inhaled;

receiving, at the portable apparatus, breath exhaled from said subject;

contacting the breath exhaled from said subject with the gas chromatograph mounted to the substrate of the portable apparatus;

producing, by the detector array coupled to the gas chromatograph and mounted to the substrate of the portable apparatus, an indicator based on the exhaled breath from said subject, the indicator being produced based at least in part on one or more analytes in the breath exhaled from said subject, and the indicator being indicative of one or more biomarkers in the exhaled breath; and

analyzing, by an analysis circuit disposed on said portable apparatus, said indicator to determine whether said subject has asthma, wherein the determination is made based on an NO concentration level in conjunction with VOC detection from the breath exhaled from said subject.

2. The method of claim 1, wherein analyzing said produced indicator includes determining a severity level of the asthma.

3. The method of claim 1, further comprising:

detecting whether the exhaled breath of said subject contains NO or VOCs.

4. The method of claim 1, wherein said VOC is one of a group consisting of 4-methyloctane, 2,4-dimethylheptane, isopropanol, toluene, isoprene, alkane, acetic, acetone, 2,6,11-trimethyl dodecane, 3,7-dimethyl undecane, 2,3-dimethyl heptane and a combination thereof.

5. The method of claim 1, further comprising:

obtaining, by the portable apparatus, periodic breath samples to monitor an efficacy of a therapeutic.

6. The method of claim 1, wherein the portable apparatus further includes a spirometer and a preconcentrator mounted thereon, and wherein the method further comprises:

measuring or controlling, by the spirometer, a volume and speed of airflow from the breath of said subject; and

increasing, by the preconcentrator, a concentration of the one or more analytes in the breath exhaled from said subject.

7. The method of claim 6, wherein exhaled breath from said subject includes a flow rate, and wherein the spirometer adjusts the flow rate of the exhaled breath.

8. The method of claim 1, wherein the breath exhaled from said subject is received via a ventilator in fluid communication with a lung of said subject.

9. The method of claim 6, wherein said preconcentrator contains a substance having affinity for NO and VOCs.

10. The method of claim 1, further comprising:

monitoring, by the portable apparatus, the ambient air;

presenting an environmental warning to said subject when a baseline concentration level of the background VOC content in the ambient air is above a threshold level.

11. The method of claim 1, further comprising:

determining a baseline concentration level of both background NO content and background VOC content in the ambient air; and

saving the baseline concentration level, wherein the indicator is produced by subtracting the baseline concentration level from output data associated with breath exhaled from said subject.

12. The method of claim 1, wherein said detector array comprises a MEMS sensor array.

13. The method of claim 1, wherein the produced indicator is analyzed via a pattern recognition algorithm.

14. The method of claim 1, wherein said detector array is removable and replaceable.

15. The method of claim 6, wherein said preconcentrator and the gas chromatograph are disposable.

16. The method of claim 15, wherein said portable apparatus further comprises a mouthpiece, and wherein the mouthpiece is removable, replaceable, and disposable.

17. The method of claim 1, wherein analyzing the produced indicator includes determining a level of the one or more biomarkers present in the breath from said subject.

18. The method of claim 1, wherein the detector array includes at least one of an acoustic resonator or a resistive sensor with a surface coating, wherein the surface coating is capable of absorbing or chemically interacting with one or more biomarkers present in the exhaled breath.

19. The method of claim 1, further comprising:

providing a quantitative assessment of asthma based on the analysis of the produced indicator.

20. The method of claim 1, wherein the breath exhaled from the subject is associated with a fluid, and wherein the method further comprises:

separating, by the gas chromatograph on the portable apparatus, individual chemicals in the fluid in a time domain such that different chemicals are separately outputted by the gas chromatograph across time, wherein the indicator is produced based on the individual chemicals in the fluid.

23. The method of claim 6, wherein the one or more analytes in the breath exhaled from said subject includes one or more VOCs, wherein the preconcentrator includes an adsorbent material that has an affinity for one or more VOCs, and wherein increasing the concentration of the one or more analytes includes heating the preconcentrator to desorb the one or more VOCs.

26. The method of claim 1, wherein the gas chromatograph and the detector array are replaceably mounted to the substrate of the portable apparatus via one or more sockets of the substrate, wherein the substrate is a printed circuit board, and wherein the one or more sockets includes a zero insertion force (ZIF) socket.

21. A portable apparatus comprising:

a substrate;

a volatile organic compound (VOC) filter configured to filter ambient air received at the portable apparatus to remove at least a portion of background VOC content in the ambient air;

a nitric oxide (NO) filter configured to further filter the ambient air to remove at least a portion of background NO content from the ambient air prior to the ambient air being inhaled by a subject;

a gas chromatograph replaceably mounted on the substrate, the gas chromatograph configured to receive a fluid associated with breath exhaled from a subject and separates individual chemicals in the fluid;

a preconcentrator configured to increase a concentration of one or more analytes in the breath exhaled from said subject;

a detector array replaceably mounted on the substrate, the detector array configured to receive the individual chemicals from the gas chromatograph and produces an indicator based on the received individual chemicals, the indicator being produced based at least in part on the one or more analytes in the breath exhaled from said subject, and the indicator being indicative of one or more biomarkers in the exhaled breath; and

an analyzer configured to analyze the produced indicator and determine an NO concentration level in conjunction with one or more VOCs from the breath exhaled from said subject.

22. The apparatus of claim 21, wherein the gas chromatograph separates individual chemicals in the fluid in a time domain such that different chemicals are separately outputted by the gas chromatograph across time.

24. The apparatus of claim 21, wherein the portable apparatus further includes one or more sockets mounted to the substrate, and wherein the detector array and the gas chromatograph are mounted to the substrate via the one or more sockets mounted to the substrate.

25. The apparatus of claim 24, wherein the substrate is a printed circuit board, and wherein the one or more sockets includes a zero insertion force (ZIF) socket.

27. A method for detecting whether a subject has a respiratory disease or monitoring a subject with a respiratory disease said method comprising:

receiving, at a handheld apparatus having a gas chromatograph coupled to a detector array, breath exhaled from said subject, wherein the handheld apparatus includes the gas chromatograph and the detector array replaceably mounted to a substrate of the handheld apparatus;

increasing, by a preconcentrator on the handheld apparatus, a concentration of one or more analytes in the breath exhaled from said subject;

contacting the increased concentration of the one or more analytes with the gas chromatograph mounted to the substrate of the handheld apparatus;

producing, by the detector array on the handheld apparatus, an indicator based on the exhaled breath from said subject, the indicator being produced based at least in part on the one or more analytes in the breath exhaled from said subject, and the indicator being indicative of one or more biomarkers in the exhaled breath; and

analyzing, by an analysis circuit disposed on said handheld apparatus, said produced indicator to determine whether said subject has the respiratory disease, wherein the determination is made based on an NO concentration level in conjunction with VOC detection from the breath exhaled from said subject.

28. The method of claim 27, further comprising:

determining a level of background VOC content; and

communicating a warning alert to the subject when the level of background VOC content exceeds a threshold level.