WO2019074922A1 - Dispositif d'analyse de la respiration - Google Patents

Dispositif d'analyse de la respiration Download PDF

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Publication number
WO2019074922A1
WO2019074922A1 PCT/US2018/055009 US2018055009W WO2019074922A1 WO 2019074922 A1 WO2019074922 A1 WO 2019074922A1 US 2018055009 W US2018055009 W US 2018055009W WO 2019074922 A1 WO2019074922 A1 WO 2019074922A1
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WO
WIPO (PCT)
Prior art keywords
pathway
sensor
breath
exhaled breath
gas flow
Prior art date
Application number
PCT/US2018/055009
Other languages
English (en)
Inventor
Apostolos ATSALAKIS
Panagiotis PAPADIAMANTIS
Konstantinos DALAKAS
Original Assignee
Endo Medical, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Endo Medical, Inc. filed Critical Endo Medical, Inc.
Publication of WO2019074922A1 publication Critical patent/WO2019074922A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/082—Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/497—Physical analysis of biological material of gaseous biological material, e.g. breath
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0015—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system
    • A61B5/002—Monitoring the patient using a local or closed circuit, e.g. in a room or building
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/097—Devices for facilitating collection of breath or for directing breath into or through measuring devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6802—Sensor mounted on worn items
    • A61B5/6803—Head-worn items, e.g. helmets, masks, headphones or goggles

Definitions

  • This invention relates to a device for measurement of breath.
  • the present invention relates to a breath analysis device suitable for use in indirect calorimetry; it also relates to a breath analysis device incorporating a moisture reducing module for dehumidifying exhaled breath.
  • the disclosure also relates to a method of measuring a breath property of a subject using the device.
  • Breath analysis is a field which has gained significant interest during recent years since it is a non-invasive technique that has many promising results. Since ancient times, physicians have been aware of the relationship between the odour of a person's breath and certain diseases. Since then it has been
  • breath could give insight into physiological and pathophysiological processes of the human body (see, for example, W. Ma, W, Liu X and J.
  • the human breath is a mixture of inorganic gases (NO, CO 2 , CO, nitrogen), volatile organic compounds (VOCs) (isoprene, ethane, pentane, acetone) and other non-volatile substances (isoprostanes, peroxynitrine, cytokines).
  • VOCs volatile organic compounds
  • other non-volatile substances isoprostanes, peroxynitrine, cytokines.
  • the components of human breath have endogenous and exogenous origins and an analysis of their composition can be related to the physiological processes that have taken place as well as to the pathways of ingestion or absorption (see K. Kim, J. Shamin and E. Kabir, "A review of breath analysis for diagnosis of human breath", Trends in Analytical Chemistry, (2012)).
  • breath can be regarded as a fingerprint of the human health and its analysis has significant medical applications.
  • breath analysis tests can be identified in their safety and non-invasive nature.
  • the simplicity of breath analysis is particularly interesting for patients who have to monitor their health daily such as patients who are diabetic, have to monitor their urea etc. (G. Guilbault, G.
  • RMR resting metabolic rate
  • thermogenesis thermogenesis that is induced by food intake.
  • RMR is determined by whole body respiratory chambers and metabolic carts but such methods are costly and require trained technicians. Moreover, mathematical models that have been developed for the prediction of RMR fail by a rate of 50% to 70% and are often found to be inaccurate in cases of obesity, anorexia nervosa and other illnesses. Thus, there is a need for an inexpensive, handheld and easy to use device to perform indirect calorimetry measurements and determine accurately the RMR of a person.
  • breathalyser that measures the human metabolism also finds use in controlling the diet of obese individuals.
  • Obesity is currently a major problem and a 2014 report by the Health & Social Information Centre reported that only 32.1 % of men and 40.6% of women in England have a normal Body Mass Index (BMI) (Statistics on Obesity, Physical Activity and Diet, Health & Social Care Information Center, (2014)).
  • BMI Body Mass Index
  • obesity is related to type II diabetes, coronary heart disease, different types of cancer (breast cancer, bowel cancer etc.) and stroke according to a report of the National Health Service
  • MedGemTM by Microlife Medical Home Solutions Inc. of 2801 Youngfield St., Suite 241 Golden, CO 80401 , USA
  • BreezingTM by Breezing, Co. of 2601 N 3rd St, Suite 108, Phoenix, AZ, 85004
  • the MedGemTM device measures only the exhaled oxygen in the breath and assumes that the expired carbon dioxide has a constant ratio of 0.85 when compared to oxygen. That of course, is only an assumption and, as it is very often not a correct assumption, it leads to erroneous measurements.
  • the MedGemTM device is unable to measure both O2 and CO2 on a breath-by-breath basis in order to deliver the required accuracy.
  • the ratio of exhaled carbon dioxide to exhaled oxygen is defined as the respiratory quotient (RQ) and varies between 0.65 and 1 .0.
  • RQ respiratory quotient
  • the accuracy of the determination of the RQ is thus very important.
  • the accurate determination of the RQ is a metric equally important to the
  • the second device that is currently available in the market place is sold under the trade name BreezingTM.
  • This device senses both oxygen and carbon dioxide. It uses consumable sensors which is disadvantageous in many settings. It means that each test requires a consumable sensor that costs approximately 5$ (USD).
  • USD 5$
  • Use of consumable parts, rather than reusable technology, is inconvenient and costly.
  • the cost of such a device again increases
  • a breath analysis device comprising: an exhaled breath flow pathway for passage of exhaled breath from an inlet to an outlet; one or more sensors for analysing a property of exhaled breath; and a moisture reduction module, said moisture reduction module comprising: a first gas flow passage and a second gas flow passage, said passages being separated by a selectively permeable membrane which permits transfer of moisture, and
  • one of said gas flow passages forms part of said exhaled breath flow pathway, and the other of said gas flow passages is a pathway for ambient air and is in communication with the ambient environment;
  • the breath analysis device described herein solves this problem by incorporating a dehumidification system which reduces breath humidity. This results in the ability to provide low cost, handheld breathalyzer devices capable of measuring both the human metabolism and the respiratory quotient (RQ) without using consumable components, and which are able to measure metabolism with a gold-standard accuracy.
  • Devices incorporating a moisture reduction module as described herein are advantageous as they allow the moisture content of exhaled breath to be reliably reduced prior to analysis by the one or more sensors.
  • Inhaled breath generally has a low relative humidity whereas exhaled breath has a very high relative humidity, but it is desirable that this humidity difference does not affect analysis of the breath.
  • exhaled and exhaled breath it is especially preferred that they are compared on the same basis.
  • a moisture reduction module is thus useful in reducing the water content or humidity of exhaled breath, e.g. to or near to ambient levels, in order to provide the same or similar moisture levels in samples of exhaled and inhaled breath, which is beneficial for the accurate analysis of the breath.
  • the exhaled breath flow pathway comprises a primary gas flow pathway for passage of exhaled breath from an inlet to a first outlet; and a secondary gas flow pathway for diverting and analysing a sample of exhaled breath, the secondary gas flow pathway being branched from the primary gas flow pathway at a branching point between the inlet and the first outlet, the secondary pathway having a second outlet.
  • the moisture reduction module comprises an outer tube and an inner tube, wherein the inner tube is made of a selectively permeable membrane and is arranged within the outer tube, the arrangement of said tubes defining said gas flow passages such that one of said gas flow passages is within the inner tube, and the other of said gas flow passages is between the outer surface of the inner tube and the inner surface of the outer tube.
  • This is a particularly convenient and compact assembly for providing the moisture reduction module, and maximises the potential surface area for water/moisture exchange between the two gas flow passages, since up to the whole surface of the inner tube may comprise a selectively permeable membrane.
  • the gas flow passage within the inner tube is a pathway for a sample of exhaled breath
  • the gas flow passage between the outer surface of the inner tube and the inner surface of the outer tube is a pathway for ambient air.
  • This is a particularly effective configuration since the arrangement readily allows for ambient air from the surrounding environment to enter the pathway for ambient air.
  • the device comprises: a primary gas flow pathway for passage of exhaled breath from an inlet to a first outlet; a secondary gas flow pathway for diverting and analysing a sample of exhaled breath, the secondary gas flow pathway being branched from the primary gas flow pathway at a branching point between the inlet and the first outlet, the secondary pathway having a second outlet; and wherein the exhaled breath gas flow passage within the inner tube forms part of the secondary gas flow pathway.
  • a primary gas flow pathway for passage of exhaled breath from an inlet to a first outlet
  • a secondary gas flow pathway for diverting and analysing a sample of exhaled breath
  • the secondary gas flow pathway being branched from the primary gas flow pathway at a branching point between the inlet and the first outlet, the secondary pathway having a second outlet
  • the exhaled breath gas flow passage within the inner tube forms part of the secondary gas flow pathway.
  • the gas in the inhaled breath is analysed; when inhaled gas is analysed, the flow of gas is reversed, and it passes from the outlet to the inlet of the primary gas flow pathway.
  • the device comprises a flow sensor between the inlet of the primary pathway and the branching point or between the branching point and the first outlet, the flow sensor being arranged to allow measurement of gas flow in the primary pathway.
  • a flow sensor in the primary pathway allows measurement of the flow rate of a user's breaths as they are exhaled.
  • the device comprises an O 2 sensor and/or a CO 2 sensor downstream of said moisture reduction module and arranged to analyse O 2 and/or CO 2 levels in a sample of exhaled breath in the secondary pathway.
  • both sensors may for example be arranged in sequence (also referred to as being in line), i.e. so that the sample of breath contacts a first sensor and then contacts a second sensor.
  • the sensors may be arranged in parallel, i.e. a portion of the breath sample comes into contact with one sensor and a different portion of the breath comes into contact with another sensor. Presence of an oxygen and/or carbon dioxide sensor allows the precise measurement of the consumed oxygen and produced carbon dioxide via a low-cost device.
  • the respiratory quotient that determines whether an individual metabolises fat, protein or carbohydrates can be accurately measured, rather than relying on assumptions for fixed values of the RQ.
  • the device does not use consumables, which reduces the cost of running the device.
  • the device is arranged to facilitate breath-by- breath analysis of exhaled breath, and in some embodiments, the device does not comprise a sampling chamber for analysis of a multi-breath sample.
  • the ability to measure oxygen and carbon dioxide production on a breath-by-breath basis is of great advantage compared to devices of the prior art.
  • the sampling chamber approach is slower and struggles to deliver a breath-by-breath analysis.
  • Sampling chambers which measure averaged values cannot draw conclusions about the profile of carbon dioxide and oxygen. Also, sampling chambers analyse only the exhaled breath.
  • preferred devices of the invention are able to track the oxygen profile, carbon dioxide profile and flow measurement on a breath-by- breath basis.
  • An in-line or parallel arrangement of oxygen and carbon dioxide sensors is useful for detecting the profiles of the oxygen, carbon dioxide and flow measurements.
  • An in-line arrangement allows real-time measurements in contrast with the sampling chamber that averages the values and is unable to measure the profiles of the measurements. Generating the profile for the oxygen, carbon dioxide and flow on every breath allows the integration of those signals to generate precise measurements of the consumed oxygen and produced carbon dioxide.
  • an in-line arrangement of said sensors is used, whereby the same portion of breath contacts the different sensors.
  • more than one sensor capable of detecting the presence of an analyte e.g. a carbon dioxide and an oxygen sensor
  • a parallel arrangement of said sensors may be used, whereby those sensors are contacted with different portions of breath.
  • that flow sensor may for example be positioned upstream of the sensors capable of detecting the presence of an analyte.
  • the O 2 sensor and/or the CO 2 sensor is a thermal conductivity detector.
  • Such sensors have a low response time, which is beneficial for obtaining fast, breath-by-breath measurements.
  • the device may further comprise one or more sensors selected from the group consisting of an acetone, nitric oxide, sulphur compound, pentane, ethanol and a hydrocarbon sensor.
  • the device may optionally comprise one or more sensors selected from the group consisting of a humidity sensor, a temperature sensor and a pressure sensor.
  • the device may optionally comprise a humidity sensor to assess the efficacy of the moisture reduction module.
  • a humidity sensor to assess the efficacy of the moisture reduction module.
  • the device may optionally comprise a temperature sensor. This allows measurements by the sensors to be compensated for or correcting factors to be applied due to changes in temperature.
  • the device may optionally comprise a pressure sensor. This allows measurements by the sensors to be compensated for changes in pressure.
  • the device may further comprise one or more further sensors. This allows the device to measure additional parameters that may be of interest.
  • the device may include a sensor of acetone, nitric oxide, sulphur compounds, pentane, ethanol and/or hydrocarbons. In particular, when a pentane and ethanol sensor are present, oxidative stress may be monitored.
  • the flow of gases can be controlled by the dimensions and configuration of the gas flow pathways; for example, tubes of smaller diameter may be used along the gas flow pathways to alter the flow rate of the exhaled breath as it passes through them.
  • the device may not comprise a pump.
  • the device comprises a pump to draw a sample of exhaled breath along the
  • the gas flow passage for ambient air merges with the secondary pathway downstream of said one or more sensors and upstream of said pump, so that, in use, the pump draws exhaled breath along the secondary pathway via the exhaled breath gas flow passage of the moisture reduction module, and also draws ambient air via the ambient air gas flow passage of the moisture reduction module.
  • This arrangement is particularly efficient, since the use of a single pump draws exhaled breath along its respective gas flow passage towards the sensors, to provide the flow advantages described above. At the same time, the pump is also drawing ambient air along its
  • the device may further comprise a valve system located between the branching point and the at least one sensor, thereby partitioning the
  • valve system comprises a valve outlet, and a valve member movable between at least a first position and a second position, and wherein:
  • the upstream portion of the secondary pathway when the valve member is in the first position, the upstream portion of the secondary pathway is in fluid connection with the downstream portion of the secondary pathway and not with the valve outlet; and when the valve member is in the second position, the upstream portion of the secondary pathway is in fluid connection with the valve outlet and not with the downstream portion of the secondary pathway.
  • This valve system enables the device to operate in different "modes" depending on the breathing rate of the user, by allowing subsequent breaths to be measured by the sensors, or, for example, every second breath, every third breath etc. when the breathing rate is higher. Whilst in some embodiments the device comprises such a valve system, in other embodiments the device does not comprise such a valve system. Typically in such other embodiments, during sampling every breath is analysed by the device.
  • the device may comprise a one-way valve positioned between the inlet and the sensor or sensors, arranged so that gas may pass in a direction from the inlet to one or more sensors only.
  • the device does not comprise a sampling chamber capable of containing multiple breaths.
  • a sampling chamber capable of containing multiple breaths.
  • Such a sampling chamber may for example be positioned along the exhaled breath flow pathway between the inlet and the outlet, or branched from the exhaled breath flow at a branching point between the inlet and the outlet.
  • the exhaled breath flow pathway comprise a primary gas flow pathway and a secondary gas flow pathway
  • the sampling chamber is preferably positioned along/branched from the secondary gas flow pathway.
  • the sampling chamber is preferably located along the exhaled breath flow pathway downstream of such faster response sensor(s), or branched from the exhaled breath flow pathway, with the slower response sensor(s) being in fluid connection with the interior of the sampling chamber, for analysing the collected breath.
  • This embodiment combines the benefits of the in-line connection of high speed sensors such as the oxygen and carbon-dioxide sensors discussed above (in particular the ability to conduct measurements on a breath-by-breath basis), which functions best with fast- response sensors, with the use of a sampling chamber which allows the use of slower response sensors that cannot be connected in-line.
  • the multi-breath sampling chamber may for example be a sampling bag. The use of a sampling bag allows a sample of multiple exhaled breaths to be collected together and subsequently analysed in a portable, low-cost and convenient manner.
  • the sampling bag is formed from a material which is deformable such that the bag may be collapsed to a reduced volume when the device is not in use, to allow convenient transport and storage of the device.
  • the device comprises a microcontroller.
  • microcontroller carries out the data processing, such as receiving the
  • the microcontroller may also power the pump.
  • the device comprises a microcontroller
  • the device also comprises a communication means for communication between the microcontroller and an external electronic device, for example a mobile phone or other device.
  • an external electronic device for example a mobile phone or other device.
  • the device is capable of functioning as an indirect calorimeter.
  • Indirect calorimetry is a useful tool for analysing the metabolism of a subject which may be useful for medical reasons, or for diet and lifestyle reasons.
  • Indirect calorimeters have several medical applications in the assessment of diabetes, obesity, anorexia, cardiovascular diseases etc., but existing indirect calorimeters are bulky and cost approximately tens of thousands of dollars.
  • the functioning of the device as an indirect calorimeter is thus advantageous as it provides an indirect calorimeter device that can conveniently be used by an individual in a domestic environment.
  • the device is portable. In some embodiments the device is handheld. This allows the device to be used in a variety of situations and for a user to use the device at any desired time of day.
  • a method of measuring a breath property of a subject comprising: providing a breath analysis device as described herein; and measuring a breath property of a subject using said breath analysis device.
  • Figure 1 shows a schematic diagram of an embodiment of a device according to the invention Part A.
  • Figure 2 shows a schematic diagram of a further embodiment of a device according to the invention Part A.
  • Figure 3 shows a schematic diagram of an embodiment of a device according to the invention Part B.
  • Figure 4 shows a schematic diagram of a further embodiment of a device according to the invention Part B.
  • the breath analysis device comprises an exhaled breath flow pathway for passage of exhaled breath from an inlet to an outlet.
  • the exhaled breath flow pathway is formed of a suitable plastic tubing, or other conventional material.
  • the device may simply comprise an exhaled breath flow pathway, a moisture reduction module and a sensor for analysing a property of the exhaled breath.
  • a suitable processing means may be present to establish an indication of the analysed property.
  • the sensor may be for detecting the presence of a particular analyte, and the processing means may for example establish a yes/no indication for the presence of a particular analyte, or a particular concentration or partial pressure of an analyte.
  • a subject breathes into the device at the inlet of the exhaled breath flow pathway.
  • the entire exhaled breath or substantially all of the exhaled breath of the user enters the exhaled breath flow pathway and the exhaled breath flow pathway is filled with the exhaled breath when the user exhales into the device.
  • the exhaled breath flow pathway comprises a primary gas flow pathway and a secondary gas flow pathway
  • a subject breathes into the device at the inlet of the primary pathway.
  • the entire exhaled breath of the user enters the primary pathway.
  • the exhaled breath flow pathway may also be used for the passage of air to be inhaled; in such cases, as the subject inhales, ambient air is drawn in the reverse direction to that of the exhaled breath, through the outlet of the exhaled breath flow pathway towards the subject.
  • the primary pathway may for example be used for drawing in air to be inhaled.
  • the user does not inhale through the mouth when using the device, and so ambient air to be inhaled does not pass through the primary pathway to the user.
  • embodiments of the device could operate either to analyse only exhaled breath or both inhaled / exhaled breath.
  • the device may comprise a facemask or a mouthpiece, for example, which facilitates capture and passage of exhaled breath into the exhaled breath flow pathway via the inlet.
  • the device comprises a moisture reduction (i.e. dehumidifying) module comprising a first gas flow passage and a second gas flow passage, said passages being separated by a selectively permeable membrane which permits transfer of moisture.
  • a moisture reduction (i.e. dehumidifying) module comprising a first gas flow passage and a second gas flow passage, said passages being separated by a selectively permeable membrane which permits transfer of moisture.
  • One of said gas flow passages forms part of said exhaled breath flow pathway, and the other of said gas flow passages is a pathway for ambient air and is in communication with the ambient environment.
  • moisture i.e. water in the breath sample
  • the exhaled breath has a high relative humidity (often up to 100% RH).
  • a high humidity is that it can lead to condensation forming in/on the sensor or sensors. Such condensation may affect the accuracy of the sensor(s) used, at least for sensors capable of detecting the presence of analytes in breath, and this is why the relative humidity of the breath is preferably reduced prior to passage across such sensors.
  • the moisture reduction module is located in the exhaled breath flow pathway upstream of one or more sensors capable of detecting the presence of an analyte (e.g. upstream of a CO 2 and/or O 2 sensor). Reduction of the relative humidity is not essential prior to contacting of exhaled breath with a flow sensor, and so in some preferred embodiments, where the device comprises a flow sensor, the flow sensor is upstream of the moisture reduction module.
  • the moisture reduction module may comprise an outer tube and an inner tube, wherein the wall of the inner tube comprises or consists of a
  • the gas flow passage within the inner tube may be a pathway for a sample of exhaled breath, and the gas flow passage between the outer surface of the inner tube and the inner surface of the outer tube is a pathway for ambient air.
  • an arrangement of an outer tube about a selectively permeable inner tube is advantageous since the inner selectively permeable tube can be kept enclosed in the device and not exposed to the environment, whilst still being able to function effectively by allowing moisture exchange with ambient air.
  • a Nafion® tube may be used as the inner tube (as described further below) which may be exposed on its outer surface to ambient air present in the outer tube in order to achieve humidity exchange between the sampled breath circulating inside the Nafion® tube and ambient air circulating outside the Nafion® tube.
  • the moisture reduction module may comprise, for example, two tubes arranged adjacent to one another, one for the passage of exhaled breath and one for the passage of ambient air, with the mutual wall between them being a selectively permeable membrane.
  • the selectively permeable membrane is permeable to water, but is impermeable or substantially impermeable to constituents of exhaled breath to be analysed.
  • the selectively permeable membrane is impermeable or substantially impermeable to oxygen and carbon dioxide.
  • the selectively permeable membrane may be made of any suitable material, but in one preferred embodiment, the moisture reduction module comprises a Nafion® tube. Nafion is a sulfonated tetrafluoroethylene based fluoropolymer-copolymer which is selectively and highly permeable to water.
  • the passage for exhaled breath may be a Nafion® tube.
  • any other suitable membrane which is selectively permeable to water may be used in the moisture reduction module.
  • Components of the moisture reduction module other than the selectively permeable membrane may be made of any suitable material.
  • the parts of the tubes which are not a selectively permeable membrane may be a suitable plastics material.
  • the outer tube may be formed from a suitable plastics material.
  • the remainder of the tubes aside from the mutual wall may be a suitable plastics material.
  • the sensors are additionally heated to further prevent or reduce the amount of condensation developing on the sensors.
  • the device may for example comprise a primary gas flow pathway for passage of exhaled breath from an inlet to a first outlet, and a secondary gas flow pathway for diverting and analysing a sample of exhaled breath, the secondary gas flow pathway being branched from the primary gas flow pathway at a branching point between the inlet and the first outlet, the secondary pathway having a second outlet.
  • a portion of the secondary pathway preferably comprises the moisture reduction module.
  • the gas flow passage for exhaled breath preferably forms part of the secondary pathway.
  • the gas flow passage for exhaled breath which forms part of the moisture reduction module, forms part of the secondary pathway and is upstream of the carbon dioxide and/or oxygen sensors.
  • the gas flow passage for exhaled breath may form a portion of the primary pathway, i.e. a moisture reduction module may be associated with the primary pathway.
  • An arrangement of a primary gas flow pathway and a secondary gas flow pathway as described above allows the fragmental sampling of each breath.
  • the exhaled breath fills the primary pathway and a portion of the breath is guided along the secondary pathway.
  • the remainder of the exhaled breath, which does not enter the secondary pathway exits the device via the outlet of the primary pathway.
  • the inhaled breath fills the primary pathway and a portion of the breath is guided along the secondary pathway.
  • the remainder of the inhaled breath, which does not enter the secondary pathway is inhaled by the user. In such way, both the inhaled and exhaled breaths may be analysed.
  • the secondary pathway is connected to the primary pathway at a branching point by a T- connector.
  • the sample of the exhaled breath to be guided along the secondary pathway is taken from or near to the periphery of the primary pathway.
  • the sample of breath is not taken from the periphery of the primary pathway.
  • the sample may be taken from the centre of the primary pathway.
  • the outlet of the secondary pathway may be to the atmosphere outside of the device, or it may be an outlet to another part of the device or to another breathing apparatus used by the patient.
  • the device comprises a flow sensor, positioned to allow determination of the flow of breath passing through the device.
  • the device comprises primary and secondary pathways
  • the device comprises a flow sensor located between the inlet of the primary pathway and the branching point (where the secondary pathway branches from the primary pathway) or between the branching point and the primary pathway outlet.
  • the flow sensor is arranged to allow measurement of the gas flow in the primary pathway.
  • other sensors such as carbon dioxide and/or oxygen sensors, discussed below, are located in the secondary pathway.
  • the flow sensor measures the flow rate of the breath. Breath flow rates are typically reported in, for example, units of imL/min.
  • the flow sensor may for example be a hot film anemometer, a micro-thermal conductivity detector, a thermal sensor element, a thermal mass flow sensor, a turbine, an ultrasonic transit time flow meter, a mass flow meter or any other appropriate sensor that can sense rapidly the flow rate of a gas mixture.
  • the device comprises primary and secondary pathways, and where the branching point is before the flow sensor, determination of the gas flow rate may involve taking into account the change in flow due to the secondary constant sampling flow.
  • the device comprises a facemask or breathing piece connected to the main body of the device via a tube.
  • the flow sensor may for example be located proximal to the facemask or breathing piece, e.g. in a chamber connecting the facemask or breathing piece to the tube. If other sensors, such as carbon dioxide and oxygen sensors, are present also, those may for example be located in the main body of the device, for example in a secondary pathway branched from the primary pathway for exhaled breath.
  • sensors such as carbon dioxide and oxygen sensors
  • those may for example be located in the main body of the device, for example in a secondary pathway branched from the primary pathway for exhaled breath.
  • Spirometry is the most common lung function test, which involves measurement of the volume of air inspired and expired by the lungs when a patient blows into a spirometer.
  • the device of the invention comprises one or more sensors for analysing one or more properties of exhaled breath.
  • the sensor or sensors are located downstream of the moisture reduction module. In other words, all sensors used for
  • determining the presence of a specific analyte or analytes are preferably located downstream of the moisture reduction module.
  • the device comprises a primary and a secondary gas flow pathway, preferably all sensors used for determining the presence of a specific analyte or analytes (e.g. all sensors other than the flow sensor, if present) are located in the secondary gas flow pathway.
  • the device may comprise an oxygen sensor which may be arranged in the secondary pathway, downstream of the moisture reduction module, to take measurements of the exhaled breath in that pathway.
  • the oxygen sensor may for example be an electrochemical partial pressure oxygen sensor, a paramagnetic oxygen sensor, fuel cell technology oxygen sensor, a light sensor that uses the fluorescence quenching properties of dye (e.g. a ruthenium based dye), a thermal conductivity detector (preferably a micro-thermal conductivity detector) (as described further below), a metal oxide semiconductor sensor, a polymer sensor or any other sensor type that is able to sense oxygen.
  • a sensor with a response rate in the range of milliseconds is especially beneficial in the devices described herein.
  • the device may comprise a carbon dioxide sensor, which may also be arranged in the secondary pathway downstream of the moisture reduction module to take measurements of the exhaled breath in that pathway.
  • the carbon dioxide sensor may for example be a non-dispersive infrared sensor (NDIR) that uses the strong and unique infrared absorption of the carbon dioxide in a gas mixture, a metal oxide semiconductor sensor, a solid state sensor that uses a potentiometric measurement, a thermal conductivity detector (preferably a micro-thermal conductivity detector (as described below)), a polymer sensor or any other carbon dioxide sensor.
  • NDIR non-dispersive infrared sensor
  • a carbon dioxide sensor with high accuracy and low-response time is especially beneficial in the devices described herein.
  • Capnography is the monitoring of the
  • the device is suitable for capnography because it is able to provide real-time carbon dioxide profiles of a patient's exhaled breath. It measures the partial pressure of carbon dioxide in the exhaled breath, and the fast response of the sensors provide information about the entire waveform of the exhaled carbon dioxide cycle (the so-called capnogram). For use as a capnograph, the device need not contain an oxygen sensor.
  • the oxygen and/or the carbon dioxide sensor of the device may be a thermal conductivity detector, preferably a micro-thermal conductivity detector.
  • This type of sensor is known for its fast response time.
  • a micro-thermal conductivity detector measures the thermal conductivity of the gas mixture.
  • the thermal conductivity of the three gas mixture (nitrogen, oxygen, carbon dioxide) of the exhaled breath can be used to calculate the concentration of carbon dioxide.
  • concentration of carbon dioxide is measured with a sensor that selectively measures carbon dioxide and the signal of the thermal-conductivity detector is used to calculate the oxygen of the exhaled breath.
  • a thermal-conductivity detector can be used as a sensor of either oxygen or carbon dioxide.
  • the oxygen sensor may be positioned upstream of the carbon dioxide sensor in the secondary pathway.
  • the carbon dioxide sensor may be positioned upstream of the oxygen sensor.
  • the oxygen and carbon dioxide sensors may be separate components.
  • the oxygen and carbon dioxide sensors may be combined as a single unit sensor, capable of sensing both oxygen and carbon dioxide.
  • an array of carbon nanotubes can be used for the simultaneous detection of oxygen and carbon dioxide among other breath biomarkers.
  • the oxygen and carbon dioxide sensor are combined in one array of carbon nanotubes (CNT's).
  • the device comprises a flow sensor and at least one sensor capable of determining the presence of a breath analyte, e.g. capable of determining the presence of a gas such as oxygen or carbon dioxide.
  • the device comprises a flow sensor, and comprises an oxygen and/or a carbon dioxide sensor.
  • the device comprises all three sensors.
  • the device comprises primary and secondary pathways, comprises a flow sensor in the primary pathway, comprises oxygen and carbon dioxide sensors in the secondary pathway, and the moisture reduction module is arranged so that the gas flow passage for exhaled breath forms part of the secondary pathway, and is upstream of said carbon dioxide and oxygen sensors.
  • one or more of an acetone, nitric oxide, sulphur compounds, pentane, ethanol and hydrocarbons sensor may be present in the device.
  • the device may comprise a flow sensor, a carbon dioxide sensor and/or an oxygen sensor, and also comprises one or more of an acetone, nitric oxide, sulphur compounds, pentane, ethanol and
  • an acetone sensor is added to the device, the glucose level of a patient can be monitored in a non-invasive way. This is particularly useful for patients that are diabetic since they need to monitor their glucose level on a day- to-day basis. It is known that the level of acetone concentration that is found in the exhaled breath is correlated to the blood glucose level. However, it is extremely difficult to determine the baseline of an individual's glucose level. In this device, by combining the information gathered about the metabolism level of an individual and/or his respiratory quotient (RQ) with the concentration of acetone that is found in his exhaled breath, it is possible to determine the baseline level by a suitable algorithm.
  • RQ respiratory quotient
  • the device can provide information regarding the user's asthma medication.
  • the nitric oxide levels that are found in the breath can give to a physician information about the effectiveness and the dose needed for the asthmatic patient, which can be used to regulate the medication for an asthma patient.
  • oxidative stress can be measured.
  • the device comprises primary and secondary pathways, preferably all sensors capable of determining the presence of an analyte (e.g. carbon dioxide sensor, oxygen sensor, acetone sensor, nitric oxide sensor, sulphur compounds sensor, pentane sensor, ethanol sensor and/or hydrocarbons sensor are arranged to take measurements in the secondary pathway).
  • an analyte e.g. carbon dioxide sensor, oxygen sensor, acetone sensor, nitric oxide sensor, sulphur compounds sensor, pentane sensor, ethanol sensor and/or hydrocarbons sensor are arranged to take measurements in the secondary pathway.
  • a subject may use the breath analysis device of an embodiment by holding it in his hands and exhaling from his mouth into the device, via a mouthpiece or facemask when present.
  • a flow sensor and oxygen and carbon dioxide sensors when a user exhales into the device, the exhaled breath passes along the primary pathway, where its flow rate is measured by the flow sensor, and a small fraction of the breath is guided along the secondary pathway via the moisture reduction module, to the oxygen and carbon dioxide sensors located in the secondary stream where measurements are taken.
  • the exhaled breath passes through one of the gas flow passages (e,g. an the inner tube) of the moisture reduction module, which is a part of the secondary pathway, moisture is
  • the device is an indirect
  • Indirect calorimetry is used to measure the human metabolism based on the amounts of O 2 and CO 2 that are found in the exhaled human breath.
  • a facemask or mouthpiece is connected to the inlet of the exhaled breath flow pathway, in particular the inlet of the primary pathway where present, and, while the flow sensor and primary pathway remain in proximity to the mouthpiece or facemask, a length of tubing may form the portion of the secondary pathway extending from the branching point.
  • a length of tubing may form the portion of the secondary pathway extending from the branching point.
  • the facemask may for example be strapped to the head of the user.
  • the tubing may comprise the moisture reduction module. Such embodiments may for example be used in VO2 max testing, anaerobic threshold identification and several others fitness applications.
  • the device comprises a pump for drawing exhaled breath through the secondary pathway.
  • the pump regulates the flow rate through the secondary pathway to ensure a constant steady flow.
  • the pump may draw the exhaled breath over/past one or more sensors.
  • the pump typically operates at a constant flow, drawing through the secondary pathway either a sample of the exhaled breath when it fills the primary pathway, or a sample of ambient air in the primary pathway in the dead time between exhalations or as air is being inhaled. Measurements of ambient air can be useful for calibration of the device.
  • a pump may additionally or alternatively be used to draw ambient air and exhaled breath through their respective gas flow passages in the moisture reduction module.
  • a pump may simultaneously function to draw both exhaled breath and ambient air along their respective gas flow passages.
  • a conduit for example a plastic tube, may connect the ambient air in the gas flow passage to a merging point with the exhaled breath flow pathway (the secondary gas flow pathway when present) upstream of the pump, and the ambient air gas flow passage is in communication with the ambient air (for example by way of an inlet provided in the ambient air gas flow passage), so that the pump steadily draws air through the gas flow passage at the same time as drawing exhaled breath through the respective gas flow passage of the moisture reduction module.
  • the conduit may branch from the ambient air gas flow passage at a branching point, and convey ambient air to the exhaled breath flow pathway downstream of one or more sensors, where the conduit merges with the exhaled breath flow pathway at a further branching point.
  • the gas flow passage for ambient air which forms part of the moisture reduction module merges with the secondary pathway
  • the pump draws exhaled breath along the secondary pathway via the exhaled breath gas flow passage of the moisture reduction module, and also draws ambient air via the ambient air gas flow passage of the moisture reduction module. Ambient air with which the exhaled breath can exchange moisture is thus drawn along the device at the same time as the exhaled breath, and using the same pump.
  • One particularly preferred type of pump for use in devices of the invention is a rotary vane pump, since it can produce a steady flow without causing any turbulence, which is advantageous for accurate measurement by the sensors.
  • the device does not comprise a pump.
  • the gas flow may instead be controlled by the diameter and configuration of the gas flow pathways.
  • tubes of smaller diameter may be used along the gas flow pathways to reduce the flow rate of the exhaled breath as it passes through them.
  • the gas flow passage for ambient air which forms part of the moisture reduction module may for example have a plurality of points at which it is in communication with the ambient environment to facilitate exchange of ambient air from the environment with air in the gas flow pathway, and thus facilitate moisture reduction.
  • the device further comprises a valve system located between the branching point and the oxygen and/or carbon dioxide sensors.
  • the valve system partitions the secondary pathway into an upstream portion between the branching point and the valve system and a downstream portion between the valve system and the outlet of the secondary pathway.
  • the components of the valve system are moveable between at least a first position and a second position.
  • the valve system has a valve outlet.
  • the valve system may comprise one or more individual valves, and the valve system is at least a two-way valve system.
  • the components of the valve system are arranged such that the upstream portion of the secondary pathway is in fluid connection with the downstream portion of the secondary pathway; and in the second position, the components of the valve system are arranged such that the upstream portion of the secondary pathway is in fluid connection with the valve outlet and not with the downstream portion of the secondary pathway.
  • the valve system allows the device to select which exhaled breaths will be analysed by the sensors in the secondary pathway, and thus allows the device to operate in multiple modes.
  • the different modes of operation allow the measurement of the consumed oxygen and produced carbon dioxide of the user independently of their breathing rate.
  • the valve system can be used to regulate the modes of operation of the device.
  • the valve member When the valve member is constantly in the first position (i.e. open), the sample of exhaled breath drawn down the secondary pathway continues through the valve system to the sensor or sensors, (e.g.
  • valve system When the valve system is in the second position (i.e. closed), the exhaled breath samples are guided to the valve outlet. In this way, the valve system regulates if a sample of a particular exhaled breath will be analysed or if it will be guided to the valve outlet to exit the device. This makes it possible for the device to be selective about which exhaled breaths are analysed, which is advantageous as it allows the device to be used in a variety of situations.
  • the device when the user is at rest and their breathing rate is not very high (for example, approximately 15 breaths per minute), the device is able to analyse the exhaled breath on a breath-by- breath basis, as the valve system will remain open and allow every exhaled breath to pass through it to the sensors.
  • the response time of the sensors may be insufficient to accurately measure two successive breaths for breath-by-breath analysis.
  • a different mode of operation of the device may be employed where not every breath is analysed: for example, every second, every third, every fourth breath may be analysed.
  • the valve system compensates for possible short-comings in the response time of the sensors used in the device.
  • the valve system is electrically operated for this purpose.
  • the valve system is typically upstream of the or each sensor in the device which is capable of determining the presence of a specific analyte.
  • the device comprises a pump
  • the valve system may be located upstream, of the pump.
  • the valve system is positioned downstream of the pump on the secondary pathway.
  • the pump and the valve system may be integral to one another.
  • the device has a power source, or is capable of connection to a power source.
  • the device is capable of connection to an external power source, such as mains electricity.
  • the device contains a power source such as a battery.
  • the device contains a rechargeable battery which, when exhausted or low on power, is capable of being recharged on connection of the device to an external power source such as electricity.
  • the device comprises a microcontroller.
  • the micro-controller may for example provide power to the pump when the pump is supplied with power from the micro-controller.
  • the microcontroller may also process the measurements detected by the sensor or sensors, for example where the device comprises a flow sensor, carbon dioxide sensor and oxygen sensor, it may process data relating to the flow-rate sensed by a flow sensor, the concentration of oxygen measured in the exhaled breath by the oxygen sensor, and the concentration of carbon dioxide sensed by the carbon dioxide.
  • each sensor may create an electrical signal that is communicated to the micro-controller and processed.
  • the microcontroller may also control the valve system, where present, and the modes in which it operates.
  • the microcontroller can be arranged so as to alter the mode of operation depending on the breathing rate as measured by the flow sensor.
  • the flow rate measured by the flow-sensor can be translated to an electrical signal which is fed to the micro-controller of the device, which accordingly determines the mode of operation of the device by controlling the valve system as described above.
  • the flow rate measurement from the flow- sensor is supplied to the microcontroller and allows the microcontroller to determine the breathing frequency (breathing rate) through a suitable algorithm.
  • the micro-controller controls the valve system to determine whether the device will analyse the user's exhaled breath on a breath-by-breath basis or not (e.g. every second breath will be analysed instead, or every third breath etc.), i.e. selects which mode the device operates in.
  • the expired breath sample is then guided either to the sensors in the secondary pathway or to the valve outlet to exit the device.
  • the device further comprises a one-way (non-rebreathing) valve positioned between the inlet and the flow sensor, through which gas may pass in a direction from the inlet to the flow sensor only.
  • a one-way (non-rebreathing) valve positioned between the inlet and the flow sensor, through which gas may pass in a direction from the inlet to the flow sensor only.
  • a non-rebreathing valve may be present for example in a mouthpiece or a facemask of the primary pathway. In this case, the user must inhale through the nose and exhale through the mouth.
  • the one-way valve may be absent.
  • the user may for example inhale and exhale from his/her mouth while his/her nose is closed with a nose-clip.
  • inhaling and exhaling needs to be done through the mouth and this can be achieved by using a mouthpiece or facemask without a non-rebreathing valve.
  • the device includes a barometric pressure sensor, a relative humidity sensor and/or a temperature sensor.
  • Such sensors are preferably located in the secondary flow pathway.
  • the signals of these sensors may be communicated to a micro-controller which processes the data generated by the or each sensor capable of determining the presence of an analyte, in order to allow changes in the ambient barometric pressure, relative humidity and/or temperature to be compensated for (e.g. a correction factor may be applied).
  • These signals enable the readings of, for example oxygen and/or carbon dioxide sensors, to be converted accurately into readings of the concentration of the respective gases in the exhaled breath. This also facilitates usage of the device in a range of conditions of humidity, altitudes and different climates.
  • the barometric pressure sensor, relative humidity sensor and/or temperature sensor may be arranged to take measurements in the primary pathway or in the secondary pathway. Preferably, they are arranged to take measurements in the secondary pathway.
  • a sampling chamber capable of containing multiple breaths may be present, positioned along the exhaled breath flow pathway between the inlet and the outlet, or branched from the exhaled breath flow pathway at a branching point between the inlet and the outlet.
  • the sampling chamber is positioned along the secondary pathway.
  • sensors such as oxygen and carbon dioxide sensors which have a fast response rate and may conduct measurements on a breath-by-breath basis
  • the sampling chamber is preferably positioned downstream of said sensors, between the sensors and the outlet of the exhaled breath flow pathway/secondary pathway.
  • One or more further sensors which may include the sensors discussed above, may be in fluid connection with the interior of the sampling chamber, for analysing the collected breath.
  • the sampling chamber may be formed as part of the exhaled breath flow pathway/secondary pathway, in line with the outlet of the exhaled breath flow pathway/secondary pathway, such that exhaled breath passes through the sampling chamber before exiting the device through the outlet.
  • the sampling chamber may be in fluid connection with the exhaled breath flow pathway/secondary pathway by way of a sampling chamber pathway branched from the secondary pathway. In this way, a portion of exhaled breath passing along the secondary pathway towards the secondary pathway outlet enters the sampling chamber.
  • the sampling chamber may for example be a bag.
  • the bag may be formed from a material which is collapsible to a reduced volume for convenient transport and storage when the device is not in use.
  • valve system may be configured such that the sampling chamber samples only exhaled breath.
  • the flow sensor may detect and differentiate between inhaled and exhaled breath, and thus send the necessary signal to the valve system to guide inhaled breaths to the valve outlet and exhaled breaths onwards to the sampling chamber.
  • the device comprises a communication means for communication between the microcontroller and a mobile phone or other external device.
  • the communication means may be a Bluetooth connection via the microcontroller, to enable communication with a mobile phone.
  • the device may be used for remote medical monitoring.
  • the communication means allows data collected by the microcontroller to be sent directly to a remotely located device, for example via the internet. Data collected may be displayed on a computer or, for example, a smartphone application.
  • a communication means may be a USB connector, a removable memory card, a cable, a wireless unit, an Ethernet shield, or a mobile broadband unit, for example.
  • the device will typically contain a casing or housing, e.g. made of suitable durable material, e.g. a suitable rigid plastics material.
  • the casing or housing will contain various components of the device, for example tubes and connectors defining the breath pathway or pathways, the moisture reduction module, sensors, electrical components etc.
  • Such a casing has appropriate openings to allow functioning of the device, e.g. providing access to the inlet and/or where a facemask or mouthpiece forms part of the device, to permit connection of the facemask or mouthpiece to the gas flow pathway. Openings may also be provided, for example, to facilitate ambient air to enter the moisture reduction module, or to accommodate the outlet or outlets of the device.
  • a device of the invention as an indirect calorimeter is based on the determination of the oxygen consumption, carbon dioxide production and the flow rate that can be determined by the exhaled breath of the user.
  • the exhaled breath fills the primary pathway.
  • the entire flow rate of the expired breath is preferably instantly measured.
  • inspiration the gas that forms the inspired breath may be analysed.
  • the exhaled human breath consists mainly (-99%) of nitrogen, oxygen and carbon dioxide.
  • the Haldane transform assumes that nitrogen is physiologically inert. This means that the volume of inspired nitrogen must be the same with the volume of expired nitrogen.
  • V, j , — ⁇ — ( )
  • Equation 1 describes that nitrogen is inert and the volume of inspired nitrogen is equal to the volume of the expired nitrogen which is the Haldane approximation.
  • Equation 2 describes that the fraction of exhaled nitrogen equals to the 99.063% of the exhaled breath minus the fraction of expired oxygen and carbon dioxide.
  • Equation 3 describes that the fraction of inspired nitrogen equals to 78.08%, which is the percentage of nitrogen in ambient air.
  • Equation 4 is the equation used to calculate the inspired flow rate when the expired flow rate, the fraction of expired oxygen and the fraction of expired carbon dioxide are known from the various sensors in the device.
  • a flow sensor, carbon dioxide sensor and oxygen sensors, pump, and valve system after entering the primary pathway (in which the flow rate of the expired, and optionally inspired, breath is measured), a portion of the breath is guided along the secondary pathway. This may be assisted by the presence of a pump in the secondary pathway to draw sample with a constant flow-rate down the secondary pathway as described above. The remainder of the exhaled breath, which does not enter the secondary pathway, exits the device via the outlet of the primary pathway. Inhaled breath which does not enter the secondary pathway is inhaled by the user.
  • the expired breath passes through the moisture reduction module, which reduces the humidity of the exhaled breath.
  • the relative humidity of the exhaled breath is reduced through the moisture reduction module, for example until it reaches the ambient relative humidity: as the exhaled breath is drawn through the exhaled breath gas flow passage of the moisture reducing module, ambient air is also drawn along the ambient air gas flow passage beside it, and moisture is transferred from the exhaled breath to the ambient air by way of the selectively permeable membrane separating the two passages.
  • the sensors may be heated to prevent condensation of humid breath on them.
  • This flow rate measurement from the flow-sensor is supplied to the microcontroller and allows the microcontroller to determine the breathing frequency (breathing rate) and to control the valve system accordingly, as described above.
  • the sensor network of the device includes a flow sensor, an oxygen sensor, a carbon dioxide sensor, a temperature sensor, a barometric pressure sensor and a humidity sensor.
  • the temperature sensor, barometric pressure sensor and the humidity sensors are used to compensate the measurements of the oxygen and carbon dioxide sensors.
  • a human's energy expenditure is divided into resting metabolic rate (RMR), physical activities and thermogenesis that is induced by food intake.
  • the device is able to measure the oxygen consumed and the carbon dioxide produced by an individual.
  • the resting energy expenditure (REE) or resting metabolic rate (RMR) in kCal/day of an individual can be calculated through the Weir equation.
  • the inhaled flow rate is calculated by equation (4), as described previously.
  • O 2 ) is constant at 0.2005 since it is the fraction of inspired oxygen from ambient air.
  • CO 2 ) is constant at 0.00039 since it is the fraction of inspired carbon dioxide from ambient air.
  • the energy expenditure of an individual is calculated by measuring the exhaled flow rate (VE), the fraction of expired oxygen (F E O 2 ) and the fraction of expired carbon dioxide (F E CO 2 ).
  • the respiratory quotient is usually between 0.65 - 1 .0 for aerobic metabolism.
  • the respiratory quotient is usually between 0.65 - 1 .0 for aerobic metabolism.
  • the respiratory quotient is usually between 0.65 - 1 .0 for aerobic metabolism.
  • the RQ is closer to the value of 0.7
  • the user of the device is metabolising fat.
  • the RQ is closer to the value of 1 .0
  • the user is metabolising carbohydrates.
  • the medium value of RQ 0.8 shows that the user is metabolising protein.
  • various other functions may be measured by the device. These include, but are not limited to, the calories burned during exercise, in which instance a facemask may be used as part of the primary pathway to facilitate use of the device while exercising.
  • the device may also be used to calculate body mass index (BMI, a measure of the fat- free mass of an individual), may track the history of the user with corresponding software (such as a smartphone application) to draw conclusions about the health status of the user, may be used as a capnometer and/or may be used as a spirometer.
  • BMI body mass index
  • the operation of the device is typically conducted through a microcontroller and, where the device comprises a communication module, the data measured can be transmitted to a smartphone or computer for example.
  • a method of measuring a breath property of a subject comprising: providing a breath analysis device as defined in any preceding claim; and measuring a breath property of a subject using said breath analysis device.
  • a method of analysing exhaled breath of a subject comprising the step of the subject breathing into a breath analysis device of the invention, as described above.
  • the device may be used to calculate concentrations and/or amounts of 0 2 and CO 2 , and/or may be used to calculate other parameters such as the respiratory quotient.
  • a method of analysing gas that forms an inhaled breath of a subject comprising the step of the subject inhaling through a breath analysis device of the invention is also provided. Summary of Part B
  • a breath analysis device comprising:
  • a secondary gas flow pathway branched from the primary pathway at a branching point between the inlet and the outlet, said secondary pathway also having an outlet;
  • a flow sensor arranged to allow measurement of the gas flow in the primary pathway
  • an oxygen sensor which is a polymer sensor
  • a carbon dioxide sensor which is a thermal conductivity detector
  • a breath analysis device comprising:
  • a secondary gas flow pathway branched from the primary pathway at a branching point between the inlet and the outlet, said secondary pathway also having an outlet;
  • a flow sensor arranged to allow measurement of the gas flow in the primary pathway
  • an oxygen sensor which is an electrochemical partial pressure oxygen sensor
  • a carbon dioxide sensor which is a nondispersive infrared sensor
  • a pump for drawing exhaled breath along said secondary pathway [00136] a pump for drawing exhaled breath along said secondary pathway; [00137] wherein said oxygen and carbon dioxide sensors are arranged to take measurements of exhaled breath in a secondary pathway; and
  • the dehumidifier is positioned in said primary pathway or secondary pathway upstream of the oxygen and carbon dioxide sensors.
  • a breath analysis device comprising:
  • a secondary gas flow pathway branched from the primary pathway at a branching point between the inlet and the outlet, said secondary pathway also having an outlet;
  • a flow sensor arranged to allow measurement of the gas flow in the primary pathway
  • the oxygen sensor and the carbon dioxide sensor are arranged to take measurements of the exhaled breath in a secondary pathway such that, in use, different portions of exhaled breath are analysed by the oxygen sensor and the carbon dioxide sensor, and wherein the device does not comprise a breath sampling bag for collecting exhaled breath.
  • a breath property of a subject comprising:
  • the invention allows the precise measurement of the consumed oxygen and produced carbon dioxide via a low-cost device.
  • the respiratory quotient that determines whether an individual metabolises fat, protein or carbohydrates can be accurately measured, rather than relying on assumptions for fixed values of the RQ.
  • the device does not use consumables and that reduces the cost of running the device.
  • the breath analysis device is preferably portable and/or handheld for ease of use.
  • the flow sensor is configured to measure the gas flow of exhaled breath of a user and the breathing rate of the user.
  • the device is configured to apply a correction factor to the signal detected by the oxygen sensor, based on measurements taken by the flow sensor. Such embodiments are suitable for facilitating particularly rapid and accurate collection of data.
  • the oxygen sensor is a polymer sensor and the carbon dioxide sensor is a thermal
  • the thermal conductivity detector when present, is a micro-thermal conductivity detector.
  • Advantages of a micro-thermal conductivity detector include the following: a) the hot wire filament of the sensor is heated more rapidly, reducing the heating time required for the sensor to function b) a micro-thermal conductivity detector has a very small wire and thus consumes much less energy to heat-up, making it especially suitable for use in a portable, battery-powered device which is designed to be used on-the-go
  • MEMS microelectromechanical systems
  • CMOS complementary metal-oxide-semiconductor
  • a micro-thermal conductivity detector can be easily mass produced with more reliable fabrication techniques.
  • a micro-thermal conductivity detector has enhanced accuracy over a traditional TCD sensor
  • the oxygen sensor is an electrochemical partial pressure oxygen sensor and the carbon dioxide sensor is a non-dispersive infrared (NDIR) sensor.
  • NDIR non-dispersive infrared
  • electrochemical sensor and an NDIR sensor provides for a robust device which has good tolerance to movement whilst maintaining a high degree of accuracy, making them particularly well suited to devices which will be moved around a lot during use.
  • these sensors may be particularly preferred in a device which may be used whilst actively exercising, when there is likely to be increased movement of the device.
  • both the electrochemical and the NDIR sensors are able to perform selective sensing of the oxygen and the carbon dioxide gases.
  • an advantage of this combination of sensor is that cross-sensitivity between the electrochemical and the NDIR sensors is minimised.
  • the electrochemical sensor senses only oxygen and there is no cross-sensing with carbon dioxide.
  • the optics of the NDIR sensor and its absorption curves are sensitive only to the carbon dioxide molecule. This provides enhanced accuracy of the device.
  • the use of a dehumidifier to dry the sample of breath prior to contact with the sensors and the use of a pump to ensure steady consistent flow of exhaled breath also provides for increased accuracy and consistency of results
  • the third aspect of the invention of Part B requires a device configured such that different portions of exhaled breath are analysed by the oxygen sensor and the carbon dioxide sensor.
  • An alternative arrangement to that is an in-line arrangement, in which oxygen and carbon dioxide sensors are in-line with each other such that the same portion of breath may be analysed by both sensors, one after the other.
  • an in-line arrangement of sensors has certain advantages, for example reduced turbulence due to the use of a single pathway for breath rather than a split pathway, it has now been found that devices configured such that the oxygen and carbon dioxide sensors analyse different portions of breath can be advantageous in certain situations, for example the third aspect of the invention of Part B is well suited for use with sensors which function optimally with different flow rates.
  • An in-line connection is less well suited to the use of sensors with different flow rate requirements.
  • the sensors can each be positioned in a different "stream" of exhaled breath configured to achieve different flow rates, such that those sensors may be used together whilst still functioning optimally.
  • the flow of each "stream" i.e.
  • each portion of exhaled breath may be tailored by, for example, adjusting the dimensions, aperture sizes, and configuration of the secondary pathway or pathways, or, for example, by using a pump or pumps to draw breath through one or more of the secondary pathways/portions of the secondary pathway at different rates.
  • the device comprises a secondary pathway branching point within the secondary pathway, wherein the carbon dioxide sensor is positioned in one branch of the secondary pathway to take measurements of the exhaled breath in that pathway, and wherein the oxygen sensor is positioned in another branch of the secondary pathway to take
  • the device comprises two independent secondary pathways branched from the primary pathway at independent branching points, wherein the carbon dioxide sensor is positioned in one secondary pathway to take
  • the oxygen sensor is positioned in the other secondary pathway to take measurements of the exhaled breath in that pathway.
  • a device according to the invention of the invention of Part B is an indirect calorimeter.
  • Indirect calorimetry is a useful tool for analysing the metabolism of a subject which may be useful for medical reasons, or for diet and lifestyle reasons.
  • Indirect calorimeters have several medical applications in the assessment of diabetes, obesity, anorexia, cardiovascular diseases etc., but existing indirect calorimeters are bulky and expensive, costing tens of thousands of US dollars.
  • the functioning of a device of the present invention as an indirect calorimeter is thus advantageous as it provides an indirect calorimeter device that can be used by an individual in a domestic environment.
  • the device is portable. In some embodiments the device is handheld. This allows the device to be used in a variety of situations and for a user to use the device at any desired time of day.
  • the device of the second aspect of the invention of Part B comprises, and the devices of the first and third aspects of the invention of Part B may comprise a dehumidifier for reducing the humidity of an exhaled breath passing through the device, wherein the dehumidifier means is positioned in the primary or secondary pathway between the inlet and the oxygen and carbon dioxide sensors.
  • a dehumidifier reduces the humidity of exhaled breath, which typically contains a lot of moisture, to reduce condensation on the sensors and thus enable more accurate measurements by the sensors.
  • Inhaled breath has a low relative humidity whereas exhaled breath has a very high relative humidity, but it is desirable that this humidity difference does not affect measurement of the breath; where inhaled and exhaled breath are both analysed, these are preferably compared on the same basis.
  • a dehumidifier is useful in reducing the humidity of exhaled breath (e.g. to ambient levels or close to ambient levels) or even zero- levels in order to provide the same humidity between exhaled and inhaled breath, which is beneficial for more accurate analysis of the breath.
  • the oxygen sensor is an electrochemical partial pressure oxygen sensor and the carbon dioxide sensor is a nondispersive infrared sensor
  • the accuracy of the reading of the electrochemical sensor may be affected by the differences of humidity during the cycles of expiration and inspiration.
  • the readings of the NDIR sensor may also be affected by humidity and condensation on the lenses of the sensor. As a result, it is advantageous to dehumidify the exhaled breath before it reaches the sensors to enhance the accuracy of the sensors.
  • Another advantage of a device which has a dehumidifier prior to the sensors in the secondary pathway is that the sensors may be calibrated using ambient air. All sensors benefit from regular calibration in order to maintain their accuracy. As a result, a portable device is preferably able to be calibrated easily without the need to use cylinder gases. Indirect calorimetry systems found in the prior-art use cylinder gases for their calibration. In contrast, devices comprising a dehumidifier prior to the sensors have the advantage that the calibration process can be carried out with ambient air that has a known concentration of
  • the system is flashed with ambient air and the dehumidifier either keeps the humidity of the gas at a constant level or drops it to 0%, depending on the dehumidifier used.
  • the humidity is preferably decreased to either ambient levels or to zero levels, matching the conditions of the calibration process. As a result, the system is able to measure accurately the exhaled breath when calibrated with ambient air.
  • the dehumidifier is preferably a desiccant and/or a tube made of a sulfonated tetrafluoroethylene based fluoropolymer-copolymer through which exhaled breath can pass.
  • a desiccant material should typically be chemically inert to carbon dioxide and oxygen so as to minimise any effect on the accuracy of the sensors and the device.
  • Desiccants which selectively absorb only moisture are preferable since they minimise any interference with the accuracy of the sensors of the device.
  • Desiccants have the advantage that they do not require exposure to the environment to perform their dehumidifying function, so can be placed within the device when in use. They are also easy to replace, and are particularly cost effective.
  • the dehumidifier may also or instead comprise a tube made of a sulfonated tetrafluoroethylene based fluoropolymer-copolymer through which exhaled breath can pass.
  • a tube made of a sulfonated tetrafluoroethylene based fluoropolymer-copolymer through which exhaled breath can pass.
  • Such materials are permeable to water but are typically impermeable or substantially impermeable to constituents of exhaled breath to be analysed.
  • one such tube is a tube sold under the trade name
  • Devices of the second aspect of the invention of Part B comprise and devices of the first and third aspects of the invention of Part B may comprise a pump for drawing exhaled breath along said secondary pathway or pathways.
  • the presence of a pump helps to ensure a constant flow rate through the secondary pathway and when contacting the sensors.
  • the devices of the first and third aspects of the invention of Part B do not comprise a pump, and the flow of gases through the sensors can be controlled by the dimensions and configuration of the gas flow pathways; for example, tubes of smaller diameter may be used along the gas flow pathways to reduce the flow rate of the exhaled breath as it passes through them. Regulation of the flow rate through the secondary pathway to a steady flow is desirable both to ensure more accurate readings of the sensors and to ensure that the dehumidifier (where present) functions efficiently.
  • the device comprises a microcontroller.
  • microcontroller carries out the data processing of the device, such as receiving the measurements from each of the sensors, determining the mode to be used from the flow sensor measurements, and controlling the valve system.
  • the microcontroller may also power the pump, where present.
  • the device comprises a one-way valve positioned between the inlet and the flow sensor, through which gas may pass in a direction from the inlet to the flow sensor only.
  • a valve requires a user to breathe out through the mouth and in through the nose, and does not allow the user to inhale by way of the primary pathway, in situations where this is desirable.
  • the device does not comprise such a one-way valve.
  • the device comprises a humidity sensor. This allows measurements by the oxygen and carbon dioxide sensors to be compensated for changes in humidity.
  • the humidity sensor can provide feedback on when the dehumidifier means, for example a desiccant, is no longer functioning optimally and/or needs to be replaced.
  • a humidity sensor can be used to notify a user when the desiccant needs to be renewed in the device.
  • the device comprises a
  • temperature sensor This allows measurements by the oxygen and carbon dioxide sensors to be compensated for changes in temperature.
  • the device comprises a pressure sensor. This allows measurements by the oxygen and carbon dioxide sensors to be compensated for changes in pressure.
  • the device may further comprise one or more further sensors, e.g. one or more further sensors for detecting a component of breath. This allows the device to measure additional parameters that may be of interest.
  • the device may include a sensor for acetone, nitric oxide, sulphur compounds, pentane, ethanol and/or hydrocarbons. For example, when a pentane and ethanol sensor are present, oxidative stress may be monitored.
  • the device comprises a communication element for communication between the microcontroller and a mobile phone or other device.
  • a communication element for communication between the microcontroller and a mobile phone or other device. This allows the user to review the collected data in a convenient and user-friendly manner, and, for example, allows for analysis of data by an application running on the mobile phone or running on a remote server with which the mobile phone is capable of communication.
  • the invention also provides a method of measuring a breath property of a subject, the method comprising: providing a device of the invention of Part B as defined herein; and measuring a breath property of a subject using said device.
  • the method will typically be used for analysing properties of exhaled breath of a subject.
  • the device may also be used in methods which involve analysis of samples from breath for inhalation by a subject, e.g. where ambient air is drawn through the primary pathway to be inhaled, and a sample of air flows into the secondary pathway or pathways and is analysed.
  • the breath analysis device comprises a primary gas flow pathway for passage of exhaled breath from an inlet to an outlet.
  • the exhaled breath flow pathway is formed of a suitable plastic tubing, or other conventional material.
  • a subject breathes into the device at the inlet of the primary pathway.
  • the entire exhaled breath of the user is led to the primary pathway and the primary pathway is filled with the exhaled breath when the user exhales the device.
  • the primary pathway may also be used for the passage of air to be inhaled; as the subject inhales, ambient air is drawn in the reverse direction to that of the exhaled breath, through the outlet of the primary pathway towards the subject.
  • the user does not inhale through the mouth when using the device, and so ambient air to be inhaled does not pass through the primary pathway to the user.
  • the device could operate either analysing only the exhaled breath or both the inhaled / exhaled breath.
  • the device may comprise a facemask or a mouthpiece, for example, which facilitates capture and passage of exhaled breath into the primary pathway via the inlet.
  • the device comprises at least one secondary gas flow pathway which is branched from the primary pathway at a branching point between the inlet and the outlet, the secondary pathway also having an outlet. This allows the fragmental sampling of each breath.
  • the exhaled breath fills the primary pathway and a portion of the breath is guided along the secondary pathway.
  • the or each secondary pathway is connected to the primary pathway at a branching point by a T-connector.
  • the oxygen and carbon dioxide sensors are arranged such that, in use, different portions of exhaled breath are analysed by the oxygen sensor and the carbon dioxide sensor.
  • such devices can provide a tailored airflow to different sensors so that, for sensors which operate better with different airflows, optimal operation of both sensors can be achieved. Every sensor has an optimal flow rate that varies for every technology or even by the manufacturer. For example two different NDIR sensors might have different optimal flow rates where they exhibit the best combination of response time and accuracy.
  • a subject may for example use the breath analysis device by holding it in their hands and exhaling from their mouth into the device, via a mouthpiece or facemask when present.
  • the exhaled breath passes along the primary pathway, where its flow rate is measured by the flow sensor, and a small fraction of the breath is guided to the oxygen and carbon dioxide sensors located in the secondary stream where measurements are taken.
  • a user is typically a human, and normally an adult.
  • the oxygen sensor is a polymer sensor or an electrochemical partial pressure sensor.
  • the carbon dioxide sensor is a thermal conductivity detector or a nondispersive infrared sensor (NDIR).
  • NDIR nondispersive infrared sensor
  • the oxygen sensor is a polymer sensor and the carbon dioxide sensor is a thermal conductivity detector.
  • the oxygen sensor is an electrochemical partial pressure sensor and the carbon dioxide sensor is a nondispersive infrared sensor.
  • the oxygen sensor is a polymer sensor and the carbon dioxide sensor is a nondispersive infrared sensor.
  • the oxygen sensor is an electrochemical partial pressure sensor and the carbon dioxide sensor is a thermal conductivity sensor, preferably a micro-thermal conductivity sensor.
  • the device does not comprise a valve system within a secondary pathway upstream of the sensors arranged in that pathway, which valve system allows for fragmental sampling of breath by being movable between a first position in which the upstream portion of said secondary pathway is in fluid communication with the downstream portion of said secondary pathway, and a second position in which the upstream portion of said secondary pathway is in fluid communication with a valve outlet and not with the downstream portion of said secondary pathway.
  • the device comprises a secondary pathway branching point within the secondary pathway, wherein the carbon dioxide sensor is positioned in one branch of the secondary pathway to take measurements of the exhaled breath in that pathway, and wherein the oxygen sensor is positioned in another branch of the secondary pathway to take measurements of the exhaled breath in that pathway.
  • a single branching point with the primary pathway may connect initially to a single secondary pathway, the secondary pathway itself then being branched into multiple branches of the secondary pathway.
  • each secondary pathway being branched from the primary pathway at its own respective branching point, wherein the carbon dioxide sensor is positioned in one secondary pathway to take measurements of the exhaled breath in that pathway, and the oxygen sensor is positioned in another secondary pathway to take measurement of the exhaled breath in that pathway.
  • the device comprises a secondary pathway merging point where two or more of the secondary pathways, or two or more branches of a secondary pathway, merge to form a single secondary pathway.
  • the oxygen sensor is positioned in one secondary pathway and the carbon dioxide sensor positioned in another secondary pathway, and the secondary pathway merging point is positioned downstream of the sensors.
  • exhaled breath passes along the primary pathway, and samples are drawn down either multiple secondary pathways with multiple branching points with the primary pathway, or down an initial single secondary pathway and then along two branched secondary pathways via a secondary pathway branching point.
  • the breath samples are then analysed by the respective sensors positioned in those pathways/branches. After passing the sensors, the breath samples are combined when the secondary pathways merge into a single downstream secondary pathway at a secondary pathway merging point.
  • a pump is used to draw breath samples through the secondary pathways/branches.
  • the oxygen and carbon dioxide sensors are arranged alongside one another in the same secondary pathway.
  • each of the sensors analyses a different portion of exhaled breath passing along a different region of the secondary pathway.
  • each secondary pathway may have its own independent outlet downstream of the sensors arranged in said pathways.
  • sampled breath is drawn down each of the secondary pathways from the primary pathway as described above, and eventually exits out of independent secondary pathway outlets.
  • the sample of the exhaled breath to be guided along the secondary pathway or pathways is taken from near to the periphery of the primary pathway.
  • the exhaled breath passing along it is less turbulent; sampling from here is preferred as it minimises turbulence in the secondary pathway and thus provides a constant flow rate in the secondary pathway, allowing more accurate sensor
  • all secondary pathways may for example sample breath from near to the periphery of the primary pathway.
  • the sampling by one or more secondary pathways is done from the centre of the primary pathway.
  • each secondary pathway is branched independently from the primary pathway, or where the device comprises sub- branches of a secondary pathway with a single branching point to the primary pathway
  • those secondary pathways/branches are configured to achieve different flow rates of exhaled breath.
  • the flow may also vary within different portions of a single secondary pathway; for example, one portion of the path along the secondary pathway may have a higher flow than another portion of the secondary pathway.
  • the flow of breath along each secondary pathway may be controlled by, for example, the dimensions and/or curvature of the secondary pathway, the position of the branching points with the secondary pathway and/or the branching point between sub-branches of a secondary pathway.
  • a narrowing element or apertures of reduced diameter may be incorporated in a secondary pathway.
  • the outlet of the one or more secondary pathways may be to the atmosphere outside of the device, or it may be an outlet to another part of the device or to another breathing apparatus which may be used by the subject.
  • the device comprises a flow sensor located in the primary pathway.
  • the flow sensor may for example be positioned between the inlet of the primary pathway and the branching point with the secondary pathway.
  • the flow sensor may for example be positioned between the branching point with the secondary pathway and the primary pathway outlet.
  • the flow sensor may alternatively be at or in-line with the branching point.
  • the flow sensor may for example be positioned between the inlet of the primary pathway and the branching point closest to the inlet of the primary pathway.
  • the flow sensor may for example be positioned between the branching point furthest from the primary pathway inlet and the primary pathway outlet.
  • the flow sensor may for example be positioned between branching points, or in-line with any of the branching points.
  • the flow sensor is arranged to allow measurement of the gas flow in the primary pathway.
  • the device comprises sensors other than a flow sensor, oxygen sensor and carbon dioxide sensor, preferably all sensors other than the flow sensor are located in the secondary pathway(s).
  • the flow sensor measures the flow rate of the breath, for example in imL/min.
  • the flow sensor is arranged to measure the entire flow or substantially the entire flow of exhaled breath.
  • the flow sensor may for example be a hot film anemometer, a micro-thermal conductivity detector, a turbine sensor, a pressure sensor, a differential pressure sensor, a gas mass flow meter, a thermal sensor element, a thermal mass flow sensor, an ultrasonic transit time flow meter or any other appropriate sensor that can sense rapidly the flow rate of a gas mixture.
  • the flow sensor is a thermal mass flow sensor.
  • Spirometry is the most common lung function test, which involves measurement of the volume of air inspired and expired by the lungs when a patient blows into a spirometer.
  • the devices comprise an oxygen sensor arranged in the secondary pathway to take measurements of the exhaled breath in that pathway.
  • the oxygen sensor may for example be an electrochemical partial pressure oxygen sensor, or a polymer sensor.
  • a polymer oxygen sensor uses a polymer to sense oxygen, wherein oxygen is detected by means of interaction of oxygen with the polymer, for example by chemical reaction, resulting in a signal being generated.
  • An example of an oxygen polymer sensor is the O1 -ES1 -O2 sensor developed by EC Sense.
  • An electrochemical oxygen sensor measures the current generated by the reduction of oxygen gas in a cell, the current being proportional to the concentration of oxygen present.
  • An example of an electrochemical oxygen sensor is the UFO 130-2 electrochemical 02 sensor developed by Teledyne. Sensors with a response rate in the range of milliseconds and/or those which are robust and can maintain accurate readings despite movement of the device during use are beneficial in devices of the invention.
  • a carbon dioxide sensor is also present in the device, and is also arranged in the secondary pathway to take measurements of the exhaled breath in that pathway.
  • the carbon dioxide sensor may for example be a non-dispersive infrared sensor (NDIR), which uses the strong and unique infrared absorption of carbon dioxide in a gas mixture or a thermal conductivity detector.
  • NDIR non-dispersive infrared sensor
  • a non-dispersive infrared sensor is a sensor comprising an infrared lamp and a sample chamber, wherein infrared light is directed through the sample of gas in the sample chamber towards a detector. The degree of absorption of specific wavelengths by the gas sample can be used to determine the gas concentration.
  • the carbon dioxide sensor may be a thermal conductivity detector, which measures changes in thermal conductivity of the breath as a result of its changing gas composition.
  • the carbon dioxide sensor is a thermal conductivity sensor, it may be a micro-thermal conductivity sensor.
  • An example of a thermal conductivity sensor is the XEN-TCG3880-P2-RR-W developed by Xensor.
  • Carbon dioxide sensors with high accuracy and low-response times, and/or which maintain accurate reading despite movement of the device during use, are beneficial in devices of the invention.
  • the presence of a carbon dioxide sensor also means that the device may be used for capnography. Capnography is the monitoring of the
  • the device comprises specific combinations of oxygen and carbon dioxide sensors, in order to provide devices which are optimised for use in different applications.
  • the oxygen and carbon dioxide sensors are arranged to sample different portions of exhaled breath, e.g. they may be located in different secondary pathways or different branches of a secondary pathway. This may be referred to as the sensors being arranged "in parallel", i.e. they are not arranged in line or in sequence in the same pathway such that they sample the same portion of the same breath sample one after the other.
  • the flow sensor is configured to measure the gas flow of exhaled breath of a user and the breathing rate of a user.
  • such devices may use an
  • acceleration algorithm which enhances the response time of the oxygen sensor or the carbon dioxide sensor.
  • Such an algorithm may be used to enhance the response time of the oxygen sensor, and facilitating more accurate and rapid sampling.
  • an adjustment or correction factor is applied to the signal of the sensor to be accelerated, based on measurements of the flow sensor, e.g. in some preferred embodiments the device may be configured to apply a correction factor or adjustment to the signal detected by the oxygen sensor, based on the measurements taken by the flow sensor.
  • such an algorithm applies an increase or gain to the signal produced by the sensor to be
  • the device may be configured to accelerate the signal of the sensor as required depending on the breathing rate, as measured by the flow sensor.
  • the signal of the sensors converge logarithmically to their final values and as a result their response time can be simulated.
  • the device is configured such that at least a portion of the signal from the oxygen or carbon dioxide sensor is amplified based on the measurement of the flow sensor.
  • the device is configured such that the flow rate as controlled by the pump is determined based on the measurement of the flow sensor.
  • the device is configured such that the flow rate as controlled by the pump is determined based on the measurement of the flow sensor, and at least a portion of the signal from the oxygen or carbon dioxide sensor is amplified based on the measurement of the flow sensor.
  • Devices which function in this way are particularly advantageous as they allow the sensor response time is reduced, thus improving the accuracy and efficiency of the device. Enhancing the speed of the sensors provides for improved accuracy whilst retaining the possibility of using inexpensive, small sensors, which are particularly suitable for use in a portable, low-cost device. Increased accuracy and speed of smaller and more affordable sensors means that the device can be manufactured to a higher accuracy standard, more cheaply and efficiently.
  • the device is capable of operation as an indirect calorimeter. Indirect calorimetry is used to measure the human metabolism based on the amounts of O 2 and CO 2 that are found in the exhaled human breath.
  • the device of the second aspect of Part B comprises a dehumidifier.
  • Devices of the first and third aspects of Part B preferably also comprise a dehumidifier for reducing the humidity of an exhaled breath passing through the device.
  • the dehumidifier is positioned in the primary or secondary pathway upstream of the oxygen and carbon dioxide sensors.
  • a portion of the or each secondary pathway upstream of the oxygen/carbon dioxide sensor comprises a dehumidifier.
  • a portion of the primary pathway may comprise the dehumidifier.
  • the dehumidifier comprises a tube made of a sulfonated tetrafluoroethylene-based fluoropolymer-copolymer, e.g. a Nafion® tube.
  • a Nafion® tube is used to dry the exhaled human breath. The exhaled breath is dried as it passes through a series of one or more Nafion® tubes along the primary and/or secondary pathways.
  • Alternative means of dehumidifying the breath may also be used, instead of or in addition to a Nafion® tube.
  • a desiccant may be used as a dehumidifying means.
  • a desiccant used is preferably chemically inert to both carbon dioxide and oxygen. It is preferred that the desiccant does not absorb oxygen or carbon dioxide when used to reduce humidity, so as not to affect the measurements of the components of the exhaled breath and thus the accuracy of the device.
  • the desiccant is preferably also inert with respect to other gases contained in breath, such as nitrogen and argon. The desiccant should also not be toxic or harmful to a user of the device.
  • Particularly preferred desiccants are those which have the following properties: a) able to absorb moisture so as to be able to reduce the humidity of exhaled breath from saturation level (100%RH) when this desiccant is placed in a steady flow stream;
  • the desiccant is preferably inert to O2, CO2, N2 and Ar;
  • c) does not absorb the gases from the gas sample. This means that the desiccant should not have any electromagnetic interaction (i.e. polar or non- polar bonding) with 02, CO2, N2 and Ar of the breath gas mixture.
  • desiccants examples include magnesium perchlorate, Sodium chloride (halite) (NaCI), Calcium chloride (CaCI2), Sodium hydroxide (NaOH), sulfuric acid (H2SO4), Copper sulphate (CuSO4), phosphorus pentoxide (P2O5 or more correctly P4O10), silica gel, hydrated salts such as Na2SO4- 10H2O, LiBr, LiCI and amines.
  • the desiccant is silica gel.
  • a humidity sensor may be used in combination with a desiccant as a dehumidifying means. In such embodiments, the humidity sensor may provide feedback to the user as to when the desiccant needs to be replaced.
  • a chamber containing a wet sponge may be located along the secondary pathway in-line with a further chamber containing one or more desiccants.
  • the exhaled breath will pass first through the wet sponge where its humidity may rise, and it will then be dried after passing through the chamber of the desiccant.
  • its humidity will be increased significantly when it passes through the wet-sponge chamber and it will get dried after passing through the chamber with the
  • the dehumidifying chamber containing a desiccant may optionally comprise a valve at its inlet and/or a valve at its outlet. Having a valve at both the inlet and the outlet of the dehumidifying chamber would allow the chamber to be closed off when the device is not in use, to prevent ambient air contacting the desiccant and thus prolong the lifetime of the desiccant.
  • only the chamber with the desiccant could be used for drying the breath.
  • a combination of a Nafion® tube, a wet sponge and a chamber with desiccant may be used.
  • a combination of a Nafion® tube and only the chamber with the desiccant may be used, without a wet sponge.
  • only a wet sponge and the chamber of desiccant could be used, only the desiccant, or only the Nafion® tube.
  • a dehumidifier is not present.
  • the sensors may, for example, instead be heated to avoid condensation forming.
  • a device may comprise a dehumidifier and one or more sensors may also be heated.
  • a facemask or mouthpiece is connected to the inlet of the primary pathway, and, while the flow sensor and primary pathway remain in proximity to the mouthpiece or facemask, a length of tubing may form the portion of the secondary pathway extending from the branching point.
  • a length of tubing may form the portion of the secondary pathway extending from the branching point.
  • the remainder of the device at the end of the long tube opposite the facemask, flow sensor and primary pathway may be kept, for example, in a pocket, bag or otherwise strapped to the user, whilst the user is using the device.
  • the facemask may be strapped to the head of the user.
  • the tubing may comprise a dehumidifier, for example if the tubing comprises a Nafion® tube drying mechanism. Such embodiments may be used in VO2 max testing, anaerobic threshold identification and several others fitness applications.
  • the device of the second aspect of the invention of Part B comprises a pump.
  • the device comprises a pump for drawing exhaled breath through the secondary pathway(s).
  • the pump regulates the flow rate through the secondary pathway to ensure a constant steady flow.
  • the pump operates at a constant flow, drawing through the secondary pathway either a sample of the exhaled breath when it fills the primary pathway, or of the ambient air via the outlet of the primary pathway in the dead time between breath exhalations.
  • Measurements of ambient air can be useful for calibration of the device.
  • One or more pumps may be used to draw breath along the one or more secondary pathways. When more than one secondary pathway is present in the device, more than one pump may be used to tailor the flow rate along each secondary pathway.
  • a single pump may be used to draw air/breath through multiple secondary pathways.
  • One particularly preferred type of pump for use in devices of the invention is a rotary vane pump, since it can produce a steady flow without causing any turbulence, which is advantageous for accurate measurement by the sensors. Any other type of pump technology can be used.
  • the device does not comprise a pump.
  • the rate of gas flow may instead be controlled by the diameter and configuration of the gas flow pathways.
  • tubes of smaller diameter may be used along the gas flow pathways to reduce the flow rate of the exhaled breath as it passes through them.
  • devices of the invention of Part B comprise a
  • the micro-controller may for example be used to power the pump.
  • the micro-controller may carry out data processing on measurements taken by the device: the flow-rate sensed by the flow sensor, the concentration of oxygen measured in the exhaled breath by the oxygen sensor, and the concentration of carbon dioxide sensed by the carbon dioxide each create an electrical signal that is communicated to the micro-controller.
  • the device comprises a one-way (non- rebreathing) valve positioned between the inlet and the flow sensor, through which gas may pass in a direction from the inlet to the flow sensor only.
  • a non-rebreathing valve may be present for example in a mouthpiece or a facemask of the primary pathway. In this case, the user must inhale through the nose and exhale through the mouth.
  • the one-way valve may be absent.
  • the user may inhale and exhale from his mouth while his nose is closed with a nose-clip.
  • inhaling and exhaling needs to be done through the mouth and this can be achieved by using a mouthpiece or facemask without a non-rebreathing valve.
  • the device includes a barometric pressure sensor, a relative humidity sensor and/or a temperature sensor.
  • the signals of these sensors may be communicated to the micro-controller in order to
  • the barometric pressure sensor, relative humidity sensor and/or temperature sensor may be arranged to take measurements in the primary pathway or in the secondary pathway(s). Preferably, they are arranged to take measurements in the secondary pathway(s). Where there are multiple secondary pathways formed as branches of a secondary pathway having a single branching point with the primary pathway as described above, the secondary pathways being branched from one another at a secondary pathway branching point, each of these sensors may independently be positioned in the initial secondary pathway portion between the branching point and the secondary pathway point. Alternatively, they may be positioned in one or more of the branched secondary pathways downstream of the secondary pathway branching point.
  • a humidity sensor may be used in combination with a desiccant as a dehumidifier.
  • the humidity sensor may provide feedback to the user as to when the desiccant needs to be replaced.
  • the efficiency of a desiccant may be reduced over time.
  • the device may comprise two humidity sensors.
  • One humidity sensor may be placed inside the device, prior to the dehumidifier, to sample ambient gas, and the second humidity sensor may be placed on the secondary pathway after the dehumidifier, to sample breath which has been dehumidified.
  • the pump is turned on and the secondary pathway or pathways are filled with ambient air.
  • the desiccant reduces the humidity of the ambient gas sampled on the secondary pathway.
  • the difference between the reading of the humidity sensor that samples ambient air and the humidity sensor that samples ambient air that has been dehumidified measures the efficiency of the desiccants and informs the user when to replace the desiccant.
  • the difference between the readings of the humidity sensor between the dried ambient air and the ambient air sample shows the efficiency of the dehumidifier.
  • the humidity sensor is connected upstream of the dehumidifier followed by a pump on the secondary pathway. By rotating the pump from pressure mode to vacuum mode it is possible to directly sample either ambient air or ambient air that has been dried through the dehumidifying mechanism. Again, the difference between the readings of the humidity sensor shows the efficiency of the dehumidifier to indicate, for example, when a desiccants should be replaced.
  • a device of the invention of Part B may comprise a first humidity sensor positioned upstream of the dehumidifier and a second humidity sensor positioned downstream of the dehumidifier, such that the decrease in humidity as caused by the dehumidifier may be measured.
  • the device may comprise a humidity sensor positioned downstream of the
  • dehumidifier and a three-way valve positioned between the dehumidifier and the humidity sensor, the valve being movable such that the humidity sensor may changeably analyse either breath which has passed through the dehumidifier or ambient air.
  • one or more further sensors may be present.
  • one or more of an acetone, nitric oxide, sulphur compounds, pentane, ethanol and hydrocarbons sensor may be present in the device.
  • Such further sensors when present, are arranged in the or a secondary pathway.
  • an acetone sensor is added to the device, the glucose level of a patient can be monitored in a non-invasive way. This is particularly interesting for patients that are diabetic since they need to monitor their glucose level on a day- to-day basis. It is known that the level of acetone concentration that is found in the exhaled breath is correlated to the blood glucose level. However, it is extremely difficult to determine the baseline of an individual's glucose level. In this device, by combining the information gathered about the metabolism level of an individual and/or his respiratory quotient (RQ) with the concentration of acetone that is found in his exhaled breath, it is possible to determine the baseline level by a suitable algorithm.
  • RQ respiratory quotient
  • a nitric oxide sensor is added to the device of the invention of Part B the device can provide information regarding the user's asthma medication.
  • the nitric oxide levels that are found in the breath can give to a physician information about the effectiveness and the dose needed for the asthmatic patient, which can be used to regulate the medication for an asthma patient.
  • the one or more further sensors may be arranged to take
  • measurements in the primary pathway or in the secondary pathway are arranged to take measurements in the secondary pathway.
  • the device comprises a
  • the communication element for communication between a microcontroller and a mobile phone or other external device.
  • the communication element may be a Bluetooth connection via the microcontroller, to enable communication with a mobile phone.
  • the device may be used for remote medical monitoring.
  • the communication element allows data collected by the microcontroller to be sent directly to a remotely located device, for example via the internet. Data collected may be displayed on a computer or, for example, a smartphone application.
  • a communication element may be a USB connector, a removable memory card, a cable, a wireless unit, an Ethernet shield, or a mobile broadband unit, for example.
  • the device will typically contain a casing or housing, e.g. made of suitable durable material, e.g. a suitable rigid plastics material.
  • the casing or housing will contain various components of the device, for example tubes and connectors defining the breath pathway or pathways, the moisture reduction module, sensors, electrical components etc.
  • Such a casing has appropriate openings to allow functioning of the device, e.g. providing access to the inlet and/or where a facemask or mouthpiece forms part of the device, to permit connection of the facemask or mouthpiece to the gas flow pathway. Openings may also be provided, for example, to accommodate the outlet or outlets of the device.
  • the operation of the devices of the invention of Part B as an indirect calorimeter is based on the determination of the oxygen consumption, carbon dioxide production and the flow rate that can be determined by the exhaled breath of the user.
  • the exhaled breath fills the primary pathway.
  • the entire flow rate of the expired breath is preferably instantly measured.
  • the gas that forms the inspired breath may be analysed.
  • the exhaled human breath consists mainly (-99%) of nitrogen, oxygen and carbon dioxide.
  • the Haldane transform assumes that nitrogen is physiologically inert. This means that the volume of inspired nitrogen must be the same with the volume of expired nitrogen.
  • V, V v - (4a )
  • Equation 1 a describes that nitrogen is inert and the volume of inspired nitrogen is equal to the volume of the expired nitrogen which is the Haldane approximation.
  • Equation 2a describes that the fraction of exhaled nitrogen equals to the 99.063% of the exhaled breath minus the fraction of expired oxygen and carbon dioxide.
  • Equation 3a describes that the fraction of inspired nitrogen equals to 78.08%, which is the percentage of nitrogen in ambient air.
  • Equation 4a is the equation used to calculate the inspired flow rate when the expired flow rate, the fraction of expired oxygen and the fraction of expired carbon dioxide are known from the various sensors in the device.
  • a subject breathes into a device according to the invention of Part B. After entering the primary pathway (in which the flow rate of the expired, and optionally inspired, breath is measured), a portion of the breath is guided along the secondary pathway(s). This may be assisted by the presence of a pump to draw sample with a constant flow-rate down the secondary pathway(s) as described above. The remainder of the exhaled breath, which does not enter the secondary pathway, exits the device via the outlet of the primary pathway. Inhaled breath which does not enter the secondary pathway is inhaled by the user.
  • the relative humidity of the exhaled breath may be reduced until it reaches the ambient relative humidity.
  • This flow rate measurement from the flow-sensor is supplied to the microcontroller and allows the microcontroller to determine the breathing frequency (breathing rate) and to control the valve system accordingly, and/or to accelerate the 02 and/or CO2 sensors, and/or to control the pump, as described above.
  • the sample of expired breath continues along the secondary pathway(s) to the network of sensors of the device.
  • the sensor network of the device includes a flow sensor, an oxygen sensor, a carbon dioxide sensor, a temperature sensor, a barometric pressure sensor and a humidity sensor.
  • the temperature sensor, barometric pressure sensor and the humidity sensors are used to compensate the measurements of the oxygen and carbon dioxide sensors when necessary.
  • the oxygen and carbon dioxide sensors measure the human breath, they create a periodic signal that resembles a function describing a wave.
  • the two waveforms, the waveform of the oxygen (f 0 2) and the waveform of the carbon dioxide (fco2) are sensed and then refitted by a customised built algorithm that is based on the following equation: where c1 and c2 are positive constants.
  • a human's energy expenditure is divided into resting metabolic rate (RMR), physical activities and thermogenesis that is induced by food intake.
  • the device is able to measure the oxygen consumed and the carbon dioxide produced by an individual.
  • FEO2 resting energy expenditure
  • RRR resting metabolic rate
  • the inhaled flow rate is calculated by equation (4a), as described previously.
  • the fraction of inspired oxygen (F1O2) is constant at 0.2005 since it is the fraction of inspired oxygen from ambient air.
  • CO 2 ) is constant at 0.00039 since it is the fraction of inspired carbon dioxide from ambient air.
  • the energy expenditure of an individual is calculated by measuring the exhaled flow rate (VE), the fraction of expired oxygen (FEO2) and the fraction of expired carbon dioxide (FECO2).
  • the respiratory quotient is usually between 0.6 - 1 .0 for aerobic metabolism.
  • the respiratory quotient is usually between 0.6 - 1 .0 for aerobic metabolism.
  • the medium value of RQ 0.8 shows that the user is metabolising protein.
  • various other functions may be measured by the device. These include, but are not limited to, the calories burned during exercise, in which instance a facemask may be used as part of the primary pathway to facilitate use of the device while exercising.
  • the device may also be used to calculate body mass index (BMI, a measure of the fat- free mass of an individual), may track the history of the user with corresponding software (such as a smartphone application) to draw conclusions about the health status of the user, may be used as a capnometer and/or may be used as a spirometer.
  • BMI body mass index
  • the operation of the device is preferably conducted through a microcontroller and the data measured can be transmitted to a smartphone or computer for example.
  • the invention also provides a method of measuring a breath property of a subject, the method comprising: providing a device as defined herein; and measuring a breath property of a subject using said device.
  • the device may be used to calculate concentrations and/or amounts of 0 2 and C0 2, and/or may be used to calculate other parameters such as the respiratory quotient.
  • a method of analysing gas that forms an inhaled breath of a subject comprising the step of the subject inhaling through a breath analysis device of the invention is also provided.
  • FIG. 1 An example of a device according to the invention of Part A is shown schematically in Figure 1 .
  • the device comprises a mouthpiece (not shown) at the inlet of the primary pathway 1.
  • a flow sensor (not shown) present in the primary pathway measures the flow rate of exhaled and inhaled breath when a user exhales and inhales into the mouthpiece.
  • a non- rebreathing valve is not present; a user may inhale as well as exhaling into the device.
  • ambient air is drawn through the outlet at the end of the primary pathway. Air may thus pass through the primary pathway in two directions.
  • the primary pathway 1 includes the mouthpiece and the flow sensor.
  • the device also includes a secondary pathway 2, which branches from the primary pathway.
  • a portion of the secondary pathway 2 is arranged concentrically within an outer tube 3 and defines a passage for exhaled breath through the moisture reduction module.
  • the portion of the secondary pathway 2 within the moisture reduction module is made from Nafion® (a selectively permeable membrane which is permeable to water but impermeable to oxygen and carbon dioxide).
  • the moisture reduction module includes an outer tube 3 for the passage of ambient air surrounding the inner tube (exhaled breath passage/secondary pathway) 2.
  • the volume between the outer surface of the inner tube and the inner surface of the outer tube defines a passage for ambient air.
  • the outer tube 3 is provided with an inlet 14 through which ambient air enters the outer tube 3.
  • the secondary pathway 2 continues through the moisture reduction module to an oxygen sensor 4 and a carbon dioxide sensor 5, which are arranged in series along the secondary pathway 2, which are downstream of the moisture reduction module. Exhaled breath passing through the secondary gas flow pathway passes the sensors and then passes into a tube having an upstream portion 10 and a downstream portion 11.
  • the interior of the outer tube 3 which forms part of the moisture reduction module is connected at exit point 7 via tube 8 to the secondary gas flow pathway, so that the ambient air gas flow passage merges with the secondary gas flow pathway at merging point 9, downstream of oxygen sensor 4 and carbon dioxide sensor 5.
  • the downstream portion of tube 11 through which the sampled exhaled breath and ambient air from the moisture reduction module pass, is in turn connected to the inlet 12 of a pump 6.
  • the pump draws exhaled breath through the exhaled breath gas flow passage of the moisture reduction module and along the secondary gas flow pathway, and at the same time draws ambient air through the ambient air gas flow passage of the moisture reduction module, and expels air to the environment via outlet 13.
  • a portion of the exhaled breath is sampled from the periphery of the primary pathway 1 and is guided along the secondary pathway 2.
  • the sample of exhaled breath is drawn through the secondary pathway at a constant flow rate by the pump 6 present in the secondary pathway.
  • the pump instead draws ambient air into the pathway, through the outlet of the primary pathway.
  • the breath sample As the breath sample is drawn through the secondary pathway 2, it passes through the portion of the secondary pathway 2 which is within the moisture reduction module and surrounded by the outer tube 3. That portion of the secondary pathway is made of Nafion®.
  • the pump 6 also draws ambient air in through the inlet 14 of the outer tube 3 of the moisture reduction module, through the outer tube, and of the outer tube via exit point 7 and along tube 8 to branching point 9 where tube 8 merges with the secondary pathway. Ambient air mixes with exhaled breath from the secondary pathway and is expelled from the pump via outlet 13.
  • the dehumidified exhaled breath exiting the moisture reduction module along the secondary pathway 2 then continues to the oxygen sensor 4 and carbon dioxide sensor 5 for analysis by the sensors.
  • Exhaled breath then exits sensor 5 via outlet 10, and continues along the secondary pathway where it merges with ambient air at merge point 9.
  • the mixture of ambient air and exhaled breath continues along single tube 11 where it is expelled via the outlet 13 of pump 6.
  • FIG. 2 An alternative embodiment of a device is shown in Figure 2. All components function in the same way as for the embodiment of Figure 1 , except that, in the embodiment of Figure 2, the oxygen sensor 4 and carbon dioxide sensor 5 are arranged in parallel rather than in series. A portion of the exhaled breath sample travelling along the secondary pathway 2 continues to the oxygen sensor 4 along a first sensor route, and the remainder of the exhaled breath sample continues instead to the carbon dioxide sensor 5 along the second sensor route, which is arranged in parallel. The exhaled breath which has passed through each sensor then merges at merge point 10, and then merges with ambient air from the moisture reduction module at merge point 9, before being expelled via outlet 13 as above.
  • FIG. 3 An example of a device according to the invention of Part B is shown schematically in Figure 3.
  • the device comprises a mouthpiece 1
  • the primary pathway 10 comprises the mouthpiece 1 , the flow sensor 2, and part of a T-shaped connector 3 which joins the primary pathway to the secondary pathway 11.
  • the T-shaped connector also forms part of the secondary pathway. A portion of the exhaled breath is sampled from the periphery of the primary pathway and is guided along the secondary pathway.
  • the sample of exhaled breath is drawn through the secondary pathway at a constant flow rate by a micro-pump 5 present in the secondary pathway, controlled by micro-controller 8.
  • the pump instead draws ambient air into the pathway, through the outlet of the primary pathway.
  • the breath sample As the breath sample is drawn through the secondary pathway, it passes through a Nafion® tube 4 which forms part of the secondary pathway (in the upstream portion of the secondary pathway). This reduces the humidity of the exhaled breath before it reaches the oxygen and carbon dioxide sensors.
  • Exhaled breath passing through the secondary pathway is divided into two portions at a secondary pathway branching point prior to reaching the oxygen and carbon dioxide sensors 6 and 7.
  • the oxygen sensor 6 is a polymeric sensor
  • the carbon dioxide sensor 7 is a thermal conductivity detector (TCD), preferably a micro-thermal conductivity detector (imTCD).
  • FIG. 4 A further example of a device according to the invention of Part B is shown in Figure 4.
  • the device comprises two secondary pathways branched from the primary pathway.
  • Each secondary pathway also contains a Nafion® tube 4 which forms part of the respective secondary pathway, and reduces the humidity of an exhaled breath stream as it passes through that secondary pathway prior to contacting a sensor.
  • the respective streams of exhaled breath are combined as the secondary pathways merge downstream of the sensors.

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Abstract

L'invention concerne un dispositif portable d'analyse de la respiration permettant d'analyser la respiration d'un sujet pour identifier le taux de certains gaz comme l'oxygène et le dioxyde de carbone. Le dispositif présente une utilité, par exemple, dans la surveillance de la santé de sujets. L'invention concerne également des méthodes de mesure d'une propriété de la respiration d'un sujet utilisant les dispositifs.
PCT/US2018/055009 2017-10-10 2018-10-09 Dispositif d'analyse de la respiration WO2019074922A1 (fr)

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CN112773409A (zh) * 2020-12-30 2021-05-11 深圳市步锐生物科技有限公司 一种手持式呼出气采样器自充电维护装置
WO2021168542A1 (fr) * 2020-02-28 2021-09-02 Picomole Inc. Appareil et procédé de collecte d'un échantillon d'haleine à l'aide d'un système de circulation d'air
CN114588467A (zh) * 2022-04-01 2022-06-07 广州蓝仕威克医疗科技有限公司 一种基于气体混合比例供气解决酒精中毒的方法及呼吸机
US11499916B2 (en) 2019-04-03 2022-11-15 Picomole Inc. Spectroscopy system and method of performing spectroscopy
EP4057896A4 (fr) * 2019-11-14 2023-11-08 Health Innovision Company Limited Analyseur de gaz et de substance volatile d'haleine portatif
DE102022111059A1 (de) 2022-05-04 2023-11-09 Cortex Biophysik Gmbh System zur Erfassung von Atemgasbestandteilen
EP4141411A4 (fr) * 2020-05-29 2024-01-24 I Pex Inc Dispositif de détection d'odeurs, procédé de détection d'odeurs et programme

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EP4057896A4 (fr) * 2019-11-14 2023-11-08 Health Innovision Company Limited Analyseur de gaz et de substance volatile d'haleine portatif
WO2021168542A1 (fr) * 2020-02-28 2021-09-02 Picomole Inc. Appareil et procédé de collecte d'un échantillon d'haleine à l'aide d'un système de circulation d'air
EP4141411A4 (fr) * 2020-05-29 2024-01-24 I Pex Inc Dispositif de détection d'odeurs, procédé de détection d'odeurs et programme
CN112773409A (zh) * 2020-12-30 2021-05-11 深圳市步锐生物科技有限公司 一种手持式呼出气采样器自充电维护装置
CN112773409B (zh) * 2020-12-30 2023-06-16 深圳市步锐生物科技有限公司 一种手持式呼出气采样器自充电维护装置
CN114588467A (zh) * 2022-04-01 2022-06-07 广州蓝仕威克医疗科技有限公司 一种基于气体混合比例供气解决酒精中毒的方法及呼吸机
DE102022111059A1 (de) 2022-05-04 2023-11-09 Cortex Biophysik Gmbh System zur Erfassung von Atemgasbestandteilen

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