SE1550376A1 - Method and device for analyte sampling from exhaled breath - Google Patents

Method and device for analyte sampling from exhaled breath Download PDF

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Publication number
SE1550376A1
SE1550376A1 SE1550376A SE1550376A SE1550376A1 SE 1550376 A1 SE1550376 A1 SE 1550376A1 SE 1550376 A SE1550376 A SE 1550376A SE 1550376 A SE1550376 A SE 1550376A SE 1550376 A1 SE1550376 A1 SE 1550376A1
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Prior art keywords
capillary
analyte
adsorbent
exhaled breath
adsorbent surface
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SE1550376A
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Swedish (sv)
Inventor
Abdel Rehim Mohamed
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Abdel Rehim Mohamed
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Publication date
Application filed by Abdel Rehim Mohamed filed Critical Abdel Rehim Mohamed
Priority to SE1550376A priority Critical patent/SE1550376A1/en
Priority to PCT/SE2016/050258 priority patent/WO2016159863A1/en
Publication of SE1550376A1 publication Critical patent/SE1550376A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/497Physical analysis of biological material of gaseous biological material, e.g. breath
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/08Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/082Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/08Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/097Devices for facilitating collection of breath or for directing breath into or through measuring devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/02Devices for withdrawing samples
    • G01N1/22Devices for withdrawing samples in the gaseous state
    • G01N2001/2244Exhaled gas, e.g. alcohol detecting
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/02Devices for withdrawing samples
    • G01N1/22Devices for withdrawing samples in the gaseous state
    • G01N1/2273Atmospheric sampling
    • G01N2001/2276Personal monitors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/2813Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
    • G01N2001/2826Collecting by adsorption or absorption
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/0004Gaseous mixtures, e.g. polluted air
    • G01N33/0009General constructional details of gas analysers, e.g. portable test equipment

Abstract

A method for collecting an analyte, such a volatile compound or biomarker sample from exhaled breath, comprising the steps of providing a sampling device comprising an adsorbent surface; and contacting exhaled breath from the subject to be sampled with the adsorbent surface whereby the analyte to be sampled binds to the adsorbent surface;the sampling device comprises a capillary with the adsorbent surface coated on the inner surface thereof. A sampling device for collecting an analyte sample from exhaled breath comprising a capillary with an adsorbent surface coated on the inner surface thereof,the adsorbent surface comprises an adsorbent selected from phenyl methyl silicone, polyethylene glycol and a sol-gel of silica.

Description

METHOD AND DEVICE FOR ANALYTE SAMPLING FROM EXHALED BREATH TECHNICAL FIELD The present invention relates to the field of analyte sampling from exhaled breath.
BACKGROUND TO THE INVENTION The early diagnosis of lung cancer is a critical issue to improve survival. Today differentmethods for diagnosis are used in clinical practice, including blood tests, X-ray, computedtomography (CT), magnetic resonance imaging (I\/|R|), and positron emission tomography(PET). ln the last two decades, a huge research interest has been focused on biomarkerdiscovery for different cancer diseases. Exhaled breath is a potential source to find newbiomarkers for lung cancer. ln addition the non-invasive and safe nature of exhaled breathanalysis allows for repeated samples to be taken within short time interval withoutdiscomfort for the patients. Thus there is an enormous interest to find new methods ofbreath analysis for detecting biomarkers. lt is also of interest to capture samples fortoxicological analysis from exhaled breath, in particular markers for exposure to substancesof abuse, to environmental or occupational hazardous chemicals, and to chemical warfare agents. lt is known that a number of pathological conditions (such as asthma and lung cancer) canbe diagnosed by analysing various analytes, such as volatile compounds present in exhaledbreath from the patient to be diagnosed. ln practice however, collecting such volatilebiomarker samples from exhaled breath is not trivial. The analytesin breath are present attrace levels, which in combination with high humidity present makes the sampling, storageand transport of samples challenging, and as discussed in the recent review by Lourenco andTurner (Metabolites, 2014, 4, 465-498) major issues still remain (see Chapter 4 in Lourenco and Turner).
PCT/US2012/027778 discloses methods and devices for collecting and measuring volatileorganic compounds from breath. Briefly, the apparatus contains a solid-phasemicroextraction (SPME) fibre in a housing through which the patient to be sampled exhales.However, the binding capacity of SPME fibres is limited and the binding is slow making it difficult to collect samples directly from exhaled breath without need for an intermediate store such as a bag or a bottle. Another major disadvantage is low sensitivity of the SPMEmethod, again necessitating large volumes of sample. Additionally, in many cases the instability of the fibre is significant issue.
Trefz et al. (Anal Bioanal Chem 2013 vol 405, pages 3105-3115) describe evaluation ofneedle trap microextraction (NTME) in breath analysis. While the results were encouraging,it was concluded that several factors strongly affected the analytical results, and that allmaterials, as well as sampling and calibration procedures have to be defined before NTMEcan be applied in a practical setting. NTME requires fairly high pressure for sample application making it inpractical for collecting samples directly from exhaled breath.
Therefore, there is still need in the art for robust methods and device for sample collectionand analysis from breath samples of analytes such as volatile compounds or biomarkers. Anobject of the present invention is to provide improved and/or alternative methods and devices for sample collection and analysis from breath samples.
DEFINITIONS The term pheny/ methylsilicone refers to those silicon compounds in which two organicgroups (phenyl + methyl) and oxygen are combined with silicon [-O-SiR2R2-]n, wherein eachR; is independently selected from methyl and phenyl. An exemplary preferred phenyl methyl silicone (dimethyl diphenyl siloxane) is shown below as Formula (I) Formula (I) The term po/yethy/ene glycol refers to a chemical compound composed of repeating ethylene glycol units H-[O-C2H2-]nOH.
The term a sol-gel ofsi/ica refers to the condensation of tetraethyl orthosilicate (TEOS) after hydrolysis in water [Si(OC2H5)4+ H20 à HO-Si(OC2H5)3 + C2H5-R-OH].
BRIEF DESCRIPTION OF THE FIGURES Figure 1 depicts a schematic drawing of a sampling device ofthe invention. (1) Glass ormetal capillary (length e.g. 50-100 mm). (2) Polymeric coating (3) Inside diameter e.g. 3-5 mm.
Figure 2 depicts a schematic flowchart of a sampling method of the invention. (5)Flow (breath) inlet. (6) Flow outlet.
Figure 3. Schematic representation of desorption ofthe volatile compounds by heatedinjector into GC-MS. (7) Coated capillary liner in the injector body. (8) Heated gas chromatography injector. (9) Gas chromatography oven. (10) I\/lass spectrometer.
Figure 4 depicts exemplary chromatograms (top) and mass-spectra (bottom) of volatilecompounds captured from exhaled breath by the method and device of the invention. A) pentane; B) decane; C) acetaldehyde; and D) octane.
Figure 5 depicts the structure of an exemplary sol-gel to be coated in capillary.
SUMMARY OF THE INVENTION The present invention relates to a method and a device for sampling analytes, such asvolatile compounds from exhaled air, in particular biomarkers or compounds of toxicological or forensic interest.
Briefly, the analytes, which are typically volatile compounds are initially captured onsampling device comprising a capillary with an adsorbent surface coated on the innersurface thereof. Subsequently, the analytes may be released from the surface for analysis with any known suitable method, such as GC-MS or the like.The present invention relates to the following items: 1. A method for collecting an analyte sample from exhaled breath, comprising the steps of: a. providing a sampling device comprising a capillary with an adsorbent surface coated on the inner surface thereof; and 10. 11. b. Contacting the exhaled breath with the adsorbent surface whereby the analyte sample to be collected binds to the adsorbent surface.
The method according to any ofthe preceding items, wherein the analyte is a volatile compound.
The method according to any ofthe preceding items, wherein the analyte is a biomarker for a disease or a condition.
The method according to any ofthe preceding items, wherein the analyte is a marker of toxicological interest.
The method according to any of the preceding items, wherein the analyte is amarker for a substance of abuse, such as an opiate, a cannabinoid, an amphetamine,or cocaine, or a marker of exposure to environmental or occupational hazardous chemical, or a marker of exposure to a chemical weapon.
The method according to any ofthe preceding items, wherein the adsorbent surfacecomprises a compound selected from the groups consisting of a phenyl methyl silicone, polyethylene glycol and a sol-gel of silica.
The method according to any ofthe preceding items, wherein the analyte to besampled is selected from the group consisting of pentane, decane, acetaldehyde and OCtaHe.
The method according to any ofthe preceding items, wherein the method is furtherfor determining the amount of an analyte in a sample from exhaled breath, and comprises the step (c) of determining the amount of bound analyte.
The method according to item 8, wherein the determination step comprises the step (c') of desorbing the bound analyte from the adsorbent surface.
The method according to item 8, wherein the determination step comprises the step(c') of desorbing the bound analyte from the adsorbent surface by means of heat, preferably at 200-300°C or a solvent such as acetonitrile or methanol.
The method according to any of items 8-10, wherein the determination stepcomprises the step (c") of determining the analyte by means of GC, LC, I\/IS or a combination ofthese methods 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
The method according to item 11, wherein the determination step comprises the step (c") of determining the analyte by means of GC-MS or LC-MS.
The method according to any ofthe preceding items, wherein the sampling device is a device according to any one of items 15-31.
The method according to any ofthe preceding items, wherein the contacting stepinvolves transporting the exhaled breath through the capi||ary by the force of exhalation ofthe subject from which the breath is exhaled.
A sampling device for co||ecting an analyte sample from exhaled breath, comprising a capi||ary with an adsorbent surface coated on the inner surface thereof.
The device according to any ofthe preceding device items, characterized in that theadsorbent surface comprises an adsorbent selected from the group consisting of pheny| methy| silicone, po|yethy|ene g|yco| and a sol-gel of silica.
The device according to any of the preceding device items, wherein the adsorbent comprises pheny| methy| silicone.
The device according to any of the preceding device items, wherein the adsorbentcomprises po|yethy|ene g|yco|.The device according to any of the preceding device items, wherein the capi||ary has an inner cross-sectional dimension of 2-10 mm.
The device according to any of the preceding device items, wherein the capi||ary has an inner cross-sectional dimension of 3-5 mm.
The device according to any ofthe preceding device items, wherein the capi||ary is 1- 10 cm or 3-7 cm in length.
The device according to any of the preceding device items, wherein the capi||ary is 5- 10 cm in length.
The device according to any ofthe preceding device items, wherein the capi||ary is su bstantially straight.
The device according to any ofthe preceding device items, wherein the capi||ary comprises one or more bends or is spiral-shaped. 25. 26. 27. 28. 29. 30. 31. 32 33 The device according to any ofthe preceding device items, wherein the capillary has a circular or substantially circular inner cross-section.
The device according to any ofthe preceding device items, wherein the capillary has a circular or substantially circular outer cross-section.
The device according to any ofthe preceding device items, wherein the capillary wall has a thickness of 0.001-2 mm, 0.003-0.5 mm, or 0.005-0.1 mm.
The device according to any of the preceding device items, wherein the capillary wall comprises a glass, a metal or a plastic, preferably glass.
The device according to any of the preceding device items, wherein the adsorbent surface is 100-400 pm in thickness.
The device according to any of the preceding device items, wherein the adsorbent surface is 200-300 pm in thickness.
The device according to any of the preceding device items, wherein the device comprises a mouthpiece and/or a handle, preferably a mouthpiece.
.A method for diagnosis of a disease or condition such as cancer, in particular lung cancer, comprising detecting a biomarker by a method involving a method according to any of items 1-13.
.A method for toxicological screening, comprising detecting an analyte being a marker for chemical exposure by a method involving a method according to any of items 1-13.
DETAILED DESCRIPTION Method for collecting a sample ln a first aspect, the present invention relates to a method for collecting an analyte sample from exhaled breath of a subject, comprising the steps of: a. providing a sampling device comprising an adsorbent surface; and b. Contacting exhaled breath from the subject from which the analyte sample isbeing taken with the adsorbent surface, whereby a sample of the analyte to be collected binds to the adsorbent surface; characterized in that the sampling device comprises a capillary with an adsorbent surface coated on the inner surface thereof, to which the analyte binds.
The capillary may have any ofthe properties such as dimensions or materials discussedbelow under ”Properties of the capillary" of the device of the second aspect oftheinvention. The adsorbent surface may comprise a compound selected from: a phenyl methylsilicone, polyethylene glycol and a sol-gel of silica. Preferably, the adsorbent surfacecomprises phenyl methyl silicone or polyethylene glycol, as these adsorbents are capable ofcapturing both hydrophobic and hydrophilic analytes. Both are stable at high temperature (>250°C) and are capable of capturing analytes of interest with different polarity.
The analyte to be sampled may be any analyte present in exhaled breath, capable of bindingto the particular adsorbent present in the sampling device. The analyte to be sampled maybe a volatile compound. The analyte may be a biomarker, such as a biomarker for a diseaseor a condition. Preferably, the analyte is a biomarker for cancer, such as lung cancer, or adisease of the respiratory system, such as astma or chronic obstructive lung diseaseincluding prodromal stage thereof. The analyte may be a compound of interest fortoxicological analysis. For instance, the analyte may be a marker for substance abuse or drugoverdose, a marker for exposure to environmental or occupational hazardous substances, amarker for exposure to a chemical weapon, or the like. Preferably, the analyte is selected from pentane, decane, acetaldehyde and octane.
The method may further comprise the step (c) of determining the amount of bound analyte.The determination step may comprise the step (c') of desorbing the bound analyte from theadsorbent surface. The desorption may preferably be performed by means of heating thesampling device, preferably at 200-300°C. A distinct advantage of the capillary format (seefurther discussion below under the second aspect) ofthe sampling device used in themethod is that desorption can be conveniently achieved in a standard GC instrument byinserting the capillary into the injector chamber. Alternatively, a solvent such as acetonitrileor methanol can be used for desorption. The solvent containing the desorbed analyte can then proceed to analysis.
Preferably, the determination step comprises the step (c") of determining the analyte bymeans of gas chromatography (GC), liquid chromatography (LC), mass spectrometry (MS) ora combination ofthese methods. Use of GC-MS or LC-MS is preferred, GC-MS being themost preferred since the capillary can be inserted in the injector for convenient analyte desorption by heating, as discussed above.
The sampling device may be a sampling device according to the second aspect of the present invention described below.
Preferably, the contacting step involves transporting the exhaled breath through thecapillary solely, substantially solely, substantially or mainly by the force ofthe subject's exhalation, without the use of collection reservoirs such as bags or pumps of any kind.Device for analyte sample collection ln a second aspect, the present invention relates to a sampling device comprising a capillarywith an adsorbent surface coated on the inner surface thereof, characterized in that theadsorbent surface comprises an adsorbent selected from the group consisting of phenyl methyl silicone, polyethylene glycol and a sol-gel of silica.
Preferably, the adsorbent surface comprises phenyl methyl silicone or polyethylene glycol,as these adsorbents are capable of capturing both hydrophobic and hydrophilic analytes.Both are stable at high temperature (>250°C) and are capable of capturing analytes with different polarity.The device may optionally comprise a mouthpiece and/or a holder to facilitate handling.Properties of the capillary The capillary may have an inner cross-sectional dimension of 2-10 mm, preferably 2.5-8 mm,more preferably 2.5-6 mm, most preferably 3-5 mm. The cross-section may have any shapecompatible with the application, such as circular, oval, triangular, square, rectangular,pentagonal and octagonal or the like. ln most applications however, a substantially circularcross-section is preferable from a practical point of view in particular in terms of handlingand availability. The same considerations apply to the outer dimensions ofthe capillary. lt ispreferred the outer cross-section is substantially circular to facilitate interfacing with common existing instruments such as GC. However, it is contemplated that in some instances the capillary could be integrated in a larger block or a module, which could beadapted for interfacing with a particular instrument. ln such case, the outer dimensions could vary greatly.
The thickness ofthe capillary wall may be 0.001-2 mm, 0.003-0.5 mm, or 0.005-O.1 mm. Thecapillary wall thickness is most relevant if easy interface with existing instruments is desired.lt is however understood that in cases where the capillary is integrated in a block or a module, there is substantially more freedom in choosing the wall thickness.
The capillary, or the channel therein may be 4-10 cm in length, preferably 4-8 cm, morepreferably 6-9 cm, most preferably 7-10 cm. The preferred measures provide a reasonablecompromise between capacity for capture of the adsorbent surface and pressure needed to move the sample through the device.
The capillary is preferably straight, as this provides advantages in terms of storage (ln a box),general handling, sampling (lowest possible back pressure) and in particular interface withstandard analytical instruments such a GC. I\/lost instruments adapted for samples incapillary are designed on the premise that capillaries are straight, having essentially circularcross-section and having a certain external diameter (about 0.5-1.5 mm) and having acertain length (about 5 cm). lt is advantageous to adhere to designs adapted to suit the instruments intended to be used for downstream analysis.
However, it is contemplated that in some instances the capillary may also be curved, havingone or more bends, or be of a spiral shape. This applies in particular in cases discussed above where the capillary is integrated in a block or a module.
Preferably, the device is arranged such that the exhaled breath can be transported throughthe device by the force of the subject's exhalation, eliminating the need for collectionreservoirs such as bags or pumps of any kind. For the adsorption directly from the exhaledbreath to be practicable, the capillary may not be too narrow, too winded or too long, sinceotherwise the pressure needed to transport a sufficient volume of exhaled breath duringthe short time that the subject is able to exhale becomes too large. On the other hand, too short or too wide capillaries do not provide unsufficient adsorption capacity.
The structural capillary wall may be made of heat-tolerant inert material such a glass, a ceramic or a metal, allowing for both heat-based and solvent-based desorption. For solvent- based dsorption a wider range of materials is acceptable, including inert plastics such aspolyamides, po|y(ether etherketone) (PEEK), poly(tetrafluoroethylene) (PTFE), polypropene or polyethylene.The adsorbent surface may be 100-400um in thickness, more preferably 200-300 um.Manufacture of device The capillary to be coated may be pre-treated, for instance a glass capillary surface may beactivated by acid/base treatment. The polymer to be coated is dissolved in a volatilesolvent, such as acetone or dichloromethane. Capillary to be coated may then be filled withthe polymer solution and left until the solvent has evaporated. The capillary may then be subjected to a heat treatment.
Thus, in summary the present invention provides the advantages of a) ease of use, b) lowcost, c) fast (possible to get results at the same day); d) potential for being used as screening method, e.g. for early stage lung cancer.
The term comprising is to be interpreted as including, but not being limited to. All references are hereby incorporated by reference.
EXAMPLES The following examples are not to be interpreted as limiting.
Example 1: Manufacture of devices for analyte sample collection Preparation of capil/aries coated with phenyl methyl silicone or poly ethy/ene glyco/ The capillary inside surface of a glass capillary was activated by acidic and basic solutionbefore the immobilization of the liquid polymer (phenyl methyl silicone or poly ethyleneglycol). For the activation of capillary surface, i.e. to produce reactive silanol groups, thecapillary was filled with strong acid such as hydrochloric acid [0.1M] and left for 60 minutesat room temperature. After 60 min the capillary was rinsed with I\/lilli-Qwater and was leftto dry. After drying, the capillary was filled with sodium hydroxide [1M] for 60 minutes toactivate the silanol groups (hydroxyl groups, OH). After an additional rinse with I\/lilli-Q water, the capillary was left to dry. 11 The polymer [phenyl methyl silicone (OV 17 from Sigma-Aldrich) or PEG 400 (Sigma-Aldrich)]to being used for coating was dissolved in acetone or dichloromethane to a concentration ofabout 2.0 mg/mL to facilitate the coating procedure. The activated capillary was filled withthe polymer solution and was left for some hours at room temperature for evaporating ofthe acetone or dichloromethane. The capillary was then left over night at 40 degrees. Thenext day the capillary was heated-treated by heating from 40 degrees up to 250 degrees and left for 2 hours at 250 degrees.The preparation of sol gel-coated capillary 1.0 mL of tetraethyl orthosilicate (TEOS) and 1.0 mL (3-aminopropyl)triethoxysilane (APTES)were mixed and then 200 mg of polyethylene glycol (PEG) was added and the solution wasvortexed for a few seconds. The mixture was then sonicated for 30 minutes in ultrasoundbath at room temperature. Subsequently, 100 uL oftrifluoroacetic acid (TFA) and 0.8 mLacetonitrile were added and mixed. Finally, 50 uL pure water added to the mixture thusproducing a final mixture being a sol-gel solution. All chemicals and reagents can be obtained from Sigma-Aldrich in Sweden.
The capillary was activated as mentioned above and then was filled with sol-gel solution andleft at room temperature for 24 hours. After that the capillary was incubated at 55°C for 36 hours.
Finally, the capillary treated with a heat gradient: at 100°C for one hour, then at 150°C forone hour and lastly at 200°C for one hour. After the heat gradient the capillary is ready for use. Figure 5 exemplifies a sol-gel coated capillary.
Example 2: Volatile compound collection from exhaled breath Breath collection: All patients and controls were instructed to not eat anything 4 hoursbefore the breath test. Each study subject performed tidal breathing of unfiltered room airfor some minutes. During this time, they inhaled through their nose and exhaled throughtheir mouth into the coated capillary obtained according to Example 1. There were noflowers or plants in the rooms, so the VOCs (volatile compounds) in the breath wereconsidered as originating from the subjects themselves. The breath samples were stored in FOOm tempeFatUFe. 12 Example 3: Volatile compound determination from collected samples The capillary from Example 2 with collected volatile compound was inserted into a GCinjector Chamber. The injector was programmed heated from 50°C to 250°C. The adsorbedanalytes were thermally desorbed into a GC column separation and then detected identifiedby mass spectrometry. Results for detection of certain volatile compounds is shown in Figure 4A-D.

Claims (10)

1. A method for collecting an analyte sample from exhaled breath, comprising the steps of: a. providing a sampling device comprising a capillary with an adsorbent surface coated on the inner surface thereof; and b. contacting the exhaled breath with the adsorbent surface whereby the analyte sample to be co||ected binds to the adsorbent surface.
The method according to any ofthe preceding claims, wherein the contacting stepinvolves transporting the exhaled breath through the capillary by the force of exhalation ofthe subject from which the breath is exhaled.
The method according to any of the preceding claims, wherein the adsorbent surfacecomprises a compound selected from the group consisting of a phenyl methyl silicone, a polyethylene glycol and a sol-gel of silica.
The method according to any ofthe preceding claims, wherein the method is furtherfor determining the amount of analyte in a sample from exhaled breath, and comprises the step (c) of determining the amount of bound analyte.
The method according to claim 4, wherein the determination step comprises the step (c') of desorbing the bound analyte from the adsorbent surface.
The method according to any ofthe preceding claims, wherein the sampling device is a device according to any one of claims 7-10.
A sampling device for collecting analytes from exhaled breath, comprising a capillarywith an adsorbent surface coated on the inner surface thereof, characterized in thatthe adsorbent surface comprises an adsorbent selected from phenyl methyl silicone, polyethylene glycol and a sol-gel of silica.
The device according to any ofthe preceding device claims, wherein the adsorbent comprises phenyl methyl silicone or polyethylene glycol.
The device according to any ofthe preceding device claims, wherein the capillary has an inner cross-sectional dimension of 2-10 mm. 14
10. The device according to any ofthe preceding device claims, wherein the adsorbent surface is 100-300 pm in thickness.
SE1550376A 2015-03-30 2015-03-30 Method and device for analyte sampling from exhaled breath SE1550376A1 (en)

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SE1550376A SE1550376A1 (en) 2015-03-30 2015-03-30 Method and device for analyte sampling from exhaled breath
PCT/SE2016/050258 WO2016159863A1 (en) 2015-03-30 2016-03-29 Method and device for analyte sampling and analyte concentration determination from exhaled breath

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JP6702868B2 (en) * 2013-08-28 2020-06-03 ユニヴァーシティー・オブ・ルイスヴィル・リサーチ・ファウンデイション・インコーポレーテッド Non-invasive detection of lung cancer using exhaled breath

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