Gas or breath sampling device that captures both aerosol and vapor fractions

Abstract

The present invention relates to a sampling device for gas or breath samples. Such a device is capable of collecting both aerosols and particles as well as volatile organic compounds (VOCs) from a gas or breath sample using one device. The obtained samples can be adapted to analytical methods to determine the presence or absence of (bio)markers without the need for extensive post-processing, thereby simplifying the use and analysis of air or breath samples.

Description

[Technical field]

[0001] FIELD OF THEINVENTION The present invention relates to a device that allows for the collection of gas or breath samples, such as breath samples from human breath, and the collection of both aerosols, particles and volatile organic compounds in one device. The presence or absence of biomarkers in the collected air or breath sample can be determined from the samples collected by the device. [Background technology]

[0002] background Typically, breath capture devices focus on only one breath fraction, either volatile organic compounds (VOCs), breath aerosols, or breath condensates. Each of these fractions contains unique information, including biomarkers, metabolites, organic compounds or particles present in the blood. One of the current severe limitations in the field is that direct blowing into a device for VOC analysis is typically not possible, as the back pressure is typically too large to facilitate without relying on mechanical mitigation methods (pumps, large dead volumes, etc.). Furthermore, analysis of the amount of biomarkers obtained must generally be performed without time, materials, and costs. Moreover, even identifying many such markers is difficult due to the complex molecular structure and / or amount of markers present in conventionally collected samples.

[0003] More specifically, the field of breath sampling has expanded rapidly in recent years. The common approach for capturing breath samples is to blow the breath sample into an air sampling bag, followed by concentration of the sampling bag contents into a thermal desorption tube packed with one or more sorbents. Some type of air sampling pump is required to draw the breath sample from the bag into the heated tube. These multiple steps are necessary because the back pressure of a typical thermal desorption tube makes it impossible for a person to blow gas directly into a TD tube. This back pressure is created by the sorbent particles and glass wool packed into the tube.

[0004] Moreover, human breath contains both aerosols and VOCs. For many years, most researchers have studied the VOC fraction of human breath. However, now, there is an increasing tendency for researchers to look at the aerosol fraction as well. Biomarkers in both fractions may allow researchers to obtain additional biomarkers that are definitely related to specific diseases or may lead to the discovery of future therapeutic drugs. All of this could lead to earlier diagnosis of diseases and treatment of these diseases in the future. Summary of the Invention [Problem to be solved by the invention]

[0005] Thus, there is a need for a device that can capture various fractions from a gas or human breath sample with a single device that can collect aerosols, particles, and volatile organic compounds (VOCs). Such devices require a pumping mechanism and must provide low or no back pressure to enable capture of these fractions from the gas or breath sample. [Means for solving the problem]

[0006] Summary of the Invention . The present invention solves the problem of collecting various fractions from a gas or breath sample by providing a device that allows the capture of two different gas or breath fractions simultaneously - both aerosols and volatile organic compounds. Such a device has a honeycomb structure that includes a filter section and an adsorbent section. This honeycomb structure allows the user or patient to blow breath directly into the device, since the packing has no gas resistance. This allows for miniaturization and can eliminate the presence of pumps or other electronic components that would otherwise be required. This completely reduces the complexity of the device for VOC analysis, while the filtered section allows the collection of aerosols and particulate matter.

[0007] That is, the present invention provides a gas or breath sampling device that allows for the capture of both fractions (aerosol and VOC) during one (breath) sampling. The device is simple to use and does not require electricity or pumps. The collected fraction by the present device allows for easy analysis of (bio)markers, considering that the collected fraction is compatible with current sample preparation workflows and is in a form that can be analyzed using existing equipment. Furthermore, the present device or the present invention allows a person to blow directly into the honeycomb-structured thermal desorption (TD) tube, thereby bypassing the use of gas sampling bags and gas sampling pumps. That is, the use of the present device simplifies the breath sample capture procedure, and also eliminates the cumbersome task of transferring the sample from the bag to the tube. Furthermore, the present device combines an aerosol or particle capture means (e.g., a filtered portion) and a VOC capture means (e.g., a honeycomb-structured portion), but requires low back pressure, allowing the user or patient to easily blow into the device for gas or breath sample collection. [Brief description of the drawings]

[0008] [Figure 1] An apparatus is shown that includes a means for collecting aerosols and particles and a means for collecting VOCs.

[0009] [Diagram 2] 1 shows the results of a sample of the headspace of a peppermint softgel in a 2 liter static dilution bottle, i.e., the identification of volatile peppermint oil components.

[0010] [Diagram 3] Actual breath samples using both an aerosol filter and a honeycomb TD tube are shown.

[0011] [Figure 4] Volatile compounds that pass through the filtered device are shown.

[0012] [Diagram 5]1 shows an overview of the device of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Detailed Description of the Invention . Currently available gas or breath sampling devices use either a filter device or a device for volatile organic compound adsorption to collect either the aerosol or particle fraction, and there is no single device that collects both fractions using the same sampling method with the same device. Typically, the means for volatile organic compound adsorption in the device creates back pressure, which requires a pumping mechanism to ensure airflow through the device. Combining such a VOC collection means with a filter device is very challenging, as it is difficult to maintain adequate airflow without a pumping mechanism. This makes it undesirable, for example, for collecting human breath samples.

[0014] The present invention solves the above problems by combining a filtered collection means for aerosol and particle collection with a honeycomb structured sorbent collection means for volatile organic compounds collection in one gas or breath sampling device. The combined device operates at low back pressure, allowing a person to blow directly into the sampling device, eliminating the need to transfer the breath sample to a sampling bag or to use a vacuum sampling pump to draw the sample from the collection device. That is, the device of the present invention is not limited by the back pressure of the VOC collection means. As a result, use of the device simplifies the collection of gas or breath samples by the user. It is relatively easy to blow into the device to collect a breath sample, and the collected sample is analyzed for the presence or absence of (bio)markers. Furthermore, the combined sampling device may incorporate a bag that expands as an indicator of whether sufficient sample breath has been collected.

[0015] As used herein, the term volatile organic compounds or VOCs, when referring to human breath sampling, refers to any organic chemical that can be excreted from the human body that is detectable in the breath and / or components of the breath. When referring to gas sampling, the term VOCs can also include semi-volatile compounds.

[0016] Further, breath biomarker or "breath analyte" as used herein refers to a chemical component of breath or breath components that infers information about the state of a subject, including, but not limited to, diagnostics, disease detection, disease progression monitoring, organ rejection monitoring, environmental monitoring, exposure to toxicants, radiation exposure, drug monitoring (both metabolized and non-metabolized molecules), pharmacokinetic and pharmacodynamic information, and metabolomics. With respect to gas sampling, the term marker refers to any compound (or combination of compounds) that can be used to indicate, for example, a characteristic of a gas related to gas quality or a gas quality or marker corresponding to a certain purpose is below a certain gas safety threshold (e.g., non-flammable or non-explosive).

[0017] In one embodiment of the present invention, an apparatus for collecting gas samples is provided, comprising: a.) a means for collecting aerosols and particles from outside air; and b.) a means for collecting volatile organic compounds (VOCs) from outside air, wherein the means for collecting aerosols and particles from outside air and the means for collecting VOCs are connected to each other such that the apparatus collects aerosols, particles and VOCs from the same volume of outside air.

[0018] In another embodiment of the present invention, there is provided an apparatus for capturing breath samples from human breath comprising: a.) a means for collecting aerosols and particles from human breath; and b.) a means for collecting volatile organic compounds (VOCs) from human breath, wherein the means for collecting aerosols and particles from human breath and the means for collecting VOCs are connected to each other such that the apparatus collects aerosols, particles and VOCs from the same volume of exhaled human breath.

[0019] In such devices, the means for collecting aerosols and particles includes a filter for trapping such aerosols and particles. Such a filter may be an electrostatic filter.

[0020] It is important that the gas or breath sample is collected without loss of sample during the collection process. Therefore, in such a gas or breath sample collection device, the means for collecting aerosols and particles and the means for collecting VOCs are connected via an airtight connection.

[0021] Volatile organic compounds are collected in the device via such a means for VOC collection, which includes a thermal desorption tube. Preferably, such a thermal desorption tube includes a honeycomb structure. The honeycomb structure is coated with an adsorbent material for VOC capture. The adsorbent material can be one type of adsorbent material or one or more different adsorbent materials for capturing a wide range of organic molecules. Examples of such adsorbent materials include activated carbon, activated charcoal, silica gel, and porous polymers. Such a collection means for VOCs provides low back pressure that ensures acquisition of gas or breath samples without the need for pumping mechanisms. Furthermore, the collected samples can be easily analyzed using conventional analytical methods, as the use of a thermal desorption tube is compatible with analytical techniques such as various chromatographic techniques.

[0022] The honeycomb thermal desorption tubes used in the apparatus of the present invention can be constructed from any type of material that provides sufficient support for the adsorbent material and can withstand temperatures of 450° C. In certain embodiments, the material can withstand temperatures up to 500° C., or up to 600° C., or up to 700° C., or up to 800° C., or up to 900° C., or up to 1000° C.

[0023] In another embodiment of the invention, a method for sampling ambient air or human exhaled breath with the device of the invention is provided.

[0024] In another embodiment of the present invention, there is provided a method for determining the presence of a biomarker of interest in a sample of exhaled human breath or ambient air comprising: a.) collecting aerosols and particles from the human breath or ambient air; b.) collecting volatile organic compounds (VOCs) from the human breath or ambient air; and c.) determining the presence of the biomarker of interest in any of the collected aerosols, particles or VOCs, wherein the aerosols, particles and VOCs are collected from the same exhaled human breath or the same volume of ambient air and are collected in a single device of the present invention.

[0025] In another embodiment of the present invention, there is provided a method for diagnosing a patient for having or at risk of having a disorder comprising determining the presence of a biomarker of interest comprising a.) collecting aerosols and particles from human breath, b.) collecting volatile organic compounds (VOCs) from the human breath, c.) determining the presence of a biomarker of interest in one of the collected aerosols, particles or VOCs, and d.) correlating the presence or absence of the biomarker of interest with a disease state, wherein the aerosols, particles and VOCs are collected from the same exhaled human breath in a single device of the present invention.

[0026] In each embodiment, the device may be used with or without means for collection of specific respiratory phase subsets such as end-tidal, mixed or late-tidal, etc. Any such means or objectives may include any of the following or any combination thereof: flow meters (measuring flow or volume via mechanical or electrical means), sensors that detect concentrations of known / common components in exhaled breath (e.g. CO2, N2, nitric oxide concentrations or others), methods that utilize timers, humidity monitoring or rebreathing protocols.

[0027] A schematic diagram of an embodiment of a gas or breath sampling device of the present invention is provided in Figure 1 and includes a VOC collection means, e.g. in the form of a honeycomb structure containing an adsorbent, an aerosol and / or particle collection means, e.g. a filtered section, and a mouthpiece for blowing or receiving the gas or breath to be sampled.

[0028] The following provides a description of exemplary embodiments of the present invention. EXAMPLES

[0029] Example 1. Use of the device for capture of both aerosols and VOCs in a peppermint breath sampling protocol. To evaluate the breath sampling device according to the present invention, breath samples were collected before and after ingestion of a peppermint softgel capsule (an over-the-counter herbal supplement). During the ingestion process, components of peppermint oil enter the bloodstream, and some components migrate from the bloodstream to the lungs and are exhaled during normal exhalation (Malaskova, 2019). Experiments were performed to show how the novel breath sampling device can be used to capture the volatile components of metabolized peppermint oil capsules.

[0030] The device uses a ceramic honeycomb coated with a carbon sorbent. The honeycomb structure presents minimal back pressure, making it easy for a person to blow a breath sample into the tube.

[0031] Honeycomb thermal desorption tubes (HCTD tubes) were constructed by coating two separate ceramic honeycombs with two different adsorbents of increasing adsorption strength. The first honeycomb was Carbopack TMOne honeycomb was coated with Carbopack C and the second honeycomb was coated with Carbopack B. The coating process was carried out by suspending nano-sized carbon sorbent particles in a solution containing methylene chloride and polysilazane, which acted as a "glue" to adhere the carbon sorbent to the ceramic honeycomb. The ceramic honeycomb was immersed in the solution coating all exposed surfaces of the ceramic honeycomb. Multiple coats were applied until a build-up was observed. The coated honeycomb was then placed in a stainless steel thermal desorption tube 6.35 mm OD x 5 mm ID x 89 mm long. The coated assembly (tube) was placed in a glass purification bomb and heated at 450°C for 10 minutes with nitrogen gas passing through to maintain an inert atmosphere during the curing process.

[0032] A breath sampling device of the present invention was fabricated by combining an aerosol and particle collection device containing a filter, such as the SensAbues device, with a honeycomb thermal desorption tube (HCTD tube) fabricated as described above (Figure 2). To combine these two devices, a hole was drilled in the storage cap on the outlet side of the filtering device so that the inlet of the HCTD tube could enter the cap. The HCTD tube was then connected to the filtered device.

[0033] The purpose of this experiment was to see if breath samples were collected with and without an electrostatic filtering device connected to a honeycomb tube.

[0034] The main purpose of connecting both devices is to capture both the aerosol and the evaporative fraction of human breath in one breath sample. When a person exhales into the combined device, the aerosol along with any particles are captured by the electrostatic filter in the device, while the volatile compounds in the gas phase pass through the filter and are then captured by the sorbent-coated HCTD tube. As long as the person continues to exhale into the device, the volatiles captured in the aerosol and then released by contact with the filter are then captured by the HCTD tube. After taking the breath sample, each sampling device is individually sealed to protect the sample integrity until analysis.

[0035] There is an additional benefit of combining a filtering device with the honeycomb thermal desorption tube. The filter protects the thermal desorption tube from retaining non-volatile compounds during breath sampling, which are not suitable for GC analysis. This prevents non-volatiles from contaminating the TD / GC sample path during thermal desorption.

[0036] Example 2: Taking breath samples with this device. Protocol used for breath sampling experiments 1. Overnight fasting (no breakfast) 2. Brush your teeth with baking soda (to prevent contamination from mint-flavored toothpaste) 3. Rinse mouth twice with bottled water - before taking breath sample 4. Baseline breath sample capture prior to peppermint capsule ingestion 5. Take 5 qty peppermint capsules and wait 1 hour for the capsules to metabolize. 6. Collect breath samples using the prototype breath sampling device.

[0037] For this experiment: 20 qty breaths were blown into the combined breath sampling device, which took approximately 6 minutes and 30 seconds to complete. The filtered device uses a small bag as an indicator so the user knows when they have blown enough gas into the device. When the filtered device was used by itself, the bag filled after approximately 20 breaths. The slight back pressure of both devices, the combined filtered device and honeycomb structure, did not cause any problems blowing the breath sample into the device.

[0038] For this experiment, the following combinations of breath samples were captured: 1. Before and after taking peppermint capsules. 2. Samples with or without a filtered device connected to the HCTD tube 3. Samples with uncoated honeycomb and sorbent-coated HCTD tubes

[0039] Prior to breath sample collection, HCTD tubes were conditioned at 330°C for 30 min using a CDS Analytical 6-tube conditioner to reduce volatile background levels. Devices with filters were used as received. Devices were placed in sealed bags and packaged in cardboard boxes.

[0040] Figure 3 shows the results of a sample of the headspace of a peppermint softgel from a 2 liter static dilution bottle, obtained by injecting 1 mL of headspace into a conventional thermal desorption tube filled with Carbopack C and Carbopack B. Identification of components was based on matching with the NIST spectral library. Individual chemical standards of each component were not obtained, and therefore quantification and identification were not performed.

[0041] Figure 4 shows layered chromatograms of breath samples using HCTD tubes and direct filtered devices. These results are for the HCTD tubes and not for the filters. The top chromatogram (black) is the breath sample before ingestion of the peppermint capsule. The middle chromatogram (blue) is the analysis of the HCTD tube 1 hour after ingestion of the peppermint capsule. The bottom chromatogram (red) is the peppermint oil headspace sample obtained from a 2-liter static dilution bottle. A syringe volume of 750 μL of peppermint oil headspace was injected into a conventional thermal desorption tube packed with Carbopack C and Carbopack B particles.

[0042] The peaks highlighted in blue are where the peppermint oil components elute. Of the 11 identified peppermint oil components, only limonene was observed in the breath sample before taking the peppermint oil capsule. Limonene is a chemical normally found in human breath, produced by the liver and can be exhaled. The main result is that the majority of the peppermint components were observed one hour after taking the peppermint oil capsule (blue chromatogram), showing how the device can retain VOCs from human breath.

[0043] FIG. 5 shows chromatogram overlays (middle and bottom chromatograms) showing how the HCTD tube with and without the filter device captures peppermint oil components. The HCTD tube with the filter device was shown to retain more volatiles than the HCTD tube without the filter device. The filter of the filter device was found to have some volatile contamination (see area highlighted in red). However, the graph shows that similar results were obtained with and without the filter device for volatile peppermint oil components. This is evidence that the volatile peppermint oil components were not captured by the filter of the filter device.

[0044] These examples demonstrate that the breath sampling device is capable of capturing volatile compounds from human breath. These examples also demonstrate that the volatile compounds pass through the filtered portion of the device and are collected in the HCTD tube.

[0045] This gas or breath sampling device of the present invention eliminates the need for transferring the sample from a gas sampling bag to a tube, which is a significant advancement as it allows for the use of more standardized breath sampling protocols when analyzing gas or breath samples to determine the presence or absence of (bio)markers.

Claims

1. 1. An apparatus for collecting a gas sample, comprising: a. a means for collecting aerosols and particles from the outside air; and b. A means for collecting volatile organic compounds (VOCs) from outside air. wherein the means for collecting aerosols and particles from the outside air and the means for collecting VOCs are connected to each other such that the device collects aerosols, particles and VOCs from the same volume of outside air.

2. 1. A device for capturing a breath sample from a human breath, comprising: a. a means for collecting aerosols and particles from human breath; and b. Means for collecting volatile organic compounds (VOCs) from human breath wherein the means for collecting aerosols and particles from the human breath and the means for collecting VOCs are connected to each other such that the device collects aerosols, particles and VOCs from the same volume of exhaled human breath.

3. 3. The apparatus of claim 1 or 2, wherein the means for collecting aerosols and particles comprises a filter for trapping such aerosols and particles.

4. 4. The apparatus of claim 3, wherein the filter is an electrostatic filter.

5. 3. The apparatus of claim 1 or 2, wherein the means for collecting aerosols and particles and the means for collecting VOCs are connected via an airtight connection.

6. 3. The apparatus of claim 1 or 2, wherein the means for collecting VOCs comprises a thermal desorption tube.

7. The apparatus of claim 6 , wherein the thermal desorption tube comprises a honeycomb structure.

8. 8. The apparatus of claim 7, wherein the honeycomb structure is made of a material capable of withstanding temperatures of 450°C or greater.

9. The apparatus of claim 7 , wherein the honeycomb structure comprises an adsorbent material.

10. 10. The apparatus of claim 9, wherein the honeycomb structure is coated with one or more adsorbent materials.

11. A method for sampling ambient air with the device of claim 1 or 2.

12. A method of sampling human breath with the device of claim 2.

13. 1. A method for determining the presence of a biomarker of interest in a sample of exhaled human breath or ambient air, comprising: a. Collecting aerosols and particles from human breath or ambient air; b. Collecting volatile organic compounds (VOCs) from human breath or ambient air; and c. determining the presence of a biomarker of interest in one of the collected aerosols, particles, or VOCs; A method, wherein aerosols, particles and VOCs are collected from the same exhaled human breath or the same volume of gas outside the device, collected with one of the devices of claims 1 or 2.

14. 1. A method for aiding in the diagnosis of whether a patient has or is at risk for a disorder comprising determining the presence of a biomarker of interest, comprising: a. Collecting aerosols and particles from human breath; b. Collecting volatile organic compounds (VOCs) from human breath; c. determining the presence of a biomarker of interest in one of the collected aerosols, particles, or VOCs; and d. Correlating the presence or absence of a biomarker of interest with a disease state; A method, wherein aerosols, particles and VOCs are collected from the same exhaled human breath with the device of claim 2.

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