breath sampler

Abstract

A device (100) for obtaining a breath sample from a patient, the device (100) comprising a mask or mouthpiece (101) for receiving exhaled breath from the patient, an outlet (102) for discharging exhaled breath from the device (100), a sampler (110), and a sample receptacle (113). The sampler (110) has a distal portion configured to protrude into the flow of exhaled breath from the mask or mouthpiece (101), and a sampler opening (118) in the distal portion for obtaining the exhaled breath sample. The sample receptacle (113) is in communication with the sampler (110) for receiving the exhaled breath sample from the sampler (110).

Description

[Technical Field]

[0001] The present invention relates to a breath sampler and a method for sampling breath to facilitate analysis of breath. [Background technology]

[0002] Breath sampling is a promising technology for facilitating noninvasive diagnostics and health monitoring. Exhaled breath contains volatile organic compounds (VOCs), which arise from metabolic processes both within the body's cells and within the microbiome that inhabits the body. These metabolic processes can be affected or disrupted by disease states, resulting in changes in the VOC profile present in exhaled breath. Therefore, analyzing the VOC profile in collected breath can identify disease states. Changes in the VOC profile can serve as biomarkers that can identify specific disease states. This is a promising and active area of ​​research.

[0003] A major obstacle to the widespread adoption of breath sampling as a diagnostic technique is the sampling methodology. Different breath sampling methods result in significant variability in the data obtained from subsequent analysis of the samples. The availability of high-quality breath sampling methods would facilitate the development of breath sampling as a diagnostic technique.

[0004] An example of an existing breath sampling device is disclosed in US2017 / 303822. Summary of the Invention

[0005] Obtaining breath samples that facilitate reliable analysis of VOC compounds in exhaled breath is challenging. Typical breath samples contain low masses of VOCs, and contaminants in the breath sample can confound accurate analysis of VOC profiles. Furthermore, breath samplers should be easy to use, maintain, and affordable enough to be deployed on a large scale.

[0006] Although considerable progress has been made in breath sampling, there is room for improvement in many areas.

[0007] According to a first aspect, 1. An apparatus for obtaining a breath sample from a patient, comprising: a mask or mouthpiece for receiving exhaled breath from the patient; an outlet for expelling exhaled air from the device; A sampler and a sample container; The sampler comprises: a distal portion configured to protrude into the flow of exhaled air from the mask or mouthpiece; a sampler opening in the distal portion for obtaining a breath sample; The sample container is A device is provided in communication with the sampler, the device being a receptacle for receiving a breath sample from the sampler.

[0008] In certain embodiments, advantages may be gained by drawing the sample through a sampler (e.g., thermal desorption tube, needle trap, arrow sampler, or solid-phase microextraction fiber) into a sample container. In some embodiments, the sampler may be configured to approximate isokinetic sampling, thereby reducing contamination of the analytical signature of the breath sample (e.g., contamination due to water and aerosol collection). In some embodiments, the breath sampling device may reduce contact of the sampler with the sample container during assembly and disassembly of the sample container.

[0009] The sampler opening may be located in a sidewall of the distal portion, which in some embodiments may better approximate isokinetic sampling conditions.

[0010] The sampler opening may be spaced from the tip of the distal portion, and the tip of the distal portion may include an end flange, which in some embodiments may prevent contact with the sampler opening and / or improve approximation of isokinetic sampling conditions.

[0011] The distal portion of the sampler may be substantially tubular (eg, cylindrical).

[0012] The sampler may include a proximal portion configured to engage the sample vessel.

[0013] The proximal portion of the sampler may be configured to seal the outside of the sample vessel.

[0014] The sampler may include an internal groove and an O-ring seal disposed within the internal groove to form a seal with the exterior of the sample vessel.

[0015] The sample container may be removable from the device by pulling on the sampler, which in some embodiments allows the sample container to be handled via the sampler during installation and removal of the sample container from the breath sampling device, thereby avoiding contact with the sample container.

[0016] The device may further include a filter (such as a HEPA filter) downstream of the sampler, which may prevent or reduce particles (e.g., viral particles) contained in the patient's breath from leaving the breath sampling device.

[0017] The device may further comprise a handle for holding the device, and the sample vessel and sampler may be housed in the handle.

[0018] The sampler may be configured to sealingly engage the handle.

[0019] The sampler may include an exterior groove and an O-ring seal disposed within the exterior groove to form a seal with the handle.

[0020] The handle may include a manually operable clip for locking and unlocking the engagement of the mask or mouthpiece with the handle.

[0021] The handle may comprise an inner sleeve and an outer sleeve, the handle being securable to the mask or mouthpiece by sandwiching the mask or mouthpiece between the inner sleeve and the outer sleeve.

[0022] The filter may be received in the inner sleeve (eg, by a push fit).

[0023] The handle may include a pressure probe for transmitting fluid pressure to a pressure sensor.

[0024] The handle may include an inhalation conduit for providing air to the mask or mouthpiece for breathing by the patient.

[0025] According to a second aspect, An air purifier for a breath sampling device is provided, comprising at least one cartridge filter (which may be cylindrical in shape) configured to purify the air supplied to the breath sampling device.

[0026] The cartridge filter may be a standard cartridge filter (e.g., a NATO 40 mm standard gas filter, such as an AX filter cartridge). In some embodiments, the use of (commercially available) cartridge filters can reduce costs associated with using and maintaining the air purifier.

[0027] According to a third aspect, There is provided a breath sampling system comprising a device according to the first aspect and an air purification system according to the second aspect.

[0028] The air purifier may include two cartridge filters for parallel flow.

[0029] The air purifier may include three (or more) cartridge filters, which may be configured for parallel flow. Placing more cartridge filters in parallel increases the flow rate and improves air purification by removing volatile organic compounds.

[0030] It may further comprise a manual latch for gaining access to the cartridge filter for replacement.

[0031] According to a fourth aspect, 1. A breath sampling consumable delivery system comprising: a sample container for receiving a breath sample; first and second end caps for sealing first and second ends of the sample vessel; a case for receiving the capped sample vessel; the case includes a first cap socket and a second cap socket; the first cap socket is a pivotable cap socket configured to rotate between an upright position and a downright position and to receive the first end cap; the second cap socket is configured to receive the second end cap; The first and second pivot cap sockets are A system is provided in which the first end cap and the second end cap are arranged together to sealingly engage the first end and the second end of the sample vessel, respectively, when received in the first cap socket and the second cap socket.

[0032] In certain embodiments, this may avoid the time-consuming sealing procedures of the sample container (eg, involving the use of tools, etc.) commonly employed in prior art breath sampling methods.

[0033] The first cap socket and the second cap socket may be configured to allow a thermal desorption tube capped by the first end cap and the second end cap to be rotated from a first upright position in which the first end cap can be received in the first cap socket to a second downright position in which the second end cap is clamped into the second cap socket.

[0034] According to a fifth aspect, there is provided a system for breath sampling comprising a breath sampling device according to the first aspect, an air purifier according to the second aspect, and a controller configured to control the flow of the breath sample through the sample container.

[0035] The controller may include a sampling port for connecting to a sample container and a pressure port for connecting to a pressure probe. The controller may include a sampling pump for drawing air through the sampling port and therefore through the sample container. The controller may include a pressure sensor for detecting pressure within the breath sampling device via the pressure port. The controller may have control logic for controlling operation of the breath sampling device. The control logic may be configured to control the sampling pump in response to the pressure sensor.

[0036] According to a sixth aspect, 1. A method of collecting exhaled breath from a patient for analysis, comprising: receiving exhaled breath from the patient via a mask or mouthpiece into a breath sampling device; drawing a sample from the flow of breath through the breath sampling device into the sample container via a sampler that engages an end of the sample container; A method is provided that includes:

[0037] The breath sampling device may be the device according to the first aspect. The method according to the sixth aspect may include any of the features of the breath sampler, air purifier and breath sampling system described herein.

[0038] The method may further include supplying clean air to the breath sampling device for the patient to breathe. The clean air supply may be provided to maintain a positive pressure within the mask or mouthpiece.

[0039] According to a seventh aspect, an apparatus for obtaining a breath sample from a patient, the apparatus comprising a mask or mouthpiece for receiving breath from the patient and a sample container for receiving the breath sample from the patient; a controller including a sample port and a sample pump configured to draw air through the sample port; a mode selection valve in fluid communication with the sample pump; a sample conduit connecting the mode selection valve and the sample container; a port for connecting to another sample container for sampling ambient air; A breath sampling system is provided, wherein the mode selection valve is operable to selectively connect the sample pump to the sample conduit to collect breath into the sample container, or to connect the sample pump to the port to collect ambient air into the other sample container.

[0040] The device for obtaining a breath sample may further comprise an outlet through which exhaled breath leaves the device, the outlet may be located in a mask or mouthpiece.

[0041] The device for obtaining a breath sample may be a device according to the first aspect.

[0042] The breath sampling system may further include an air purifier configured to supply air to the mask or mouthpiece, and the air purifier may include at least one cartridge filter (which may be cylindrical) configured to purify the air provided to the mask or mouthpiece.

[0043] The air purifier may be the air purifier according to the second aspect.

[0044] The mask or mouthpiece may be fluidly coupled to the air purifier by a flexible tube.

[0045] The air purifier and the controller may be contained in a container or housing.

[0046] The mode selection valve may be contained in a container or housing.

[0047] The air purifier, controller, and mode selection valve may be housed in the same container or housing, as may other components of the breath sampling system. The container or housing may facilitate transportation of the breath sampling system.

[0048] The housing or container may be a briefcase. In some embodiments, components of the breath sampling system can be operated without being removed from the housing or container. For example, the controller, air purifier, and mode selection valve may be controlled while contained within the container or housing. This may allow for faster system setup or easier system operation.

[0049] The container or housing may further include a holding fixture configured to hold the device for obtaining a breath sample. In some embodiments, the container or housing may be a briefcase, and the holding fixture may be a holder on the inside surface of the lid of the briefcase. The holding fixture may make operation of the system more convenient for the user by providing a storage location for the mask or mouthpiece while the user performs other tasks. It may also prevent the mask or mouthpiece from being placed on an unsterilized surface.

[0050] The controller may be configured to wirelessly connect to a remote computer.

[0051] The remote computer may be a mobile computing device, such as a smartphone.

[0052] The mobile computing device may include software for controlling the controller and / or the air purifier, which may be an app installed on a smartphone.

[0053] The app may be an app configured to run on an iOS and / or Android smartphone. In some embodiments, the app may allow a user to control the controller and / or the air purifier. User input on the app may be used to control the controller and / or the air purifier, as needed, to obtain environmental samples, control samples, or breath samples from the patient.

[0054] In some embodiments, the app may be configured to generate and / or record additional information related to a sample obtained using the breath sampling system. For example, a user may use user input on the app to instruct the controller to obtain an environmental sample, a control sample, or a breath sample from a patient. The app may then record a log related to the sample. The log may include, for example, date and time information for the sample (which may be provided by the smartphone operating system), additional information about the sample related to user input entered on the app before the sample was obtained (e.g., sample type), additional information manually entered by the user on the app (e.g., notes about the user observations), etc.

[0055] The app may generate a reference code that can be used to associate a log on the app with a sample taken using the breath sampling system. The reference code can be an alphanumeric sequence that a user writes on a sample after taking the sample and correspondingly logging into the app. In some embodiments, each sample can have an identifying marker (e.g., a QR code, a barcode, an alphanumeric sequence, etc.). The app and smartphone camera can be used to scan the identifying marker to find the log corresponding to each sample.

[0056] In some embodiments, the app may provide the user with instructions or information regarding operation of the breath sampling system. For example, the app may provide the user with sequential instructions that guide the user through obtaining an environmental sample, a control sample, and then a breath sample with the breath sampling system. Such instructions and information may be provided by the app in a number of user-selectable languages.

[0057] According to an eighth aspect, 1. A method for collecting exhaled breath from a patient using a breath sampling system, comprising: obtaining an environmental sample of ambient air; obtaining a control sample using a device for obtaining a breath sample from a patient; and A method is provided which comprises obtaining a breath sample from a patient using the device for obtaining a breath sample from a patient.

[0058] The breath sampling system may be a system according to the seventh aspect.

[0059] The environmental sample may be taken using a port for sampling ambient air, and the control sample and the exhaled breath sample may be taken using sample conduits connected to a mask or mouthpiece of the device for obtaining exhaled breath samples from a patient.

[0060] The method comprises: After obtaining the environmental sample and before obtaining the control sample, the method may further include moving a selection valve from a first position in which a sample pump is fluidly coupled to the port to sample ambient air to a second position in which a sampler pump is coupled to the sample conduit connected to the mask or mouthpiece.

[0061] The method may further include providing a supply of clean air to the mask or mouthpiece for the patient to breathe through. The clean air supply may be provided by an air supply connected to an air purifier. The air supply may be turned on and off as needed. The air supply may be used to maintain a positive pressure within the mask or mouthpiece.

[0062] The method may further comprise obtaining the control sample while the device for obtaining the breath sample is housed in a holding fixture of a receptacle or housing of a breath sampling system.

[0063] The method may further comprise, after obtaining the control sample and prior to obtaining the breath sample from the patient, removing the device for obtaining the breath sample from the holding fixture and attaching the device to the patient.

[0064] The method may further include, using a mobile computing device, at least partially instructing the breath sampling system to obtain at least one of the samples in response to user input.

[0065] The mobile computing device may be a smartphone, and the user input may include pressing a button on an app, the button pressing instructing the breath sampling system to obtain one of the samples.

[0066] The app may be one according to the seventh aspect.

[0067] Embodiments of the present invention will now be described, purely by way of example, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0068] [Figure 1] FIG. 1 is a side view of one embodiment of a device for obtaining a breath sample. [Figure 2] FIG. 2 is a side cross-sectional view of the embodiment of FIG. 1. [Figure 3] FIG. 3 is an exploded perspective view of the exemplary device of FIGS. 1 and 2. [Figure 4] FIG. 2 is a detailed view of the sampler. [Figure 5] 1 is a series of cross-sectional views showing the ends of an exemplary device. [Figure 6] FIG. 6 shows an exemplary system for obtaining breath samples comprising the device of FIGS. 1 to 5 and an air purification system. [Figure 7] FIG. 1 is a detailed diagram of an exemplary air cleaning system according to one embodiment. [Figure 8] FIG. 10 illustrates an alternative air purification system with three cartridge filters according to one embodiment. [Figure 9] FIG. 1 shows a gas chromatography-mass spectrometry (GC-MS) plot comparing results obtained from an air purification system according to one embodiment with results obtained from a prior art device. [Figure 10] FIG. 1 illustrates a delivery system for breath sampling consumables. [Figure 11] FIG. 10 is a diagram showing how the sample container is locked in the sample case in a face-down position. [Figure 12] FIG. 1 illustrates a breath sampling system including a breath sampling device, an air pump, an air purification system, and a controller. [Figure 13] FIG. 13 shows an exemplary breath sampling system (BreathTrace) similar to FIG. 12, further comprising a quality control system. [Figure 14] FIG. 1 shows a GC-MS analysis comparing results obtained from a breath sampling system according to one embodiment with results obtained from breath samples obtained using a prior art device. [Figure 15] FIG. 1 shows a GC-MS analysis comparing results obtained from a breath sampling system according to one embodiment with results obtained from breath samples obtained using a prior art device. [Figure 16] FIG. 14 shows a breath sampling system similar to that of FIG. 13. [Figure 17] FIG. 14 illustrates an exemplary method for collecting breath samples using a breath sampling system similar to that of FIG. 13. DETAILED DESCRIPTION OF THE INVENTION

[0069] 1-5, an exemplary device 100 for obtaining a breath sample from a patient is shown. The device 100 includes a mask 101, a handle 120, a sampler 110, and a sample container 113 for receiving the breath sample.

[0070] The mask 101 may be constructed from a flexible material. The mask 101 is configured to conform to the contours of the patient's face. The mask 101 may be a disposable consumable item, replaced for each new patient sampled. The mask 101 is removable from the handle 120 (without tools) using a manual clip 130, which is described in more detail below.

[0071] In use, the patient places the mask 101 on their face and breathes into the device 100. Exhaled air is received by the mask 101 and directed to the handle 120. Exhaled air exits the handle via an outlet 102 having a one-way valve. Air is received into the handle 120 via an inhalation conduit 105, allowing the patient to breathe through the mask 101. Optionally, the interior of the mask 101 and handle 120 may be maintained at a positive pressure by a pumped flow of air received by the inhalation conduit 105. The incoming air may be purified (e.g., to reduce background contaminants in the exhaled air that do not originate from the patient).

[0072] The handle 120 houses a sample container 113. The sample container 113 receives a breath sample from the exhaled breath flow to the mask 101. The sample container 113 in this example is preferably a thermal desorption tube 113, although other embodiments may use different types of sample containers (suitable for sampling VOCs), including needle traps, arrow samplers, or solid-phase microextraction fibers. The sample container 113 may be configured to retain VOC compounds in the exhaled breath by reversible adsorption. Heating the sample container 113 then releases (by desorption) the VOCs for analysis (e.g., using gas chromatography with mass spectrometry detection, GC-MS).

[0073] To reliably identify trace VOCs collected in the sample container 113, e.g., for biomarker-based diagnostics, it is important to avoid contamination of the sample. Prior art devices typically have difficulty avoiding such contamination. Applicant has determined that a source of contamination can arise from handling the sample container 113. Even gloved hands can introduce contaminants into the sample container during handling, and these contaminants can potentially confound or obscure accurate profiling of VOC compounds in the breath sample. Therefore, certain embodiments of the present device are configured to minimize contact with the sample container 113 during installation of the sample container 113 in the device 100 and removal of the sample container 113 from the device 100 (after breath sampling).

[0074] The proximal portion of the sampler 110 is configured to engage the sample vessel 113 by receiving a portion of the sample vessel 113 in a recess within the sampler 110. The sampler 110 includes a seal 116 that engages the inner surface of the sampler 110 and the outer surface of the sample vessel 113. In this embodiment, the seal 116 includes an O-ring 116 held in an internal groove in the sampler 110.

[0075] Once the sample container 113 is received in sealing engagement with the sampler 110, the sample container 113 can be removed by holding the sampler 110. As a result, the sample container 113 can be handled by holding the sampler 110 rather than the sample container 113, for example, placing the sample container 113 into the device 100 and removing the sample container from the device 100. Placing the sample container 113 into the device involves first assembling the sample container 113 in sealing engagement with the sampler 110 and then placing the assembled sample container 113 and sampler 110 into the device 100. The sample container 113 is received within a sample container housing 133, which is at an acute angle to the flow direction 105 of exhaled air from the mask 101 to the outlet 102 (which may more easily achieve isokinetic sampling).

[0076] The sampler 110 engages the handle 120 when installed in the device 100. An external O-ring 117 is held in an external groove 126 of the sampler 110 to form a seal between the handle 120 and the sampler 110. In the exemplary embodiment, the sampler 110 seals against an inner sleeve 121 of the handle.

[0077] The sampler 110 includes a sampler opening 118 and an internal channel for transmitting a breath sample from the sampler opening 118 to the interior of an engaged sample container 113. A sample conduit 134 is connected to the sample container housing 133 and draws the breath sample into the sample container 113 (e.g., by application of negative pressure to the sample conduit 134).

[0078] A further problem with prior art breath sampling devices arises from the fact that the sample flow rate in the sampling path is not adequately matched to the flow rate of the breath through the sampling device. Under these conditions, aerosols and condensate droplets can be introduced into the sample. A more representative sample can be obtained by more closely matching the sampling conditions to isokinetic sampling conditions, where there is no divergence or convergence of flow lines near the sample inlet.

[0079] Applicant has determined that in certain embodiments, a more representative sample may be obtained from a sampler opening 118 in the sidewall of the sampler 110, as shown in FIG. 4 . In certain embodiments, the sampler 110 may include a locator (e.g., a radial protrusion) that defines the rotational direction of the sampler 110 when engaging with the handle 120, thereby defining the orientation of the sampler opening 118 relative to the flow of exhaled breath through the handle 120. A preferred orientation of the sampler opening 118 may be facing perpendicular to the flow direction of exhaled breath through the handle 120, as shown in FIG. 1 . The sampler opening 118 may be positioned to be located in a substantially central region of the flow path of exhaled breath from the mask 101 to the outlet 102.

[0080] The sampler opening 118 is spaced from the tip of the sampler 110 so that the sampler 110 can be easily handled without touching the sampler opening 118, thereby reducing contamination of the breath sample due to handling. The distal tip of the sampler 110 is provided with an end flange 115, which further reduces the possibility of contact with the sampler opening 118 by providing a point of purchase for grasping and removing the sampler 110 and sample container 113.

[0081] The handle 120 includes an inner sleeve 121 and an outer sleeve 122. The inner sleeve 121 is cylindrical and concentric with the outer sleeve 122. The inner sleeve 121 includes a latch 130 that is resiliently biased outward. The outer sleeve 122 has an opening configured to receive a portion of the latch. When the inner sleeve 121 is pushed into the outer sleeve, the latch 130 engages the outer sleeve 122, locking the inner sleeve 121 in place. Once the inner sleeve 121 is locked in place, the mask 101 is sandwiched between the flange 123 of the inner sleeve 121 and the outer sleeve 122. The inner sleeve 121 can be removed from the outer sleeve 122 by squeezing the latches on both sides of the handle with one hand. This allows the inner sleeve 121 to be easily separated from the handle 120, and the mask or mouthpiece to be easily separated from the handle 120. The inner sleeve 121 does not need to be removed from the handle 120 to remove the sampler 110 and sample container 113.

[0082] A filter 135 may be provided between the mask 101 and the outlet 102, preferably downstream of the sampler 110. In an exemplary embodiment, the filter 135 is provided to be received in a recess in the inner sleeve 121. The filter 135 may comprise, for example, a HEPA filter, which may be easily replaced (without the use of tools) by removing the inner sleeve 121 from the handle, as described above.

[0083] To facilitate control of breath sampling at the appropriate time in the patient's respiratory cycle (e.g., by controlling a pump connected to sample conduit 134), a pressure sensing probe 136 is provided to communicate pressure within the handle (via pressure conduit 132) to a pressure sensor. The pressure sensor may be located in a controller external to the breath sampling device. Separating the control system from the breath sampler may reduce the ownership and use costs of the overall sampling system, as the breath sampling device can be easily disassembled and cleaned / sterilized for reuse, while the controller remains free from patient contact and potential contamination. Breath sampling device 100 may be free of electronics and sensors.

[0084] Referring to Figure 6, a system 200 is shown. System 200 comprises the breath sampling device 100 shown in Figures 1-5, and further comprises an inlet conduit 125 connecting breath sampling device 100 to an air cleaner 160. A pressure conduit 132 and a sample conduit 134 exit the inlet conduit 125 before the air cleaner 160 and are connected to a control system. Such a control system may comprise a microprocessor, a pump, and a pressure sensor, and may be configured to control the sampling of the breath.

[0085] The air purifier 160 receives air (e.g., from an air pump such as 170 in FIG. 12) and removes background contaminants (including VOCs), thereby improving detection of biomarkers in breath samples (by removing background contaminants).

[0086] The air cleaner 160 is shown in detail in Figure 7. The air cleaner 160 comprises an intake manifold 162, an outlet manifold 161, a first filter cartridge 166, a second filter cartridge 167, and a housing 165.

[0087] An intake manifold 162 includes an inlet 163 through which air is provided to the air cleaner 160 (e.g., from an air pump). Air is supplied from the intake manifold 162 to first and second filter cartridges 166, 167 arranged in parallel. The first and second filter cartridges may comprise standard filter cartridges (e.g., conforming to EN 14387 A1 and / or meeting the requirements of European Directive 89 / 686 EEC, such as Moldex A1 or compatible cartridges). Thus, the first and second filter cartridges 166, 167 may be relatively low-cost and easy to replace (in contrast to prior patented air cleaning systems, which generally have very high maintenance costs).

[0088] The outlet manifold 161 receives clean air from the first and second cartridges 166, 167 and delivers it to the inhalation conduit 125. The inhalation conduit 125 delivers clean air to the breath sampling device 100. The pressure conduit 132 and the sample conduit 134 exit the inhalation conduit 125 adjacent to the outlet manifold 161 and are connected to a control system.

[0089] The intake manifold 162 and outlet manifold 161 are fastened to a housing 168. The outlet manifold is fastened to the housing 168 with a rotating cam lock system 164, allowing the outlet manifold 162 to be easily removed for replacement of the filter cartridges 166, 167.

[0090] FIG. 8 illustrates an example of an air purification system 160 similar to that shown in FIG. 7. The left side of the figure shows the air purification system 160, including an outlet manifold 161, an intake manifold 162, an intake conduit 125, and a housing 165. The right side of the figure shows the air purification system 160, with the outlet manifold 161 shown as transparent for clarity. The air purification system is configured to accommodate three cartridge filters (although only two cartridges are shown in this figure) connected by the outlet manifold 161 and the intake manifold 162 for parallel flow. Using three cartridges may provide higher flow rates and improved filtration of volatile organic compounds compared to a system with two cartridges. In FIG. 8, the outlet manifold 161 is coupled to the housing 165 and the inlet manifold 162 using fasteners such as screws. Coaxial holes 169 are provided in the outlet manifold 161, the housing 165, and the inlet manifold 162 to receive such fasteners. Alternatively, an arrangement such as that shown in FIG. 7 may be used.

[0091] Figure 9 illustrates the effectiveness of an air purification system (similar to that shown in Figure 7) according to one embodiment, showing counts per scan (inverted) for a prior art breath sampling air purification system 172 and an air purifier according to one embodiment 160. The level of contaminants present in the purified air is substantially lower with the air purifier according to one embodiment.

[0092] 10 and 11 show a system 250 for transporting breath sampling consumables. The system 250 includes an insulated case (with a base 257 and a lid 258), a tray 254, a pivotable cap socket 252, a fixed cap socket 263, and a coolant container 251. The storage consumables include a sample container 113, a sampler 110, non-transitory machine-readable instructions 255 (e.g., a user manual for a breath sampling device or system or instructions for setting up a computer to control a breath sampling system), for example, on a USB drive, a mask 101, a mouthpiece 103, and / or human-readable instructions 256, 104.

[0093] The system 250 is configured to allow the sample vessels 113 to sealingly engage (mate) with the tray 254 while minimizing contact with the sample vessels 113. For example, the tray 254 includes slots for the sample vessels 113 that engage with the sampler 110. The sample vessel caps 108 may be placed in the pivoting sockets 252, and the exposed ends of the sample vessels 113 may be inserted into the end cap (while retaining the sampler 110). The sampler caps 109 may then be placed over the sampler 110 to seal the sampler opening 118. The sample vessels 113 and sampler 110 may then be rotated (as indicated by arrow 260 in FIG. 11 ) such that the sampler cap 109 is received and held in place by a locking socket defined in the tray 254.

[0094] Alternatively, the sampler 110 may be removed from the sample container 113 and the sample container caps 108 may be used to seal each end of the sample container 113. One of the tube caps 108 may again be received in the pivot socket 252, and the sample container 113 may then be rotated to engage the other end cap in the fixed socket 263. This system makes it easy to cap the sample container 113 with minimal effort and minimal contact, reducing the risk of sample contamination.

[0095] To ensure that the VOCs are retained within the sample container 113 and remain stable during transport, the system may be provided with a coolant bag to maintain a low temperature inside the insulated case. The coolant bag may contain, for example, water or a suitable phase change material such as sodium polyacrylate.

[0096] FIG. 12 illustrates a breath sampling system. The breath sampling system includes a breath sampling device 100, an air purifier 160, an air pump 170, and a controller 180. The breath sampling device 100 may be, for example, as shown in FIGS. 1 to 5, and the air purifier may be as shown in FIGS. 6 and / or 7. The air pump 170 is connectable to the air purifier 160 and pumps air through the air purifier 160 to supply to the breath sampling device 100. This allows positive pressure to be maintained while the breath sampling device 100 is placed on the patient's face. A controller 180 is provided that includes the sampling pump, a pressure sensor, and control logic (e.g., a microprocessor). The controller 180 includes a sampling port and a pressure port for connection to the sample conduit 134 and the pressure conduit 132, respectively. The controller may be configured to pump a breath sample into a sample container during a specific, preselected portion of the patient's respiratory cycle. For example, the end tidal portion of the respiratory cycle may be targeted for sampling based on pressure fluctuations detected by a pressure sensor via pressure conduit 132 .

[0097] FIG. 13 is a diagram of an alternative breath sampling system (BreathTrace) similar to FIG. 12. As in FIG. 12, the breath sampling system includes a breath sampling device, an air purifier, an air pump, and a controller. The breath sampling system of FIG. 13 further includes a quality control system 190. A thermal desorption tube can be placed in a port of the quality control system 190. The quality control system 190 includes a valve connected to the controller. This allows the system to collect environmental samples or system blank samples.

[0098] 14 and 15 show example results 301 obtained by GC-MS analysis of a sample obtained according to an embodiment, compared with results 302 obtained using an existing market-leading breath sampling device. Results 302 from the prior art breath sampling device contain contamination from the collected water, which can interact with the active phase in the thermal desorption trap and the stationary phase in the gas chromatography column to produce cyclic siloxanes. This can result in continuous and irreversible hydrolysis and degradation of analytes, resulting in retention time variations and the separation of features useful as biomarkers. This variation complicates data modeling and reduces the likelihood of discovering potential biomarkers and their validity and accuracy. Sampler 110 provides more constant-rate sampling, thereby reducing the amount of water collected, protecting sample container 113 from operator contact and reducing the likelihood of glove-related VOCs being included in the analytical sample. These improvements are evident from the comparison of results 301 and 302. Results obtained from market leading prior art devices include a contaminant feature C associated with water retention in the collected breath sample, which is avoided in certain embodiments.

[0099] Figure 16 shows a breath sampling system 400 similar to that of Figure 13. As shown in this example, the breath sampling system may be contained in a single container or housing, such as a briefcase 401. In other examples, the housing may take other forms, such as a box with a removable lid. The left-hand view shows the exemplary system 400 presented in operation, with the lid of the briefcase 401 open. The right-hand view shows the system 400 with the faceplate 402 removed, exposing the interior of the system 400 contained in the bottom half of the briefcase 401.

[0100] The faceplate 402 is secured to the briefcase using screws 403 when not removed. In other embodiments, the inner faceplate may be secured with other mechanisms, such as a rotating cam lock or latch. The faceplate 402 of FIG. 16 is configured to allow operation of the system 400 while in place. The faceplate 402 has an air supply intake 404. The inner faceplate is configured to allow user access to a sample pump control 405, a selector dial 406, and an air supply on / off button 407.

[0101] 16, the internal faceplate 402 is further configured with a conduit joint 408 passing through the faceplate 402. The conduit joint 408 fluidly couples the air cleaner 160 to the intake conduit 125. The conduit joint 408 may be disconnected from the air cleaner 160 when the faceplate 402 is removed. In some embodiments, the conduit joint 408 may be attached with a twist lock mechanism or screws.

[0102] The housing 401 or faceplate 402 may be configured to hold the handle 120 or mask of the breath sample obtaining device when the housing 401 is closed or open. The faceplate shown has recesses in which the handle 120 and mask 101 can be stored. Additionally, the lid of the briefcase 401 includes a retaining fixture 409. The retaining fixture 409 can be used to hold the handle 120 and mask 101 connected during operation.

[0103] Beneath the faceplate 402, the briefcase 401 also houses the air supply 170 and the sample pump 180. Removing the faceplate 402 allows the user to access the locking mechanism 164 of the air filter 160, for example if the filter cartridge needs replacing, or to access the battery release button 410 of the air supply.

[0104] The system 400 may also include a pump charging connector 411 and a USB laptop connector 412 accessible through the housing 401 .

[0105] According to one embodiment, the selector dial 406 is configured to operate a mode selection valve. In one example, the selector dial 406 has two positions corresponding to two operating modes of the mode selection valve. In the first position, the selector valve fluidly couples the sample pump 180 to a port to collect ambient air. A sample container may be inserted into the port to obtain a sample of ambient air. In the second position, the mode selection valve fluidly couples the sample pump to a sample conduit located inside the inhalation conduit 125 so that a sample of the patient's exhaled breath is obtained in the sample container. With the selector dial 406 and mode selection valve, the example system can take both an ambient or environmental sample and a sample of the patient's exhaled breath.

[0106] FIG. 17 illustrates an exemplary method 500 for obtaining a breath sample using a breath sampling system (such as the system shown in FIG. 16).

[0107] The breath sample collection method 500 of FIG. 17 includes the following steps. i) Pre-sampling Pre-sampling involves inspecting the inventory to be used, sanitizing the system, drying, recording the sanitizer used, checking tubing, and ensuring sampling containers are securely capped. ii) Environmental Test 520. Environmental Test 520 involves setting the system selector dial 406 to the correct position (first position), turning on the air supply, turning on the sampler pump, starting the software app, inserting the thermal desorption tube 511, and pressing the app sample button to allow air to flow into the thermal desorption tube 511. iii) Control Test 530 The control test 530 includes setting the system selector dial 406 to the correct position (second position), inserting a new mask 101 and handset filter, inserting the thermal desorption tube 512 with the head 110, pressing the app sample button (which allows air to flow into the control thermal desorption tube 512), and removing and capping the thermal desorption tube 512. iv) Breath test 540 The breath test 540 includes inserting a new thermal desorption tube 513 with the head 110, allowing the patient to wear the mask 101 for comfort, pressing the learn button on the app, pressing the start button on the app to collect breath into the thermal desorption tube 513, removing and capping the thermal desorption tube 513, and removing the mask 101 and filter. v) Post-sampling 550 Post-sampling 550 includes storing the samples in a refrigerator and recording the results and outcomes as required.

[0108] At the start of the control test 530, the mask 101 may be attached to the handle 120 of the device to obtain a breath sample. The mask 101 may be detached from the handle at the end of the breath test 540. During the control test 530, the mask 101 and handle 120 may be stored in the handle fixture 409.

[0109] In some examples, samples may be taken, such as an environmental sample 511, a control sample 512, and a breath sample 513. The samples may be collected in a container, such as a thermal desorption tube. The container may include a cap 108 and a sampler head 110. The head 110 may be attached to the tube or container with a groove 126.

[0110] While specific embodiments have been described, variations are possible and the scope of protection should be determined with reference to the appended claims.

Claims

1. 1. An apparatus for obtaining a breath sample from a patient, comprising: a mask or mouthpiece for receiving exhaled breath from the patient; an outlet for expelling exhaled air from the device; A sampler and a sample container for sampling volatile organic compounds; a handle for holding the device; Equipped with The sampler comprises: a distal portion configured to protrude into the flow of exhaled air from the mask or mouthpiece; a sampler opening in a sidewall of the distal portion for obtaining a breath sample; a proximal portion configured to engage the sample vessel and seal the exterior of the sample vessel; The sample container is a receptacle for receiving a breath sample from the sampler, the receptacle being in communication with the sampler; the sample vessel and the sampler are housed in the handle; The sample container is removable from the device by pulling on the sampler.

2. The device of claim 1 , wherein the sampler opening is spaced from the tip of the distal portion.

3. The device of claim 2 , wherein the tip of the distal portion comprises an end flange.

4. 10. The apparatus of claim 1, wherein the sampler comprises an internal groove and an O-ring seal, the O-ring seal disposed within the internal groove to form a seal with the exterior of the sample container.

5. The apparatus of claim 1 , further comprising a filter downstream of the sampler.

6. 6. The device of claim 1, wherein the sampler is configured for sealing engagement with the handle.

7. 7. The device of claim 1, wherein the handle comprises a manually operable clip for locking and unlocking engagement of the mask or mouthpiece with the handle.

8. 8. The device of claim 7, wherein the handle comprises an inner sleeve and an outer sleeve, the handle being securable to the mask or mouthpiece by sandwiching the mask or mouthpiece between the inner sleeve and the outer sleeve.

9. 9. The device of claim 1, wherein the handle comprises a pressure probe for transmitting fluid pressure to a pressure sensor.

10. 10. The device of any one of claims 1 to 9, wherein the handle comprises an inhalation conduit for providing air to the mask or mouthpiece for breathing by the patient.

11. 11. A breath sampling system comprising a device according to any one of claims 1 to 10 and an air purifier having at least one cartridge filter configured to purify the air supplied to the device.

12. The breath sampling system of claim 11, wherein the air purifier includes two cartridge filters, and the two cartridge filters are configured in parallel so that air supplied to the device is branched and introduced into the two cartridge filters, purified, and then supplied to the device.

13. 12. The breath sampling system of claim 11, further comprising a manual latch for gaining access to the cartridge filter for replacement of the cartridge filter.

14. 14. A system for breath sampling, comprising: a breath sampling system according to any one of claims 11 to 13; and a controller configured to control the flow of the breath sample through the sample container.

15. 1. A method of collecting exhaled breath from a patient for analysis, comprising: receiving exhaled breath from the patient via a mask or mouthpiece into a breath sampling device; and drawing a sample from the flow of breath through the breath sampling device into a sample container for sampling volatile organic compounds via a sampler that engages an end of the sample container; the sample container and sampler are housed in a handle for holding the breath sampling device; the sample container is removable from the breath sampling device by pulling on the sampler; 11. A method, wherein the breath sampling device is a device according to any one of claims 1 to 10.

16. 16. The method of claim 15, further comprising providing a supply of clean air to the breath sampling device for the patient to breathe.

17. an apparatus for obtaining a breath sample from a patient, the apparatus comprising a mask or mouthpiece for receiving breath from the patient, a handle for holding the apparatus, a sampler, and a sample container for sampling volatile organic compounds for receiving the breath sample from the patient, the sample container and sampler being housed in the handle, and the sample container being removable from the apparatus by pulling on the sampler; a controller including a sample port and a sample pump configured to draw air through the sample port; a mode selection valve in fluid communication with the sample pump; a sample conduit connecting the mode selection valve and the sample container; a port for connecting to another sample container for sampling ambient air; The sampler comprises: a distal portion configured to protrude into the flow of exhaled air from the mask or mouthpiece; a sampler opening in a sidewall of the distal portion for obtaining a breath sample; a proximal portion configured to engage the sample vessel and seal the exterior of the sample vessel; The mode selection valve is operable to selectively connect the sample pump to the sample conduit to collect exhaled breath into the sample container, or to connect the sample pump to the port to collect ambient air into the other sample container.

18. 18. The breath sampling system of claim 17, wherein the device for obtaining a breath sample further comprises an outlet through which exhaled breath exits the device.

19. 19. A breath sampling system as claimed in claim 17 or 18, wherein the device for obtaining a breath sample is a device as claimed in any one of claims 1 to 10.

20. 20. The breath sampling system of any one of claims 17 to 19, further comprising an air purifier configured to supply air to the mask or mouthpiece.

21. 21. The breath sampling system of claim 20, wherein the air purifier comprises at least one cartridge filter configured to purify the air supplied to the device.

22. 22. The breath sampling system of claim 20 or 21, wherein the mask or mouthpiece is fluidly coupled to the air purifier by a flexible tube.

23. 23. A breath sampling system as described in any one of claims 20 to 22, wherein the air purifier and controller are contained in a container or housing.

24. 24. A breath sampling system as described in any one of claims 17 to 23, wherein the mode selection valve is contained in a container or housing.

25. 25. A breath sampling system according to claim 23 or 24, wherein the container or housing further comprises a holding fixture configured to hold the device for obtaining a breath sample.

26. 26. A breath sampling system according to any one of claims 17 to 25, wherein the controller is configured to wirelessly connect to a remote computer.

27. 27. The breath sampling system of claim 26, wherein the remote computer is a mobile computing device.

28. 28. The breath sampling system of claim 27, wherein the mobile computing device comprises software for controlling the controller and / or air purifier.

29. 1. A method for collecting exhaled breath from a patient using a breath sampling system, comprising: obtaining an environmental sample of ambient air; obtaining a control sample using a device for obtaining a breath sample from a patient; and obtaining a breath sample from a patient using said device for obtaining a breath sample from a patient; The apparatus for obtaining a breath sample from a patient comprises: a mask or mouthpiece for receiving exhaled breath from the patient; a handle for holding the device; A sampler and a sample container for sampling volatile organic compounds; The sampler comprises: a distal portion configured to protrude into the flow of exhaled air from the mask or mouthpiece; a sampler opening in a sidewall of the distal portion for obtaining a breath sample; a proximal portion configured to engage the sample vessel and seal the exterior of the sample vessel; the sample container is a container for receiving a breath sample from the patient; the sample container and sampler are housed in the handle; The method wherein the sample vessel is removable from the device by pulling on a sampler.

30. 30. The method of claim 29, wherein the breath sampling system is a system according to any one of claims 17 to 28.

31. the environmental sample is taken using a port for sampling ambient air, and the control sample and the exhaled breath sample are taken using sample conduits connected to a mask or mouthpiece of the device for obtaining exhaled breath samples from a patient; The method comprises:

31. The method of claim 30, further comprising, after obtaining the environmental sample and before obtaining the control sample, moving a selection valve from a first position in which a sample pump is fluidly coupled to the port to sample ambient air, to a second position in which a sampler pump is coupled to the sample conduit connected to the mask or mouthpiece.

32. 32. The method of any one of claims 29 to 31, further comprising providing a supply of clean air to a mask or mouthpiece for the patient to breathe.

33. 33. The method of any one of claims 29 and 32, further comprising obtaining the control sample while the device for obtaining the breath sample is housed in a holding fixture of a container or housing of a breath sampling system.

34. 34. The method of claim 33, further comprising, after obtaining the control sample and prior to obtaining the breath sample from the patient, removing the device for obtaining the breath sample from the holding fixture and attaching the device to the patient.

35. 34. The method of any one of claims 29 to 33, further comprising at least partially instructing the breath sampling system to obtain at least one of the samples in response to user input using a mobile computing device.

36. 36. The method of claim 35, wherein the mobile computing device is a smartphone, and the user input comprises pressing a button on an app, the button pressing instructing the breath sampling system to obtain one of the samples.

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