WO2021250261A1 - Device for sampling gases exhaled by a patient - Google Patents

Device for sampling gases exhaled by a patient Download PDF

Info

Publication number
WO2021250261A1
WO2021250261A1 PCT/EP2021/065849 EP2021065849W WO2021250261A1 WO 2021250261 A1 WO2021250261 A1 WO 2021250261A1 EP 2021065849 W EP2021065849 W EP 2021065849W WO 2021250261 A1 WO2021250261 A1 WO 2021250261A1
Authority
WO
WIPO (PCT)
Prior art keywords
gases
patient
exhaled
sampling
sensor
Prior art date
Application number
PCT/EP2021/065849
Other languages
French (fr)
Inventor
Jean-Luc WOJKIEWICZ
Nathalie REDON
Cyril Lahuec
Paul LE MAOUT
Original Assignee
Institut Mines Telecom
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 Institut Mines Telecom filed Critical Institut Mines Telecom
Publication of WO2021250261A1 publication Critical patent/WO2021250261A1/en

Links

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
    • 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
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/0803—Recording apparatus specially adapted therefor
    • 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
    • A61B5/083—Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
    • A61B5/0836—Measuring rate of CO2 production
    • 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
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/682—Mouth, e.g., oral cavity; tongue; Lips; Teeth

Definitions

  • the present invention relates to the field of the analysis of gases exhaled by a patient, in order to detect and / or treat pathologies of which one or more biomarkers could be present in the patient's breath.
  • a sample is necessary and can be done in several ways: filling a bag, absorbing the gases on absorbents or sending the gases directly to the system. analysis.
  • the composition of the breath is determined in two stages: collecting the gases then sending them to the analysis system for analysis and in the last case direct sending to the gas system. to analyse.
  • a commercially available breath sampling system consisting of a mask which collects air from the alveolar tract using absorbents for subsequent analysis. The air is collected on four absorbent tubes and then each tube is heat-desorbed to send to the analysis system. The cost of this device is high, as are the costs of analysis.
  • the results obtained by the analysis system show a very high variability of the compounds present in the breath for the same pathology. This can be explained in several ways: either the samples do not distinguish between the upper tract and that of the alveoli and therefore the results are very disturbed, or they are done by different methods, which does not allow an objective comparison of those. -this.
  • the system is further limited only to the absorption of breath gaseous compounds on absorbents with subsequent analysis. The time to get the result is also very long, on the order of several weeks to get the result, and expensive.
  • the subject of the invention is thus a device for sampling the gases exhaled by a patient, comprising at least a first and a second sampling channels intended to alternately or simultaneously receive the gases exhaled by the patient, and a control member for directing the gases. expired gases to the first or second sampling channel, the device comprising a sensor making it possible to provide information concerning the origin of the expired gases, namely whether the expired gases come from the upper passages of the patient's respiratory system or whether the expired gases come from alveoli in the patient's lungs.
  • the advantage of the sampling device according to the invention is to make it possible to separate, in the exhaled gases, those originating from the upper passages of the respiratory system from those originating from the pulmonary alveoli.
  • the composition of the gases coming from the upper passages is strongly influenced by the air in the room where the patient is located and therefore the measurement can be disturbed by compounds which are not representative of the patient's state of health.
  • the gases exhaled from the alveoli of the lungs are representative of the blood exchanges with the alveoli and therefore of the modifications caused by a given pathology.
  • the device according to the invention is advantageously non-invasive, insofar as the patient only has to blow into it.
  • the sampling device is universal, that is to say that the gases sampled can be analyzed by any analysis system, whether in real time or off-line. It can be used for medical diagnosis or to assess the effectiveness of a medical treatment associated with a given pathology.
  • the sampling device according to the invention is at the same time simple, space-saving and low-energy consuming, for example having a consumption of less than 35 mW, being light and portable.
  • the gases exhaled by a patient may contain biomarkers of one or more diseases from which that patient may suffer.
  • the detection and analysis of these biomarkers can thus allow a diagnosis of the disease, in particular an early diagnosis, as well as a follow-up of the course of the disease, and in particular of the effectiveness of a treatment.
  • the analysis can for example allow a discrimination between healthy patient and sick patient, which allows the development of a diagnosis.
  • the disease can be chosen from the following list, which is not exhaustive: cancer, in particular lung cancer, liver cancer, breast cancer, renal failure, neurodegenerative disease, in particular Parkinson's disease, Alzheimer's disease, diabetes, liver disease, bowel disease, colorectal cancer, intraoral haliotis, COVID-19.
  • the biomarkers to be identified can be chosen, according to the pathology targeted, from the following list, which is not exhaustive: isopropanol, methanol, isoprene, acetone, methyl mercaptan, ammonia, dimethyl sulfide, methane, formaldehyde, acetaldehyde, amines, alkanes , toluene Examples of compounds identified as potential biomarkers for certain pathologies will be given in Table 1 below.
  • the controller can be configured to direct exhaled gases to the first or second sample channel based on information received from the sensor.
  • control member may include one or more solenoid valves to direct the exhaled gases to the first or the second sampling path.
  • control member may include a single solenoid valve and non-return valves to separate the exhaled gas streams. It can thus include a first non-return valve controlling access to the first sampling. It may also include a second non-return valve controlling access to the second sampling channel.
  • control unit may in particular include two solenoid valves each controlling access to a sampling channel. It can thus include a first solenoid valve controlling access to the first sampling channel. It may also include a second solenoid valve controlling access to the second sampling channel.
  • the exhaled gases are received, before being directed to the sampling channel (s), in a reception tube.
  • the receiving tube can be a straight tube, devoid of the Venturi effect. It is not necessary in the invention to measure the flow rate of exhaled gases.
  • the receiving tube may be located between one or more antibacterial filters and the solenoid valve (s) or the non-return valve (s).
  • the information received from the sensor can be used to determine the current phase of the patient's respiratory cycle.
  • the exhaled gases originate from the upper airways of the patient's respiratory system or the exhaled gases originate from the alveoli in the patient's lungs, and the composition of the exhaled gases is not the same.
  • the sensor may include a pressure sensor.
  • the breathing cycle has three distinct phases, namely (i) a first phase of expiration during which the pressure increases when the patient begins to expire, during which it is the gases of the upper passages which are expelled, (ii) a second phase during which the pressure stabilizes, it is about the alveolar gases which are expelled, and finally (iii) a third phase of rapid decrease in pressure, when the patient inhales.
  • the senor can be configured to detect the level of carbon dioxide in the exhaled gases.
  • the exhaled gases are of alveolar or upper tract origin.
  • the level of C02 it is possible to determine which sampling path to direct the exhaled gases to.
  • the sampling device can also include a temperature sensor and / or a humidity sensor.
  • C02, pressure, temperature and humidity sensors can be viewed by physicians to monitor the patient's physiological parameters to see if everything is going well during the sample. Such monitoring can, for example, make it possible to identify a hypo or hyper ventilation alert or the like.
  • the sensor (s) of the sampling device may not have a laser.
  • the sampling device may include a gas analysis system, which may be integrated into the device or external to it.
  • the sampling device can be configured to be able to be connected to a gas analysis system external to the device.
  • the sampling device includes an expired gas analysis system.
  • the exhaled gases can be analyzed in real time, that is to say as the sample is taken.
  • the gases sampled can be stored in a storage device, and be analyzed subsequently.
  • the sampling device may include a storage device, for example one or more bags in polyvinyl fluoride (PVF) called "Tedlar".
  • the storage device may alternatively or additionally comprise an absorbent surface for the exhaled gases.
  • the exhaled gas analysis system can detect biomarkers present in exhaled gases.
  • the analysis system can be any. Indeed, the sampling device according to the invention can be adapted to all possible analysis systems.
  • the analysis can be carried out by one of the analysis systems from the following list, which is not exhaustive: GC-MS (gas chromatography coupled with mass spectrometry), PTR-MS (proton transfer reaction before analysis by mass spectrometry), SIFT-MS (mass spectrometry by selected ion flow), or any other analyzer of volatile organic compounds.
  • GC-MS gas chromatography coupled with mass spectrometry
  • PTR-MS proto transfer reaction before analysis by mass spectrometry
  • SIFT-MS mass spectrometry by selected ion flow
  • the analysis can thus make it possible to define a chemical fingerprint.
  • the analysis system may allow an electronic fingerprint to be defined.
  • it may include a matrix of cross-reactive sensors, also called an "electronic nose”.
  • the analysis can be carried out in real time, as soon as the sample has been taken, or off-line, that is to say that the exhaled gases are trapped and / or stored for a certain time before being analyzed.
  • the results of the analysis may be able to discriminate healthy patients from sick patients. In addition, they can be used to determine the disease from which a patient is suffering. Finally, they can be used to measure the course of the disease, for example in order to report on the effectiveness of a treatment.
  • the sampling device may include a mask to be placed on the patient's face.
  • the mask can be configured to allow collection of exhaled gases through the mouth, nose, or both mouth and nose.
  • the mask can be reusable.
  • the sampling device may include a mouthpiece intended to allow the sampling of the gases exhaled through the mouth only.
  • the mouthpiece can be disposable.
  • the patient may be invited to blow into the sampling device, in particular through the mask or through the mouthpiece.
  • the sampling device may include an antibacterial filter making it possible to filter the exhaled gases.
  • the antibacterial filter can be placed at the inlet of the sampling device, in particular upstream of the sensor.
  • the antibacterial filter prevents any bacterial contamination of the sampling device.
  • the sampling device may include a purification system making it possible to purify the inspired gases. It can, for example, be placed at the entrance to the mask, so that the incoming air, inspired by the patient, is devoid of volatile organic compounds or other contaminants. The patient thus receives clean air and the reliability of the analysis can be improved.
  • a purification system making it possible to purify the inspired gases. It can, for example, be placed at the entrance to the mask, so that the incoming air, inspired by the patient, is devoid of volatile organic compounds or other contaminants. The patient thus receives clean air and the reliability of the analysis can be improved.
  • Figure 1 is a schematic view of a sampling device according to the invention.
  • Figure 2 is a diagram showing the change in the concentration of carbon dioxide in the exhaled gases, as a function of time expressed in seconds.
  • FIG 3 is a schematic view of an alternative embodiment of the sampling device.
  • FIG 4 is a schematic view of an alternative embodiment of the sampling device.
  • FIG. 1 shows a device 1 for sampling the gases exhaled by a patient, which firstly comprises a mask 10 to be placed on the patient's face, which in the example described has the shape of a mouthpiece intended to allow the sampling of gases exhaled through the mouth only. The patient may be prompted to blow into the collection device through the mouthpiece. The device is thus non-invasive. The mouthpiece must be renewed for each patient.
  • the sampling device further comprises an antibacterial filter 12 making it possible to filter the exhaled gases.
  • the antibacterial filter 12 is here disposed at the inlet of the sampling device, just downstream of the mouthpiece.
  • the device then comprises a first SI and a second S2 sampling channels. These channels are called SI and S2. They are intended to alternately or simultaneously receive the gases exhaled by the patient.
  • the sampling device further comprises a control member 15 for directing the exhaled gases towards the first S 1 or the second S2 sampling channel.
  • the device comprises a sensor 20 making it possible to provide information concerning the origin of the expired gases, namely whether the expired gases originate from the upper passages of the patient's respiratory system or whether the expired gases originate from the alveoli of the patient's lungs.
  • the control member 15 is configured to direct the exhaled gases towards the first or the second sampling channel according to the information received from the sensor.
  • it is a sensor 20 configured to detect the level of carbon dioxide in the exhaled gases. Depending on the level of carbon dioxide, it can be determined whether the exhaled gases are of alveolar or upper tract origin.
  • the breathing cycle illustrated in Figure 2 there are three distinct phases, namely (i) the first phase AB of expiration during which the concentration of carbon dioxide increases when the patient begins expiration, during which they are the gases of the upper passages which are expelled, (ii) the second phase BC during which the level of carbon dioxide stabilizes, these are the alveolar gases which are expelled, and finally (iii) the third phase CD of rapid decay the level of carbon dioxide when the patient inhales.
  • the first phase AB of expiration during which the concentration of carbon dioxide increases when the patient begins expiration, during which they are the gases of the upper passages which are expelled
  • the second phase BC during which the level of carbon dioxide stabilizes, these are the alveolar gases which are expelled
  • the third phase CD of rapid decay the level of carbon dioxide when the patient inhales.
  • the device could also include a pressure sensor. Indeed, the pressure variations also make it possible to determine the current phase of the patient's respiratory cycle.
  • the sampling device could include a temperature sensor and / or a hygrometry sensor, as will be seen below.
  • the control member 15 comprises two solenoid valves each controlling access to a sampling channel, namely a first solenoid valve EV1 controlling access to the first sampling channel and a second solenoid valve EV2 controlling access to the second sampling channel. sampling.
  • the sampling device 1 is connected downstream to a gas analysis system 30, which in this example is external to it.
  • the exhaled gas analysis system 30 is configured to detect biomarkers present in the exhaled gases.
  • the gases sampled are analyzed in real time, as soon as the sample has been taken, or later, being then stored in a storage device 35, to be analyzed subsequently.
  • the sampling device comprises a storage device, for example one or more bags in polyvinyl fluoride (PVL) called "Tedlar".
  • PVL polyvinyl fluoride
  • the storage device may alternatively or additionally comprise an absorbent surface for the exhaled gases.
  • the pressure sensor makes it possible to produce a time base making it possible to control the solenoid valves by means of a control chain comprising a computer 16 receiving information from the sensor, a calculation card 17, and a control relay 18 for the solenoid valves.
  • a control chain comprising a computer 16 receiving information from the sensor, a calculation card 17, and a control relay 18 for the solenoid valves.
  • the first solenoid valve EV 1 is open and the second solenoid valve EV2 is closed.
  • the exhaled gases are sent to outlet 1. These are the exhaled gases coming from the upper passages of the patient's respiratory system.
  • the first solenoid valve EV1 closes and the second solenoid valve EV2 opens.
  • the exhaled gases are sent to outlet 2. These are the exhaled gases which come from the alveoli in the patient's lungs.
  • the gases are sent to a gas analysis system.
  • the embodiment illustrated in Figure 3 differs from the previous one in that the exhaled gases are withdrawn by means of a mask to be placed on the patient's face, which is configured to allow the withdrawal of the exhaled gases at a time through the patient's face. mouth and nose.
  • the pressure sensor is associated with a carbon dioxide sensor, making it possible to control the solenoid valves EV1 and EV2.
  • a temperature sensor and a hygrometry sensor are added.
  • the pressure sensor is associated with a carbon dioxide sensor for controlling a single solenoid valve and non-return valves to separate the exhaled gas streams.
  • a temperature sensor and a humidity sensor are also added.
  • the control chain may include a computer 16 receiving information from the sensors, and a control relay 18 for the solenoid valve.
  • a first non-return valve is opened towards the outlet 1 and a second non-return valve is closed.
  • the exhaled gases are sent to outlet 1. These are the exhaled gases coming from the upper passages of the patient's respiratory system.
  • the first non-return valve closes and the second non-return valve opens towards outlet 2.
  • the exhaled gases are sent to outlet 2. These are the exhaled gases which come from the alveoli. of the patient's lungs.
  • the gases are sent to a gas analysis system, as described above.
  • the device can operate without a computer.
  • the materials used can be designed to be weak emitters and / or weak absorbers of volatile organic compounds, so as not to disturb the measurements of gas concentrations emitted by the patient. Ease of use, patient comfort and the lightness of the system are improved.
  • the sampling time with the device according to the invention can be between 1 and 15 minutes, better still between 2 and 12 minutes, or even between 2.5 and 10 minutes, or even between 3 and 7 minutes. The sampling time may be less than 5 minutes.
  • the device can be supplied electrically by a 12V power supply 19, or as a variant a power supply via a USB port, or even by a battery, or any other suitable system.
  • the device described above was used to detect ammonia in the breath of patients undergoing dialysis, the sample being taken before and after dialysis. It has been shown that it is possible to define an electronic breath fingerprint and that it is possible to discriminate healthy patients from sick patients.
  • Such an early diagnosis can help slow the progression of the disease, and optimize the treatment of patients, thereby reducing the overall cost of treatment, and the discomfort of multiple dialysis treatments for the patient.
  • the patient's chances of survival are improved, without hampering his quality of life.
  • the device has also been used to study lung cancer, so as to identify those affected, early and non-invasively.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physiology (AREA)
  • Physics & Mathematics (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

Disclosed is a device (1) for sampling gases exhaled by a patient, comprising at least a first and a second sampling channel (S1, S2) intended to alternately or simultaneously receive the gases exhaled by the patient, and a control member (15) for directing the exhaled gases towards the first or second sampling channel (S1, S2), the device comprising a sensor (20) allowing a piece of information to be provided concerning the provenance of the exhaled gases, namely whether the exhaled gases come from the upper respiratory tract of the patient or whether the exhaled gases come from the pulmonary alveoli of the patient.

Description

Description Description
Titre : DISPOSITIF DE PRELEVEMENT DES GAZ EXPIRES PAR UN PATIENT Title: DEVICE FOR SAMPLING EXPIRED GAS BY A PATIENT
Domaine technique Technical area
La présente invention concerne le domaine de l’analyse des gaz expirés par un patient, afin de détecter et/ou de traiter des pathologies dont un ou des biomarqueurs pourraient être présents dans l’haleine du patient. The present invention relates to the field of the analysis of gases exhaled by a patient, in order to detect and / or treat pathologies of which one or more biomarkers could be present in the patient's breath.
Technique antérieure Prior art
Pour permettre l’analyse des gaz expirés issus de l’haleine d’un patient, un prélèvement est nécessaire et peut se faire de plusieurs façons : remplissage d’un sac, absorption des gaz sur des absorbants ou envoi des gaz directement sur le système d’analyse. Dans les deux premiers cas, la détermination de la composition de l’haleine se fait en deux temps : collecte des gaz puis envoi de ceux-ci sur le système d’analyse pour analyse et dans le dernier cas envoi direct sur le système d’analyse. To allow the analysis of the exhaled gases coming from the breath of a patient, a sample is necessary and can be done in several ways: filling a bag, absorbing the gases on absorbents or sending the gases directly to the system. analysis. In the first two cases, the composition of the breath is determined in two stages: collecting the gases then sending them to the analysis system for analysis and in the last case direct sending to the gas system. to analyse.
On connaît par exemple un système disponible dans le commerce de prélèvement d’haleine constitué par un masque qui collecte l’air des voies alvéolaires à l’aide d’absorbants pour une analyse ultérieure. L’air est collecté sur quatre tubes absorbants puis chaque tube est thermo-désorbé pour envoi vers le système d’analyse. Le coût de cet appareil est élevé, de même que les coûts d’analyse. For example, a commercially available breath sampling system is known consisting of a mask which collects air from the alveolar tract using absorbents for subsequent analysis. The air is collected on four absorbent tubes and then each tube is heat-desorbed to send to the analysis system. The cost of this device is high, as are the costs of analysis.
Par ailleurs, les résultats obtenus par le système d’analyse présentent une très grande variabilité des composés présents dans l’haleine pour une même pathologie. Ceci s’explique de plusieurs manières : soient les prélèvements ne font pas la distinction entre les voies supérieures et celui des alvéoles et donc les résultats sont très perturbés, soient ils se font par différentes méthodes, ce qui ne permet pas une comparaison objective de ceux-ci. Le système est en outre limité uniquement à l’absorption des composés gazeux de l’haleine sur des absorbants avec une analyse ultérieure. Le temps d’obtention du résultat est également très long, de l’ordre de plusieurs semaines pour avoir le résultat, et coûteux. Furthermore, the results obtained by the analysis system show a very high variability of the compounds present in the breath for the same pathology. This can be explained in several ways: either the samples do not distinguish between the upper tract and that of the alveoli and therefore the results are very disturbed, or they are done by different methods, which does not allow an objective comparison of those. -this. The system is further limited only to the absorption of breath gaseous compounds on absorbents with subsequent analysis. The time to get the result is also very long, on the order of several weeks to get the result, and expensive.
Ce procédé est ainsi peu adapté à une pratique quotidienne de dépistage sur un grand nombre de patients. Il n’est pas non plus adapté aux autres méthodes d’analyse des gaz, en particulier aux systèmes d’analyse en temps réel. On connaît également d’autres systèmes par les demandes US 2005/177056, WO 2012/059768, et EP 0650051. This process is thus ill-suited to daily screening practice on a large number of patients. It is also not suitable for other gas analysis methods, especially real-time analysis systems. Other systems are also known from applications US 2005/177056, WO 2012/059768, and EP 0650051.
L’article ‘ Development of a C02 triggered alveolar air sampler ’ de Di Francesco et al, IEEE 2007, présente également un système de prélèvement, dans lequel les gaz sont orientés vers une unique voie de prélèvement ou rejetés sans être analysés. Ce système est équipé d’un tube Venturi pour mesurer le débit. En outre, le système présenté fait état d’une mesure de C02 en utilisant une diode laser et un amplificateur à détection synchrone. Ce système est adapté uniquement pour que l’air alvéolaire soit collecté par des sacs dit ‘Tedlar’ . The article "Development of a C02 triggered alveolar air sampler" by Di Francesco et al, IEEE 2007, also presents a sampling system, in which gases are directed to a single sampling path or rejected without being analyzed. This system is equipped with a Venturi tube to measure the flow. In addition, the presented system reports a measurement of CO2 using a laser diode and a synchronous detection amplifier. This system is only suitable for the alveolar air to be collected by so-called "Tedlar" bags.
Il existe donc un besoin pour bénéficier d’un dispositif de prélèvement qui soit à la fois pratique, rapide, efficace, peu coûteux et fiable. There is therefore a need to benefit from a sampling device which is at the same time practical, fast, efficient, inexpensive and reliable.
Résumé de l’invention Summary of the invention
L’invention a ainsi pour objet un dispositif de prélèvement des gaz expirés par un patient, comportant au moins une première et une deuxième voies de prélèvement destinées à recevoir alternativement ou simultanément les gaz expirés par le patient, et un organe de commande pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement, le dispositif comportant un capteur permettant de fournir une information concernant la provenance des gaz expirés, à savoir si les gaz expirés proviennent des voies supérieures du système respiratoire du patient ou si les gaz expirés proviennent des alvéoles des poumons du patient. The subject of the invention is thus a device for sampling the gases exhaled by a patient, comprising at least a first and a second sampling channels intended to alternately or simultaneously receive the gases exhaled by the patient, and a control member for directing the gases. expired gases to the first or second sampling channel, the device comprising a sensor making it possible to provide information concerning the origin of the expired gases, namely whether the expired gases come from the upper passages of the patient's respiratory system or whether the expired gases come from alveoli in the patient's lungs.
L’intérêt du dispositif de prélèvement selon l’invention est de permettre de séparer dans les gaz expirés ceux provenant des voies supérieures du système respiratoire de ceux provenant des alvéoles pulmonaires. En effet la composition des gaz provenant des voies supérieures est fortement influencée par l’air de la pièce où se situe le patient et donc la mesure peut être perturbée par des composés non représentatifs de l’état de santé du patient. Au contraire, les gaz expirés provenant des alvéoles des poumons sont représentatifs des échanges sanguins avec les alvéoles et donc des modifications provoquées par une pathologie donnée. The advantage of the sampling device according to the invention is to make it possible to separate, in the exhaled gases, those originating from the upper passages of the respiratory system from those originating from the pulmonary alveoli. In fact, the composition of the gases coming from the upper passages is strongly influenced by the air in the room where the patient is located and therefore the measurement can be disturbed by compounds which are not representative of the patient's state of health. On the contrary, the gases exhaled from the alveoli of the lungs are representative of the blood exchanges with the alveoli and therefore of the modifications caused by a given pathology.
Il est donc très utile de pouvoir, lors du prélèvement, faire la sélection entre les gaz des voies supérieures et les gaz alvéolaires. Par ailleurs, le dispositif selon l’invention est avantageusement non invasif, dans la mesure où le patient ne doit que souffler dedans. It is therefore very useful to be able, during sampling, to make the selection between the gases of the upper passages and the alveolar gases. Furthermore, the device according to the invention is advantageously non-invasive, insofar as the patient only has to blow into it.
Le dispositif de prélèvement selon l’invention est universel, c’est-à-dire que les gaz prélevés peuvent être analysé par n’importe quel système d’analyse, que ce soit en temps réel ou en différé. Il peut être utilisé pour du diagnostic médical ou pour évaluer l’efficacité d’un traitement médical associé à une pathologie donnée. The sampling device according to the invention is universal, that is to say that the gases sampled can be analyzed by any analysis system, whether in real time or off-line. It can be used for medical diagnosis or to assess the effectiveness of a medical treatment associated with a given pathology.
Il est particulièrement simple à utiliser et peu cher, et est adapté pour être utilisé en temps réel et utilisable par du personnel non spécialisé. Il peut servir dans des campagnes de dépistage de maladies en dehors des hôpitaux, par exemple en médecine du travail, médecine scolaire, dépistage, chez un médecin généraliste. It is particularly simple to use and inexpensive, and is suitable for use in real time and for use by non-specialized personnel. It can be used in disease screening campaigns outside hospitals, for example in occupational medicine, school medicine, screening, with a general practitioner.
Il peut également permettre d’éviter de faire subir au patient des traitements avec des rayons X ou des biopsies, tout en permettant un diagnostic précoce pour un traitement plus efficace des pathologies visées. It can also make it possible to avoid subjecting the patient to treatments with X-rays or biopsies, while allowing an early diagnosis for a more effective treatment of the pathologies concerned.
Enfin, du fait d’un diagnostic précoce rendu possible, le taux de survie des patients peut être amélioré. Finally, due to an early diagnosis made possible, the survival rate of patients can be improved.
Le dispositif de prélèvement selon l’invention est à la fois simple, peu encombrant et peu consommateur d’énergie, par exemple ayant une consommation inférieure à 35 mW, étant léger et portable. The sampling device according to the invention is at the same time simple, space-saving and low-energy consuming, for example having a consumption of less than 35 mW, being light and portable.
Les gaz expirés par un patient peuvent comporter des biomarqueurs d’une ou de maladies dont peut souffrir ledit patient. La détection et l’analyse de ces biomarqueurs peut ainsi permettre un diagnostic de la maladie, notamment un diagnostic précoce, ainsi qu’un suivi de l’évolution de la maladie, et notamment de l’efficacité d’un traitement. L’analyse peut par exemple permettre une discrimination entre patient sain et patient malade, ce qui permet l’élaboration d’un diagnostic. The gases exhaled by a patient may contain biomarkers of one or more diseases from which that patient may suffer. The detection and analysis of these biomarkers can thus allow a diagnosis of the disease, in particular an early diagnosis, as well as a follow-up of the course of the disease, and in particular of the effectiveness of a treatment. The analysis can for example allow a discrimination between healthy patient and sick patient, which allows the development of a diagnosis.
La maladie peut être choisie dans la liste suivante, qui n’est pas limitative : cancer, notamment cancer du poumon, cancer du foie, cancer du sein, insuffisance rénale, maladie neurodégénérative, notamment maladie de Parkinson, maladie d’Alzheimer, diabète, maladie du foie, maladie de l’intestin, cancer colorectal, haliotis intra orale, COVID- 19. The disease can be chosen from the following list, which is not exhaustive: cancer, in particular lung cancer, liver cancer, breast cancer, renal failure, neurodegenerative disease, in particular Parkinson's disease, Alzheimer's disease, diabetes, liver disease, bowel disease, colorectal cancer, intraoral haliotis, COVID-19.
En fonction de la maladie, on peut utiliser tous les gaz expirés, ou bien seulement les gaz expirés provenant des alvéoles des poumons. Les biomarqueurs à identifier peuvent être choisis, selon la pathologie visée, dans la liste suivante, qui n’est pas limitative : isopropanol, méthanol, isoprène, acétone, méthyl mercaptan, ammoniac, diméthyle sulfure, méthane, formaldéhyde, acétaldéhyde, amines, alcanes, toluène On va donner dans le tableau 1 qui suit des exemples de composés identifiés comme biomarqueur potentiel pour certaines pathologies. Depending on the disease, all exhaled gases may be used, or only exhaled gases from the alveoli of the lungs may be used. The biomarkers to be identified can be chosen, according to the pathology targeted, from the following list, which is not exhaustive: isopropanol, methanol, isoprene, acetone, methyl mercaptan, ammonia, dimethyl sulfide, methane, formaldehyde, acetaldehyde, amines, alkanes , toluene Examples of compounds identified as potential biomarkers for certain pathologies will be given in Table 1 below.
[Tableau 1]
Figure imgf000006_0001
[Table 1]
Figure imgf000006_0001
Tableau 1 Exposé de l’invention Table 1 Disclosure of the invention
L’organe de commande peut être configuré pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement en fonction de l’information reçue du capteur. The controller can be configured to direct exhaled gases to the first or second sample channel based on information received from the sensor.
Dans un mode de réalisation, l’organe de commande peut comporter une ou plusieurs électrovannes pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement. In one embodiment, the control member may include one or more solenoid valves to direct the exhaled gases to the first or the second sampling path.
Dans un mode de réalisation, l’organe de commande peut comporter une unique électrovanne et des clapets anti-retour pour séparer les flux de gaz expirés. Il peut ainsi comporter un premier clapet anti-retour commandant l’accès à la première voie de prélèvement. Il peut également comporter une deuxième clapet anti-retour commandant l’accès à la deuxième voie de prélèvement. In one embodiment, the control member may include a single solenoid valve and non-return valves to separate the exhaled gas streams. It can thus include a first non-return valve controlling access to the first sampling. It may also include a second non-return valve controlling access to the second sampling channel.
En variante, l’organe de commande peut notamment comporter deux électrovannes comandant chacune l’accès à une voie de prélèvement. Il peut ainsi comporter une première électrovanne commandant l’accès à la première voie de prélèvement. Il peut également comporter une deuxième électrovanne commandant l’accès à la deuxième voie de prélèvement. As a variant, the control unit may in particular include two solenoid valves each controlling access to a sampling channel. It can thus include a first solenoid valve controlling access to the first sampling channel. It may also include a second solenoid valve controlling access to the second sampling channel.
Les gaz expirés sont reçus, avant d’être orientés vers la ou les voies de prélèvement, dans un tube de réception. Le tube de réception peut être un tube droit, dépourvu d’effet Venturi. Il n’est pas nécessaire dans l’invention de mesurer le débit des gaz expirés. Le tube de réception peut être situé entre un ou des filtres antibactériens et la ou les électrovannes ou le ou les clapets anti-retours. The exhaled gases are received, before being directed to the sampling channel (s), in a reception tube. The receiving tube can be a straight tube, devoid of the Venturi effect. It is not necessary in the invention to measure the flow rate of exhaled gases. The receiving tube may be located between one or more antibacterial filters and the solenoid valve (s) or the non-return valve (s).
L’information reçue du capteur peut permettre de déterminer la phase en cours du cycle respiratoire du patient. En fonction de la phase en cours du cycle respiratoire du patient, les gaz expirés proviennent des voies supérieures du système respiratoire du patient ou les gaz expirés proviennent des alvéoles des poumons du patient, et la composition des gaz expirés n’est pas la même. The information received from the sensor can be used to determine the current phase of the patient's respiratory cycle. Depending on the current phase of the patient's respiratory cycle, the exhaled gases originate from the upper airways of the patient's respiratory system or the exhaled gases originate from the alveoli in the patient's lungs, and the composition of the exhaled gases is not the same.
Le capteur peut comporter un capteur de pression. Le cycle de respiration comporte trois phases distinctes, à savoir (i) une première phase d’expiration durant laquelle la pression augmente lorsque le patient commence l’expiration, durant laquelle ce sont les gaz des voies supérieures qui sont expulsés, (ii) une deuxième phase durant laquelle la pression se stabilise, il s’agit des gaz alvéolaires qui sont expulsés, et enfin (iii) une troisième phase de décroissance rapide de la pression, lorsque le patient inspire. The sensor may include a pressure sensor. The breathing cycle has three distinct phases, namely (i) a first phase of expiration during which the pressure increases when the patient begins to expire, during which it is the gases of the upper passages which are expelled, (ii) a second phase during which the pressure stabilizes, it is about the alveolar gases which are expelled, and finally (iii) a third phase of rapid decrease in pressure, when the patient inhales.
Ainsi, lorsque les gaz expirés proviennent des voies supérieures du système respiratoire du patient, alors la pression augmente. D’autre part, lorsque les gaz expirés proviennent des alvéoles des poumons du patient, alors la pression se stabilise. On peut alors parler d’air alvéolaire. Ensuite, la pression diminue quand le patient inspire Avant l’expiration du patient, l’air est au repos, donc le capteur de pression mesure la pression atmosphérique. Les variations de pression permettent de déterminer la phase en cours du cycle respiratoire du patient. So when the exhaled gases come from the upper passages of the patient's respiratory system, then the pressure increases. On the other hand, when the exhaled gas comes from the alveoli in the patient's lungs, then the pressure stabilizes. We can then speak of alveolar air. Then the pressure decreases when the patient inhales Before the patient exhales, the air is at rest, so the pressure sensor measures atmospheric pressure. The variations in pressure make it possible to determine the current phase of the patient's respiratory cycle.
En variante, le capteur peut être configuré pour détecter le taux de dioxyde de carbone dans les gaz expirés. En fonction du taux en dioxyde de carbone, on peut déterminer si les gaz expirés sont d’origine alvéolaire ou des voies supérieures. Dans le cycle de respiration, on retrouve les trois phases distinctes, à savoir (i) la première phase d’expiration durant laquelle la concentration de dioxyde de carbone augmente lorsque le patient commence l’expiration, durant laquelle ce sont les gaz des voies supérieures qui sont expulsés, (ii) la deuxième phase durant laquelle le taux de dioxyde de carbone se stabilise, il s’agit des gaz alvéolaires qui sont expulsés, et enfin (iii) la troisième phase de décroissance rapide du taux de dioxyde de carbone, lorsque le patient inspire. Ainsi, en fonction du taux de C02, on peut déterminer vers quelle voie de prélèvement orienter les gaz expirés. Alternatively, the sensor can be configured to detect the level of carbon dioxide in the exhaled gases. Depending on the carbon dioxide content, it is possible to determine whether the exhaled gases are of alveolar or upper tract origin. In the breathing cycle, we find the three distinct phases, namely (i) the first phase of exhalation during which the concentration of carbon dioxide increases when the patient begins to exhale, during which these are the gases of the upper passages which are expelled, (ii) the second phase during which the level of carbon dioxide stabilizes, these are the alveolar gases which are expelled, and finally (iii) the third phase of rapid decrease in the rate of carbon dioxide, when the patient inhales. Thus, depending on the level of C02, it is possible to determine which sampling path to direct the exhaled gases to.
Le dispositif de prélèvement peut également comporter un capteur de température et/ou un capteur d’hygrométrie. Les capteurs de C02, de pression, de température et d’hygrométrie peuvent être visualisés par les médecins pour contrôler les paramètres physiologiques du patient pour voir si tout se passe bien lors du prélèvement. Une telle surveillance peut par exemple permettre d’identifier une alerte d’hypo ou d’hyper ventilation ou autre. The sampling device can also include a temperature sensor and / or a humidity sensor. C02, pressure, temperature and humidity sensors can be viewed by physicians to monitor the patient's physiological parameters to see if everything is going well during the sample. Such monitoring can, for example, make it possible to identify a hypo or hyper ventilation alert or the like.
Le ou les capteurs du dispositif de prélèvement peuvent être dépourvus de laser.The sensor (s) of the sampling device may not have a laser.
Le dispositif de prélèvement peut comporter un système d’analyse des gaz, lequel peut être intégré au dispositif ou extérieur à celui-ci. Le dispositif de prélèvement peut être configuré pour pouvoir être relié à un système d’analyse des gaz extérieur au dispositif. The sampling device may include a gas analysis system, which may be integrated into the device or external to it. The sampling device can be configured to be able to be connected to a gas analysis system external to the device.
Dans un mode de réalisation, le dispositif de prélèvement comporte un système d’analyse des gaz expirés. Ainsi, les gaz expirés peuvent être analysés en temps réel, c’est- à-dire au fur et à mesure du prélèvement. In one embodiment, the sampling device includes an expired gas analysis system. Thus, the exhaled gases can be analyzed in real time, that is to say as the sample is taken.
Dans une variante de réalisation, les gaz prélevés peuvent être stockés dans un dispositif de stockage, et être analysés ultérieurement. A cet effet, le dispositif de prélèvement peut comporter un dispositif de stockage, par exemple un ou des sacs en polyvinyle fluoride (PVF) dit ‘Tedlar’. Le dispositif de stockage peut en variante ou additionnellement comporter une surface absorbante pour les gaz expirés. In an alternative embodiment, the gases sampled can be stored in a storage device, and be analyzed subsequently. For this purpose, the sampling device may include a storage device, for example one or more bags in polyvinyl fluoride (PVF) called "Tedlar". The storage device may alternatively or additionally comprise an absorbent surface for the exhaled gases.
Le système d’analyse des gaz expirés peut permettre de détecter des biomarqueurs présents dans les gaz expirés. Le système d’analyse peut être quelconque. En effet, le dispositif de prélèvement selon l’invention peut être adapté à tous les systèmes d’analyse possibles. The exhaled gas analysis system can detect biomarkers present in exhaled gases. The analysis system can be any. Indeed, the sampling device according to the invention can be adapted to all possible analysis systems.
L’analyse peut être effectuée par l’un des systèmes d’analyse de la liste suivante, qui n’est pas limitative : GC-MS (chromatographie en phase gazeuse couplée à la spectrométrie de masse), PTR-MS (réaction de transfert de proton avant analyse par spectrométrie de masse), SIFT-MS (spectrométrie de masse par flux d’ions sélectionnés), ou tout autre analyseur de composés organiques volatils. L’analyse peut ainsi permettre de définir une empreinte chimique. The analysis can be carried out by one of the analysis systems from the following list, which is not exhaustive: GC-MS (gas chromatography coupled with mass spectrometry), PTR-MS (proton transfer reaction before analysis by mass spectrometry), SIFT-MS (mass spectrometry by selected ion flow), or any other analyzer of volatile organic compounds. The analysis can thus make it possible to define a chemical fingerprint.
En variante, le système d’analyse peut permettre de définir une empreinte électronique. Il peut à cet effet comporter une matrice de capteurs à réactivité croisée, aussi appelée ‘nez électronique’ . Alternatively, the analysis system may allow an electronic fingerprint to be defined. For this purpose, it may include a matrix of cross-reactive sensors, also called an "electronic nose".
L’analyse peut être effectuée en temps réel, dès que le prélèvement a été effectué, ou en différé, c’est-à-dire que les gaz expirés sont piégés et/ou stockés pendant un certain temps avant d’être analysés. The analysis can be carried out in real time, as soon as the sample has been taken, or off-line, that is to say that the exhaled gases are trapped and / or stored for a certain time before being analyzed.
Les résultats de l’analyse peuvent permettre de discriminer les patients sains des patients malades. En outre, ils peuvent permettre de déterminer la maladie dont souffre un patient. Enfin, ils peuvent permettre de mesurer l’évolution de la maladie, afin par exemple de rendre compte de l’efficacité d’un traitement. The results of the analysis may be able to discriminate healthy patients from sick patients. In addition, they can be used to determine the disease from which a patient is suffering. Finally, they can be used to measure the course of the disease, for example in order to report on the effectiveness of a treatment.
Le dispositif de prélèvement peut comporter un masque à placer sur le visage du patient. Le masque peut être configuré pour permettre le prélèvement des gaz expiré par la bouche, le nez, ou à la fois la bouche et le nez. Le masque peut être réutilisable. The sampling device may include a mask to be placed on the patient's face. The mask can be configured to allow collection of exhaled gases through the mouth, nose, or both mouth and nose. The mask can be reusable.
En variante, le dispositif de prélèvement peut comporter un embout buccal destiné à permettre le prélèvement des gaz expirés par la bouche uniquement. L’embout buccal peut être à usage unique. As a variant, the sampling device may include a mouthpiece intended to allow the sampling of the gases exhaled through the mouth only. The mouthpiece can be disposable.
Le patient peut être invité à souffler dans le dispositif de prélèvement, notamment par le masque ou par l’embout buccal. The patient may be invited to blow into the sampling device, in particular through the mask or through the mouthpiece.
Le dispositif de prélèvement peut comporter un filtre antibactérien permettant de filtrer les gaz expirés. Le filtre antibactérien peut être disposé à l’entrée du dispositif de prélèvement, notamment en amont du capteur. Le filtre antibactérien permet d’éviter toute contamination bactérienne du dispositif de prélèvement. The sampling device may include an antibacterial filter making it possible to filter the exhaled gases. The antibacterial filter can be placed at the inlet of the sampling device, in particular upstream of the sensor. The antibacterial filter prevents any bacterial contamination of the sampling device.
Le dispositif de prélèvement peut comporter un système de purification permettant de purifier les gaz inspirés. Il peut par exemple être disposé à l’entrée du masque, de sorte que l’air entrant, inspiré par le patient, est dépourvu de composés organiques volatils ou autres contaminants. Le patient reçoit ainsi de l’air épuré et la fiabilité de l’analyse peut en être améliorée. Brève description des dessins The sampling device may include a purification system making it possible to purify the inspired gases. It can, for example, be placed at the entrance to the mask, so that the incoming air, inspired by the patient, is devoid of volatile organic compounds or other contaminants. The patient thus receives clean air and the reliability of the analysis can be improved. Brief description of the drawings
[Fig 1] La figure 1 est une vue schématique d’un dispositif de prélèvement conforme à l’invention. [Fig 1] Figure 1 is a schematic view of a sampling device according to the invention.
[Fig 2] La figure 2 est un diagramme représentant l’évolution de la concentration en dioxyde de carbone dans les gaz expirés, en fonction du temps exprimé en secondes. [Fig 2] Figure 2 is a diagram showing the change in the concentration of carbon dioxide in the exhaled gases, as a function of time expressed in seconds.
[Fig 3] La figure 3 est une vue schématique d’une variante de réalisation de dispositif de prélèvement. [Fig 3] Figure 3 is a schematic view of an alternative embodiment of the sampling device.
[Fig 4] La figure 4 est une vue schématique d’une variante de réalisation de dispositif de prélèvement. [Fig 4] Figure 4 is a schematic view of an alternative embodiment of the sampling device.
Description détaillée detailed description
On a illustré à la figure 1 un dispositif de prélèvement 1 des gaz expirés par un patient, qui comporte tout d’abord un masque 10 à placer sur le visage du patient, qui a dans l’exemple décrit la forme d’un embout buccal destiné à permettre le prélèvement des gaz expirés par la bouche uniquement. Le patient peut être invité à souffler dans le dispositif de prélèvement par l’embout buccal. Le dispositif est ainsi non invasif. L’embout buccal est à renouveler à chaque patient. FIG. 1 shows a device 1 for sampling the gases exhaled by a patient, which firstly comprises a mask 10 to be placed on the patient's face, which in the example described has the shape of a mouthpiece intended to allow the sampling of gases exhaled through the mouth only. The patient may be prompted to blow into the collection device through the mouthpiece. The device is thus non-invasive. The mouthpiece must be renewed for each patient.
Le dispositif de prélèvement comporte en outre un filtre antibactérien 12 permettant de filtrer les gaz expirés. Le filtre antibactérien 12 est ici disposé à l’entrée du dispositif de prélèvement, juste en aval de l’embout buccal. The sampling device further comprises an antibacterial filter 12 making it possible to filter the exhaled gases. The antibacterial filter 12 is here disposed at the inlet of the sampling device, just downstream of the mouthpiece.
Le dispositif comporte ensuite une première SI et une deuxième S2 voies de prélèvement. On nomme ces voies SI et S2. Elles sont destinées à recevoir alternativement ou simultanément les gaz expirés par le patient. The device then comprises a first SI and a second S2 sampling channels. These channels are called SI and S2. They are intended to alternately or simultaneously receive the gases exhaled by the patient.
Le dispositif de prélèvement comporte en outre organe de commande 15 pour orienter les gaz expirés vers la première S 1 ou la deuxième S2 voie de prélèvement. The sampling device further comprises a control member 15 for directing the exhaled gases towards the first S 1 or the second S2 sampling channel.
Par ailleurs, le dispositif comporte un capteur 20 permettant de fournir une information concernant la provenance des gaz expirés, à savoir si les gaz expirés proviennent des voies supérieures du système respiratoire du patient ou si les gaz expirés proviennent des alvéoles des poumons du patient. L’organe de commande 15 est configuré pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement en fonction de l’information reçue du capteur. Dans l’exemple décrit, il s’agit d’un capteur 20 configuré pour détecter le taux de dioxyde de carbone dans les gaz expirés. En fonction du taux en dioxyde de carbone, on peut déterminer si les gaz expirés sont d’origine alvéolaire ou des voies supérieures. Furthermore, the device comprises a sensor 20 making it possible to provide information concerning the origin of the expired gases, namely whether the expired gases originate from the upper passages of the patient's respiratory system or whether the expired gases originate from the alveoli of the patient's lungs. The control member 15 is configured to direct the exhaled gases towards the first or the second sampling channel according to the information received from the sensor. In the example described, it is a sensor 20 configured to detect the level of carbon dioxide in the exhaled gases. Depending on the level of carbon dioxide, it can be determined whether the exhaled gases are of alveolar or upper tract origin.
Dans le cycle de respiration illustré à la figure 2, on retrouve trois phases distinctes, à savoir (i) la première phase AB d’expiration durant laquelle la concentration de dioxyde de carbone augmente lorsque le patient commence l’expiration, durant laquelle ce sont les gaz des voies supérieures qui sont expulsés, (ii) la deuxième phase BC durant laquelle le taux de dioxyde de carbone se stabilise, il s’agit des gaz alvéolaires qui sont expulsés, et enfin (iii) la troisième phase CD de décroissance rapide du taux de dioxyde de carbone, lorsque le patient inspire. Ainsi, en fonction du taux de C02, on peut déterminer vers quelle voie de prélèvement orienter les gaz expirés. In the breathing cycle illustrated in Figure 2, there are three distinct phases, namely (i) the first phase AB of expiration during which the concentration of carbon dioxide increases when the patient begins expiration, during which they are the gases of the upper passages which are expelled, (ii) the second phase BC during which the level of carbon dioxide stabilizes, these are the alveolar gases which are expelled, and finally (iii) the third phase CD of rapid decay the level of carbon dioxide when the patient inhales. Thus, depending on the level of C02, it is possible to determine which sampling path to direct the exhaled gases to.
Le dispositif pourrait comporter également un capteur de pression. En effet, les variations de pression permettent également de déterminer la phase en cours du cycle respiratoire du patient. Le dispositif de prélèvement pourrait en variante encore comporter un capteur de température et/ou un capteur d’hygrométrie, comme on le verra plus loin. The device could also include a pressure sensor. Indeed, the pressure variations also make it possible to determine the current phase of the patient's respiratory cycle. As a further variant, the sampling device could include a temperature sensor and / or a hygrometry sensor, as will be seen below.
L’organe de commande 15 comporte deux électrovannes comandant chacune l’accès à une voie de prélèvement, à savoir une première électrovanne EV1 commandant l’accès à la première voie de prélèvement et une deuxième électrovanne EV2 commandant l’accès à la deuxième voie de prélèvement. The control member 15 comprises two solenoid valves each controlling access to a sampling channel, namely a first solenoid valve EV1 controlling access to the first sampling channel and a second solenoid valve EV2 controlling access to the second sampling channel. sampling.
Le dispositif de prélèvement 1 est relié en aval à un système d’analyse des gaz 30, lequel est dans cet exemple extérieur à celui-ci. Le système d’analyse 30 des gaz expirés est configuré pour permettre de détecter des biomarqueurs présents dans les gaz expirés. The sampling device 1 is connected downstream to a gas analysis system 30, which in this example is external to it. The exhaled gas analysis system 30 is configured to detect biomarkers present in the exhaled gases.
Les gaz prélevés sont analysés en temps réel, dès que le prélèvement a été effectué, ou en différé, étant alors stockés dans un dispositif de stockage 35, pour être analysés ultérieurement. A cet effet, le dispositif de prélèvement comporte un dispositif de stockage, par exemple un ou des sacs en polyvinyle fluoride (PVL) dit ‘Tedlar’. Le dispositif de stockage peut en variante ou additionnellement comporter une surface absorbante pour les gaz expirés. The gases sampled are analyzed in real time, as soon as the sample has been taken, or later, being then stored in a storage device 35, to be analyzed subsequently. For this purpose, the sampling device comprises a storage device, for example one or more bags in polyvinyl fluoride (PVL) called "Tedlar". The storage device may alternatively or additionally comprise an absorbent surface for the exhaled gases.
Dans l’exemple de réalisation illustré à la figure 1, le capteur de pression permet de réaliser une base de temps permettant de commander les électrovannes au moyen d’une chaîne de commande comportant un ordinateur 16 recevant les informations du capteur, une carte de calcul 17, et un relais de commande 18 des électrovannes. Dans une première phase, la première électrovanne EV 1 est ouverte et la deuxième électrovanne EV2 est fermée. Dans cette première phase, les gaz expirés sont envoyés vers la sortie 1. Il s’agit des gaz expirés provenant des voies supérieures du système respiratoire du patient. In the embodiment illustrated in FIG. 1, the pressure sensor makes it possible to produce a time base making it possible to control the solenoid valves by means of a control chain comprising a computer 16 receiving information from the sensor, a calculation card 17, and a control relay 18 for the solenoid valves. In a first phase, the first solenoid valve EV 1 is open and the second solenoid valve EV2 is closed. In this first phase, the exhaled gases are sent to outlet 1. These are the exhaled gases coming from the upper passages of the patient's respiratory system.
A un instant tl, la première électrovanne EV1 se ferme et la deuxième électrovanne EV2 s’ouvre. Ainsi, les gaz expirés sont envoyés vers la sortie 2. Il s’agit des gaz expirés qui proviennent des alvéoles des poumons du patient. At a time tl, the first solenoid valve EV1 closes and the second solenoid valve EV2 opens. Thus, the exhaled gases are sent to outlet 2. These are the exhaled gases which come from the alveoli in the patient's lungs.
Après les sorties 1 ou 2, les gaz sont envoyés vers un système d’analyse des gaz.After exits 1 or 2, the gases are sent to a gas analysis system.
Le mode de réalisation illustré à la figure 3 diffère du précédent par le fait que les gaz expirés sont prélevés au moyen d’un masque à placer sur le visage du patient, qui est configuré pour permettre le prélèvement des gaz expiré à la fois par la bouche et le nez. The embodiment illustrated in Figure 3 differs from the previous one in that the exhaled gases are withdrawn by means of a mask to be placed on the patient's face, which is configured to allow the withdrawal of the exhaled gases at a time through the patient's face. mouth and nose.
En outre le capteur de pression est associé à un capteur de dioxyde de carbone, permettant de commander les électrovannes EV1 et EV2. Un capteur de température et un capteur d’hygrométrie sont ajoutés. In addition, the pressure sensor is associated with a carbon dioxide sensor, making it possible to control the solenoid valves EV1 and EV2. A temperature sensor and a hygrometry sensor are added.
Dans l’exemple de réalisation illustré à la figure 4, le capteur de pression est associé à un capteur de dioxyde de carbone permettant de commander une unique électrovanne et des clapets anti-retours pour séparer les flux de gaz expirés. Un capteur de température et un capteur d’hygrométrie sont également ajoutés. La chaîne de commande peut comporter un ordinateur 16 recevant les informations des capteurs, et un relais de commande 18 de l’électrovanne. Dans une première phase, un premier clapet anti-retour est ouvert vers la sortie 1 et un deuxième clapet anti-retour est fermé. Dans cette première phase, les gaz expirés sont envoyés vers la sortie 1. Il s’agit des gaz expirés provenant des voies supérieures du système respiratoire du patient. In the exemplary embodiment illustrated in Figure 4, the pressure sensor is associated with a carbon dioxide sensor for controlling a single solenoid valve and non-return valves to separate the exhaled gas streams. A temperature sensor and a humidity sensor are also added. The control chain may include a computer 16 receiving information from the sensors, and a control relay 18 for the solenoid valve. In a first phase, a first non-return valve is opened towards the outlet 1 and a second non-return valve is closed. In this first phase, the exhaled gases are sent to outlet 1. These are the exhaled gases coming from the upper passages of the patient's respiratory system.
A un instant tl, le premier clapet anti-retour se ferme et le deuxième clapet anti retour s’ouvre vers la sortie 2. Ainsi, les gaz expirés sont envoyés vers la sortie 2. Il s’agit des gaz expirés qui proviennent des alvéoles des poumons du patient. At an instant tl, the first non-return valve closes and the second non-return valve opens towards outlet 2. Thus, the exhaled gases are sent to outlet 2. These are the exhaled gases which come from the alveoli. of the patient's lungs.
Après les sorties 1 ou 2, les gaz sont envoyés vers un système d’analyse des gaz, comme décrit précédemment. After exits 1 or 2, the gases are sent to a gas analysis system, as described above.
En variante encore, le dispositif peut fonctionner en étant dépourvu d’ordinateur.As a further variant, the device can operate without a computer.
Les matériaux utilisés peuvent être étudiés pour être de faibles émetteurs et/ou faibles absorbeurs de composés organiques volatils, afin de ne pas perturber les mesures de concentrations de gaz émis par le patient. La facilité d’emploi, le confort du patient, la légèreté du système sont améliorés. La durée de prélèvement avec le dispositif selon l’invention peut être compris entre 1 et 15 minutes, mieux entre 2 et 12 minutes, voire entre 2,5 et 10 minutes, voire encore entre 3 et 7 minutes. La durée de prélèvement peut être inférieure à 5 minutes. The materials used can be designed to be weak emitters and / or weak absorbers of volatile organic compounds, so as not to disturb the measurements of gas concentrations emitted by the patient. Ease of use, patient comfort and the lightness of the system are improved. The sampling time with the device according to the invention can be between 1 and 15 minutes, better still between 2 and 12 minutes, or even between 2.5 and 10 minutes, or even between 3 and 7 minutes. The sampling time may be less than 5 minutes.
Le dispositif peut être alimenté électriquement par une alimentation 19 en 12V, ou en variante une alimentation par port USB, ou encore par une batterie, ou tout autre système adapté. The device can be supplied electrically by a 12V power supply 19, or as a variant a power supply via a USB port, or even by a battery, or any other suitable system.
Exemples Examples
Le dispositif décrit ci-dessus a été utilisé pour détecter l’ammoniac dans l’haleine de patients soumis à une dialyse, le prélèvement ayant été effectué avant et après dialyse. Il a été démontré qu’il est possible de définir une empreinte électronique de l’haleine et qu’il est possible de discriminer les patients sains des patients malades. The device described above was used to detect ammonia in the breath of patients undergoing dialysis, the sample being taken before and after dialysis. It has been shown that it is possible to define an electronic breath fingerprint and that it is possible to discriminate healthy patients from sick patients.
Un tel diagnostic précoce peut permettre de ralentir l’évolution de la maladie, et d’optimiser le traitement des patients, réduisant ainsi le coût global du traitement, et l’inconfort des multiples dialyses pour le patient. En outre, les chances de survie du patient sont améliorées, sans entraver sa qualité de vie. Such an early diagnosis can help slow the progression of the disease, and optimize the treatment of patients, thereby reducing the overall cost of treatment, and the discomfort of multiple dialysis treatments for the patient. In addition, the patient's chances of survival are improved, without hampering his quality of life.
Le dispositif a également été utilisé pour étudier le cancer du poumon, de façon à identifier les personnes atteintes, de manière précoce et non invasive. The device has also been used to study lung cancer, so as to identify those affected, early and non-invasively.

Claims

Revendications Claims
1. Dispositif de prélèvement (1) des gaz expirés par un patient, comportant au moins une première et une deuxième voies de prélèvement (SI, S2) destinées à recevoir alternativement ou simultanément les gaz expirés par le patient, et un organe de commande (15) pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement (SI, S2), le dispositif comportant un capteur (20) permettant de fournir une information concernant la provenance des gaz expirés, à savoir si les gaz expirés proviennent des voies supérieures du système respiratoire du patient ou si les gaz expirés proviennent des alvéoles des poumons du patient. 1. Device (1) for sampling the gases exhaled by a patient, comprising at least a first and a second sampling path (SI, S2) intended to alternately or simultaneously receive the gases exhaled by the patient, and a control member ( 15) to direct the expired gases towards the first or the second sampling channel (SI, S2), the device comprising a sensor (20) making it possible to provide information concerning the origin of the expired gases, namely whether the expired gases come from the upper passages of the patient's respiratory system or if the exhaled gas originates from the alveoli in the patient's lungs.
2. Dispositif de prélèvement selon la revendication précédente, l’organe de commande (15) étant configuré pour orienter les gaz expirés vers la première ou la deuxième voie de prélèvement (SI, S2) en fonction de l’information reçue du capteur (20). 2. Sampling device according to the preceding claim, the control member (15) being configured to direct the expired gases towards the first or the second sampling channel (SI, S2) according to the information received from the sensor (20). ).
3. Dispositif de prélèvement selon la revendication précédente, dans lequel l’information reçue du capteur (20 permet de déterminer la phase en cours du cycle respiratoire du patient, en fonction de la composition des gaz expirés, notamment de l’hygrométrie ou du taux de dioxyde de carbone dans les gaz expirés, ou de leur pression ou de leur température. 3. Sampling device according to the preceding claim, wherein the information received from the sensor (20 makes it possible to determine the current phase of the patient's respiratory cycle, as a function of the composition of the exhaled gases, in particular the humidity or the rate. of carbon dioxide in the exhaled gases, or their pressure or temperature.
4. Dispositif de prélèvement selon la revendication précédente, le capteur (20) comportant un capteur de pression. 4. Sampling device according to the preceding claim, the sensor (20) comprising a pressure sensor.
5. Dispositif de prélèvement selon l’une des revendications 3 ou 4, le capteur (20) étant configuré pour détecter le taux de dioxyde de carbone dans les gaz expirés. 5. Sampling device according to one of claims 3 or 4, the sensor (20) being configured to detect the level of carbon dioxide in the exhaled gases.
6. Dispositif de prélèvement selon l’une des revendications 3 ou 4 ou 5, le capteur (20) comportant un capteur de température et/ou un capteur d’hygrométrie. 6. Sampling device according to one of claims 3 or 4 or 5, the sensor (20) comprising a temperature sensor and / or a humidity sensor.
7. Dispositif de prélèvement selon l’une quelconque des revendications précédentes, comportant un système d’analyse (30) des gaz intégré au dispositif. 7. Sampling device according to any one of the preceding claims, comprising a gas analysis system (30) integrated into the device.
8. Dispositif de prélèvement selon l’une quelconque des revendications 1 à 6, configuré pour pouvoir être relié à un système d’analyse (30) des gaz extérieur au dispositif. 8. Sampling device according to any one of claims 1 to 6, configured to be able to be connected to an analysis system (30) of gases external to the device.
9. Dispositif de prélèvement selon l’une quelconque des revendications 7 ou 8, le système d’analyse (30) des gaz expirés permettant de détecter des biomarqueurs présents dans les gaz expirés, par détection d’une empreinte chimique ou électronique. 9. Sampling device according to any one of claims 7 or 8, the analysis system (30) of the expired gases making it possible to detect biomarkers present in the expired gases, by detecting a chemical or electronic fingerprint.
10. Dispositif de prélèvement selon l’une quelconque des revendications précédentes, comportant un masque (10) à placer sur le visage du patient. 10. Sampling device according to any one of the preceding claims, comprising a mask (10) to be placed on the patient's face.
11. Dispositif de prélèvement selon l’une quelconque des revendications précédentes, comportant un embout buccal (10) destiné à permettre le prélèvement des gaz expirés par la bouche uniquement. 11. Sampling device according to any one of the preceding claims, comprising a mouthpiece (10) intended to allow the sampling of gases exhaled through the mouth only.
12. Dispositif de prélèvement selon l’une quelconque des revendications précédentes, comportant un filtre antibactérien (12) permettant de filtrer les gaz expirés. 12. Sampling device according to any one of the preceding claims, comprising an antibacterial filter (12) for filtering the exhaled gases.
13. Dispositif de prélèvement selon l’une quelconque des revendications précédentes, comportant un système de purification permettant de purifier les gaz inspirés. 13. Sampling device according to any one of the preceding claims, comprising a purification system for purifying the inspired gases.
PCT/EP2021/065849 2020-06-12 2021-06-11 Device for sampling gases exhaled by a patient WO2021250261A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR2006141A FR3111266A1 (en) 2020-06-12 2020-06-12 Device for sampling gases exhaled by a patient
FRFR2006141 2020-06-12

Publications (1)

Publication Number Publication Date
WO2021250261A1 true WO2021250261A1 (en) 2021-12-16

Family

ID=73401582

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2021/065849 WO2021250261A1 (en) 2020-06-12 2021-06-11 Device for sampling gases exhaled by a patient

Country Status (2)

Country Link
FR (1) FR3111266A1 (en)
WO (1) WO2021250261A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0650051A2 (en) 1993-10-25 1995-04-26 Kyoto Dai-ichi Kagaku Co., Ltd. Expiration collecting method and automatic expiration collector
US20050177056A1 (en) 2002-03-03 2005-08-11 Oridion Breathid Ltd Breath collection system
WO2012059768A1 (en) 2010-11-05 2012-05-10 The University Of Manchester Apparatus and methods for breath sampling
US20150065901A1 (en) * 2013-08-30 2015-03-05 Capnia, Inc. Universal breath sampling and analysis device

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0650051A2 (en) 1993-10-25 1995-04-26 Kyoto Dai-ichi Kagaku Co., Ltd. Expiration collecting method and automatic expiration collector
US20050177056A1 (en) 2002-03-03 2005-08-11 Oridion Breathid Ltd Breath collection system
WO2012059768A1 (en) 2010-11-05 2012-05-10 The University Of Manchester Apparatus and methods for breath sampling
US20150065901A1 (en) * 2013-08-30 2015-03-05 Capnia, Inc. Universal breath sampling and analysis device

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DE SILVA GEETHANGA ET AL: "Microcontroller-based real-time alveolar breath sampling system", 2013 IEEE 56TH INTERNATIONAL MIDWEST SYMPOSIUM ON CIRCUITS AND SYSTEMS (MWSCAS), IEEE, 4 August 2013 (2013-08-04), pages 975 - 978, XP032525782, ISSN: 1548-3746, ISBN: 978-1-4799-4134-6, [retrieved on 20131124], DOI: 10.1109/MWSCAS.2013.6674814 *
DI FRANCESCO ET AL.: "Development of a C02 triggered alveolar air sampler", 2007, IEEE

Also Published As

Publication number Publication date
FR3111266A1 (en) 2021-12-17

Similar Documents

Publication Publication Date Title
US20230125894A1 (en) System and Method for Drug Detection in Exhaled Breath
EP1976431B1 (en) Analysis of gases
AU724417B2 (en) Condensate colorimetric nitrogen oxide analyzer
JPH0954040A (en) Method for optically measuring component in exhalation
US20190307396A1 (en) Device and method for detection of cannabis and other controlled substances using faims
CN111157480A (en) Real-time dynamic quantitative detection device for carbon dioxide in human body exhaled air
US20220317122A1 (en) System and method for determining onset and disease progression
WO2021250261A1 (en) Device for sampling gases exhaled by a patient
JP4452783B2 (en) Cirrhosis test method and apparatus using breath analysis apparatus
JPH0647047A (en) Method for clinical inspection of expiration and device therefor
JP2004279228A (en) Method and apparatus for measuring concentration of component gas in exhalation
JPH10186A (en) Method and device of analyzing specified gas component in expired air
JP5289837B2 (en) Biological component gas analyzer and disease determination support device
CH699885A2 (en) Exhaled alveolar air collecting method for e.g. screening lung cancer, involves compensating pressure in container by increasing volume of cylinder, where volume of container is variable and proportional to pressure of exhaled air
EP2713869B1 (en) Apparatus for diagnostic analysis of nitric oxide
JP3065498B2 (en) Breath collection device
De Lema et al. Exhaled breath condensate: standardized collection of samples from healthy volunteers
CN214096808U (en) Gas collection device
JP7493501B2 (en) Method and system for correlating chemical emissions with corresponding genetic, medical and/or pathological conditions - Patents.com
Petrus et al. BREATH AMMONIA DETECTION IN PATIENTS WITH SCHIZOPHRENIA USING LASER PHOTOACOUSTIC SPECTROSCOPY
CN117770793A (en) Gas signal molecule expiration detection method, system and electronic equipment
ES2366230T3 (en) GAS ANALYSIS.
FR2981158A1 (en) Gas analysis module for use in anesthesia ventilator for analyzing concentration of compounds present in e.g. inspiratory flow of patient, has hollow optical fiber guiding infra-red signal emitted by transmitter to detector
CN115153499A (en) Expiratory sampling method and device

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21730632

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21730632

Country of ref document: EP

Kind code of ref document: A1