Breath analysis device

Abstract

The present techniques relate to a breath analysis device and a system for using such a breath analysis device. We also describe a method for using the breath analysis device. The breath analysis device comprises a filtering mechanism (which may also be termed a filter stack) for removing interferent chemicals to increase the accuracy of detection, identification and quantification of specific chemicals. Exhaled human breath comprises a multiplicity of vapour phase chemicals and the function of the filtering mechanism is removal, retardation and separation of chemicals other than the specific chemicals to be determined by the sensing element(s). Removal, retardation and separation of the chemicals other than those of interest reduces error by reducing cross sensitivities when using broadly selective sensors such as metal oxide semiconductors. One example use of the breath analysis device may be to enable users who suffer from digestive health problems, particularly irritable bowel syndrome (IBS) or small intestinal bacterial overgrowth (SIBO), to monitor symptoms based on detection of specific chemicals such as hydrogen and / or methane in their breath over time.

Description

[0001] Breath analysis device

[0002] Technical Field

[0003]

[0001] The present application relates to a breath analysis device, particularly a hand-held breath analysis device which includes a filtering mechanism for removing interferent chemicals.

[0004] Background

[0005]

[0002] A breath analysis device (alternatively termed a breath detection device) is typically used to detect, identify and / or quantify specific individual chemicals within exhaled breath. In addition to the specific individual chemicals which are being detected, there are typically many interferent chemicals such as water vapour, acetone, ethanol and isoprene. These interferent chemicals interfere with the analysis of a breath and there may be a resulting loss of accuracy and precision in detecting, identifying and / or quantifying specific individual chemicals.

[0006]

[0003] Filtering mechanisms are known in different technical fields. For example, US2021 / 0164929 describes a gas detection unit in which the outside atmosphere is introduced through filters to the gas detection unit. One filter removes siloxanes and another filter removes alcohols and both filters allow gases to be detected. As another example “Towards Enhanced Gas Sensor Performance with Fluoropolymer Membranes” by Graunke et al published in Sensors in 2016 describes increasing the selectivity of gas sensors by using fluoropolymer membranes. In the field of non-invasive medical diagnostics, “Highly selective gas sensing enabled by filters” by van de Broek et al published in Materials Horizons in 2021 describes the engineering of sorption, size-selective and catalytic filters for gas sensors. US2019 / 113501 A1 describes a breath sensor apparatus and methods of use where a flow control apparatus may generally comprise a sampling chamber defining a volume and one or more openings into the sampling chamber, at least one sensor in fluid communication with the sampling chamber, wherein the at least one sensor is configured to detect the analyte.

[0007]

[0004] The applicant has recognised the need for a breath analysis device with an improved filtering mechanism to remove interferent chemicals.

[0008] Summary of the invention

[0009]

[0005] According to the present invention there is provided a breath analysis device and method as set forth in the appended claims. Other features of the invention will be apparent from the dependent claims, and the description which follows.

[0006] According to a first aspect of the present techniques, we describe a breath analysis device for detecting a target chemical within a breath sample, the breath analysis device comprising: a housing having: an inlet for a breath sample to flow into the housing; and an outlet forthe breath sample to flow out of the housing; a sensorwithin the housing, wherein the sensor is configured to detect the target chemical within a breath sample received in the housing; and a filtering mechanism which is within the housing and which is positioned closer to the inlet than the sensor. The filtering mechanism comprises a first filter component which is configured to retard passage of a first interferent chemical within the breath sample relative to passage of the target chemical through the first filter component; and a second filter component which is configured to retard passage of a second interferent chemical within the breath sample relative to passage of the target chemical through the second filter component, wherein the second interferent chemical is different from the first interferent chemical. By retarding passage, it is meant that the first and second interferent chemicals pass through the respective filter components more slowly than the target chemical.

[0010]

[0007] The breath detection device may be used to detect one or more target chemicals within a breath sample, using one or more sensors. Similarly, each filter component may be used to retard and / or remove one or more interferent chemicals. The use of the filtering mechanism enables greater accuracy and precision of detection of the target chemical than without the filtering mechanism.

[0011]

[0008] The sensor may have a broad sensitivity and may detect at least one target chemical and other chemicals which may be termed interferent chemicals. As described in more detail below, examples of interferent chemicals include water vapour, hydrogen sulphide, carbon monoxide, acetone, isoprene, ethanol, ethane and the like. By positioning the filtering mechanism closer to the inlet than the sensor, the filtering mechanism is upstream from the sensor and at least retards the passage of the first and second interferent chemicals so that the target chemical(s) reach the sensor before the interferent chemical(s). For example, the target chemical(s) may pass through each filter component within a minute or less and each interferent chemical(s) may pass through the respective filter component in a greater period of time (e.g. several minutes) or may be prevented from passing through the associated filter component. In other words, each filter component may remove the associated interferent chemical(s). Thus, the function of the filter mechanism within the breath analysis device is to improve the selectivity, sensitivity, accuracy and precision of the information (e.g. concentration) reported about the target chemicals by the sensor.

[0012]

[0009] There may be a plurality of sensors, e.g. two. Each sensor may be configured to detect a different target chemical or a different combination of target chemicals. There may be a filtering mechanism associated with each sensor. For example, the sensor may be for detecting a first target chemical (e.g. hydrogen) and the breath analysis device may comprise a second sensor for detecting a second target chemical (e.g. methane) which is different from the first target chemical. The or each sensor may be suitable for detecting the target chemical(s) in the breath sample at a ppm level. The or each sensor may be suitable for detecting the target chemical(s) at a concentration between 0 ppm and 1000 ppm, suitably between 0.5 ppm and 500 ppm, suitably between 1 ppm and 100 ppm. The or each sensor may be a metal oxide sensor, a catalytic bead sensor, a thermal conductivity sensor, or any other suitable sensor.

[0013]

[0010] The device may comprise a second filtering mechanism which is positioned closer to the inlet than the second sensor for removing at least one interferent chemical. The second filtering mechanism may comprise at least one of the first filter component and the second filter component. Each filtering mechanism may be the same (e.g. remove the same interferent chemicals) or may be configured to match the requirements of the associated sensor.

[0014]

[0011] The first filter component may be configured to retard the passage of or remove water. In other words, the first interferent chemical may include water. The first filter component may comprise a hydrophobic material, for example PTFE (polytetrafluoroethylene), PVF (polyvinyl fluoride), Teflon, polyvinylidene fluoride (PVDF) or other fluorinated polymers. The first filter component may be a layer of hydrophobic material. The first filter component may be in the form of a porous membrane having a pore size which is selected to allow the passage of the target chemical and to retard water. The pore size may be selected by chemically modifying the hydrophobic material. When there are multiple sensors and multiple filtering mechanisms, the pore size may be different in each filtering mechanism or may be the same, depending on the pore size of the target chemical which is detected by the sensor. For example, the pore size may be in the range of 0.1 pm to 1 .5 pm, suitably in the range from 0.1 pm to 0.45 pm. The inclusion of a filter layer suitable for removing water from the breath sample may reduce the humidity of the breath sample before it is detected by the sensor.

[0015]

[0012] The second filter component may be configured to retard the passage of or remove a volatile organic compound (VOC) from the breath sample. Examples of VOCs include sulphides, hydrogen sulphide, dimethyl sulphide, alkanes, such as ethane and pentane, aldehydes such as decanal, ketones such as acetone, carboxylic acids such as pentanoic acid, alcohols such as ethanol and alkenes such as isoprene. The second filter component may be configured to retard the passage of or remove multiple VOCs.

[0016]

[0013] The second filter component may comprise an adsorbent and / or absorbent material. For example, the second filter component may be a molecular sieve or similar component which is porous at a molecular level. Merely as examples, the molecular sieves may be 3A, 4A or 13X molecular sieves. The second filter component may comprise a plurality of particles in the form of beads, granules and / or grains having properties which are selected to remove or retard the volatile organic compound, for example by removing, entrapping or retarding molecules within the volatile organic compound. In otherwords, the properties may be selected to affect desirable changes in the chemical selectivity of the overall filtering mechanism. These properties may include at least size, weight and polarity of the beads, granules and / or grains. The properties may be varied to enhance diffusion rates of the target chemical(s). The beads, granules and / or grains may be supported on a support structure such as impregnated cloth or foam or may be part of a molecular sieve. Alternatively, the adsorbent and / or absorbent materials may be free standing or self-supporting. The second filter component may comprise at least one of carbon, activated charcoal granules, graphene, carbon fibre, zeolites, molecular sieves, carbonised molecular sieves, porous polymers, Tenax™, adsorbent polymers, absorbent polymers, superabsorbent polymers, activated alumina, silica, silica gel, mesoporous silica, celite, glass wool, beads, glass beads, quartz beads, metal organic frameworks (MOFs), The beads, granules and / or grains may originate from bitumen, wood, or fibrous materials such as coconut shells.

[0017]

[0014] The filtering mechanism may comprise a third filter component which is configured to retard passage of or remove a third interferent chemical within the breath sample relative to passage of the target chemical through the third filter component. Inclusion of the third filter material may enable removal of additional interferent chemicals from the breath sample before it is detected by the sensor. For example, the third filter component may be configured to retard the passage of or remove at least one volatile organic compound which is different from the volatile organic compound which is retarded or removed by the second filter component.

[0018]

[0015] The filtering mechanism may comprise a fourth filter component which is configured to retard passage of or remove a fourth interferent chemical within the breath sample relative to passage of the target chemical through the fourth filter component. The fourth interferent chemical may be the same as the first, second or third interferent chemical. In particular, the fourth interferent chemical may be water.

[0019]

[0016] Each of the filter components may be in the form of layers, e.g., hydrophobic materials and one or more different absorbent or adsorbent materials. The layers may have the same area and may be co-terminous. The layers may have different thicknesses. The layers may be adjacent each other and may form a stack of layers. For example, the second filter component may be between the first and third filter components and the third filter component may be between the second and fourth filter components. Each filter mechanism may thus be termed a filter stack. The filter components may be arranged to successively remove or retard interferent chemicals. In otherwords, the function of the filter stack may be divided into subunits each with a different function, thus accommodating the different chemical functionalities to reflect the chemicals present in exhaled human breath and the particular target chemical(s). The filter stack may be vertical or horizontal in orientation.

[0020]

[0017] The filtering mechanism may further comprise a structural component for providing mechanical support. The structural component may be a separate component or layer or may be incorporated in one or more filter components. In other words, in addition to the chemical functions described above, the filtering mechanism may also incorporate structural functionality. Each component or layerwithin the filtering mechanism may have one or multiple functions. For example, upper and lower components may provide mechanical strength as well as allowing passage of the target chemical(s).

[0021]

[0018] A direct flow-path may be defined between the inlet and the outlet and the direct flow-path may be along a channel. The filtering mechanism and the sensor may be positioned directly to one side (i.e. transversally) of the direct flow-path. In other words, the sensor and filtering mechanism are not in the direct flow-path, nor in the channel. The housing may comprise a side compartment or side chamber which is directly connected to the channel, e.g. via an aperture in a side wall of the channel. The sensor and the filtering mechanism may be located in the side compartment. The breath sample may diffuse into and out of the side compartment whereby there is approximately a zero flow rate across the sensor. When the filtering mechanism and the sensor are positioned directly to one side (i.e. transversally) of the direct flow-path, the breath sample and contaminants from the breath sample can easily escape from the side chamber by diffusion back into the direct flow-path. Thus, the sample and contaminant do not accumulate over time. Therefore, it will be understood that this arrangement reduces contamination and damage of the sensors, thus, improving the lifetime of the sensors and maintaining reliability of the sensors over a longer period of time. When there are multiple sensors and filtering mechanisms, each sensor and associated filtering mechanism may be located in a separate side compartment which is preferably directly to one side of the direct flow path.

[0022]

[0019] It will be appreciated that the filtering mechanism may be made as a stand-alone component, such as a replaceable cartridge which may be positioned in a side chamber when used. Thus, we also describe in a second aspect of the present techniques a filtering mechanism for use in a breath analysis device as described above the filtering mechanism comprises: a first filter component which is configured to retard passage of a first interferent chemical within the breath sample relative to passage of the target chemical through the first filter component; and a second filter component which is configured to retard passage of a second interferent chemical within the breath sample relative to passage of the target chemical through the second filter component, wherein the second interferent chemical is different from the first interferent chemical.

[0020] In a third aspect of the present techniques, we describe a method of using the breath analysis device described above for detection of at least one target chemical within a breath sample. The method comprises; receiving a breath sample in the inlet; at least retarding passage of at least one first interferent chemical within the breath sample through the first filter component; at least retarding passage of at least one second interferent chemical within the breath sample through the second filter component; and analysing the breath sample using the sensor to detect the at least one target chemical after the breath sample has passed through the first and second filter components. In other words, the breath sample is exposed to the filtering mechanism described above.

[0023]

[0021] In a fourth aspect of the present techniques, we describe a system for analysing the target chemical within a breath sample, the system comprising; a breath analysis device as described above and a mobile device which is connected to the breath analysis device to receive sensor data from the breath analysis device. The mobile device may also be configured to display information, for example, the mobile device may comprise a user interface configured to assist the user in collection of breath detection information. The system may comprise a server. The mobile device may be connected to the server and may be configured to transmit data collected from the breath analysis device to the server for further analysis.

[0024] Brief description of drawings

[0025]

[0022] For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example only, to the accompanying diagrammatic drawings in which:

[0026]

[0023] Figure 1 shows a perspective view of a breath analysis device;

[0027]

[0024] Figures 2a and 2b shows a perspective view and a cross-sectional view of a filtering mechanism which may be included in the breath analysis device of Figure 1 ;

[0028]

[0025] Figure 3 shows an exploded drawing of the breath analysis device of Figure 1 ;

[0029]

[0026] Figure 4a is a schematic block diagram of a breath analysis device of Figure 1 showing the location of the filtering mechanisms and sensors relative to the main flow path;

[0030]

[0027] Figure 4b is a schematic block diagram of a known design of breath analysis device for comparison with the diagram of Figure 4a;

[0028] Figure 5a shows a block diagram of a system which incorporates the breath analysis device and a mobile electronic device; and

[0031]

[0029] Figure 5b shows a method of using the system of Figure 5a;

[0032]

[0030] Figure 6 is a graph of results from an experiment using a specific arrangement of breath analysis device; and

[0033]

[0031] Figure 7 plots sensor response (mV) against time during an experiment in which the same gases were passed through a breath analysis device without and with a sensor stack.

[0034] Detailed description of drawings

[0035]

[0032] The present techniques relate to a breath analysis device and a system for using such a breath analysis device. We also describe a method for using the breath analysis device. The breath analysis device comprises a filtering mechanism (which may also be termed a filter stack) for removing interferent chemicals to increase the accuracy of detection, identification and quantification of specific chemicals. Exhaled human breath comprises a multiplicity of vapour phase chemicals and the function of the filtering mechanism is removal, retardation and separation of chemicals other than the specific chemicals to be determined by the sensing element(s). Removal, retardation and separation of the chemicals other than those of interest reduces error by reducing cross sensitivities when using broadly selective sensors such as metal oxide semiconductors. One example use of the breath analysis device may be to enable users who suffer from digestive health problems, particularly irritable bowel syndrome (IBS) or small intestinal bacterial overgrowth (SIBO), to monitor symptoms based on detection of specific chemicals such as hydrogen and / or methane in their breath over time.

[0036]

[0033] Figure 1 shows an example breath analysis device 100 (which may also be termed a gas analysis device) which comprises a housing 1 10 having an inlet 112, into which a user exhales, and an outlet 114 through which the breath exits the device. Within the housing 110, there is a filtering mechanism which in use removes interferent chemicals from the user’s breath and one or more sensors which detect and / or identify specific or target chemicals (e.g. methane or hydrogen). As shown in Figure 1 , the breath analysis device is compact and handheld.

[0037]

[0034] Figures 2a and 2b show the detail of one example of a filtering mechanism 200 (which may also be termed a filter stack). The filter stack comprises a plurality of layers (which may also be termed components) and the different layers may perform different functions. The breath passes through the filter stack in the direction indicated by the arrows A. The filter stack comprises a first filter component 210 through which the breath passes into the filter stack. The filter stack comprises a second filter component 212 which is between the first filter layer and an optional third filter component 214 whereby the breath passes first through the second filter component 212 and then the third filter component 214. Optionally, the filter stack may comprise a fourth filter component 216 through which the filtered breath exits the filter stack. The first and fourth filter components 210, 216 are relatively thin compared to the second and third filter components 212, 214 and may thus be termed filter layers. Merely as example dimensions, the first and fourth filter components 210, 216 may have a thickness of approximately 0.15 mm to 1 mm and the second and third filter components 212, 214 of between 1 mm and 2.7mm. In other words, the first and fourth filter components 210, 216 may be ten to thirty times thinner than the second and third filter components 212, 214. In this arrangement, each component has a circular cross-section and may have a diameter of 7mm.

[0038]

[0035] The first filter component 210, and when included the fourth filter component 216, are used to remove a first class of interferent chemicals from the breath sample. The first class of interferent chemicals may include water. One or both of the first and fourth filter components 210, 216 are in the form of a semipermeable membrane and in particular are permeable for the target compounds such as hydrogen and / or methane but reduce passage of water. The pore size may be in a range from 0.1 pm to 1 .5 pm, suitably in the range from 0.1 pm to 0.45 pm.

[0039]

[0036] The first and fourth filter components layers 210, 216 may be made from the same material, for example a hydrophobic material such as PTFE (polytetrafluoroethylene). When the filter layer is made from a hydrophobic material, it may be termed a hydrophobic layer. The use of a hydrophobic material reduces the humidity in the breath sample to a lower level and may even remove the humidity (water vapour) from the breath sample.

[0040]

[0037] The material and / or parameters (e.g. pore size) of the first and fourth filter components 210, 216 may also be selected to reduce the difference in relative temperature between the ambient atmosphere and the breath sample. In this way, when the filtered breath sample is sensed by one or more sensors, the error in the humidity and temperature measurements is reduced because the values for pre-breath sample (i.e. ambient atmosphere) and breath sample are closer in absolute value.

[0041]

[0038] The second filter component 212, and when included the third filter component 214, are used to remove a second class of interferent chemicals from the breath sample. The second class of interferent chemicals may be volatile organic compounds and may include for example any of: sulphides, hydrogen sulphide, dimethyl sulphide, alkanes, such as ethane and pentane, aldehydes such as decanal, ketones such as acetone, carboxylic acids such as pentanoic acid, alcohols such as ethanol, alkenes such as isoprene or a combination thereof. The second and third filter components 212, 214 are permeable for the target compounds such as hydrogen and / or methane. The second and third filter components may be made from adsorbent or absorbent materials and may thus be termed adsorbent or absorbent layers respectively.

[0042]

[0039] As an example, the second filter component 212 may comprise loose activated charcoal which is suitable for removal of higher molecular weight compounds, such as volatile organic compounds (VOCs) from a breath sample. The target compounds, e.g. hydrogen and / or methane, are able to diffuse through the loose activated charcoal. Examples of activated charcoal include, Carbograph, Carbosieve, Carboxen, Carbopack, Carbotrap. The loose activated charcoal may be in any suitable form, e.g. beads or granules, within a suitable inert supporting structure. The activated charcoal granules may have a specific surface area in excess of 3000 m2g1. The parameters such as bead size and bead spacing may be selected to ensure maximum separation between the interferent chemicals and the target compounds. It will be understood that alternative adsorbent and / or absorbent materials may be used in place of loose activated charcoal to remove interferent chemicals. Examples of alternative adsorbent and / or absorbent materials are, zeolites, molecular sieves, carbonised molecular sieves, porous polymers, Tenax, adsorbent polymers, absorbent polymers, superabsorbent polymers, silica, celite, glass wool, beads, glass beads, quartz beads.

[0043]

[0040] In this example, the third filter component 214 is made from charcoal and is in the form of a disc. The charcoal disc is suitable for removal of higher molecular weight compounds, such as volatile organic compounds (VOCs) from a breath sample. The target compounds, e.g. hydrogen and / or methane, are able to diffuse through the charcoal disc. The parameters of the charcoal disc may be selected to ensure maximum separation between the interferent chemicals and the target compounds.

[0044]

[0041] In this example, the second filter component layer 212 is thicker than the third filter component 214. Merely as an example, the second filter component 212 may have a thickness in the range of 2.5 mm to 3.5 mm and the third filter component may have a thickness in the range 0.5 mm to 1 .5 mm. It will be appreciated that the materials and dimensions for the second and third filter components are exemplary only and others may be used.

[0045]

[0042] The use of two or more materials for the removal of high molecular weight compounds, such as volatile organic compounds (VOCs) from a breath sample, enables improved selectivity. In other words, the filter stack may be designed to maximise the removal of a large proportion of chemicals from the breath sample other than those intended for detection, identification and quantification. The multi-layer and multi-functional arrangement of the filter stack removes the majority of compounds including water vapour within a breath except the target compounds (e.g. methane and hydrogen).

[0043] The parameters of the various layers can be designed to maximise separation between the materials being sensed (hydrogen and methane) and the interferent materials such as sulphides, hydrogen sulphide, dimethyl sulphide, alkanes, such as ethane and pentane, aldehydes such as decanal, ketones such as acetone, alcohols such as ethanol, and carboxylic acids such as pentanoic acid. For example, hydrogen and methane are not retained by the filter stack assembly because hydrogen and methane particles are smaller and faster than the particles of the interferent chemicals. Therefore, the micro / meso structure does not trap the target compounds. This removal of interferent chemicals improves the accuracy and precision level of target compound detection and identification. The various layers may be designed so that the target compounds diffuse through the filter stack in around 20 seconds to allow measurements to be taken in real time.

[0046]

[0044] Figure 3 is an exploded drawing showing the components of the breath analysis device of Figure 1 . A breath sample flows into the housing through the inlet 7 and out through the outlet 3. The inlet 7 is in the form of an aperture in a mouth piece into which the user exhales. A breath flow path indicated by the Arrow B is thus defined between the inlet 7 and the outlet 3 and in this example is along a longitudinal axis of an elongate channel which may be termed a welded manifold. In this example, the device comprises two filter stacks similarto those shown in Figures 2a and 2b. Neither filter stack is positioned in-line with the breath flow path between the inlet 7 and the outlet 3. Both filter stacks are arranged directly to one side of (transversally to) the breath flow path and a portion of the breath sample passes into each filter stack through a corresponding aperture in a side wall of the elongate channel. The portion of breath sample which passes through each filter stack is then sensed by a corresponding sensor 15, 16 each of which is housed in an enclosed chamber. By arranging the filter stack and corresponding sensor in this way, there is no net flow of breath sample into and out of the chamber comprising the sensor. Also, there is no stagnation of breath sample and / or contaminants in the side chamber because the breath sample can diffuse back out of the chamber into the direct flow path channel.

[0047]

[0045] In the arrangement of Figure 3, each filter stack comprises a filter layer 20, a first adsorbent layer 21 and a second adsorbent layer 22. The filter layer may be a hydrophobic disc membrane as described above. The first adsorbent layer 21 may comprise loose activated charcoal and the second adsorbent layer 22 may be in the form of a charcoal disc as described above. Both filter stacks are supported on a support 13 in the form of a manifold plate.

[0048]

[0046] The support 13 comprises a first opening which is surrounded by a seal 27 and which is connected to a first sensor 15. The first sensor 15 may be a gas sensor for sensing a first target compound, e.g. hydrogen. The support 13 comprises a second opening which is surrounded by a seal 26 and which is connected to a second sensor 16. The second sensor 16 may be different to the first sensor and may be for sensing a different target compound, e.g. methane. Any suitable mechanism, e.g. screws 18 and 19, may be used to secure the filter stacks and sensors to the support 13 and to the elongate channel.

[0049]

[0047] There are various types of sensors which can be used for detection of methane and hydrogen. These include optical sensors, calorimetric sensors, pyroelectric sensors, semiconducting metal oxide sensors, and electrochemical sensors among others. Metal oxide based sensors are used for a wide range of applications because they are inexpensive compared to other sensing technologies, lightweight and robust. Examples of suitable methane gas detection sensors are described for example in “A Review of Methane Gas Detection Sensors: Recent Developments and Future Perspectives” by Aldhafeeri et al published in Inventions in 2020.

[0050]

[0048] As an alternative to using specific sensors, the arrangement of Figure 3 allows the first and second sensors 15 and 16 to be non-selective sensors because each filter stack filters out the interferent chemicals. In other words, the use of non-selective sensors for detection and identification of specific individual chemicals is possible because chemicals other than the target chemicals have been removed. This arrangement, therefore, provides the benefit of enabling cheap, non-selective sensors to be used for detection, identification and quantification of specific individual chemicals through selective removal of interferent chemicals that might be present in a breath sample.

[0051]

[0049] Each filter stack provides a means of removal of interferent chemicals which does not require electrical input and may significantly increase capacity and lifetime of the device. For example, each filter stack may significantly increase capacity and lifetime of the device through removal of polysiloxanes and or other air borne-chemicals that have irreversible effects on the sensors sensitivity. The device may have a reduced size, weight and power consumption, when compared to in-line filtration or the use of a GO (gas chromatography) column as a separation method. Each filter stack also provides a means for chemical purification of a test gas mixture (in this case a breath sample) without adversely affecting the chemicals of interest. Each filter stack enables a smaller volume of adsorbent material to be used while enhancing lifetime and reducing size, weight and power required by the device, thus facilitating sample purification in a handheld breath analysis device. These are requirements of any handheld, portable breath analysis system. In this way, the handheld breath collection device has improved accuracy and precision through selective chemical removal of undesirable, interferent chemicals that are present on breath samples.

[0052]

[0050] For completeness, it is noted that the example breath analysis device has a housing which comprises a top panel 1 , a bottom panel 2 and two side panels 4, 5. The top and bottom panels may be in form of clam shells. The side panels may comprise a USB side panel 4 and a button side panel 5. The button side panel may comprise a button rubber 10 which covers a portion of the button side panel 5 and a first button light 8 which lights up to indicate when the device is ready for a measurement to be taken. The top panel may comprise a second button light 9 which lights up when the device has finished taking a measurement. It will be appreciated that the button lights could be located at different points on the housing. The USB side panel comprises a USB rubber 11 which covers a portion of the USB side panel 4. A screw cover 12 covers the screw 18 to protect the screws 18 which hold the top and bottom panels together.

[0053]

[0051] There are additional optional components within the housing. For example, a haptic motor 14 may be included to provide haptic feedback through the housing, e.g. through the bottom panel 2. There may be a controller PCB 25 which may include an FPC connector 17 and the second button light 9. The FPC connector may be used to enable a light and compact electronics package. The HAM controller PCB 25 may enable storage of data collected by the sensors and communication with the mobile electronic device. There may also be a battery pad 23 to protect the battery 24 which provides power to the device. A HAM controller PCB 25 is located on top of the flow-path 3. There may be an additional filter 6 in the mouth piece.

[0054]

[0052] Figure 4a shows a breath analysis device 40 such as the one in Figure 3 and schematically shows the location of the sensors 45,46 and the filtering mechanisms 43,44 relative to the main flow path from the inlet 41 to the outlet 42. As shown each sensor is located in a side chamber which is arranged directly to one side of the main flow path. By arranged directly, it is meant that there is no connecting chamber between the side chamber and the main flow path. Breath can flow directly from the main flow path into the side chamber. The response from the sensor is typically flow dependent and thus to achieve a response from the sensor which is proportional to the concentration of a target chemical the net flow rate over the sensor should be at or as near to zero as possible. By placing each sensor in such a chamber (or compartment having only one open side through which the breath flows), the breath sample flows into and out of the chamber using diffusion. Flow in and out of the chamber is shown by the pair of arrows and the net flow rate over the sensor approximates to the desired rate of 0 mL / min. Each sealed chamber may thus also be termed a blind channel. Small gas molecules such as hydrogen and methane are fast-moving and can diffuse in and out of the chamber essentially without retardation by the filtering mechanisms. By contrast, the movement of larger and polar molecules, VOCs and water, are retarded by the filter mechanisms as explained above.

[0055]

[0053] An additional advantage of the filtering mechanism and sensor being located transversally to the breath flow-path is that the device is easier to breath through because the flow path is not mechanically blocked. A further advantage is that the pressure change across the flow-path is minimised because there are fewer components in the flow-path.

[0054] For comparison, Figure 4b shows a breath analysis device 60 in which the filtering mechanism 62 and sensors 64, 66 are in-line with the main flow-path of the breath. In such an arrangement, all of the breath sample comes into contact with the filtering mechanism 62. Furthermore, as indicated by the arrow, there is a flow across the sensors 64, 66 and this flow rate is relatively high compared to the approximately zero flow rate achieved in the previous arrangement. The average person exhales around 4L of breath in one exhalation, having a humidity of 80% and a temperature higher than 30°C. Typically, the breath analysis device 60 is kept at room temperature. The rapid change in temperature, coupled with the high humidity of breath, may create condensation on the filtering mechanism which means that the filtering mechanism is likely to deteriorate more quickly than in the arrangement of Figure 4a. There is also a risk of contaminating the sensors 64,66 with water droplets from the condensed breath. Additionally, when the filtering mechanism is located in-line with the breath flow-path, the filtering mechanism contacts more interferent chemicals (and other analytes) which may result in rapid saturation of the filter mechanism, thus reducing the lifetime of the breath analysis device when compared to the arrangement shown in Figure 4a.

[0056]

[0055] Figure 5a shows a system 400 comprising a breath analysis device 402 which is connected to a mobile electronic device 420, for example a mobile phone. It will be appreciated that a mobile phone is just one example of a mobile electronic device and other mobile electronic devices such as tablets and smart watches may be included. The mobile electronic device 420 may be connected to the breath analysis device 402 using any suitable mechanism, e.g. USB, Bluetooth or Wi-Fi. The mobile electronic device 420 may also be connected to a third party server 440, e.g. via the cloud or any suitable mechanism, to enable a third party to access and analyse data as described below.

[0057]

[0056] Figure 5a schematically illustrates the key components of the breath analysis device 410. In use, the user provides a breath sample by inhaling into the inlet 410, the user’s breath flows into the flow-path 412 (e.g. the elongated channel shown above) towards the outlet 414. Between the inlet 410 and the outlet 414, a first portion of the breath sample is drawn through a filter stack 416, for example by diffusion. As the first portion of breath sample diffuses through the filter stack, at least one filter layer removes humidity from the sample and at least one adsorbent layer removes volatile organic compounds which are not target compounds from the sample. The filter (or treated) first portion of the breath sample then reaches a sensor 418 which senses one or more target compounds (e.g. hydrogen or methane). The treated first portion of the breath sample exits the device by diffusion. In this simplified example, a single filter stack 416 is shown but it will be appreciated that there may be two filter stacks as shown in Figure 3 or more filter stacks depending on the number and nature of the target compounds.

[0057] The mobile device comprises the standard components of a mobile device, for example a display 424 (e.g. a screen) which displays information to a user and a user interface 426 through which a user can enter an input. The user interface may be any known user interface including a touch-sensitive screen, a keyboard or a voice activated interface. The mobile device comprises a processor 422 which processes instructions from apps running on the device and memory 428 for storing information, including apps which have been downloaded. The mobile device comprises a communication module 430 which allows the mobile device to connect to the breath analysis device and / or a third party server 440.

[0058]

[0058] The breath analysis device 402 records sensor data, e.g. the concentration of sensed target compound. The data may be transmitted to the mobile device 420 and may be stored on the mobile device 420, e.g. within a dedicated mobile application. The data may be transmitted for storage in an external database and / or sent to a third party server 440 for analysis. The third party server is a server which is physically removed from the mobile device. The data may be used to monitor a user’s symptoms, for example of gastrointestinal illness, over time.

[0059]

[0059] Figure 5b shows a method of using a mobile device such as that shown in Figure 5a. In a first step S10, the user launches an app which may have been pre-loaded on the mobile device. The user may launch the app, for example, because they wish to collect a sample. Once the app has been launched, the mobile device may detect an input (step S12). For example, the launch of the app causes a user interface to be displayed on the mobile device through which the user is able to make inputs. The input may not be generated by the user, for example an input may be a message from a third party, e.g. a healthcare professional. The input may be generated by the user, for example, the user may input their symptoms, lifestyle, dietary intake. Alternatively, the input may be a detected event, e.g., breath flow detected within the breath analysis device. As other examples of detected events, a clock in the mobile phone may detect that it is a meal time or another time for taking a measurement, or a camera in the mobile phone may be used to detect food on a plate and identify potential triggers. Another detected event may be a proximity signal when a user travels to certain locations e.g. locations, such as restaurants, known to serve foods which may lead to exacerbated symptoms of IBS or other gastrointestinal disorders.

[0060]

[0060] In response to the input, the mobile device displays a command to prompt a user to start providing a breath sample, S14. For example, the user interface can display a button labelled as “start collection” which can be selected or clicked by a user to initiate collection of data by the breath analysis device. It will be appreciated that a “start collection” button is just one way to present a user friendly interface.

[0061] The user input causes the breath analysis device to automatically start collecting sample data (step S16). For example, for a breath sample, the user exhales into the breath analysis device for a predetermined amount of time, e.g. between 10 to 20 seconds, more particularly approximately 15 seconds. The predetermined amount of time may be determined based on the input and / or may be determined according to requirements prescribed by a third party, such as a healthcare professional.

[0061]

[0062] The breath analysis device may determine whether or not the collected sample data meets the required collection criteria (step S18). The collection criteria may comprise a minimum time for the collection, e.g. the predetermined amount of time, and / or additional information from the mobile device, for example a detection limit, or information provided by the user or a third party. If the sample data meets the collection criteria, the user interface may inform the user or a third party and report and store the data (step S20). If the sample data does not meet the collection criteria, e.g. the predetermined amount of time was not met, the user may be prompted to repeat the measurement (step S19). If the user decides to repeat the measurement, steps S14 to S18 may be repeated. If the user decides not to repeat the measurement, the data may be discarded (step S21).

[0062]

[0063] The invention enables the collection of a rich data-set for use by the user, to better understand and manage their condition, and for use by a third party, for example to observe longitudinal trends and for meta-analysis. The invention will enable monitoring of the levels of target compounds such as hydrogen and / or methane on breath over time.

[0063]

[0064] Figure 6 plots sensor response (mV) against time during an experiment in which different samples were passed through a breath analysis device such as the one shown above. In this experiment, the target chemical that the sensor is detecting is hydrogen and the filtering mechanism adjacent the sensor comprises four components. There are first and fourth filter components both of which are hydrophobic layers of PTFE for removing water vapour. These first and fourth filter components form upper and lower layers for the filtering mechanism and thus provide structural support for the filtering mechanism. The second filter component which is beneath the first PTFE layer comprises loose activated charcoal for the retardation / removal of VOCs. The third filter component which is between the second and fourth layers is in the form of a charcoal disc and also retards / removes VOCs.

[0064]

[0065] The first sample which passes through the breath analysis device is ambient air to provide a baseline of approximately 200mV for the sensor. At 15 minutes, a second sample which may be described as a saturated vapour sample is passed through the breath analysis device. The saturated vapour sample is generated by a headspace syringe and has a total volume of 50 mL. The saturated vapour sample comprises isoprene, acetone, ethanol, pentanoic acid and decanal at approximately 640,000 ppm, 230,000 ppm, 77,000ppm, 263 ppm and 132 ppm respectively. This resulted in a gradual increase in sensor response from 204 mV at 14 minutes to a maximum of 231 mV at 39 minutes. At 40 minutes, a third sample which is a representative on-breath sample is passed through the breath analysis device. The on-breath sample is generated from a gas cylinder and comprises isoprene, acetone, ethanol, ethane and carbon monoxide at 2.6ppm, 145.5ppm, 2.8ppm, 1.4ppm and 43ppm respectively. The sensor response increased from 231 mV at 39 minutes to 245 mV at 48 minutes before decreasing to 238 mV. In other words, there is only a modest change in the sensor response and thus the filter stack is effectively retarding / removing the VOCs.

[0065]

[0066] The sensitivity of the sensor to hydrogen was also tested. At 55 minutes, hydrogen at a concentration of 100 ppm was provided to the breath analysis device and the sensor response increased rapidly from 238 mV to 400 mV within a minute and furtherto 420 mV within 5 minutes. At 60 minutes, the concentration of hydrogen provided to the breath analysis device was reduced to 50 ppm and the sensor response decreased accordingly to 343 mV at 61 minutes. At 65 minutes the concentration of hydrogen provided to the breath analysis device was reduced to 25 ppm and the sensor response decreased accordingly to 285 mV at 66 minutes. When hydrogen was no longer provided to the breath analysis device at 70 minutes, the sensor response decreased rapidly to 243 mV at 71 minutes and then gradually returned to 234 mV at 75 minutes. The presented data demonstrates that the filter stack allows hydrogen to pass rapidly through to the sensor, but delays or prevents interferent chemicals such as for example isoprene, acetone, ethanol, ethane and carbon monoxide from interfering with the sensor measurement.

[0066]

[0067] Figure 7 plots sensor response (mV) against time during an experiment in which the same gases were passed through a breath analysis device such as the one shown above. There are four sets of results (traces) showing breath analysis devices with and without a filter stack for two different types of sensor. In this experiment, trace 1 and trace 2 show the results for two different sensors without a filter stack over them. Trace 1 corresponds to the measurement of gases using a device comprising the sensor TGS2611 without the filter stack and trace 2 corresponds to the measurement of gases using a device comprising the sensor TGS8100 without the filter stack. Trace 3 and 4 are the results for the same sensors as that of trace 1 and trace 2 with the filter stacks over them. That is trace 3 corresponds to the measurement of gases using a device comprising the sensor TGS261 1 and a filter stack, and trace 4 corresponds to the measurement of gases using a device comprising the sensor TGS8100 and a filter stack.

[0067]

[0068] All four sets of results are conducted in the same atmosphere and each arrangement sees the same gases at the same time (isoprene, acetone, ethanol, pentanoic acid, and decanal). The first peaks of trace 1 and trace 2 at approximately 15 minutes are the interferent, while the second square peak starting at around 30 minutes and continuing until approximately 60 minutes is the sensors’ response to hydrogen. The data demonstrates that when the sensors are exposed to the interferent when the filter stack is not present a response to the interferent is seen (traces 1 and 2). By contrast, when the filter stack is present the injection of interferent did not produce a peak (traces 3 and 4). The hydrogen response is seen in all four traces from all four sensors including those with the filter stack present. Additionally, the sensor response to the interferent as shown in traces 1 and 2 is 2200 mV which is much higher than the maximum sensor response exhibited in traces 3 and 4 of approximately 500 mV (corresponding to the detection of hydrogen). As explained above, the selective removal of interferent by the filter stack enables a more accurate and precise calculation of hydrogen and methane concentrations, additionally exposure of the sensors to the interferent can cause accumulation of interferent on the sensors, damaging them and reducing the lifetime and sensitivity of the sensors.

[0068]

[0069] The sensors used in the experiment shown in Figure 7 are TGS2611 and TGS8100. TGS261 1 is a semiconductor type gas sensor which can be purchased from Figaro and detects methane and natural gas in the range from 500 ppm to 10,000 ppm by measuring the resistance change of the metal oxide due to adsorption of gases (MOS-type sensing). TGS8100 is a MEMS- type semiconductor sensor which can be purchased from Figaro and which detects hydrogen, ethanol and other air contaminants in the range from 1 ppm to 30 ppm.

[0069]

[0070] The interferent gases used in the experiment shown in Figure 7 were isoprene, acetone, ethanol, pentanoic acid and decanal. The interferant gases used were provided as a 50ml volume of headspace / saturated vapour of the following five chemicals. The 50ml volume, was injected from a syringe, as a bolus dose, into a gas stream that flowed across the sensors and filter stacks and it was administered over approximately 10 seconds. The approximate concentration, in parts per million (ppm), of each interferent gas is provided below in table 1 .

[0070] Table 1 : Concentration of each interferent gas provided in the experiment shown in Figure 7

[0071]

[0071] At least some of the example embodiments described herein may be constructed, partially or wholly, using dedicated special-purpose hardware. Terms such as ‘component’, ‘module’ or ‘unit’ used herein may include, but are not limited to, a hardware device, such as circuitry in the form of discrete or integrated components, a Field Programmable Gate Array (FPGA) or Application Specific Integrated Circuit (ASIC), which performs certain tasks or provides the associated functionality. In some embodiments, the described elements may be configured to reside on a tangible, persistent, addressable storage medium and may be configured to execute on one or more processors. These functional elements may in some embodiments include, by way of example, components, such as software components, object-oriented software components, class components and task components, processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuitry, data, databases, data structures, tables, arrays, and variables. Although the example embodiments have been described with reference to the components, modules and units discussed herein, such functional elements may be combined into fewer elements or separated into additional elements. Various combinations of optional features have been described herein, and it will be appreciated that described features may be combined in any suitable combination. In particular, the features of any one example embodiment may be combined with features of any other embodiment, as appropriate, except where such combinations are mutually exclusive. Throughout this specification, the term “comprising” or “comprises” means including the component(s) specified but not to the exclusion of the presence of others.

[0072]

[0072] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0073]

[0073] All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0074]

[0074] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

CLAIMS1. A breath analysis device for detecting a target chemical within a breath sample, the breath analysis device comprising: a housing having: an inlet for a breath sample to flow into the housing; an outlet for the breath sample to flow out of the housing; and a direct flow path between the inlet and outlet along a channel; a sensor within the housing, wherein the sensor is configured to detect the target chemical; a filtering mechanism which is within the housing and which is positioned closer to the inlet than the sensor, and a side chamber in which the sensor and filtering mechanism are located, wherein the side chamber is positioned directly to one side of the direct flow path; wherein the filtering mechanism comprises: a first filter component which is configured to retard passage of a first interferent chemical within the breath sample relative to passage of the target chemical through the first filter component; and a second filter component which is configured to retard passage of a second interferent chemical within the breath sample relative to passage of the target chemical through the second filter component, wherein the second interferent chemical is different from the first interferent chemical.

2. The breath analysis device according to claim 1 , wherein the first filter component is configured to remove the first interferent chemical and / or the second filter component is configured to remove the second interferent chemical.

3. The breath analysis device according to claim 1 or claim 2, wherein the first filter component is configured to retard the passage of or remove water.

4. The breath analysis device according to claim 3, wherein the first filter component comprises a hydrophobic material.

5. The breath analysis device according to claim 3 or claim 4, wherein the first filter component is a porous membrane having a pore size which is selected to allow passage of the target chemical.

6. The breath analysis device according to any one of the preceding claims, wherein the second filter component is configured to retard the passage of or remove a volatile organic compound.

7. The breath analysis device according to claim 6, wherein the second filter component comprises an absorbent material for absorbing the volatile organic compound or an adsorbent material for adsorbing the volatile organic compound.

8. The breath analysis device according to claim 6 or claim 7, wherein the second filter component comprises a plurality of particles having properties which are selected to remove or retard the volatile organic compound.

9. The breath analysis device according to claim 8, wherein the second filter component comprises a support structure for the particles.

10. The breath analysis device according to any one of the preceding claims, wherein the filtering mechanism comprises a third filter component which is configured to retard passage of or remove a third interferent chemical within the breath sample relative to passage of the target chemical through the third filter component.11 . The breath analysis device of claim 10, wherein the third filter component is configured to retard the passage of or remove a different volatile organic compound to the second filter component.

12. The breath analysis device according to claim 10 or claim 11 , wherein the filtering mechanism comprises a fourth filter component which is configured to retard passage of or remove a fourth interferent chemical within the breath sample relative to passage of the target chemical through the third filter component.

13. The breath analysis device of claim 12, wherein the fourth filter component is configured to retard the passage of or remove the same interferent chemical as the first filter component.

14. The breath analysis device according to any one of the preceding claims, wherein each of the filter components are in the form of adjacent layers.

15. The breath analysis device according to any one of the preceding claims, wherein the sensor is for detecting a first target chemical and the breath analysis device comprises a second sensor for detecting a second target chemical which is different form the first target chemical.

16. The breath analysis device according to any one of the preceding claims, further comprising a second filtering mechanism which is positioned closer to the inlet than the secondsensor and which comprises at least one of the first filter component and the second filter component.

17. A filter stack for use in a breath analysis device according to any one of the preceding claims, wherein the filtering mechanism comprises: a first filter component which is configured to retard passage of a first interferent chemical within the breath sample relative to passage of the target chemical through the first filter component; and a second filter component which is configured to retard passage of a second interferent chemical within the breath sample relative to passage of the target chemical through the second filter component, wherein the second interferent chemical is different from the first interferent chemical.

18. A method of using the breath analysis device according to any one of the preceding claims for detecting of at least one target chemical within a breath sample, the method comprising; receiving a breath sample in the inlet; channelling the breath sample along the channel from the inlet to the outlet; receiving, direct from the channel, a portion of the breath sample in the side chamber in which the sensor and filtering mechanism are located; at least retarding at least one first interferent chemical within the breath sample by diffusion of the breath sample through the first filter component; at least retarding at least one second interferent chemical from the breath sample by diffusion of the breath sample through a second filter material; analysing the breath sample using a sensor to detect the at least one target chemical after removal of the interferent chemicals from the breath sample.

19. A system for detecting at least one target chemical within a breath sample comprising; a breath analysis device according to any one of claims 1 to 16; and a mobile device which is connected to the breath analysis device to receive sensor data from the breath analysis device.

20. The system of claim 19 wherein the mobile device is connected to a server and is configured to transmit data collected from the breath analysis device to the server for further analysis.

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