Sampling device and method for exhalation sample

Abstract

To provide a sampling device and method for an exhalation sample.SOLUTION: An exhalation input interface is configured to receive discharged exhalation. A conduit system is configured to extend from the exhalation input interface and receive an exhalation sample storage device in a first end of the conduit system. A storage device valve is arranged in the conduit system toward the first end of the conduit system. At least one controller is configured to allow the exhalation storage valve to be opened and allow the conduit system between the exhalation input interface and the storage device valve to be filled with the exhalation received via the exhalation input interface before the exhalation sample storage device is connected to the first end of the conduit system, and to allow the storage device valve to be closed before the exhalation sample storage device is connected to the conduit system.SELECTED DRAWING: Figure 4B

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application is a continuation of U.S. Patent Application No. 16 / 805,156, filed on February 28, 2020, the entire content of which is incorporated herein by reference.

[0002] This specification generally relates to sample collection systems, and more particularly to an apparatus and method for collecting breath samples.

Background Art

[0003] Conventionally, breath sample collection has been performed by collecting a patient's breath into a large container. Thereafter, the breath sample is extracted from the container and transferred directly to an analyzer.

[0004] More recently, breath samples have been collected in a breath sample storage device known as an adsorbent tube or a thermal desorption tube. An adsorbent tube is a tube containing a solid adsorbent material with a large surface area. When a gas sample is passed through the adsorbent tube, some components such as oxygen and carbon dioxide flow out from the opposite end of the adsorbent tube, while other components are adsorbed by the adsorbent. This enables many components in the breath sample to be captured by the adsorbent while allowing the most voluminous components to flow out, thereby concentrating the breath sample. As a result, most of the components of the breath sample can be collected within a smaller volume.

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, there are many problems with devices that allow humans to directly fill these adsorbent tubes. There is a significant amount of humidity in human breath that can interfere with exhale collection in this mode. This humidity can cause condensation inside the conduit that directs the exhale to the adsorbent tube. This condensation attracts many of the components of the exhale that freely adhere to water molecules. As a result, many of the exhale sample components do not reach the adsorbent tube and thus do not appear in at least part of the exhale sample to be analyzed.

[0006] Another problem is that the adsorbent tube more effectively captures the components of the exhale at a specific flow rate of the exhale through the adsorbent tube. In prior art devices, the rate at which the exhale flows through the adsorbent tube is driven by the rate at which a person blows the exhale into these devices. This leads to some loss of the exhale sample.

Means for Solving the Problems

[0007] In one aspect, there is provided a device for collecting an exhale sample, comprising an exhale input interface configured to receive the exhaled breath, a container connected to the exhale input interface for storing at least a portion of the exhale, and at least one controller configured to control the flow of at least a portion of the exhale from the container to at least one adsorbent tube connected to the container, asynchronously with respect to when the exhale is received.

[0008] The container can have a cavity in which at least a portion of the exhale is stored, and the volume of the cavity is controllable. The volume of the cavity can be controllable by the at least one controller. The container can include a piston chamber having a piston disposed therein, and the position of the piston controls the volume of the cavity. The at least one controller can be configured to operate the piston to increase the volume of the cavity as at least a portion of the exhaled breath is received.

[0009] The device may further include a valve located between the exhalation input interface and the container, a first conduit system connecting the exhalation input interface and the valve, and a second conduit system connecting the container to the at least one adsorbent tube. The at least one controller may be configured to control the closing of the valve and to control the operation of the piston to push out at least a portion of the exhaled air through a subset of the at least one adsorbent tube. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The at least one controller may be configured to control each of the at least one tube inlet valve to select the subset of the at least one adsorbent tube through which at least a portion of the exhaled air flows.

[0010] The subset may be a first subset, and the device may further include an inlet valve disposed along the second conduit system between the inlet and the container. The at least one controller may be configured to open the inlet valve and to control the operation of the piston to draw air into the cavity through the inlet. The at least one controller may be configured to close the inlet valve and to propel the drawn-in air from the cavity through the second conduit system. The at least one controller may be configured to control the operation of the piston to propel the drawn-in air through a second subset of the at least one adsorbent tube. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The at least one controller may be configured to control each of the at least one tube inlet valve to select the second subset of the at least one adsorbent tube through which the drawn-in air flows.

[0011] ​The container may include at least a partially flexible collapsible receptacle. The apparatus may further include a valve intermediate the exhalation input interface and the container, a first conduit system connecting the exhalation input interface and the valve, and a second conduit system connecting the container to the at least one adsorbent tube. The apparatus may further include a pump controlled by the at least one controller and capable of propelling at least a portion of the exhalation through a subset of the at least one adsorbent tube from the container. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The at least one controller may be configured to control each of the at least one tube inlet valve to select the subset of the at least one adsorbent tube through which at least a portion of the exhalation flows.

[0012] The pump may be disposed between the valve and the container, and the at least one controller may be configured to control the pump to draw at least a portion of the exhaled breath into the container.

[0013] The subset may be a first subset, and the apparatus may further include an inlet valve disposed along the second conduit system between the inlet and the container. The at least one controller may be configured to close the inlet valve and control the pump to flow air from the container through a second subset of the at least one adsorbent tube. The at least one controller may be configured to open the inlet valve and control the pump to flow air through the inlet into the cavity. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The at least one controller may be configured to control each of the at least one tube inlet valve to select the first subset of the at least one adsorbent tube through which at least a portion of the exhalation flows.

[0014] The device may further include a valve intermediate the exhalation input interface and the container, and a first conduit system connecting the exhalation input interface and the valve. The at least one controller may be configured to control the volume of the container by closing the valve when the target volume of exhalation is captured within the container, and to propel at least a portion of the exhalation through a subset of the at least one adsorbent tube. The at least one controller may be configured to control the volume of the container to decrease with one of at least two exhalation flow rates at which the at least one controller can control the volume of the container to propel the exhalation through the subset of the at least one adsorbent tube.

[0015] In another aspect, a method of collecting an exhaled sample is provided, the method including receiving exhaled breath through an exhalation input interface, storing at least a portion of the exhalation in a container connected to the exhalation input interface, and controlling, via at least one controller, a flow rate of at least a portion of the exhalation from the container to at least one adsorbent tube connected to the container asynchronously with receiving the exhaled breath.

[0016] The step of storing may include storing at least a portion of the exhaled breath in the cavity of the container, and the volume of the cavity may be controllable. The method may further include controlling the volume of the cavity via the at least one controller. The method may further include operating a piston disposed in the piston chamber of the container via the at least one controller, wherein the position of the piston controls the volume of the cavity. The method may further include operating the piston to increase the volume of the cavity when receiving at least a portion of the exhaled breath. The method may further include controlling the flow of at least a portion of the exhaled breath via a valve intermediate the breath input interface and the container, with a first conduit system connecting the breath input interface and the valve, and a second conduit system connecting the container to the at least one adsorbent tube. The method may further include controlling the at least one controller to close the valve and controlling the operation of the piston to propel at least a portion of the breath through a subset of the at least one adsorbent tube. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube, and the method may further include controlling each of the at least one tube inlet valve to select the subset of the at least one adsorbent tube through which at least a portion of the breath flows.

[0017] The method may further include controlling the at least one controller to close the valve, controlling to open an inlet valve that separates the container from the inlet, controlling the operation of the piston to draw air into the cavity through the inlet, controlling to close the inlet valve, and controlling the operation of the piston to propel the drawn air from the cavity through the second conduit system.

[0018] The method may further include controlling the operation of the piston to propel the captured air through a second subset of the at least one adsorbent tube. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The method may further include controlling each of the at least one tube inlet valve to select the second subset of the at least one adsorbent tube through which the captured air flows.

[0019] The container may include at least a partially flexible collapsible receptacle. The method may further include controlling the flow of at least a portion of the exhaled breath through a valve intermediate the exhalation input interface and the container, a first conduit system connecting the exhalation input interface and the valve, and a second conduit system connecting the container to the at least one adsorbent tube. The method may further include controlling a pump to flow at least a portion of the exhaled breath from the container through a subset of the at least one adsorbent tube. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The method may further include controlling each of the at least one tube inlet valve to select the subset of the at least one adsorbent tube through which at least a portion of the exhaled breath flows.

[0020] The pump may be disposed between the valve and the container, and the method may further include controlling the pump to draw at least a portion of the exhaled breath into the container.

[0021] The subset can be a first subset, and the method may further include closing the valve, opening an inlet valve intermediate the inlet and the container, and controlling the pump to flow air through a second subset of the at least one adsorbent tube. The method may further include opening the inlet valve and controlling the pump to flow air through the inlet into the cavity. A tube inlet valve may be disposed between each of the container and the at least one adsorbent tube. The method may further include controlling each of the at least one tube inlet valve to select the subset of the at least one adsorbent tube through which at least a portion of the exhaled breath flows.

[0022] The method may further include controlling the flow of the exhaled breath discharged through the valve to the container from a first conduit system to which the exhaled breath input interface is connected. The method may further include controlling to close the valve and controlling the volume of the container to flow at least a portion of the exhaled breath through a subset of the at least one adsorbent tube when a target volume of the exhaled breath is captured within the container. During the step of controlling the volume, the volume may be controlled to decrease at one of at least two exhaled breath flow rates such that the volume decreases to propel the exhaled breath through the subset of the at least one adsorbent tube.

[0023] In a further aspect, there is provided an apparatus for collecting an exhaled breath sample, the apparatus comprising: an exhaled breath input interface configured to receive the exhaled breath; a metering device configured to measure a component level in the received exhaled breath; a first conduit system extending from the exhaled breath input interface and connected to at least one exhaled breath sample storage device; a valve disposed along the first conduit system and configured to control the flow of the exhaled breath towards the at least one exhaled breath sample storage device; and at least one controller configured to determine whether the component level is within a component level target range, determine whether a rate of change of the component level is within a component level rate of change target range, and control the valve to open based at least in part on whether the component level is within the component level target range and whether the rate of change is within the component level rate of change target range.

[0024] The metering device can be a capnometer, the component level can be a carbon dioxide level, the component level target range can be a carbon dioxide level target range, and the component level rate of change target range can be a carbon dioxide level rate of change target range. The apparatus can further include a flow meter configured to measure a flow rate of the received exhaled breath, and the at least one controller can be configured to control the valve to open based at least in part on the measured flow rate being within a flow rate target range. The apparatus can further include a display, and the at least one controller can be configured to control the display to present a flow rate notification on the display.

[0025] The apparatus can further include at least one optical element, and the at least one controller can be configured to control the at least one optical element to present a flow rate notification with the at least one optical element.

[0026] The apparatus may further include a speaker, and the at least one controller is configured to control the speaker to play an audible flow rate notification via the speaker.

[0027] The component level target range may span between a component level minimum threshold and an infinite upper limit.

[0028] The component level change rate target range may span between a negative infinite lower limit and a component level change rate maximum threshold.

[0029] The flow rate target range may span between a minimum flow rate threshold and an infinite upper limit.

[0030] The at least one controller may be configured to monitor the component level after opening the valve.

[0031] The apparatus may further include a flow meter configured to measure the flow rate of the exhaled breath received, and the at least one controller is configured to monitor the flow rate after opening the valve and control to close the valve at least partially based on the measured flow rate being within a flow rate end range.

[0032] In yet another aspect, a method of collecting an exhaled breath sample is provided, the method including the step of receiving the exhaled breath through an exhalation input interface through which a first conduit system extends toward at least one exhaled breath sample storage device, a valve being arranged to control the movement of the exhaled breath from the first conduit system to the at least one exhaled breath sample storage device, and determining, via at least one controller, whether the component level in the received exhaled breath is within a component level target range, and determining that a rate of change of the component level is within a component level rate of change target range, and controlling the valve to open at least partially based on whether the component level is within the component level target range and whether the rate of change is within the component level rate of change target range.

[0033] The component level can be a carbon dioxide level, the component level target range can be a carbon dioxide level target range, and the component level rate of change target range can be a carbon dioxide level rate of change target range.

[0034] The method can further include the step of measuring a flow rate of the received exhaled breath, and capturing can be performed at least partially based on the measured flow rate being within a flow rate target range. The method can further include the step of controlling a display to present a flow rate notification on the display. The method can further include the step of controlling at least one optical element to present a flow rate notification with the at least one optical element.

[0035] The method can further include the step of controlling a speaker to reproduce an audible flow rate notification through the speaker.

[0036] The carbon dioxide level target range can span between a carbon dioxide level minimum threshold and an infinite upper limit.

[0037] The carbon dioxide level change rate target range can span between the negative infinity lower limit and the carbon dioxide level change rate maximum threshold value.

[0038] The flow rate target range can span between the minimum flow rate threshold value and positive infinity.

[0039] The method may further include a step of monitoring the carbon dioxide level after opening the valve.

[0040] The method may further include a step of measuring the flow rate of the exhaled breath received, and the at least one controller is configured to monitor the flow rate after opening the valve and control the valve to close based at least in part on the measured flow rate being within the flow rate end range.

[0041] In yet another aspect, there is provided an apparatus for collecting an exhaled breath sample, the apparatus comprising an exhaled breath input interface configured to receive exhaled breath, a first conduit system connected to the exhaled breath input interface, a valve configured to control fluid communication between the first conduit system and at least one exhaled breath sample storage device configured to store an exhaled breath sample, an air circulation system configured to circulate air through the first conduit system upon completion of the first received exhaled breath, and at least one controller configured to control the valve upon completion of the first received exhaled breath based at least in part on a humidity level within the first conduit system.

[0042] The at least one controller may be configured to control the valve based at least in part on whether a rate of change of the humidity level is within a target range of the humidity level rate of change. The at least one controller may be configured to close the valve to inhibit passage of subsequent exhaled breath from the first conduit system to the at least one exhaled breath sample storage device until the rate of change of the humidity level in the first conduit system is within the target range of the humidity level rate of change. The apparatus may further include a hygrometer connected to the first conduit system and configured to measure the humidity level in the first conduit system. The apparatus may further include a notification system for indicating when the rate of change of the humidity level in the first conduit system is within the target range of the humidity level rate of change.

[0043] The first conduit system may include an exhaled breath suction conduit extending between the exhaled breath input interface and the valve, and the hygrometer may be connected to an exhaust conduit of the first conduit system that branches from the exhaled breath suction conduit. The fluid circulation system may be directly connected to the exhaust conduit. The exhaust conduit may include a flow meter configured to measure a flow rate along the exhaust conduit.

[0044] The at least one controller may be configured to control the valve based at least in part on whether the humidity level is within a target range of the humidity level. The at least one controller may be configured to close the valve to inhibit passage of subsequent exhaled breath from the first conduit system to the at least one exhaled breath sample storage device until the humidity level in the first conduit system is within the target range of the humidity level.

[0045] In another aspect, a method for collecting an exhaled breath sample is provided, the method comprising receiving the exhaled breath through an exhaled breath input interface connected to a first conduit system; collecting at least a portion of the exhaled breath through at least one exhaled breath sample storage device connected to the first conduit system; detecting the completion of the exhaled breath; closing a valve between the first conduit system and the at least one adsorbent tube upon detection of the completion of the exhaled breath; circulating air through the first conduit system connected to the exhaled breath input interface after detecting the completion of the exhaled breath; monitoring a humidity level within the first conduit system; and controlling the valve at least in part based on the humidity level within the first conduit system via at least one controller.

[0046] The controlling step may include determining whether a rate of change of the humidity level is within a target range of humidity level change rates. The method may further include controlling to close the valve and suppress passage of subsequent exhaled breath from the first conduit system to the at least one exhaled breath sample storage device until the rate of change of the humidity level within the first conduit system is within the target range of humidity level change rates. The method may further include measuring the humidity level within the first conduit system via a hygrometer connected to the first conduit system. The method may further include indicating when the rate of change of the humidity level is within the target range of humidity level change rates.

[0047] The first conduit system may include an exhaled breath suction conduit extending between the exhaled breath input interface and the valve, and the measuring step of the humidity level is performed by a hygrometer connected to an exhaust conduit of the first conduit system branching from the exhaled breath suction conduit. The fluid circulation system may be directly connected to the exhaust conduit. The method may further include measuring a flow rate along the exhaust conduit via a flow meter along the exhaust conduit.

[0048] The step of controlling may include determining whether the humidity level is within a target humidity level range. The method may further include controlling to close the valve and suppress passage of subsequent exhaled breath from the first conduit system to the at least one exhaled breath sample storage device until the humidity level in the first conduit system is within the target humidity level range.

[0049] In a further aspect, an exhaled breath sample collection device is provided, the device comprising an exhaled breath input interface configured to receive exhaled breath, a first conduit system connected to the exhaled breath input interface, and at least one exhaled breath sample storage device connected to the exhaled breath input interface via an exhaled breath intake conduit of the first conduit system extending between the exhaled breath input interface and the exhaled breath collection system, the at least one exhaled breath sample storage device being configured to capture at least a portion of the exhaled breath and further comprising at least one metering device for measuring at least one characteristic, the at least one metering device being arranged along the exhaust conduit of the first conduit system branching off from the exhaled breath intake conduit.

[0050] The at least one metering device may include a flow meter for measuring the flow rate of the exhaled breath along the exhaust conduit of the first conduit system. The at least one metering device may be arranged along the exhaust conduit of the first conduit system and may include a capnometer for measuring the carbon dioxide level in the exhaled breath.

[0051] The at least one metering device may include a hygrometer arranged along the exhaust conduit of the first conduit system for measuring the humidity level in the discharge conduit. The device may further include a pump arranged along the exhaust conduit of the first conduit system for flowing air through the exhaust conduit.

[0052] In yet another aspect, a method for collecting an exhaled breath sample is provided, the method comprising receiving the exhaled breath through an exhalation input interface, including a first conduit system connected to the exhalation input interface, and further capturing the exhaled breath through the exhalation collection system connected to the exhalation input interface via an exhalation suction conduit of the first conduit system extending between the exhalation input interface and the exhalation collection system, and measuring at least one characteristic along an exhaust conduit of the first conduit system branching from the exhalation suction conduit via at least one metering device disposed along the exhaust conduit.

[0053] The at least one metering device may include a flow meter, and the at least one characteristic may include the flow rate of the exhaled breath along the exhaust conduit.

[0054] The at least one metering device may include a capnometer, and the at least one characteristic may include the carbon dioxide level of the exhaled breath.

[0055] The method may further include measuring a humidity level along the exhaust conduit via a hygrometer disposed along the exhaust conduit of the first conduit system. The method may further include flowing air through the exhaust conduit via a pump disposed along the exhaust conduit.

[0056] In yet another aspect, an apparatus for collecting an exhaled breath sample is provided, the apparatus comprising an exhalation input interface configured to receive the exhaled breath, a container connected to the exhalation input interface for receiving at least a portion of the exhaled breath and having a controllable volume cavity, and at least one controller configured to control the volume of the cavity to increase at a volume increase rate that is at most equal to the flow rate of the exhaled breath received by the exhalation input interface.

[0057] The inhalation and exhalation conduit of the first conduit system can extend from the exhalation input interface towards the container. The exhaust conduit of the first conduit system branches from the exhalation collection part at its first end and has an outlet at its second end. The apparatus may further include a flow meter arranged to measure the flow rate along the exhaust conduit. The rate of increase in the volume of the container may be proportional to the flow rate along the exhaust conduit. The volume of the container may be directly mechanically controllable by the at least one controller. The container may include a piston chamber having an operable piston disposed therein, and the position of the piston in the piston chamber defines the volume of the cavity. The apparatus may further include a valve arranged to control the movement of the exhaled breath into the piston chamber. The apparatus may further include at least one adsorbent tube connected to the container, and the at least one controller is configured to control the valve to close and control the operation of the piston to propel the exhaled breath in the cavity through the at least one adsorbent tube.

[0058] The container may include at least a partially flexible collapsible receptacle, and the apparatus may further include a pump configured between the exhalation input interface and the container to be able to propel the exhaled breath into the at least partially flexible collapsible receptacle at the rate of increase in volume. The apparatus may further include at least one adsorbent tube connected to the at least partially flexible collapsible receptacle, and the at least one controller is configured to control the pump to propel the exhaled breath in the cavity through a subset of the at least one adsorbent tube. The apparatus may further include a valve arranged to control the movement of the exhaled breath into the piston chamber.

[0059] The device may further include a valve arranged to control the movement of the exhaled breath into the piston chamber. The device may further include a metering device arranged to measure a component level in the exhaust conduit, and the at least one controller is configured to determine whether the component level is within a component level target range, determine whether a rate of change of the component level is within a component level rate of change target range, and control the valve to open at least partially based on whether the component level is within the component level target range and whether the rate of change is within the component level rate of change target range. The metering device may be a capnometer, the component level may be a carbon dioxide level, the component level target range may be a carbon dioxide level target range, and the component level rate of change target range may be a carbon dioxide level rate of change target range.

[0060] The device may further include an exhalation suction conduit of a first conduit system extending from the exhalation input interface towards the container, and a flow meter arranged to measure a flow rate of the exhaled breath along the exhalation suction conduit. The rate of increase of the volume of the container can be made proportional to the flow rate along the exhalation suction conduit. The volume of the container may be directly mechanically controllable by the at least one controller. The container may include a piston chamber having an operable piston disposed therein, and the position of the piston within the piston chamber defines the volume of the cavity. The device may further include a valve arranged to control the movement of the exhaled breath into the piston chamber. The device may further include at least one adsorbent tube connected to the container, and the at least one controller is configured to control the valve to close and control the operation of the piston to propel the exhaled breath within the cavity through a subset of the at least one adsorbent tube.

[0061] The container may include at least a partially flexible collapsible receptacle, and the apparatus may further include a pump configured intermediate the exhalation input interface and the container to propel the exhalation into the at least partially flexible collapsible receptacle at the volume increase rate.

[0062] In yet another aspect, a method of collecting an exhaled sample is provided, the method including receiving exhaled breath through an exhalation input interface and storing at least a portion of the exhaled breath in a container connected to the exhalation input interface, the container having a controllable volume cavity, and further including controlling, via at least one controller, the volume of the container to increase at a volume increase rate that is at most equal to the flow rate of the exhaled breath received by the exhalation input interface.

[0063] The exhalation suction conduit of the first conduit system can extend from the exhalation input interface toward the container, and the exhaust conduit of the first conduit system may branch from an exhalation collection section at its first end and have an outlet at its second end. The method may further include measuring the flow rate along the exhaust conduit via a flow meter. The volume increase rate of the volume of the container may be proportional to the flow rate. The method may further include directly mechanically controlling the volume of the container. The container may include a piston chamber in which a piston is disposed, the position of the piston defining the volume of the cavity, and the directly mechanically controlling step includes operating the piston. The method may further include moving the exhaled breath into the piston chamber via a valve disposed between the exhalation input interface and the container. The method may include controlling the valve to close and controlling the operation of the piston to propel the exhaled breath in the cavity through at least one adsorbent tube connected to the container.

[0064] The container may include at least a partially flexible foldable receptacle, and the method may further include propelling the exhaled breath into the at least partially flexible foldable receptacle at the rate of volume increase via a pump intermediate the exhalation input interface and the container.

[0065] The method may further include controlling the pump to propel the breath in the cavity through a subset of the at least one adsorbent tube connected to the at least partially flexible foldable receptacle. The method may include controlling the movement of the exhaled breath into the piston chamber via a valve.

[0066] The method may further include controlling the movement of the exhaled breath into the piston chamber via a valve. The method may further include measuring a component level in the exhaust conduit, comparing the component level with a component level target range via the at least one controller, comparing a rate of change of the component level with a component level rate of change target range, and controlling to open the valve at least partially based on whether the component level is within the component level target range and whether the rate of change is within the component level rate of change target range. The component level may be a carbon dioxide level, the component level target range may be a carbon dioxide level target range, and the component level rate of change target range may be a carbon dioxide level rate of change target range.

[0067] The exhalation suction conduit of the first conduit system can extend from the exhalation input interface towards the container, and the method can further include the step of measuring the flow rate of the exhaled breath along the exhalation suction conduit via a flow meter. The rate of increase in the volume of the container can be proportional to the flow rate. The method can further include the step of directly mechanically controlling the volume of the container by the at least one controller. The container can include a piston chamber having an operable piston disposed therein, and the method can further include the step of actuating the position of the piston in the piston chamber that defines the volume of the cavity. The method can further include the step of controlling the movement of the exhaled breath into the piston chamber via a valve. The method can further include the step of controlling the valve to close and the step of controlling the actuation of the piston to propel the exhaled breath in the cavity through a subset of at least one adsorbent tube connected to the container.

[0068] The container can include at least a partially flexible collapsible receptacle, and the method can further include the step of propelling the exhaled breath at the rate of increase in volume into the at least partially flexible collapsible receptacle via a pump disposed intermediate the exhalation input interface and the container.

[0069] Other technical advantages will be readily apparent to one skilled in the art from consideration of the following figures and description.

[0070] For a better understanding of the embodiments (s) described herein and to more clearly illustrate how the embodiments (s) may be implemented, reference will now be made, by way of example only, to the accompanying drawings.

Brief Description of the Drawings

[0071]

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Embodiments for Carrying Out the Invention

[0072] Unless otherwise specified, the articles depicted in the drawings are not necessarily drawn to scale.

[0073] For the sake of simplicity and clarity of the illustration, reference numerals may be repeated between figures to indicate corresponding or similar elements where considered appropriate. Further, numerous specific details are defined to provide a thorough understanding of one or more embodiments described herein. However, it will be understood by those skilled in the art that the embodiments described herein may be practiced without these specific details. In other instances, well-known methods, procedures, and components are not described in detail so as not to obscure the embodiments described herein. Typical embodiments are shown in the figures and described below, but it should first be understood that the principles of the present disclosure may be implemented using any number of techniques, whether currently known or not. The present disclosure should in no way be limited to the typical embodiments and techniques illustrated in the drawings and described below.

[0074] Throughout this specification, various terms can be interpreted as follows, unless the context indicates otherwise. "Or" used throughout is inclusive as if written "and / or", and singular articles and pronouns used throughout include their plurals and vice versa, and similarly, gender pronouns include their corresponding pronouns, so pronouns should not be understood to limit anything described herein to use, implementation, performance, etc. by a single gender, and "exemplary" should be understood as "illustrative" or "exemplifying" and not necessarily "preferred" over other embodiments. Further definitions of terms may be described herein and, as will be understood from reading this specification, may apply to prior and subsequent instances of those terms.

[0075] Without departing from the scope of the present disclosure, modifications, additions, or omissions may be made to the systems, apparatuses, and methods described herein. For example, the components of the systems and apparatuses may be integrated or separated. Further, the operations of the systems and apparatuses disclosed herein may be performed by more, fewer, or other components, and the methods described may include more, fewer, or other steps. Further, the steps may be performed in any suitable order. "Each" as used herein refers to each component of a set or each component of a subset of a set.

[0076] Any module, unit, component, server, computer, terminal, engine, or device that executes the commands may include a computer-readable medium such as a storage medium like a magnetic disk, optical disk, or tape, a computer storage medium, or a data storage device (removable and / or non-removable), or may access a computer-readable medium. The computer storage medium may include volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information such as computer-readable instructions, data structures, program modules, or other data. Examples of computer storage media include RAM, ROM, EEPROM, flash memory or other memory technologies, CD-ROM, digital versatile disk (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and can be accessed by an application, module, or both. Any such computer storage medium may be part of the device, or may be accessible or connectable to the device. Further, unless specifically stated otherwise in the context, any processor or controller defined in this specification may be implemented as a single processor or as multiple processors. The multiple processors may be arranged or distributed, and although a single processor is illustrated, any processing function referred to in this specification may be executed by one processor or by multiple processors. Any method, application, or module described in this specification may be stored by such a computer-readable medium or otherwise held and may be implemented using computer-readable / executable instructions that can be executed by one or more processors.

[0077] Figure 1 shows an exhaled breath sampling device 20 according to one embodiment. The exhaled breath sampling device 20 is capable of collecting an exhaled breath sample in an adsorbent tube asynchronously when the exhaled breath is provided. The exhaled breath sampling device 20 includes a container for receiving the exhaled breath. The exhaled breath is then flowed through one or more adsorbent tubes asynchronously when receiving the exhaled breath. Flowing the exhaled breath through one or more adsorbent tubes can be performed by generating a positive relative pressure difference to propel the exhaled breath, by generating a negative relative pressure difference to draw in the exhaled breath, or by any other suitable method. As a result, the adsorption of the exhaled breath by the adsorbent tube can be more precisely controlled.

[0078] The exhaled breath sampling device 20 includes an exhaled breath input interface 24 for receiving exhaled breath from a person. The exhaled breath input interface 24 includes a mouthpiece 36 fixed to an exhaled breath suction end 40 of an exhaled breath suction conduit 44 of a pre-sampling conduit system 46.

[0079] The mouthpiece 36 is preferably made of inexpensive polypropylene or other suitably safe material so as to be disposable / replaceable. More preferably, the mouthpiece 36 does not off-gas volatile organic compounds ("VOCs") or off-gases VOCs at a low rate so as not to significantly contaminate the exhaled breath sample. The mouthpiece 36 may include a virus / bacteria filter to exclude bacteria and fine particles from the sample. By making the mouthpiece 36 disposable, a new filter can be provided for each patient to avoid secondary contamination of the sample and the transmission of viruses, bacteria, etc.

[0080] The polypropylene of the mouthpiece 36 is transparent and slightly cloudy when the humidity is high. Since it may not be desirable to have condensation in the exhaled breath sampling device 20, this feature can be used to visually detect condensation.

[0081] In other embodiments, the exhaled breath input interface can be configured to receive exhaled breath from other animals.

[0082] The conduit of the exhaled breath sampling device 20 is made of stainless steel coated with an inert coating. The inert coating can be made of any suitably inert material such as a silica-based or quartz material.

[0083] The exhaust conduit 48 is connected to the exhaled breath suction conduit 44 at its first end and branches therefrom. A set of metering devices including a hygrometer 52 for measuring the humidity within the exhaust conduit 48 are arranged along the exhaust conduit 48. Condensation can deteriorate the function of the exhaled breath sampling device 20 in that components of a person's exhaled breath are trapped by this condensation and thus do not accurately appear in the sampled exhaled breath. Further, a certain level of humidity and / or condensation can affect the function of other components of the exhaled breath sampling device 20. A capnometer 56 is arranged along the exhaust conduit 48 to measure the carbon dioxide content of the patient's exhaled breath. Similarly, along the exhaust conduit 48, a flow meter 60 for measuring the flow rate of the exhaled breath along the exhaust conduit 48 is arranged. A low-pressure resistance portion 64 along the exhaust conduit 48 provides a low amount of resistance to the flow of gas along the exhaust conduit 48 towards the exhaust conduit outlet 68 at the second end of the exhaust conduit 48. The low-pressure resistance portion 64 functions as a cap on the exhaust conduit 48 to suppress the return diffused gas from entering the exhaust conduit 48 while allowing gas to flow in both directions as necessary. The low-pressure resistance portion 64 may be provided using any suitable structure such as a flexible or hinged flap, a constricted cross-section, or a section of conduit having a change (s) in direction.

[0084] The air circulation system includes a pump conduit 76 that branches from the exhaust conduit 48 and terminates at a pump 72 driven by a motor. The pump 72 is configured to draw ambient air through the exhaust conduit 48 and the exhaled breath suction conduit 44, and discharge it to the surrounding environment, if necessary, such as via the mouthpiece 36. Any fluid pump suitable for use with gases can be employed.

[0085] The inner diameter sizes of the mouthpiece 36 and the conduit portions 44, 48 are selected to provide only a slight resistance to the exhaled breath passing through the mouthpiece 36. Further, the conduit portions 44, 48 can be heated or cooled as desired to control the formation of condensation along there. This may be desirable to reduce the possibility of condensation passing through an exhaled breath sampling device such as an adsorbent tube.

[0086] The exhaled breath sampling valve 80 is connected to the exhaled breath suction conduit 44 and controls the flow of gas from the exhaled breath input interface 24 of the exhaled breath suction conduit 44 to the exhaled breath sampling conduit 84 of the exhaled breath capture conduit system 82. The exhaled breath suction conduit 44 forms part of a direct path between the exhaled breath input interface 24 and the exhaled breath capture conduit system 82. The suction valve 88 controls the flow of gas entering and leaving the exhaled breath sampling conduit 84 via the ambient air inlet 92. The air filter 96 is disposed between the ambient air inlet 92 and the suction valve 88 to filter the incoming ambient air and suppress the intrusion of particulate contamination therein.

[0087] The container is in fluid communication with the exhaled breath sampling conduit 84 and is configured to store the exhaled breath received from the exhaled breath sampling conduit. The container in this embodiment includes a piston chamber 100 having therein a cavity 104 at least partially defined by the inner wall of the piston chamber 100. The piston chamber 100 has a capacity of 2 liters and may have any suitable cross - sectional shape. The piston 108 is shaped to correspond to the piston chamber 100, is disposed within the piston chamber 100, and is driven by a piston motor 112. The piston 108 provides a hermetic seal against the side of the piston chamber 100. The piston motor 112 can be any suitable type of motor for operating the piston 108 within the piston chamber 100.

[0088] The volume of the cavity 104 can be directly mechanically controlled by the positioning of the piston 108 within the piston chamber 100 by the piston motor 112. Further, the rate of change of the volume of the cavity 104 is either to increase the volume of the cavity 104 to define a volume increase rate by operating the piston 108 within the piston chamber 100 at a corresponding speed to further move into the piston chamber 100, or to decrease the volume of the cavity 104 to define a volume decrease rate by further moving out of the piston chamber 100, and can be controlled by either of these.

[0089] In another embodiment, the piston chamber is configured to have an internal space, and the piston has a similar cross-sectional shape for slidably moving through the internal space of the piston chamber.

[0090] The exhalation collection conduit 84 is connected to the tube manifold 116. The tube inlet manifold 116 branches into four tube inlet valves 120. The bypass conduit 124 branches from the exhalation collection conduit 84 and has a bypass valve 128 disposed along the bypass conduit 124 to prevent or allow the flow of gas therealong. The outlet valve 132 is disposed toward the outlet 136 to control the flow of gas through the outlet 136. The tube outlet manifold 140 is connected to the bypass conduit 124 and branches into four tube outlet valves 144. The tube inlet valves 120 and the tube outlet valves 144 have connectors for receiving the adsorbent tubes. In other embodiments, the exhalation sample collection device 20 can be configured to receive and use any number of adsorbent tubes.

[0091] The controller 148 controls the operation of the exhalation sample collection device 20. The controller 148 is connected to the valves 80, 88, 120, 128, 132, and 144 and opens and closes these valves as described later in this specification. In other embodiments, the functions of the controller 148 can be performed by two or more controllers.

[0092] The display 150 is controlled by the controller 148, presents instructions and information to a person, and also presents measurements taken by the exhaled breath sampling device 20, such as the degree of completion of the procedure and the estimated remaining time.

[0093] Internal components that come into contact with the exhaled breath are generally inert. The conduits and valves are made of stainless steel and are provided with an inert coating. The sealing element within the valve is made of FKM, a family of fluoroelastomer materials, or other suitable elastic materials with a very low off-gassing rate. The mouthpiece 36 made of polypropylene may off-gas, but the level is within the acceptable tolerance level.

[0094] Referring now to FIG. 2, an exemplary adsorbent tube 152 is shown. The adsorbent tube 152 has a tubular stainless steel casing 156 that defines openings 160 at each of its ends. The receiving end 164 of the adsorbent tube 152 receives the gaseous fluid to be adsorbed. In a typical described embodiment, the gaseous fluid is human exhaled breath taken from a human for testing. A foam separator 168 is disposed towards the receiving end and is configured to more uniformly disperse the fluid pressure across the cross-section of the stainless steel casing 156. The adsorbent 172 is disposed adjacent to the foam separator 168 and another foam separator 110. The separators may alternatively be made of wire mesh or other suitable materials. The adsorbent 172 is highly porous, has a relatively high surface area, and is selected to sample specific compounds in order to capture and retain the target compound even in the presence of other compounds. Further, the adsorbent 172 enables the collected compound to be easily desorbed or extracted for analysis. Further, the selected solid adsorbent does not react with the sample. In a particular example, the solid adsorbent is Tenax TA or a carbon material. When the gaseous fluid is received via the receiving end 164, the sample is concentrated towards the receiving end 164 of the adsorbent tube 152. In other embodiments, the composition and configuration of the adsorbent tube may vary as would be understood by those skilled in the art.

[0095] Next, a method 200 for collecting an exhaled breath sample using the exhaled breath sampling device 20 will be described with reference to FIGS. 1, 3, and 4A to 4G.

[0096] The method 200 begins by drawing ambient air into the system (210). The system draws in ambient air and then discharges it through conduits 44, 48, 68, 76, 84, and 124 to flush out any stagnant residual air. This is done to ensure that there is no cross - contamination between the currently collected exhaled breath and the exhaled breath from the previous person. The stagnant indoor air within the system is replaced with fresh indoor air during this flushing.

[0097] First, it is confirmed that valves 80, 120, and 128 are closed. Next, the controller 148 instructs the suction valve 88 to open and operates the piston motor 112 to instruct the piston 108 within the piston chamber 100 to retract. When the piston 108 is retracted within the piston chamber 100, the volume of the cavity 104 defined by the inner wall of the piston chamber 100 and the piston 108 hermetically sealed therein increases. As a result, the pressure within the cavity 104 rapidly decreases. Ambient air is drawn into the cavity 104 through the ambient air inlet and the air filter 96.

[0098] FIG. 4A shows the cavity 104 filled with the drawn - in ambient air. Hereinafter, for the sake of explanation, open valves are shown with dotted markings and closed valves have no dotted markings. The air filter 96 removes fine particles from the ambient air when the ambient air is being drawn in and before it enters the exhaled breath collection conduit 84. During this inhalation of ambient air, the exhaled breath collection valve 80 is closed, but there may be traces of the previous person's exhaled breath along the exhaled breath suction conduit 44 and the exhaust conduit 48. It is desirable to keep the exhaled breath collection valve 80 closed and take in only ambient air and filter it through the air filter 96.

[0099] When ambient air is drawn into the piston chamber 100, the ambient air is used to flush the system (208). When the controller retracts the piston 108 within the piston chamber 100, it closes the suction valve 88 and then opens all other valves. When valves 80, 120, 128, 132, and 144 are opened, the controller 148 instructs the piston motor 112 to drive the piston 108 into the piston chamber 100 and direct the ambient air therein to exit through the exhalation collection conduit 84 and the tube inlet valve 120 through the tube inlet manifold 116, to exit through the exhaust conduit 48 from the exhaust conduit outlet 68 to exit the mouthpiece 36 through the exhalation suction conduit 44, and also to exit through the bypass conduit 124 and the tube outlet manifold 140 from the outlet 136 and the tube outlet valve 144. As a result, the system conduits are effectively filled with ambient air.

[0100] FIG. 4B shows the flushing of the exhalation sample collection device 20.

[0101] After the system has been flushed with ambient air, valves 80, 120, 132, and 144 are closed again.

[0102] Upon completion of the flushing, the controller 148 determines whether to repeat the flushing (212). The flushing is repeated 5 to 10 times with about 10 - 20 liters of air to reduce the probability that the previous person's exhalation contaminates the sample of exhalation to be collected. If it is determined that the required number of flushes has not yet been completed, the controller 148 starts the process of drawing in ambient air again at 204.

[0103] Alternatively, if it is determined that sufficient flushing has occurred, one or more adsorbent tubes 152a - 152d (or hereinafter collectively referred to as adsorbent tubes 152) are loaded into the exhalation sample collection device 20 (213). The bypass valve 128 and the outlet valve 132 are closed. Thereafter, 1 - 4 adsorbent tubes 152 are loaded into the exhalation sample collection device 20.

[0104] In this embodiment, a sample of ambient air is used as a control against which the exhaled breath samples can be compared. The ambient air inhaled by a person while providing an exhaled breath sample can contain some of the compounds that are to be quantified during the analysis of the exhaled breath sample. To identify these compounds in the ambient air in the space where the exhaled breath sampling device 20 is located, the ambient air can be adsorbed onto one or more adsorbent tubes 152. The exhaled breath sampling device 20 samples the ambient air in a manner somewhat similar to the sampling of exhaled breath. Thus, at least two adsorbent tubes 152 are loaded such that at least one can trap ambient air and at least one other can trap exhaled breath.

[0105] Once the adsorbent tubes are loaded, as shown in FIG. 4C, ambient air is drawn into the piston chamber 100 (214). By controlling the piston motor 112 to operate the piston 108, the exhaled breath sampling device 20 draws in the ambient air of a room. When the piston 108 is retracted within the piston chamber 100, the size of the cavity 104 increases and ambient air is drawn into the cavity 104 through the inlet 92, through the air filter 96 and the inlet valve 88.

[0106] Once the ambient air is drawn into the piston chamber 100, the ambient air is flowed through a subset of the adsorbent tubes 152, as shown in FIG. 4D (215). The controller 148 opens the first tube inlet valve of the tube inlet valves 120, the first tube outlet valve of the tube outlet valves 144, and the outlet valve 132. Next, the controller 148 instructs the piston motor 112 to operate the piston 108 and move it into the piston chamber 100 to reduce the volume of the cavity 104. As the cavity volume decreases, the ambient air in the cavity 104 is pushed out through the first adsorbent tube 152a and out through the outlet 136. The rate at which the ambient air is flowed through the adsorbent tube 152a is selected to provide effective adsorption while being time efficient.

[0107] If it is determined that the target volume of ambient air to be passed through the adsorbent tube 152a to capture an ambient air sample exceeds the capacity of the piston chamber (about 2 liters), 214 and 215 are repeated as necessary until the ambient air sample is captured by the adsorbent tube 152a.

[0108] Next, the person 180 from whom an exhaled breath sample is to be collected is instructed via the display 150 to exhale into the mouthpiece 36 during a process called "pre-exhalation" as shown in FIG. 4E (216). "Pre-exhalation" is used to accustom the person 180 to the sensation of exhaling into the exhaled breath sampling device 20 in a predetermined manner according to criteria defined for the operation of the exhaled breath sampling device 20. The display 150 presents an instruction regarding a target exhaled breath volume of 20 liters per minute to the person 180. By accustoming the person 180 to the method of exhaling into the exhaled breath sampling device 20, the person 180 typically becomes more stable in exhaling. A person typically becomes much better at controlling their exhaled breath volume even with just one exhalation training session. Further, the conduit of the system is primed using the exhaled breath provided during the pre-exhalation phase.

[0109] When the exhalation collection valve 80 is closed, the exhaled breath exhaled by the person 180 passes through the exhalation suction conduit 44 and moves along the exhaust conduit 48.

[0110] During the pre-exhalation phase, the capnometer 56 samples air and measures the level of carbon dioxide therein. Since the capnometer 56 samples air frequently, the capnometer 56 can also measure the rate of change of the carbon dioxide level. The flow meter 60 measures the flow rate of the exhaled breath. The low-pressure resistance portion 64 provides a very low flow restriction to the exhaled breath by the person 180, and the exhaled breath exits through the exhaust conduit outlet 68.

[0111] The controller 148 constantly monitors the signals from the capnometer 56 and the flowmeter 60 and determines whether a set of exhalation collection criteria are met. These exhalation collection criteria are that (a) the carbon dioxide level reported by the capnometer 56 is within a target range defined by a minimum threshold and an infinite upper limit, (b) the rate of change of the carbon dioxide level is within a rate-of-change target range defined by an infinite lower limit and a maximum rate-of-change threshold, and (c) the flow rate of the exhaled breath is within a target range defined by a minimum flow threshold and a maximum flow threshold. In this embodiment, the minimum flow threshold is 20 liters per minute and the maximum flow threshold is 25 liters per minute. The exhaled breath being within the target range gives consistency to the exhaled breath provided by the person 180. As can be understood, the target range can be said to be defined by the threshold at one boundary of the target range, because the other boundary can be logically satisfied by an infinite or zero boundary, etc.

[0112] The first portion of the exhaled breath of the person 180 includes air from the mouth and / or throat where oxygen / carbon dioxide exchange in the lungs did not occur, thereby providing a higher proportion of oxygen. As the person 180 continues to exhale, a larger portion of the exhaled breath is from the lungs where oxygen / carbon dioxide exchange occurs. As a result, the carbon dioxide released from the bloodstream becomes a larger accompanying portion (about 3 - 7%) of the exhaled breath. And when the rate of change of carbon dioxide decreases sharply, the carbon dioxide level hits the knee. This indicates that it is exhaled breath from the lungs rather than from the mouth or trachea. Such exhaled breath is called alveolar exhalation. In this embodiment, the target range of the carbon dioxide level is from 3% to an infinite upper limit of the exhaled breath, and the target range of the rate of change of the carbon dioxide level is 0% - 2% of the exhaled breath per second.

[0113] FIG. 5 shows the carbon dioxide level over time in the exhaled breath with respect to the threshold Ω. The rate of change of the carbon dioxide level generally rises consistently until alveolar exhalation is exhaled, at which point the rate of change of the carbon dioxide level drops significantly. This rate of change is reflected as the knee K. Thereafter, the carbon dioxide level in the exhaled breath stabilizes.

[0114] In this configuration, the criteria for exhaled breath collection are as follows. The carbon dioxide level is 2% or more of the threshold value. This level is well above the level in the atmosphere but below the level expected to be seen in humans (for example, 3% is the minimum from a person with reduced lung function). The rate of change of the carbon dioxide level is below a predetermined threshold value. Further, the flow rate of exhaled breath is over 20 liters per minute.

[0115] These three criteria prevent the activation of exhaled breath collection under non-ideal situations in many cases.

[0116] When all three criteria are met, as shown in FIG. 4F, exhaled breath collection is started (224). When the three criteria are met, the controller 148 opens the exhaled breath collection valve 80, instructs the piston motor 112 to drive the piston 108, and increases the volume of the cavity 104 as exhaled breath is received. The piston 108 is controlled to operate at a speed that depends on the flow rate reported by the flow meter 60 in order to provide a rate of increase in the volume of the cavity 104. In this particular embodiment, the rate of increase in the volume of the cavity 104 achieved as a result of operating the piston 108 is proportional to the flow rate detected by the flow meter 60 along the exhaust conduit 48. In other embodiments, the rate of change of the volume of the cavity 104 can be changed in a different manner as a function of the flow rate reported by the flow meter 60.

[0117] As the volume of the cavity 104 increases, due to the resulting pressure difference, it becomes easier for the person 180 to exhale. When the person 180 is exhaling at 20 liters per minute, as a result of the increase in the volume of the cavity 104, 16 liters per minute are drawn out by the pressure difference within the system, so the person 180 is only exhaling with the force required for 4 liters per minute. This can enable a person with a reduced ability to exhale forcefully, as can be the case in lung cancer and respiratory diseases, to provide an exhaled breath sample.

[0118] As previously shown, the flowmeter 60 is positioned along the normal downstream path for the air flow to prevent the currently collected breath sample from being contaminated by the breath from a previous breath sample provider adhering to the flowmeter 60. If the operating speed of the piston 108, and thus the rate of increase of the cavity volume, was fixed, when the person 180 exhaled faster, some of the exhaled breath would be discharged through the flowmeter 60. For this reason, the exhaled breath may escape more than the desired amount along the exhaust conduit 48, and problems may occur when the flow rate falls below the rate of increase of the volume of the cavity 104.

[0119] In this configuration, the controller 148 controls the piston 108 to increase the volume of the cavity 104 at a rate that depends on the flow rate measured by the flowmeter 60. In particular, the volume of the cavity 104 is increased by four times the flow rate measured by the flowmeter 60. That is, the increase in the volume of the cavity 104 captures 80% of the exhaled breath received from the person 180.

[0120] The hygrometer 52, the capnometer 56, and the flowmeter 60 are all arranged along the exhaust conduit 48 away from the breath inhalation conduit 44. These measuring devices can off-gas VOCs. Furthermore, these measuring devices may be contaminated by the breath of a person who previously provided a breath sample. By arranging these measuring devices along the exhaust conduit 48 and having the breath flow along the exhaust conduit 48 away from the direct path along the breath inhalation conduit 44, contamination by other breath or off-gassed VOCs is suppressed. Additionally, these measuring devices and conduits are provided with an inert internal coating to reduce the probability of exhaled breath or off-gassed VOCs adhering to their internal surfaces, thereby further reducing the probability of contamination of the breath sample by previously received breath and off-gassed VOCs.

[0121] By moving a portion of the received exhaled breath along an exhaust duct 48 along which a hygrometer 52, a capnometer 56, and a flow meter 60 are disposed, an overall generally unrestricted exhaled breath volume can be measured. This exhaled breath volume is equal to the flow rate measured by the flow meter 60 plus the rate of increase in the volume of the cavity 104 measured based on the operating speed of the position of the piston 108. And, using this exhaled breath volume, it is possible to determine at what speed to increase the volume of the cavity 104. By keeping the rate of increase in the volume of the cavity 104 below the measured exhaled breath volume, a portion of the exhaled breath always moves under the exhaust duct 48, enabling continuous monitoring of the overall exhaled breath volume.

[0122] This ratio of 80% of the overall exhaled breath volume is selected with a margin for the reaction time buffer so that when a person's exhaled volume drops rapidly, there is little possibility of exceeding the exhaled breath volume and the rate of increase in the volume of the cavity 104 can be adjusted with a slight lag. If the rate of increase in the volume of the cavity 104 exceeds the person's exhaled breath volume, the pressure difference within the system can draw exhaled breath unnaturally from the person, which can result in an undesirable outcome and may draw in ambient air through the exhaust duct outlet 68.

[0123] Information regarding the overall exhaled volume is presented to the person 180 on a display 150 and can prompt the person 180 to exhale within a target range or at least at a threshold speed.

[0124] When the person 180 increases the exhaled volume up to a threshold of 25 liters per minute, the piston 108 is actuated by the controller to move so as to increase the volume of the cavity 104 such that 80% of the exhaled breath is collected within the cavity 104.

[0125] When the person 180 decreases the exhaled volume, the piston speed is adjusted such that the volume change of the cavity 104 is always less than the exhaled volume, ensuring that air is not drawn in through the flow meter route and that the flow rate of the exhaled breath can be measured through the flow meter 60.

[0126] When the flow rate detected by the flow meter 60 enters the flow rate end range, the movement of the piston 108 is stopped, and the collection of exhaled air in the piston chamber 100 is stopped. The flow rate end range in the present embodiment is from the infinite lower limit to 2 liters of exhaled air per minute.

[0127] The person 180 may not have enough exhaled air to fill the entire piston chamber 100. Therefore, when the flow meter 60 reports that the discharge volume has dropped below a certain value, the movement of the piston 108 and thus the collection of exhaled air are stopped.

[0128] Next, the controller 148 determines whether the target volume for priming the system has been collected (228). The exhaled air sampling device 20 collects 1 liter of exhaled air to prime the system. If less than 1 liter of exhaled air, which is the target volume, is collected, the controller 147 controls the exhaled air sampling device 20 at 216 to perform pre-exhaled air collection.

[0129] Alternatively, if it is determined at 228 that enough exhaled air has been collected to prime the system, as shown in FIG. 4G, the system is primed using the collected exhaled air (232). The controller 184 instructs the exhaled air collection valve 80 to close and instructs the bypass valve 128 and the outlet valve 132 to open. Further, the piston motor 112 is instructed to drive the piston 108 into the piston chamber 100, thereby reducing the volume of the cavity 104. As the volume of the cavity 104 decreases (i.e., the volume reduction rate), the exhaled air contained in the cavity 104 is propelled through the exhaled air collection conduit 84, the tube inlet manifold 116, the tube outlet manifold 140, the bypass conduit 124, and the outlet 136. Thereby, these conduits are primed with the exhaled air collected from the person 180.

[0130] When the capture conduit system 82 is primed, exhalation is again collected using the same general approach from 216 to 228. That is, pre-exhalation collection is again performed (240). During pre-exhalation collection, the controller 148 determines whether the exhalation expiration criteria are met (244). If they are met, exhalation is collected as shown in FIG. 4H (248).

[0131] Next, it is determined whether the target volume of exhalation for adsorption has been collected or whether the piston chamber 100 is full (252). If the target volume of exhalation for adsorption into the adsorbent tube(s) 152 has not yet been collected and the piston chamber 100 is not full, further exhalation is again collected starting from the pre-exhalation collection at 240. The person 180 is instructed to breathe again.

[0132] Instead, at 252, if it is determined that the target volume of exhaled breath has been collected or that the piston chamber 100 is full, the exhaled breath is flowed through a second subset of the adsorbent tubes 152 (256). FIG. 4I shows that the piston chamber 100 is filled with exhaled breath. The controller 148 is configured to control the flow of at least a portion of the exhaled breath from the container to a subset of the adsorbent tubes 152 asynchronously with when it receives the exhaled breath. That is, the flow of exhaled breath from the container to a subset of the adsorbent tubes 152 can be performed independently of the timing of receiving the exhaled breath, apart from the fact that it must occur after receiving the exhaled breath. The second subset can be any number of the adsorbent tubes 152 that are not adsorbed with ambient air among the adsorbent tubes 152 connected to the exhaled breath sampling device 20. After priming the conduit, when the machine collects exhaled breath for a full piston chamber, the controller 148 closes the exhaled breath sampling valve 80 and controls each of the tube inlet valves 120 to leave the tube inlet valves 120 in their previously closed or open states, or opens and closes each of the tube inlet valves 120 to select a subset of the adsorbent tubes 152 through which at least a portion of the exhaled breath flows. In this embodiment, the controller 148 opens the corresponding one of the tube inlet valve 120 and the tube outlet valve 144 for the adsorbent tube 152 on which the sample is adsorbed, and opens the outlet valve 132. The piston 108 is controlled by the controller 148 to slowly move the exhaled breath therein at a predetermined speed to push the exhaled breath through the selected adsorbent tube 152.

[0133] When the breath is flowing through the second subset of the adsorbent tube 152, air is simultaneously flowed through the pre-sampling conduit system 46 (260) to reduce internal condensation. In particular, the controller 148 turns on the pump 72 and controls to draw ambient air from the mouthpiece 36 and the exhaust conduit outlet 68 through the exhaust conduit 48 to assist in alleviating condensation from the line. Since the metering device does not function optimally under very high humidity conditions, the pump 72 acts to reduce condensation / humidity in the exhaust conduit 48. When the pump 72 operates, the humidity level is monitored via the hygrometer 52.

[0134] Figure 6 shows a typical graph of the humidity level detected by the hygrometer 52 over time. Before the pump 72 is turned on at t1, the humidity is at the first level h1. High levels of condensation may be observed on the transparent mouthpiece 36. After the pump 72 is turned on, since the humidity decreases over time, the rate of change of humidity is negative. When the rate of change of the humidity level is within the rate-of-change target range at time t2, the controller 148 determines that there is relatively little condensation in the pre-sampling conduit system 46 and that continuing the operation of the pump 72 is of relatively little value, and thus ends the operation of the pump 72. In this embodiment, this rate-of-change target range of the humidity level is from -0.05% relative humidity per second to 0% relative humidity per second, but it can be varied in other scenarios. In this way, the exhaled breath sample collection device 20 can perform maintenance during otherwise idle time. In other embodiments, this condensation reduction step can be performed via the use of a secondary external hygrometer based on the humidity level being outside the humidity level target value range from zero to the humidity level of the ambient air.

[0135] The rate at which exhaled breath is flowed through the adsorbent tube 152 is 500 milliliters per minute. The leakage volume of the adsorbent tube 152 has been found to be affected by the adsorbent flow rate. The leakage volume is the volume at which half of the sample is captured by the adsorbent tube 152 and the other half flows into the opposite side of the adsorbent tube 152. In terms of the leakage volume, the adsorbent within the adsorbent tube 152 has sufficient surface area such that molecules can pass through as easily as they are captured. Increasing the flow rate of the exhaled breath through the adsorbent tube 152 decreases the leakage volume. As a result, the captured sample is biased towards heavier molecules and fewer smaller molecules. By controlling the flow rate of the exhaled breath through the adsorbent tube 152, the adsorption rate for specific molecules can be controlled.

[0136] Next, it is determined whether the target volume has flowed through a subset of the adsorbent tubes 152 (264). If the desired amount of exhaled breath has not yet flowed through a subset of the adsorbent tubes 152, the method 200 returns to 240 where more exhaled breath is collected to flow through a subset of the adsorbent tubes 152.

[0137] Upon determining that the target volume has flowed through the currently selected adsorbent tube 152, the controller 148 can terminate the flow of exhaled breath through the adsorbent tube 152 via the tube inlet and outlet valves 120, 144 and begin flowing exhaled breath through another adsorbent tube among the adsorbent tubes 152.

[0138] The exhaled breath sampling device 20 can be configured to select different sized subsets of ambient air and adsorbent tubes for the exhaled breath sample. In a preferred embodiment, an ambient air sample for two adsorbent tubes and an exhaled breath sample for two adsorbent tubes are collected. In other embodiments, the ambient air may not be collected.

[0139] Although not explicitly shown, it will be understood that the controller 148 is connected to each of the valve, the hygrometer 52, the capnometer 56, the flowmeter 60, the pump 72, the piston motor 112, and the other components of the exhaled sample collection device 20.

[0140] In other embodiments, the container having a controllable volume may be any other structure for providing a cavity having a controllable volume. For example, in one particular embodiment, the container may include a bellows-like structure.

[0141] FIG. 7A shows an exhaled sample collection device 300 according to another embodiment. The exhaled sample collection device 300 is similar to the exhaled sample collection device 20 of FIGS. 1 and 4A-4I, except that the exhaled sample collection device 300 uses a two-way pump 304 and a container including at least partially flexible collapsible receptacle 308 instead of the piston chamber 100 and the piston 108. The at least partially flexible collapsible receptacle 308 is fixed to the two-way pump 304, and the two-way pump 304 is fixed to the exhaled air collection conduit 84.

[0142] In this embodiment, the at least partially flexible collapsible receptacle 308 is a bag made of polyvinyl fluoride, a very flexible material having high tensile properties. Polyvinyl fluoride is not impermeable, but has suitably low permeability that does not significantly affect its performance in this application. Further, polyvinyl fluoride is relatively inert. Other suitably flexible, relatively non-porous, relatively inert materials may be used additionally or alternatively in other embodiments. Further, the receptacle may also include non-flexible portions.

[0143] The at least partially flexible collapsible receptacle 308 has an internal cavity having a volume defined by the amount of fluid therein. In FIG. 7A, the at least partially flexible collapsible receptacle 308 is shown to have substantially no exhaled or ambient air therein, and thus the cavity has substantially no volume. In this folded state, the at least partially flexible collapsible receptacle 308 can be compressed to facilitate packing.

[0144] The bidirectional pump 304 has a controllable flow rate and flows exhaled air and / or ambient air in both directions. The bidirectional pump 304 is controllable by the controller 148, which draws exhaled air and / or ambient air from the exhalation collection conduit system 82 into the at least partially flexible collapsible receptacle 308 and also draws exhaled air and / or ambient air from the at least partially flexible collapsible receptacle 308 into the exhalation collection conduit system 82. Thus, the controller 148 can control the bidirectional pump 304, and as a result, control the at least partially flexible collapsible receptacle 308 to provide the same general functionality as the piston chamber 100, the piston motor 112, and the piston 108. That is, the controller 148 can control the volume of the at least partially flexible collapsible receptacle 308 through operation of the pump.

[0145] FIG. 7B shows the at least partially flexible collapsible receptacle 308 after the bidirectional pump 304 has drawn exhaled air and / or ambient air therein, thus expanding the cavity of the at least partially flexible collapsible receptacle 308 and the at least partially flexible collapsible receptacle 308 itself.

[0146] The exhaled breath sample collection device 300 also differs in that it has an array of optical elements in the form of LEDs 312 and a voice speaker 316 instead of a display. The flow rate notification can be presented to the user via the LEDs 312. For example, the array of LEDs 312 can include a sequence of a red LED, a yellow LED, a green LED, a yellow LED, and a red LED. If the flow rate of the exhaled breath through the exhaled breath input interface 24 is too low, the corresponding red or yellow LED can be lit. If the flow rate of the exhaled breath through the exhaled breath input interface 24 is satisfactory, the green LED can be lit. Similarly, if the flow rate of the exhaled breath through the exhaled breath input interface 24 is too high, the corresponding second red or yellow LED can be lit. In this way, a person can be visually shown how their exhaled breath flow rate is compared to the target flow rate. In other embodiments, other types of optical elements can be employed.

[0147] The voice speaker 316 can be used in a similar way, and the flow rate notification is provided by clicks of different frequencies, sounds of different frequencies, different sounds, etc.

[0148] FIG. 8 shows an exhaled breath sample collection device 400 according to a further embodiment. In this embodiment, the flowmeter 60 is arranged along the exhaled breath intake conduit 44. Accordingly, the flowmeter 60 measures the total exhaled breath volume along the exhaled breath suction conduit 44. During exhaled breath collection, the controller 148 can control the piston motor 112 to operate the piston 108 such that the rate of change of the volume of the cavity 104 is set to a percentage of the flow rate measured by the flowmeter 60. In a preferred embodiment, the rate of change of the volume of the cavity 104 is set to 80% of the flow rate measured by the flowmeter 60 during exhaled breath collection. The excess exhaled breath flows along the exhaust conduit 48 and exits from the exhaust conduit outlet 68.

[0149] In the above embodiments, a capnometer is employed to measure the level of carbon dioxide in exhaled breath. However, in other embodiments, other types of metering devices may be employed to measure the levels of other components in exhaled breath, such as those that can be indicated when alveolar exhalation is detected. These metering devices can determine when alveolar exhalation is detected by detecting the levels of these other components and the rate of change of these levels. For example, the metering device can measure the oxygen level in exhaled breath and, when it detects that the change in the oxygen level falls within a rate-of-change target range having a maximum rate-of-change threshold, it can determine that alveolar exhalation is currently being detected.

[0150] In other embodiments, other types of exhaled breath sample storage devices may be employed separately from the adsorbent tube. For example, solid-phase microextraction ("SPME") fibers can alternatively be used to store exhaled breath samples. Another example is silica gel. Still other examples are chemical reactions that provide a visible indication (e.g., Drierite turns purple in the presence of moisture), or powders that produce byproduct chemical substances that can be more easily analyzed later. Those skilled in the art will envision other types of exhaled breath sample storage devices.

[0151] The volume of the container can be mechanically controlled in other ways. In one particular embodiment, the container can include a bellows that can be actuated to expand and contract.

[0152] Although specific advantages were listed above, various embodiments may include some, none, or all of the listed advantages.

[0153] Those skilled in the art will understand that many more alternative implementations and modifications are possible, and that the above examples are merely illustrative of one or more embodiments. Accordingly, the scope is limited only by the claims appended hereto.

Description of Reference Numerals

[0154] 20 Exhaled Breath Sampling Device 24 Exhalation input interface 36 Mouthpiece 40 Exhalation suction end 44 Exhalation suction conduit 46 Pre-sampling conduit system 48 Exhaust conduit 52 Hygrometer 56 Capnometer 60 Flowmeter 64 Low-pressure resistance part 68 Exhaust conduit outlet 72 Pump 76 Pump conduit 80 Exhalation sampling valve 82 Capture conduit system 84 Exhalation sampling conduit 88 Suction valve 92 Ambient air inlet 96 Air filter 100 Piston chamber 104 Cavity 108 Piston 112 Piston motor 116 Tube inlet manifold 120 Tube inlet valve 124 Bypass conduit 128 Bypass valve 132 Outlet valve 136 Outlet 140 Tube outlet manifold 144 Tube outlet valve 148 Controller 150 Display 152 Adsorbent tube 156 Stainless steel casing 160 Opening 164 Receiver end 168 Foam separator 172 Adsorbent 176 Foam separator 180 Person 200 Method 204 Draw in ambient air 208 Flushing device 212 Repeat flushing? 213 Load the adsorbent tube 214 Draw in ambient air 215 Flow air through the first subset of the adsorbent tube 216 Exhaled breath pre-sampling 220 Meet the exhaled breath discharge criteria? 224 Collect exhaled breath and prime the system 228 Target volume? 232 Prime the system with the collected exhaled breath 236 Load the adsorbent tube 240 Exhaled breath pre-sampling 244 Meet the exhaled breath discharge criteria 248 Collect exhaled breath 252 Is the target volume or the container full? 256 Flow exhaled breath through the adsorbent tube(s) 260 Flow air through the pre-sampling conduit system to reduce condensation 264 Target volume? 300 Exhaled breath sampling device 304 Bidirectional pump 308 Flexible foldable receptacle 312 LED 316 Speaker

Claims

1. An apparatus for collecting an exhaled breath sample, comprising: an exhaled breath input interface configured to receive exhaled breath that has been exhaled; a conduit system extending from the exhaled breath input interface and configured to receive a breath sample storage device at its storage device inlet port, the conduit system having an outlet; a storage device valve disposed in the conduit system and oriented toward the storage device inlet port; a bypass valve disposed in the conduit system between the storage device inlet port and the outlet; at least one controller configured to adjust at least the storage device valve and the outlet valve to at least a priming state that enables the exhaled breath received via the exhaled breath input interface to flow through the conduit system and through the bypass valve when the storage device valve is closed and the outlet valve is open, and a collection state that enables exhaled breath to be induced into the breath sample storage device when the storage device valve is open and the outlet valve is closed.

2. The apparatus according to claim 1, wherein the breath sample storage device is an adsorbent tube, the conduit system is a first conduit system, the apparatus further comprises a second conduit system configured to receive the adsorbent tube at its storage device outlet port, such that the adsorbent tube extends between the first conduit system and the second conduit system, an adsorbent tube outlet valve is disposed in the second conduit system and oriented toward the storage device outlet port, the second conduit system is in fluid communication with the first conduit system, and the adsorbent tube outlet valve is closed in the priming state and open in the collection state to enable exhaled breath to flow through the adsorbent tube.

3. The apparatus according to claim 2, wherein the at least one controller is configured to open an outlet valve disposed toward the outlet of the first conduit system to enable the exhaled breath received via the exhaled breath input interface to exit from the outlet.

4. The apparatus according to claim 1, further comprising a container disposed along the conduit system and configured to store at least a portion of the exhaled breath received from the exhaled breath input interface.

5. The apparatus according to claim 4, wherein the container has a cavity for storing at least a part of the exhaled breath, and the volume of the cavity is controllable by the at least one controller.

6. The apparatus according to claim 5, wherein the container includes a piston chamber having a piston disposed therein, and the position of the piston controls the volume of the cavity.

7. The apparatus according to claim 6, wherein the at least one controller is configured to operate the piston to increase the volume of the cavity as at least a part of the exhaled breath is received via the breath input interface.

8. The apparatus according to claim 7, further comprising a breath sampling valve intermediate the breath input interface and the container along the conduit system.

9. The apparatus according to claim 8, wherein the at least one controller is configured to control the closing of the breath sampling valve and control the operation of the piston to propel at least a part of the exhaled breath through the conduit system towards its first end.

10. A method for collecting an exhaled breath sample, comprising flowing the exhaled breath received via a breath input interface through a conduit system having a reservoir inlet port configured to receive a breath sample storage device, the conduit system including a reservoir valve disposed towards the reservoir inlet port and a bypass valve disposed between the reservoir inlet port and the outlet of the conduit system, opening the reservoir inlet valve and closing the bypass valve via at least one controller to flow the received exhaled breath to the exhaled breath sample storage device.

11. An apparatus for collecting an exhaled breath sample, a breath input interface configured to receive the exhaled breath, a flow meter configured to measure the flow rate of the exhaled breath, an exhaled breath sample storage device configured to store at least a part of the exhaled breath, a valve disposed to control the flow of the exhaled breath to the at least one exhaled breath sample storage device, at least one controller configured to control the opening of the valve based at least in part on the flow rate being within a flow rate target range. An apparatus comprising... **Claim 12** An apparatus for collecting an exhaled breath sample, comprising: An exhaled breath input interface configured to receive the exhaled breath; A flow meter configured to measure the flow rate of the exhaled breath; An exhaled breath sample storage device configured to store at least a portion of the exhaled breath; A display configured to present a display of the flow rate to a user of the apparatus; An apparatus comprising... **Claim 13** The apparatus for collecting an exhaled breath sample according to claim 12, wherein the display corresponds to one of a range of a series of flow rates. **Claim 14** A method for collecting an exhaled breath sample, comprising: Collecting an ambient air sample from a room into a first sample storage device; Collecting an exhaled breath sample from a person in the room into a second sample storage device; Analyzing the ambient air sample to generate an ambient air analysis; Analyzing the exhaled breath sample to generate an exhaled breath sample analysis; Comparing the ambient air analysis with the exhaled breath sample analysis. A method comprising...

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