Portable sampling device and method for detection of biomarkers in exhaled breath

• US 10,359,417 B2
• Filed: 03/08/2013
• Issued: 07/23/2019
• Est. Priority Date: 03/08/2012
• Status: Active Grant

• Current Assignee: Sensa Bues AB
• Original Assignee: Sensa Bues AB
• Inventors: Hammarlund, Bo, Beck, Olof
• Primary Examiner(s): Roberts, Herbert K
• Application Number:
  US14/383,846
• Publication Number:
  US 20150033824A1
• Time in Patent Office: 2,328 Days
• 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: 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

A portable method and sampling device for collecting aerosols comprising biomarkers from exhaled breath of a subject for further sensor based analysis. The sampling device (41) comprising a housing (406) comprising at least one inlet (407) and at least one outlet (408) for the exhaled breath to exit through, and a sampling membrane arranged in the housing. The sampling membrane is arranged to collect the aerosols from said exhaled breath.

Claims

1. A method of detecting biomarkers from exhaled breath of a subject, comprising:

collecting a sample of aerosols from a deep breath reaching exhaled breath from central or peripheral lung regions in a sampling membrane arranged in a handheld and portable collection device, the collection device includes a chamber made from two parts jointed together for the exhaled breath to be exhaled through, wherein the sampling membrane comprises at least two layers, and wherein at least one layer is gas permeable and another layer is an electrostatic non-woven filter, the sampling membrane is arranged transversal to a flow of exhaled breath in the chamber to collect said aerosols from the exhaled breath, and wherein said sampling membrane is configured for a low pressure drop through said handheld and portable collection device for said subject to exhale through said handheld and portable device un-aided, so that said exhaled breath flows unaided from an inlet to an outlet of said device;

the device further comprises a detachable tubular element having a lumen in flow connection with the inlet of the collection device;

wherein the tubular element is formed by two opposite parts, each part having at least one baffle such that when connected the tubular element comprises at least two baffles arranged on opposite sides of said lumen to provide a non-straight path through the tubular element, said baffles protrude into said lumen at a distance larger than a radius of said lumen;

the device further comprises a volume measure unit for determining that a pre-defined volume of said exhaled breath has passed through said sampling membrane, wherein the volume measure unit is connected through a port in the tubular element, and wherein said volume measuring unit is a non-elastic bag with a predetermined volume;

sealing said inlet and said outlet by mounting plugs in the inlet and the outlet for transportation;

extracting a content from said sampling membrane, wherein said content is extracted from said sampling membrane using a solvent; and

employing a sensor unit for detecting traces of biomarkers in said content, wherein said sensor unit performs an analyzing method based on liquid chromatography mass-spectroscopy (LC/MS).

2. The method of claim 1, comprising investigating a health status of a subject based on an analysis of said traces of biomarkers.

3. The method of claim 2, wherein said investigating comprises diagnosing a medical condition of said subject, and said method further includes diagnosing said subject based on a measurement signal or result obtained from said sensor unit related to said biomarkers.

4. The method according to claim 1, including measuring a pre-defined fraction of said exhaled breath volume for determining a specific total volume of said exhaled breath passing through said sampling membrane, and when said specific total volume is determined as having passed through said sampling membrane terminating said exhalation.

5. The method according to claim 1, further comprising sending the collection device to a lab for extracting said content.

6. The method according to claim 1, including performing on-site analysis.

7. The method according to claim 1, wherein said sampling membrane comprises at least one further layer being a spunbonded carrier with a scrim weight of 10 to 20 g/m³.

8. The method according to claim 1, wherein said sampling membrane has a filter surface to be passed by exhaled gas of approximately 800 mm² and a pressure drop of 36 Pa at 9.5 m/min media velocity.

9. The method according to claim 1, wherein said sampling membrane is made of a blend of acrylic fibers and polypropylene fibers.

10. The method according to claim 1, wherein

the at least two baffles form a selective trap section that permits aerosols in said exhaled breath to pass through said tubular element.

11. The method according to claim 10, wherein each baffle comprises orifices with a size that only permit said aerosols to pass through.

12. The method according to claim 1, wherein said aerosols comprise non-volatile biomarkers in said exhaled breath;

wherein said aerosols comprise non-volatile compounds of at least one biomarker in said exhaled breath and wherein said biomarker is comprised in the list comprising lipids, peptides, nucleotides, prostanoids, proteins, DNA or RNA.

13. A portable sampling device for collecting aerosols comprising biomarkers from exhaled breath of a subject for further sensor based analysis, comprising:

a housing configured to be handheld comprising at least one inlet and at least one outlet for said exhaled breath to exit through, the housing includes a chamber made from two parts jointed together for the exhaled breath to be exhaled through and a sampling membrane comprising at least two layers, wherein at least one layer is gas permeable and another layer is an electrostatic non-woven filter, the sampling membrane being arranged transversal to a flow of exhaled breath in the chamber to collect said aerosols from the exhaled breath;

plugs to be mounted in the inlet and the outlet for transportation of the device; and

wherein said sampling membrane is a fiber based filter membrane, wherein said filter membrane comprises at least one layer of non-woven filtration media arranged transversal to the flow of exhaled breath in said chamber to collect said aerosols from said exhaled breath and wherein said sampling membrane is configured for a low pressure drop through said portable sampling device for allowing said subject to exhale through said handheld and portable device un-aided from the inlet to the outlet of said device; and

wherein a content in said sampling membrane is extractable from said sampling membrane using a solvent for analysis with liquid chromatography-mass-spectroscopy;

wherein the device further comprises a detachable tubular element having a lumen in flow connection with the inlet to the chamber;

wherein the tubular element is formed by two opposite parts, each part having at least one baffle, which when connected comprises at least two baffles arranged on opposite sides of said lumen to provide a non-straight path through the tubular element, said baffles protrude into said lumen at a distance larger than a radius of said lumen;

the device further comprises a volume measure unit for determining that a pre-defined volume of said exhaled breath has passed through said sampling membrane, wherein the volume measure unit is connected through a port in the tubular element; and

wherein said volume measure unit is a non-elastic bag with a predetermined volume.

14. The device according to claim 13, wherein the tubular element comprises a mouthpiece section for said subject to exhale into, and a selective trap section in fluid communication with said mouthpiece and said inlet of said housing, said selective trap section has the non-straight path for letting primarily aerosols pass through said tubular element.

15. The device according to claim 13, wherein said sampling membrane comprises at least one further layer being a spunbonded carrier with a scrim weight of 10 to 20 g/m³.

16. The device according to claim 13, wherein said sampling membrane has a filter surface to be passed by exhaled gas of approximately 800 mm² and a pressure drop of 36 Pa at 9.5 m/min media velocity.

17. The device according to claim 13, wherein said sampling membrane is made of a blend of acrylic fibers and polypropylene fibers.

18. The device according to claim 13, wherein said housing has at least two outlets.

19. The device according to claim 13, wherein each baffle defines orifices with a size that only permit said aerosols to pass through.

20. The device according to claim 13, wherein said aerosols comprise non-volatile biomarkers in said exhaled breath;

wherein said aerosols comprise non-volatile compounds of at least one biomarker in said exhaled breath and wherein said biomarker is comprised in the list comprising lipids, peptides, nucleotides, prostanoids, proteins, DNA or RNA.

21. A method for non-invasive sampling of exhaled breath for diagnosis of diseases or illnesses, comprising sampling said exhaled breath using a portable sampling device as recited in claim 13.

22. A system for diagnosing a patient by detecting a presence and/or determining a quantitative amount of at least one biomarker in exhaled breath, said system comprising the device of claim 13 and a sensor unit for analyzing a sample collected from exhaled breath of a subject by means of said device, wherein said sensor unit performs an analyzing method based on liquid chromatography mass-spectroscopy (LC/MS).

23. The method according to claim 21, wherein said diseases or illnesses comprise cancer, inflammation, infection and/or oxidative stress.