Device and method for analysing gaseous biomarkers

Abstract

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Description

Device and method for analyzing gaseous biomarkers Technical field

[0001] The present invention relates to a device and a system for detecting and analyzing gaseous biomarkers. The device which is the subject of the present invention makes it possible in particular to detect the presence of one or more gaseous biomarkers and to establish a profile of the detected gaseous biomarkers, as well as to monitor the evolution of such a profile over time. The present invention further relates to a diagnostic method making it possible to identify a pathology in a non-invasive manner, on the basis of the identified biomarkers. The present method also makes it possible to monitor the evolution of a pathology on the basis of the identified biomarkers and to adapt the treatment accordingly. State of the art

[0002] Devices can be used to measure biomarkers emitted by a patient's breath at specific times and to determine the presence of such biomarkers at specific time intervals. However, these devices require physical contact with the patient, who must generally blow into a collector so that their breath can be analyzed. However, the biomarkers sought are not detectable uniformly with each of the patient's exhalations. Their concentration can even vary significantly over time without necessarily being correlated with the patient's physiological state. One-off analyses are therefore subject to interpretation errors or require frequent repeat measurements, which can be cumbersome.

[0003] Targeted biomarkers can, for example, determine a patient's blood glucose level, as described in WO2022233771.

[0004] Devices such as the one described in EP4244617 allow for continuous monitoring of an enclosed space such as an office or classroom, in order to identify the presence of potential contaminants. Even when used in a hospital setting, such devices do not allow for precise diagnoses and are limited to the detection of specific biomarkers.

[0005] Document US2023127176 describes a device comprising a ventilator and a gaseous biomarker sensor, coupled with a mass spectrometer, for identifying potential contaminants or pathogens likely to spread epidemics. Monitoring the premises does not constitute a diagnosis or therapeutic monitoring of a patient. Individual identification of gaseous biomarkers does not necessarily allow for an accurate and reliable diagnosis.

[0006] Gaseous biomarker analysis is not yet fully integrated into therapeutic processes. There is scope for further exploitation of gaseous biomarkers for diagnostic, therapeutic monitoring, and research purposes. Brief summary of the invention

[0007] An aim of the present invention is to propose an improved device and / or system making it possible in particular to continuously monitor the gaseous biomarker profile of a patient over time, preferably without physical contact with the patient. Another aim of the present invention is to propose a device and / or system making it possible to monitor the state of health of a patient under treatment and to deduce the relevance of the treatment.

[0008] Another aim of the invention is to propose a method for monitoring over time, continuously, the gas biomarker profile of a patient, preferably without physical contact with the patient, so as to establish a diagnosis. Another aim of the present The invention is to propose a method for evaluating a patient's treatment, in particular to avoid unsuitable treatments and promote the most appropriate treatments.

[0009] Another aim of the present invention is to propose a system and / or a method for easily and remotely monitoring the state of health of a patient under treatment and for assessing the relevance of their treatment. Remote monitoring allows in particular more efficient and less expensive outpatient care for patients.

[0010] Another objective of the present invention is to provide a system and / or method for limiting the harmful effects of treatments, in particular antibiotics. The objective is to limit bacterial resistance.

[0011] Another objective of the present invention is to provide a system and / or a method for identifying a pathology and selecting and / or simulating a therapeutic treatment.

[0012] Another objective of the present invention is to provide an objective, a system and / or a method allowing the detection of a pathology early and / or more precisely than the methods currently used.

[0013] According to the invention, these aims are achieved in particular by means of the device, the system and the method which are the subject of the independent claims and detailed in the dependent claims.

[0014] This solution has the advantage over the prior art of detecting pathologies early and offering faster, more effective and more comfortable therapeutic solutions. This solution also makes it possible to minimize analysis costs for diagnostic purposes. Brief description of the figures

[0015] Examples of implementation of the invention are indicated in the description illustrated by the following figures: • Figure 1: Schematic representation of the detection elements of the detection device according to an embodiment of the present invention, • Figure 2: Schematic representation of a detection device according to an embodiment of the present invention, • Figure 3: Schematic representation of the analysis system according to an embodiment of the present invention. • Figure 4: Schematic cross-sectional representation of a device according to an exemplary embodiment of the present invention. • Figure 5a: Representation of early biomarker measurements and growth of Escherichia coli. • Figure 5b: Representation of early biomarker measurements and growth of Klebsielle pneumomiae. • Figure 5c: Representation of early biomarker measurements and growth of Pseudomonas aeruginosa. • Figure 6: representation of the biomarker profiles determined according to the present invention for Escherichia coli, Klebsielle pneumomiae and Pseudomonas aeruginosa Example(s) of embodiment of the invention

[0016] The present invention relates to a device 10 for detecting volatile compounds, in particular volatile organic compounds also known by the English acronym VOC (volatile organic compounds). The detection device 10 makes it possible to detect a wide variety of volatile compounds present in the atmosphere in which it is placed. The detection device 10 can be calibrated to detect certain volatile compounds more precisely. In particular, the detection device 10 can be intended to detect volatile products present in an interior, such as a home, a hospital room, a private or public building or any enclosed area. The present detection device 10 is particularly suitable for detecting volatile products emitted by biological systems, in this case one or more patients, in a room.For this purpose, the detection device 10 is placed near the person being monitored and analyzes one or more air samples likely to contain the organic products emitted by the person present in the room. Typically, the analysis device 10 is in the form of a housing comprising openings on at least one of its faces so as to allow the ambient air to pass to the detection elements arranged within the housing. In this case, the detection device is not intended to precisely and exclusively collect the air exhaled by a patient. It is therefore devoid of a mask or collector usually placed on the mouth of a patient to collect the breath. As a result, the detection device 10 according to the present invention collects all the volatile compounds present in the room regardless of their origin. The air sample(s) here correspond to an aliquot of the atmosphere.

[0017] According to another embodiment, an air sample denotes a volume of air exhaled by a patient, taken from his face and conveyed to the detection device 10. This arrangement can be useful during urgent detection for rapid diagnosis, for example. in a pharmacy or when integrating a patient into a hospital environment. This provision does not exclude that monitoring can then be established by means of the detection device described here without contact with the patient. The same detection device 10 can thus be used in different configurations.

[0018] According to another embodiment, the detection device 10 according to the present description can be integrated into a laboratory analysis machine. For example, cell culture samples can be confined in an enclosure whose air is sampled and / or analyzed by means of the detection device 10 described here. According to a particular arrangement, the same detection device 10 can be dedicated to the monitoring or analysis of several separate enclosures.

[0019] The present detection device 10 is further not necessarily provided with a fan concentrating the air towards the internal detection elements, as long as the air can reach the internal detection elements. However, certain applications may require such a fan or an equivalent element making it possible to direct an air flow towards the internal detection elements.

[0020] According to one embodiment, the detection device 10 may be arranged at a predetermined height, such as 80 cm to 1.5 m above a patient's bed. This arrangement is particularly suitable for monitoring a bedridden patient, whether in a hospital setting or at home. Alternatively, the detection device 10 may be placed on a piece of furniture in the room, at a height suitable for optimally collecting volatile organic compounds. In this case, an intermediate height between the floor and the ceiling is preferred so as to be able to best capture all the volatile elements in the room. Such an arrangement is more suitable for monitoring mobile people who reside for a long time in a given room.

[0021] It is hereby specified that volatile organic compounds, or gaseous biomarkers, can be emitted by any type of living organism and can be detected in several products secreted by a patient, including urine, perspiration, blood, breath and any other bodily fluid. As such, the detection device described herein can be dedicated to the more specific analysis of one or other of these secretions.

[0022] According to one embodiment, the detection device 10 can be calibrated so as to detect only the volatile organic compounds emitted by a person and which can be interpreted as biomarkers. It can alternatively allow the detection of other volatile or suspended compounds such as pollens, chemical or biological contaminants, possibly present in the monitored space. The detection of volatile or suspended compounds other than the potential biomarkers can be the subject of specific processing. For example, although they are physically detected or detectable by the detection device 10, the data collected can obscure or not take into account their presence. Alternatively, the data relating to volatile or suspended compounds, contaminants, can be analyzed jointly or separately from the data relating to the possible biomarkers so as to provide a more precise analysis.

[0023] According to one embodiment, the detection device 10 makes it possible to establish a profile of the volatile compounds present in one or more air samples, whether ambient air or air collected from a particular source such as a cell culture chamber or at the level of a patient's face. The detection device 10 comprises at least one, preferably several, sensors 10a, 10b, 10c, 10n capable of producing a digital response in contact with one or more of the volatile compounds. Depending on the nature of the volatile compounds, the response of a given sensor may be different, in particular in terms of response intensity. The response intensity of a sensor therefore does not necessarily reflect the quantity of a volatile compound in the air or its concentration. Furthermore, the nature of a volatile compound may not be determined by a given sensor.

[0024] The detection device 10 may therefore not be fully suitable for the direct identification of volatile compounds present in the air samples. In particular, a sensor may not be specific for a given volatile compound. The important aspect is that in response to the detection of the volatile compounds, the sensor(s) produce a profile representative of the volatile compounds present in the air sample.

[0025] According to one embodiment, one or more of the sensors 10a, 10b, 10c, 10n of the detection device 10 may be calibrated using a known volatile compound at varying concentrations and / or under controlled conditions to determine their response. Alternatively or in addition, known mixtures of identified volatile compounds may be used for the calibration of one or more sensors 10a, 10b, 10c, 10n. The responses obtained produce profiles representative of the analyzed mixtures.

[0026] A profile here designates, for example, an electrical response of one or more sensors 10a, 10b, 10c, 10n. It can be materialized by a measurement of electrical intensity, conductance, frequency, magnetic fields, light wavelength or any appropriate physical value. Alternatively, a profile can be materialized or completed by the variation of one or more of these physical values. Such variations can occur in particular during changes in the detection conditions, whether controlled and deliberate or resulting from uncontrolled external factors. Typically, temperature or humidity conditions can vary the response of one or more of the sensors of the detection device 10.

[0027] According to a particular arrangement, the detection device 10 according to the present invention, illustrated by FIG. 1, comprises detection elements internal to its housing. Such detection elements comprise at least one, preferably several, distinct cells 11a, 11b, 11c, 11n. All the cells are in contact with the air sample(s). However, they may not be in communication with each other. the others, so that the air passing through a given cell is not analyzed by other cells. Alternatively, the cells or part of the cells may be arranged in series so that a given air flow can pass through several cells. The number of cells is not limiting. Preferably, the detection device 10 comprises two or more cells, in particular 4 or a multiple of 4.

[0028] Each of the cells 11a, 11b, 11c, 11n is provided with at least one sensor 10a, 10b, 10c, 10n capable of reacting upon contact with at least one volatile organic compound. In other words, a sensor produces a measurable electrical signal upon contact with such volatile compounds. Such sensors may, for example, comprise metal oxides or be of the metal oxide type such as those designated by the acronym MOS (Metal Oxide sensors). Other types of sensors may be used as required. In this case, colorimetric sensors may be used instead of or in addition to the MOS type sensors.

[0029] According to one embodiment, a given cell comprises more than one sensor. The sensors of a given cell can thus be identical so as to produce a more reliable measurement. In this case, the response of the sensors of a cell can be combined or averaged. Alternatively, the sensors of a given cell can be of different types or if they are of the same type, such as MOS or colorimetric, they can be calibrated to produce a different response upon contact with a given volatile compound or a mixture of given composition. Thus, within the same cell, a volatile compound or a mixture of volatile compounds can be identified differently by several sensors, which makes it possible to provide a more precise response, in particular in terms of the composition of the air analyzed.

[0030] Alternatively or in addition, the different cells 11a, 11b, 11c, 11n of the detection device 10 may be provided with means for controlling at least one measurement parameter. The measurement parameters include in particular temperature, humidity or pressure. The value of one or more of these parameters can therefore be determined so that the response of the corresponding sensor(s) can be modulated accordingly. For example, the response of a sensor to certain volatile compounds may vary depending on the value of the measurement parameters. It is therefore appropriate to combine, correct or weight the data obtained by the sensors with the values ​​of the measurement parameters or some of them.

[0031] Furthermore, controlling the measurement parameters may involve actively and controlledly modifying the value of one or more of the measurement parameters within a given cell 11a, 11b, 11c, 11n. According to one embodiment, one or more of the cells of the detection device comprises a device for regulating at least one of the measurement parameters. Typically, one or more of the cells may comprise a thermal regulation device 12a, 12b, 12c, 12n for varying the temperature within the corresponding cells in a controlled manner.

[0032] The term cell may refer to physically separate spaces within the detection device 10. Alternatively, the cells may be limited to detection areas provided with the corresponding sensors. In this case, the measurement parameters may be controlled directly at the sensor 10a, 10b, 10c, 10n or in the vicinity. For example, one or more of the sensors may be combined with a thermoregulatory device so that the gases present in the air are detected independently by each sensor at a predetermined temperature.

[0033] According to one embodiment, a set of cells 11a, 11b, 11c, 11n forms a detection unit U. The detection device 10 may comprise several detection units U1, U2, U3, each comprising several cells such as those described above (Figure 2). The temperature of each of the cells of a detection unit U may be individually controlled.

[0034] According to one embodiment, the detection device 10 comprises at least one detection unit U, preferably two or more detection units, suitable for static measurements in which the measurement parameters do not vary. For example, the detection device 10 may comprise a first detection unit U1 comprising 4 cells 11a, 11b, 11c, 11n of respective temperatures Ta1, Tb1, Tel and Tn1. The temperature value may be fixed and determined between a minimum value Tm1 and a maximum value TM1. The minimum value may be of the order of 80°C or 100°C. The maximum value may be of the order of 200°C or 300°C or 400°C or more depending on requirements. The temperature difference between the cells of a unit of measurement U can be an absolute value of the order of a few tens of degrees, for example 15°C, 20°C or 25°C or 30°C or multiples or combinations of these values.Alternatively, the temperature difference between the cells of a detection unit U may be determined relatively, for example based on a percentage of the temperature of the neighboring cell. The temperature may for example be greater or smaller from one cell to the neighboring cell by a value of 5%, 10% or 15% or by a multiple of these values.

[0035] According to one example, the temperatures Ta1, Tb1, Tel, and Tn1 of the cells of the first detection unit U1 are respectively 100°C, 150°C, 175°C and 200°C. In this way, the air is analyzed simultaneously by the cells of the first detection unit U1 at different temperatures and the gases it contains are detected therein under separate controlled conditions.

[0036] The detection device 10 may comprise a second measurement unit U2 comprising 4 cells 11a, 11b, 11c, 11n of respective temperatures Ta2, Tb2, Tc2 and Tn2. The temperature value may be fixed and determined between a minimum value Tm2 and a maximum value TM2. The minimum Tm1 and maximum TM2 values ​​of the temperatures of the second detection unit U2 may be identical to or different from those of the first detection unit U1. The temperature differences between the cells of the second detection unit U2 may be determined identically or differently from the first detection unit U1.

[0037] According to one embodiment, the temperature range of the second detection unit U2 is different from that of the first detection unit U1. For example, the minimum temperature Tm2 of the second detection unit U2 may be of the order of 200°C or 220°C or 250°C. The maximum temperature TM2 of the second detection unit U2 may be of the order of 400°C or more.

[0038] According to one example, the temperatures Ta2, Tb2, Tc2, and Tn2 of the cells of the second detection unit U2 are respectively 250°C, 300°C, 350°C and 400°C. In this way, the gases are detected by the cells of the second detection unit U2 at different temperatures and in a different temperature range than that of the first detection unit.

[0039] The first U1 and second U2 detection units, as described above, operate in so-called static mode, i.e. with a constant measurement parameter. They are suitable for high or relatively high concentrations of volatile organic compounds.

[0040] The measurement parameters here are limited to temperature. However, it is not excluded that other measurement parameters may be considered.

[0041] According to one embodiment, one or more of the detection units U of the detection device 10 are adapted for dynamic measurements, in which at least one of the measurement parameters varies during a measurement. For example, the detection device 10 may comprise a third detection unit U3, composed of 4 cells 11a, 11b, 11c, 11n of respective temperatures Ta3, Tb3, Tc3 and Tn3 which can vary independently between a minimum value and a maximum value. The minimum and maximum values ​​of the cells of a detection unit U may be identical. In this case, the temperature variation of the different cells takes place according to different progressions. Alternatively or in addition, at least one of the minimum and maximum values ​​differs from one cell to another within the detection unit.

[0042] According to one embodiment, the temperature variation within a cell can be linear and rectilinear. Alternatively, it can be established according to an exponential variation. Alternatively, it can be established by jumps with stages of determined duration. The temperature variation conditions can be adapted as needed. The temperature variation is preferably negative. It can nevertheless be positive.

[0043] According to one example, the temperatures of the cells 11a, 11b, 11c, 11n of the third detection unit U3 vary respectively from 400°C to 100°C, from 400°C to 150°C, from 400°C to 200°C and from 400°C to 250°C.

[0044] The dynamic detection mode is favorable for the detection of low concentrations of volatile compounds. In addition, better selectivity is obtained. During temperature variation, the relaxation of the conductance, particularly in the case where MOS type sensors are used, is measured for each of the sensors 10a, 10b, 10c, 10n of the cells considered.

[0045] Preferably, the temperature variation is rapid, so as to promote sensitivity. Typically, the temperature variation occurs within an interval of the order of 1 second, or a few hundredths of a second.

[0046] According to one embodiment, several temperature cycles are repeated for each of the cells of a detection unit U. The minimum and maximum values ​​as well as the temperature variation conditions are reproduced identically for each cycle. Alternatively, one or other of the minimum, maximum and variation values ​​change from one thermal cycle to another.

[0047] The variable measurement parameter here is temperature. However, it cannot be ruled out that other measurement parameters are also considered in the context of a dynamic measurement, as a replacement or in addition to temperature.

[0048] According to one embodiment, a detection unit U of the detection device 10 is used for standard detection of volatile compounds. The standard detection aims to produce an overall signal corresponding to the volatile compounds present in the atmosphere. Such an overall signal is not in itself sufficient to establish the profile of the detected biomarkers but can be used as a reference in the processing of the collected data.

[0049] Standard detection can be carried out under controlled conditions. Alternatively, the measurement conditions correspond to ambient conditions and do not require controlling the measurement parameters. Under these conditions, the air is analyzed at room temperature. The other measurement parameters such as humidity or pressure can also be those of the environment. This arrangement does not exclude the possibility that one or more of the measurement parameters, in particular the ambient temperature, is determined at the level of the corresponding detection unit. According to this arrangement, all the cells of the detection unit U have the same measurement parameters. The nature of the sensors 10a, 10b, 10c, 10n within these cells can advantageously be different from one cell to another or calibrated differently.

[0050] According to one embodiment, the detection device 10 is suitable for detecting volatile compounds simultaneously in static mode and in dynamic mode. According to one embodiment, the detection device 10 is suitable for detecting volatile compounds simultaneously in static mode, in dynamic mode and in standard mode. According to one embodiment, the detection device 10 is suitable for detecting volatile compounds simultaneously in static mode and in standard mode. According to one embodiment, the detection device 10 is suitable for detecting volatile compounds simultaneously in dynamic mode and in standard mode. The mode combinations mentioned here represent hybrid modes.

[0051] For example, a first U1, a second U2 and a third U3 detection units can be used in dynamic mode, according to which the temperature of each of the cells of a detection unit varies independently from a maximum temperature to a minimum temperature or vice versa. The temperature ranges and / or the variation conditions can vary from one detection unit to another. A fourth detection unit U4 can be dedicated to the standard measurement of volatile compounds.

[0052] According to another example, a first U1, a second U2 and a third U3 detection units can be used in dynamic mode, according to which the temperature of all the cells of a detection unit varies simultaneously from a maximum temperature to a minimum temperature or vice versa. The temperature ranges and / or the variation conditions can vary from one detection unit to another. A fourth detection unit U4 can be dedicated to the standard measurement of volatile compounds.

[0053] According to another example, a first U1 and a second U2 detection units can be used in dynamic mode, in which the temperature of all the cells of a detection unit varies simultaneously from a maximum temperature to a minimum temperature or vice versa. A third detection unit U3 is used in static mode as described above. A fourth detection unit U4 can be dedicated to the standard measurement of volatile compounds.

[0054] According to a particular embodiment, the mode is automatically adapted according to the measurement conditions. For example, a static mode can be initiated by default for at least one measurement unit U. If the signal of one or more of the cells of the corresponding measurement unit is lower than a predetermined value, the unit of detection can be controlled in a dynamic mode. A dynamic mode can be selected by default, where for example the temperature of all cells in the detection unit, or detection units, varies simultaneously from a maximum temperature to a minimum temperature or vice versa.

[0055] According to one embodiment, the first U1, second U2 and third U3 detection units are by default in static mode and the fourth detection unit U4 is in standard mode. Each of the first U1, second U2 and third U3 detection units can automatically switch to dynamic mode independently if the signal of one or more of the corresponding cells is lower than a threshold value.

[0056] The variety of static, dynamic and hybrid modes, which are not limited to those actually described here, allows great flexibility and measurement precision.

[0057] The static, dynamic, standard and hybrid modes are described here in combination with MOS type sensors. This is not intended to limit the application to sensors of this type only. According to one embodiment, the inequality of the cells of one or more of the detection units U, or some of them, comprises sensors other than those of the MOS type. For example, colorimetric type sensors or other types can constitute a detection unit. In this case, the measurement conditions can be adapted in a similar manner to those described above.

[0058] Each of the sensors 10a, 10b, 10c, 10n produces a response signal under controlled measurement conditions. The response signals are processed per cell and per detection unit so as to establish a profile representative of the composition of the air in terms of volatile compounds.

[0059] The detection device 10 comprises for this purpose a data processing unit 13 for the collected data to establish such a profile. Alternatively, a data processing unit 13 can be connected to the detection device 10 so as to process the data remotely.

[0060] The detection device 10 further comprises a control unit 14 of the different detection units U1, U2, U3, Un making it possible in particular to detect and / or control the measurement parameters, in particular the temperature, and to select the detection mode(s) of the detection units from among a static mode, a dynamic mode, a standard mode and a hybrid mode. The control parameters of the control unit 14 can be programmed or imported therein.

[0061] A detection device according to the present invention typically takes the form of a rigid housing comprising at least one opening allowing air flow towards the detection elements. The opening(s) may be provided with dust filters. It may comprise one or more human-machine interfaces such as a start-up and stop device, a system for entering or selecting data or pre-established programs, a device for displaying at least certain data such as the status of a measurement cycle or one or more detection parameters, a connection means capable of transmitting data, such as a wifi, bluetooth, wired, internet or any equivalent connection, a power supply system and / or a battery.

[0062] According to one embodiment, the present device comprises a means for channeling the air to be analyzed onto at least one of the sensors. For example, a detection unit U may comprise one or more channels 30 adapted to channel one or more air flows F to be analyzed (figure 4). A channel 30 is in contact with at least one detection cell 11a, 11b, 11c, 11d by means of passages 31, 31a making it possible to place the sensors 10a, 10b, 10c, 10d of the cells in contact with the air passing through the channel 30. A passage 31, 31a may be of a calibrated size to divert a determined fraction of the air circulating in the channel 30. The detection cell may be in the form of a cavity 32, 32a in which a sensor 10a is arranged, the cavity being in fluid communication with the channel 30 via the corresponding passage 31. The portion of air diverted from the air flow F is thus in contact with the sensor so that any markers it contains can be detected. The volume of the cavity 32 can also be calibrated, so that the response of the sensor 10a can be correlated with the volume of the cavity 32, 32a. The air flow F in the channel 30 can furthermore be precisely controlled, for example by means of a fan (not shown). The air flow rate channeled into the channel 30 is thus known and can be adjusted as required.

[0063] According to one embodiment, the response of the sensors 10a, 10b, 10c, 10d is correlated to the flow rate of the air flow F, and / or to the volume of the cell cavities, so as to evaluate or measure a concentration of the markers identified by the sensors. The air flow can be constant and regulated so as to remain stable. For better measurement, it is possible to vary the flow rate of the air flow F and to correlate the values ​​obtained by the sensors with these different air flow rates. The flow rate of the air flow can be between 1 L / h and more than 10 L / h, typically around 2 to 6 or 8 L / h.

[0064] According to a possible arrangement, a channel 30 may be in contact with several detection cells 11, 11a, 11b, 11c, 11d. The flow rate of the air flow is thus homogeneous for all of the detection cells. Figure 4 illustrates such an arrangement. The detectors may be arranged on a first surface 40, the temperature of which is optionally regulated. A distribution structure 42 may be arranged on, or combined with, the first surface 40, which makes it possible to define the cavities in which the sensors 10, 10a, 10b, 10c, 10d are arranged and the passages 31 of the detection cells. The distribution structure thus defines a wall of the channel 30 in which the different detection cells are inserted. A second surface 41, arranged opposite the distribution structure 42, determines the dimensions of the channel 30. The second surface 41 can be arranged at a distance H30 from the distribution structure 42.The distance H30 is typically a few millimeters, for example between 1 and 10 mm or of the order of 1.5 to 5 mm, or even of the order of 2 to 4 mm or 3 mm. The width of the channel 30 can be determined so as to correspond to the width of the cells. The section of the channel 30 can thus be square or rectangular in shape. Other shapes can nevertheless be envisaged.

[0065] The channel 30 may comprise an inlet 30a and an outlet 30b defining the path of the air flow within the detection unit U, where the detection cells are arranged on this path between the inlet 30a and the outlet 30b.

[0066] According to one embodiment, several individual outlets may be provided at the detection cells, in addition to or in replacement of the outlet of the channel 30b. In this way, the air passing through each of the cells is not returned to the air flow or analyzed by the other detection cells. It is also possible to generate an overpressure, in particular by providing an inlet 30a wider than the outlet 30b or than any individual outlets at the detection cells. Such an overpressure can promote the concentration of volatile products at the detection cells.

[0067] According to one embodiment, the channel 30 may have a flared shape at the inlet 30a so as to concentrate the air flow F at the detection cells.

[0068] According to another embodiment, not shown, the channel 30 can be divided into several independent channels each serving one or more detection cells. The flow rate of each of the independent channels can thus be adjusted individually as required.

[0069] The device architecture described above has the advantage of lowering the detection thresholds for volatile products. In addition, the airflow rate F is controlled. This arrangement allows for the measurement of small quantities of volatile products in a reliable and reproducible manner. The measurement of small quantities of volatile products advantageously allows for early determination of the emergence of a pathology. The measurements Adequate measures can thus be taken in advance and allow for better treatment, or the adjustment of ongoing treatment.

[0070] The present invention further covers an analysis system 1 comprising one or more detection devices 10 as described here (figure 3). The analysis system 1 comprises a unit 20 for analyzing the data collected by the detection device(s) 10. The data analysis unit 20 may comprise an artificial intelligence module 21 or deep learning or any program capable of self-learning. The artificial intelligence module makes it possible in particular to deduce from the profiles received by the detection device(s) 10 the presence of at least one gaseous biomarker, preferably several gaseous biomarkers emitted by a person under surveillance. It also makes it possible to determine the variation in concentration of the identified biomarker(s) over time. The variations in concentrations may be determined absolutely or relatively with reference to the different volatile compounds detected.Variation includes decrease, increase, cyclical variations, relative concentrations of several biomarkers.

[0071] The identification of one or more gaseous biomarkers can be obtained for example by comparison with one or more pre-established databases comprising the profiles of gaseous biomarkers and mixtures of such gaseous biomarkers.

[0072] The artificial intelligence module 21 may be able to extract collected data from those relating to possible contaminants detected by the detection device(s) 10. The contaminant profiles may for example be compared to those in a database. A deconvolution method or any other method suitable for identifying a particular profile within a superposition of profiles may be used.

[0073] According to one embodiment, the possible contaminants as well as the variation in their concentration where applicable, can be identified by the artificial intelligence module 21.

[0074] The analysis unit 20 may further be connected to one or more types of environmental sensors C1, C2, Cn distinct from the detection device 10 or integrated into the detection device 10. Such environmental sensors include ambient temperature sensors, hygrometers, barometers, visible, UV or infrared light irradiation sensors, noise sensors such as microphones, presence and / or movement sensors. Non-environmental sensors, in particular physiological sensors such as body temperature, blood pressure, oxygenation, blood glucose sensors may further be connected to the data processing unit 20.

[0075] The data processing unit 20 is able to correct, weight, modify the profiles emitted by the detection device(s) 10 based on the data collected by the environmental and / or non-environmental sensors.

[0076] Alternatively or in addition, the data processing unit 20 comprises means for accessing third-party databases D1, D2, Dn comprising, for example, meteorological data, including forecast data, pollen maps, air quality or pollution data including, for example, concentrations of microparticles, nanoparticles, ozone, carbon dioxide, carbon monoxide, and other gases or elements suspended in the air.

[0077] According to one embodiment, the data processing unit is able to correct, weight or modify the profiles emitted by the detection device 10 based on the data collected in one or more of these third-party databases D1, D2, Dn.

[0078] According to one embodiment, the data processing unit 20 is able to distinguish volatile compounds originating from pathogens or markers of a pathology, from those which are not originating from pathogens. It is indeed possible that certain volatile compounds can be naturally emitted by a healthy person. In this case, the specific profile linked to certain volatile compounds can make it possible to distinguish between a healthy situation and a pathological situation. The nature of the pathogen can further be identified on the basis of the profile of the volatile compounds detected.

[0079] According to one embodiment, the data processing unit 20 is able to identify one or more gaseous biomarkers representative of a pathology or the state of health of the patient.

[0080] According to one embodiment, the data processing unit 20 is able to identify one or more gaseous biomarkers representative of side effects of a treatment of a pathology.

[0081] According to one embodiment, the data processing unit 20 is able to model the evolution of a pathology or its possible complications on the basis of the data collected by the detection device(s) 10.

[0082] The data processing unit 20 comprises the processors, memories and software suitable for processing the data according to the method described below. The data processing unit 20 makes it possible to generate, automatically or on request, on the basis of the profiles received from the detection device(s) 10 and the data received by the environmental, non-environmental sensors C1, C2, Cn and by the third-party databases D1, D2, Dn, where applicable, analysis results R1, R2, Rn. The data processing unit 20 comprises the algorithms suitable for producing such analysis results.

[0083] The R1, R2, and Rn analysis results include the identification of pathogens responsible for the volatile compounds detected in the environment of one or more patients. Pathogens can be identified at an early stage of an infection or pathology. Preferably, the pathogens are those of a respiratory disease for which sampling for laboratory analysis is difficult or impossible. However, pathogens of other nature such as those of a non-respiratory infection or organ dysfunction can be detected. The identification of such pathogens can be correlated with the body temperature of the person being monitored, the sound of a possible cough, and other physiological parameters. A distinction can be made between a bacterial pathogen and a viral pathogen, for example. Such an analysis report can suggest appropriate treatment based on the pathogen identification.Typically, in the case of a viral pathogen, treatment may not suggest the use of antibiotics. For a bacterial pathogen, the test result may be able to suggest a suitable antibiotic to avoid the unsuccessful use of inactive antibiotics. The test result may include, where appropriate, a known resistance of the pathogen to certain treatments.

[0084] Alternatively or in addition, the analysis reports can make it possible to identify the volatile compounds most representative of a pathology, which must then be monitored with the greatest attention. The relevant volatile compounds or their profiles are analyzed in themselves to allow them to be assigned the status of gaseous biomarkers. Not all the volatile compounds detected are representative of a pathology. They may also be emitted in proportions that do not indicate a pathology. Thus, the detection of volatile compounds according to the present invention can be used for research or investigation purposes, in addition to the diagnostic and therapeutic monitoring applications described herein.

[0085] The analysis results may include parameters favorable or unfavorable to the identified pathology, for example on the basis of environmental conditions such as humidity, temperature or the presence of volatile contaminants.

[0086] The analysis results may include a model of the evolution of the pathology based on continuous measurements using the detection device 10 and, where appropriate, data collected by environmental and / or non-environmental sensors C1, C2, Cn and forecast or real-time data from third-party databases.

[0087] The analysis results may include a correlation between the collected and analyzed data and a treatment administered to the patient. The analyzed profiles can be used to attest to a remission of a pathology, for example, by reducing specific gaseous biomarkers.

[0088] The analysis results are not limited to those actually described here. They may take the form of written and / or digital reports. The analysis results may also be structured and distributed in agreement with the recipient. The analysis results may have, for example, several recipients, including a treating physician, a researcher, an insurer, or the patient himself. Thus, certain results of a given analysis may be transmitted only to certain specific recipients. For example, in the case of home monitoring, analysis results concerning the effect of a treatment may be transmitted to the treating physician.

[0089] According to one embodiment, the analysis results comprise a graphical visualization of the detected volatile product profiles, for example in the form of characteristic fingerprints (Figure 6).

[0090] The present invention further covers a method for detecting one or more volatile biomarkers using at least one detection device such as the detection device 10 described herein. The detection method comprises a step of arranging at least one detection device in a room so as to analyze the air of the room. The room is preference occupied by one or more persons whose health is monitored.

[0091] The detection method comprises the step of autonomously and / or automatically analyzing one or more air samples so as to identify possible gaseous biomarkers. The analysis can be carried out continuously or by successive analysis cycles. An analysis cycle comprises one or more modes from among the static, dynamic, standard and mixed modes described above. The analysis of the air samples can include the control of an air flow rate in at least one channel 30 for channeling the air towards the detectors. The control of the flow rate of the air flow F entering the channel 30 can be limited to maintaining the flow rate at a constant and reproducible value. Alternatively, the flow rate of the air flow F can vary in a controlled manner, for example from a minimum value to a maximum value continuously or in stages.The response of the sensors can thus be correlated to the value of the air flow rate F in order to evaluate or measure the concentration of the different volatile compounds in the sample.

[0092] The detection method may include a step of automatically selecting a mode in the event that the responses obtained are below a predetermined intensity threshold.

[0093] The detection method may comprise a step or cycle of cleaning the detection device, preferably automatically, when the responses obtained are below a predetermined intensity threshold. A cleaning step or cycle may comprise heating one or more detection elements of the detection device to a temperature above 200°C or 300°C or between 300°C and 400°C or a cyclical temperature variation, so as to destroy any contaminants without damaging the detection elements. The cleaning may or may not be associated with an air flow making it possible to evacuate any contaminants. Alternatively or in addition, UV or infrared irradiation of one or more detection elements may be envisaged. The cleaning step or cycle may be carried out during a period deemed adequate to restore the sensitivity and / or accuracy of the sensing elements. For example, a thermal cycle of one minute or less may be considered.

[0094] The detection method comprises a step of collecting the response signals from the detection device so as to establish the profile of the volatile compounds present in the room at the time of the measurement. The collection of the signals is carried out during a detection period and / or according to a detection mode. A detection operation can last of the order of one minute or less than one minute. The profile of the volatile compounds can be established by means of a data processing unit 13 associated with or integrated into the detection device. The detected profile can be stored in a memory of the detection device temporarily or transmitted to an analysis unit 20. Alternatively or in addition, the detected profile can be read by a device capable of collecting the data stored in the detection device, such as a terminal, a telephone device or any equivalent.

[0095] The detection method may involve iterating multiple detection periods at predetermined or automatically initiated intervals.

[0096] The detection method may include a step of calibrating the detection device according to the volatile components to be identified. Such calibration may, for example, be carried out by measuring known volatile components at controlled concentrations and conditions, and recording the response signal.

[0097] The present invention further covers a method of analysis by means of a unit for analyzing the data 20 emitted by the detection device(s). The analysis method may comprise correction, weighting, reprocessing of the profiles emitted by the detection device(s) with external data such as data received by Tl environmental or non-environmental sensors C1, C2, Cn, or third-party databases D1, D2, Dn, using appropriate algorithms.

[0098] The analysis method further comprises a step of transmitting analysis results R1, R2, Rn in response to a specific request or for a routine analysis carried out automatically. The analysis results can be split into subsets each transmitted to different recipients.

[0099] The analysis method described here may involve several detection devices placed, for example, in several rooms of a hospital or in several patients under home monitoring. The data collected and then analyzed may be transmitted to a treating physician or any other healthcare personnel. The data collected may differ from one patient to another. This analysis method makes it possible, for example, to compare the data successively received by the analysis unit 20 and to determine their evolution over time. The analysis may thus make it possible to detect the remission or deterioration of a patient, any cofactors influencing the evolution of their pathology, any microbial resistance, any nosocomial contamination, any epidemic epicenters. The analysis method makes it possible to model the evolution of a pathology, the effectiveness of a treatment, and any side effects of a treatment.

[0100] This analysis method may further comprise the step of detecting and storing previously unidentified profiles for subsequent analysis purposes.

[0101] For the purposes of this description, volatile organic compounds refer to any volatile compound present in the air in gaseous form. A gaseous biomarker refers to an organic volatile compound of metabolic origin. A gaseous biomarker may be of fungal, bacterial, viral origin, or originate from the cellular activity of a living being, in particular a patient. A biomarker is preferably indicator or characteristic of a pathology and preferably allows the pathology to be identified. A gaseous biomarker profile is preferably used to characterize a pathology. A pathology here refers to any abnormal metabolic functioning that may be linked to an infection, contamination, inflammation or dysfunction. A pathology can refer to a respiratory disease of viral or bacterial origin or other. A respiratory disease can be, for example, tuberculosis, bronchitis, pneumonia, pleurisy, bronchopneumonia. Examples In vitro tests were performed to determine the characteristic fingerprints of different bacteria, including Escherichia coli (ATCC BAA-2471) (Figure 5a), Klebsielle pneumomiae (ATCC BAA-2472) (Figure 5b), Pseudomonas aeruginosa (Figure 5c), isolated from human respiratory diseases. The bacteria were cultured in vitro in monoculture fluid. Three samples were prepared per cultured strain. Continuous measurement of volatile products was performed above the culture medium after inoculation of the culture media with 100 CFU / mL of bacteria. Cell concentration is determined by serial dilutions and counting. Tests show that volatiles can be detected before the bacteria's exponential growth. The bacteria's characteristic fingerprint profiles are also determined (Figure 6). The culture medium is used as a negative control. Strain detection times by measuring volatile products are 6 hours for Escherichia coli, 7 hours for Klebsielle pneumomiae and 11 hours for Pseudomonas aeruginosa. Reference numbers used in the figures 1 Analysis system 10 VOC detection device 10a, 10b, 10c, Sensors 10n 11a, 11b, 11c, Cells 11n 12a, 12b, 12c, 12n thermoregulators 13 Data processing unit 14 Control unit 20 Data Analysis Unit 21 Artificial Intelligence Module 30 Channel 30a Canal Entrance 30b Canal exit 31, 31a Passages 32 Cavity 40 First surface 41 Second surface 42 Distribution structure H30 Distance between distribution structure and upper surface C1, C2, Cn Environmental or physiological sensors D1, D2, Dn Third-party databases F Airflow R1, R2, Rn Analysis results U1, U2, U3 One Detection units Ta1, Tb1, Tc1, Cell temperatures Tn1 Tm1, Tm2 Minimum temperature value TM1, TM2 Maximum temperature value

Claims

Claims 1. Detection device (10) suitable for analyzing one or more air samples comprising: - several sensors (10a, 10b, 10c, 10n) of organic volatile compounds, - means for determining and / or controlling at least one detection parameter (12a, 12b, 12c, 12n) arranged near or at the level of each of the sensors (10a, 10b, 10c, 10n), adapted to independently determine or modify the detection conditions of the sensors, - a data processing unit (13) capable of collecting the signals emitted by the sensors in contact with the air sample(s), characterized in that the device comprises a means of channeling the air onto said sensors so as to create an air flow (F) and a means of determining or controlling the flow rate of the air flow (F), the signals emitted by the sensors being correlated with the flow rate of the air flow (F) and processed by the data processing unit (13) so as to generate a profile of organic volatile compounds.

2. Device according to claim 1, the sensors (10a, 10b, 10c, 10n) being arranged in, or forming, detection cells (11a, 11b, 11c, 11n), each detection cell comprising one or more sensors of identical or different nature.

3. Device according to claim 2, said detection cells being grouped into one or more detection units (U1, U2, U3, Un) each comprising several detection cells.

4. Detection device according to one of claims 1 to 3, in which the means for channeling the air comprises at least one channel (30) comprising an inlet (30a) adapted to the passage of an air flow (F), said sensors being arranged on a first surface (40) and brought into contact with the air of the air flow (F).

5. Device according to one of claims 1 to 4, said sensors being arranged within a cavity (32) of defined volume and comprising a passage (31) in fluid communication with the means for channeling the air.

6. Device according to one of claims 1 to 5, said means for channeling the air comprising a flared shape adapted to concentrate the air at the level of said detectors.

7. Device according to one of claims 1 to 6, said detection parameters being selected from temperature, humidity and pressure, preferably temperature.

8. Device according to one of claims 1 to 8, in which said sensors are selected from MOS type or colorimetric type sensors.

9. Analysis system (1) for organic volatile compounds comprising: - at least one detection device (10) according to one of claims 1 to 8, - one or more environmental or non-environmental sensors (C1, C2, Cn), means of accessing one or more third-party databases (D1, D2, Dn) and an analysis unit (20), characterized in that the analysis unit (20) is connected to said at least one detection device, to said sensors (C1, C2, Cn) and to said third-party databases (D1, D2, Dn) so as to correct, modulate, weight and / or modify said profile of organic compounds transmitted by said at least one detection device (10) with the data received by said sensors (C1, C2, Cn) and third-party databases (D1, D2, Dn).

10. Analysis system (1) according to claim 9, wherein the analysis unit (20) comprises an artificial intelligence module (21) capable of identifying at least one gaseous biomarker linked to a pathology.

11. Method for detecting organic volatile compounds in one or more air samples using a detection device according to one of claims 1 to 8, comprising the steps of: - placing the sensors (10a, 10b, 10c, 10n) of organic volatile compounds in contact with the air sample(s), the detection parameters at each sensor being determined and / or controlled independently, said detection parameters comprising one or more parameters among temperature, hygrometry and pressure, - acquiring and processing the response signal from the sensors by means of the data processing unit (13), and - generating a profile of organic volatile compounds based on the signal from the sensors, characterized in that the air sample(s) are brought into contact with said sensors by means of an air flow (F) whose flow rate is determined and / or controlled.

12. Method according to claim 11, said sensors being grouped in several detection units (U1, U2, U3) and the acquisition of the response signal from the sensors being carried out independently for each of the detection units according to one of the modes among a static mode, a dynamic mode, a standard mode and a hybrid mode.

13. Method according to claim 12, the static mode being defined by a constant and different detection parameter for each sensor of a given detection unit, the dynamic mode being defined by an independently variable detection parameter for each detector of a given detection unit, the standard mode being defined by a detection parameter corresponding to the ambient conditions for all the detectors of a given detection unit, and the mixed mode combining several static, dynamic and standard modes on several detection units.

14. Method according to claim 13, the detection parameter being the temperature, said temperature being determined between a minimum temperature and a maximum temperature for each sensor of a detection unit in a static mode, said temperature varying independently between a minimum temperature and a maximum temperature for each sensor of a detection unit in dynamic mode, said temperature being the ambient temperature for all the sensors of a detection unit in standard mode.

15. Detection method according to one of claims 11 to 14, further comprising a step of self-cleaning at least one of the sensors when the corresponding signal is below a predetermined intensity threshold.

16. Method according to one of claims 12 to 15, further comprising the automatic selection of one of the detection modes when the response signal of one or more sensors of a detection unit is lower than a predetermined intensity threshold.

17. Method for analyzing organic volatile compounds using an analysis system according to one of claims 9 and 10, comprising: - comparing the profiles of organic volatile compounds received by the analysis unit (20) with those of a pre-established database, said pre-established database comprising profiles of gaseous biomarkers, - the identification of gaseous biomarkers present among volatile organic compounds, - the determination of a concentration of at least one of the identified biomarkers, and - the production of an analysis result (R1, R2, Rn) based on the identified gaseous biomarkers.

18. The method of analysis of claim 17, further comprising one or more of the steps of: - characterize a pathology on the basis of identified gaseous biomarkers, - compare gaseous biomarkers over time and determine their evolution, - correlate the evolution of biomarkers with a treatment administered as a remedy for the pathology and / or with possible contaminants and / or with possible environmental conditions, - distinguish a viral or bacterial origin of the identified pathology, - identify possible resistance or possible side effects linked to a treatment, - model the evolution of an identified pathology, and - identify key biomarkers of a given pathology.