System and method for VOC analysis by LTP-MS

Abstract

The present invention relates to a system and method for analyzing VOCs adsorbed on an adsorbent membrane by LTP-MS. The system comprises a receptacle for receiving the adsorbent membrane, a low-temperature plasma ionizer adapted to emit a plasma stream in a plasma emission direction, thereby ionizing the VOCs adsorbed by the membrane and forming an ionized gas laden with VOCs, and a mass spectrometer for analyzing the ionized VOCs. Abstract figure: Figure 1

Description

Title of the invention: System and method for analyzing VOCs by LTP-MS Technical field

[0001] The present disclosure relates to the field of detection of volatile organic compounds, VOCs. In particular, the present disclosure relates to the field of VOC analysis systems, and more particularly VOCs adsorbed on an adsorbent membrane, as well as methods of analyzing such VOCs. Prior art

[0002] Several strategies are commonly used for diagnosis based on VOC analysis. Some rely, for example, on mass spectrometry (MS) methods. However, these methods do not allow real-time and in vivo analysis. The most commonly used techniques for VOC analysis are presented below. In addition, most diagnoses are based on the analysis of exhaled air.

[0003] Thus, among these methods, the technique coupling gas chromatography and mass spectrometry (in English: gas chromatography-mass spec-trometry, GC-MS) or flame ionization detection (in English: gas chromatography-FlD) are considered by the American Environmental Protection Agency (in English: Environmental Protection Agency, EPA, https: / / www.epa.gov) as the references for the analysis of VOCs. However, they do not allow direct analysis in real time like the analysis of exhaled air and ambient air and require preconcentration of the samples on resins or adsorbent stationary phases. The samples are then desorbed at high temperature (from 200°C to 300°C) and then introduced into the GC column, thus allowing their separation and then their online detection by MS or FID. Nevertheless, these techniques remain to this day those providing the most information in terms of identification and quantification.However, they have the disadvantage of requiring a long analysis time of approximately 30 min. In addition, FIDs are only sensitive to carbon compounds and provide little qualitative information and do not allow identification.

[0004] There is also selected-ion flow-tube mass spectrometry (SIFT-MS). This technique was developed in the 1970s and allows for the online, real-time analysis of traces of VOCs from gaseous samples (e.g., exhaled air) or biological fluids such as urine and blood using the so-called headspace method. It is based on the production of ions primary ions in a plasma source from air and water vapor. From this plasma, a single ion species is selected using a quadrupole, such as H3O+, NO+ and O2+ ions, which are injected into a cell in order to ionize the VOCs present for analysis based on their mass-to-charge ratio (m / z) in a second quadrupole. Since ionization is gentle, this mainly results in the formation of molecular ions, thus simplifying the interpretation of mass spectra, particularly in the case of complex mixtures such as exhaled air. This technique allows three primary ions to be independently selected, allowing three different mass spectra to be obtained; which is interesting for the analysis of compounds with different properties. In addition, SIFT-MS allows real-time analysis and simultaneous quantification of several VOCs without prior pretreatment.It is therefore rapid, easy to handle and offers a detection limit of the order of ppb. However, it has the disadvantage of exclusively analyzing gaseous samples and does not allow surface analysis.

[0005] Another known technique is proton transfer mass spectrometry (PTR-MS). This technique was developed in the mid-1990s, is an evolution of SIFT and is based on the gas-phase proton transfer reaction between hydronium ions (H3O+) and VOCs. The proton transfer reaction takes place in a drift cell, limiting the formation of clusters with water molecules in the ambient air. Since the exothermicity of the proton transfer is low, little or no fragmentation is observed, allowing the detection of intact species, thus simplifying the identification of VOCs. Originally, the PRT-MS was equipped with a quadrupole as an analyzer, but other instruments such as the ion trap or time of flight (TOF) have been integrated into the PTR-MS.In the 2000s, the introduction of TOF made it possible to detect VOCs with greater resolution and also greater mass measurement accuracy. PTR-MS has a detection limit of the order of ppt and, above all, does not require sample preconcentration, which can be time-consuming. In addition, the advantage of this technique is that it analyzes almost in real time without the need to adsorb and then desorb the sample; however, these adsorption and desorption processes can lead to losses related to the properties of the support. Since PTR-MS is a rapid and easy-to-handle VOC analysis technique, the number of samples that can be studied is significantly higher than in gas chromatography-mass spectrometry (GC-MS), although the amount of information remains lower.However, like SIFT-MS, this technique only allows the analysis of gaseous samples and does not allow this of surfaces. Furthermore, this technique is based on the transfer . of proton, it is limited to analytes whose proton affinity is greater than that of the hydronium ion H3O+.

[0006] There is also membrane introduction mass spectrometry (MIMS). This technique was introduced in 1963 and allows the direct and continuous analysis of VOCs included in a complex mixture. MIMS is based on the use of semi-permeable membranes, such as polydimethylsiloxane (PDMS) (or silicone) membranes, as an interface between the sample and the mass spectrometer. The membrane allows the preconcentration of VOCs according to their physicochemical properties and their transfer into the mass spectrometer while simultaneously removing the remainder of the unretained sample. The adsorbed VOCs diffuse through the membrane and are evaporated directly into the ion source. Consequently, ion suppression phenomena related to the sample matrix are greatly reduced.The direct coupling between semi-permeable membranes and the mass spectrometer allows for a rapid, continuous analysis method with minimal sample preparation. The selectivity and sensitivity of this technique are governed by the ionization efficiency and the mass spectrometer, but also by the selectivity of the membranes used. This technique is applicable to liquid or gaseous samples.

[0007] Finally, the technique combining low temperature plasma and mass spectrometry (LTP-MS) was introduced in 1996. A plasma is generated using a dielectric barrier discharge (DBD) obtained by applying a high voltage and using gases such as helium. This plasma allows the ionization of VOCs directly on the surface of solid or liquid samples, but also of VOCs already present in the gas phase (ambient air and exhaled breath). LTP is a soft ionization source allowing the real-time analysis of VOCs from solid, liquid or gaseous samples, and possibly directly on their surface. This technique is also compatible with the analysis of exhaled air and ambient air. Abstract

[0008] The present disclosure improves the situation.

[0009] Thus, the present invention provides a (SI) system for analyzing VOCs adsorbed on an adsorbent membrane by LTP-MS, comprising: - a receptacle for receiving the adsorbent membrane; - a low-temperature plasma ionizer adapted to emit a plasma flow in a plasma emission direction, thereby ionizing the VOCs adsorbed by the membrane and forming an ionized gas loaded with VOCs; and - a mass spectrometer to analyze ionized VOCs.

[0010] (S2) System according to SI, further comprising a heater for heating the adsorbent membrane.

[0011] (S3) System according to SI or S2, in which the receptacle is arranged outside the flow of plasma.

[0012] (S4) System according to S3, in which: - the receptacle is a resealable container so as to form a confined environment except for an inlet and an outlet; - the container comprises a carrier gas inlet for the arrival of a carrier gas inside the container and a gas outlet for the exit of a gas potentially loaded with VOCs.

[0013] (S5) System according to S4, further comprising: - a carrier gas injection tube extending along a gas injection axis and one of the ends of which, the outlet end, opens into the closed container, the closed container being configured to hold the adsorbent membrane so that its surface is perpendicular to the gas injection axis, thus allowing the carrier gas to be charged with VOCs as it passes through the membrane; and - a guide tube for conveying the VOC-laden carrier gas to the ionizer.

[0014] (S6) System according to S5, comprising heating, and in which the heating is arranged around the injection tube for heating the carrier gas.

[0015] (S7) System according to S5 or S6, in which the closed container comprises a support of membrane for supporting a membrane, a sampling inlet for the entry of a sample gas and the loading of the membrane with VOCs, a sampling outlet for the exit of the sample gas, a carrier gas inlet.

[0016] (S8) System according to S7, in which the membrane support is a magazine of membranes configured to be put into rotational and / or translational motion and comprises a plurality of membrane housings, the membrane magazine being mounted so as to place a single housing, housing under analysis, opposite the outlet end of the injection tube and the inlet end of the guide tube.

[0017] (S9) System according to S7 or S8, in which the membrane magazine is mounted so as to place a single housing, sample-load housing, between the sampling inlet and the sampling outlet.

[0018] (S10) System according to S4, further comprising a guide tube and in which: - the outlet of the container is extended by the guide tube whose free end is close to the plasma flow when it is emitted so that the plasma ionizes the charged gas at the outlet of the tube.

[0019] (SI 1) System according to S4, further comprising a three-arm connector, and in which: - a first arm is connected to the outlet of the container; - a second arm has one end directed towards the entrance of the spectrometer of mass ; - the ionizer is configured so that the plasma flow is directed towards the third arm in operation.

[0020] (S 12) System according to SI or S2, in which the receptacle is arranged under the plasma flow so that the plasma flow is directed towards the membrane when the latter is received in the receptacle.

[0021] (S 13) System according to S12, in which: - the receptacle is a resealable container so as to form a confined environment with the exception of inlets and one outlet; - the container comprises a carrier gas inlet for the arrival of a carrier gas inside the container, a gas outlet for the exit of the ionized gas and a plasma inlet; - the outlet is extended by a guide tube for guiding the ionized gas towards the inlet of the mass spectrometer.

[0022] (S14) System according to one of SI to S13, in which the ionizer is a single or two electrodes.

[0023] (S 15) System according to S14, in which the ionizer is configured for an injection of inert gas at a flow rate between 50 and 1000 mL / min.

[0024] (S16) System according to one of SI to S15, further comprising a power supply for the power supply of the ionizer, in particular at a voltage between 1 and 30 kV and in particular at a frequency between 0.8 and 30 kHz.

[0025] (P17) Method for analyzing VOCs adsorbed on an adsorbent membrane by LTP- MS, including: - the supply of an adsorbent membrane on which VOCs have been adsorbed; - desorption of VOCs adsorbed on the adsorbent membrane; - low-temperature plasma ionization of desorbed VOCs, thus forming an ionized gas; and - mass spectrometry analysis of the ionized gas.

[0026] (P18) Method according to P17, further comprising heating the membrane.

[0027] (P19) Method according to P17 or P18, in which the ionization is carried out at a distance from the desorption.

[0028] (P20) Method according to P21, in which the desorption is carried out in a confined medium with the exception of a gas inlet and outlet, the adsorbent membrane being arranged in the confined medium; the method further comprising the injection of a carrier gas through the gas inlet to carry away the desorbed VOCs, thus forming a gas loaded with VOCs.

[0029] (P21) Method according to P20, further comprising the injection of a carrier gas perpendi cularly on the surface of the adsorbent membrane; and the guidance of the gas loaded in VOCs from vector gas injection to ionization.

[0030] (P22) Method according to P21, further comprising heating the carrier gas during his injection.

[0031] (P23) Method according to P20, further comprising guiding the gas loaded with VOCs from the desorption site to the ionization site and in which ionization is carried out in the open air.

[0032] (P24) Method according to P20, further comprising guiding the VOC-laden gas from the place of desorption towards the place of ionization and in which the ionization is carried out in a confined environment.

[0033] (P25) Method according to P17 or P18, in which the ionization is carried out in the vicinity immediate desorption, in particular by the formation of a plasma flow directed towards the adsorbent membrane.

[0034] (P26) Method according to P25, in which the desorption and ionization are carried out in a confined medium except for a gas inlet and outlet and where the adsorbent membrane is arranged; the method further comprising injecting a carrier gas through the gas inlet.

[0035] (P27) Method according to one of P17 to P26, in which the low temperature plasma generated during ionization is obtained from an inert gas, in particular nitrogen or a rare gas, for example argon, helium or neon.

[0036] (P28) Method according to P27, in which the flow rate of the internal gas is between 50 and 1000 mL / min.

[0037] (P29) Method according to one of P17 to P28, in which the ionization is powered by a voltage source between 1 and 30 kV.

[0038] (P30) Method according to one of P17 to P29, in which the ionization is powered by an energy source at a frequency between 0.8 and 30 kHz.

[0039] (P31) Method according to one of P17 to P30, further comprising the adsorption of VOCs on the adsorbent membrane.

[0040] (P32) Method according to P31, in which the adsorption comprises the preconcentration of the VOC on the adsorbent membrane.

[0041] (P33) Method according to P32, in which the preconcentration is carried out by sampling static headspace sampling, dynamic headspace sampling, or solid-phase microextraction.

[0042] (P34) Method according to P33, in which the preconcentration is carried out by sampling static headspace scavenging by suction or static headspace sampling by gas sweeping.

[0043] (P35) Method according to one of P17 to P34, in which the analysis comprises the com comparison of spectra obtained with a molecular fingerprint database.

[0044] (P36) Diagnostic assistance method, comprising the method according to P35, in which VOCs from the patient were adsorbed onto the adsorbent membrane, the method further comprising determining the medical status of the patient based on the comparison.

[0045] (P37) Method according to P36, wherein the medical status of the patient comprises an in training concerning at least one of the stage, grade and type of cancer the patient has.

[0046] (P38) Method according to P36 or P37, in which the method is a method of assisting the breast cancer diagnosis.

[0047] (P38) Method according to P38, in which the adsorption is carried out by contacting of the adsorbent membrane with the patient's skin for the adsorption of VOCs. Brief description of the drawings

[0048] Other characteristics, details and advantages will appear on reading the detailed description below, and on analyzing the attached drawings, in which: Fig.l

[0049] [Fig.l] shows a diagram of a first system where desorption and ionization are carried out at the same place or in the immediate vicinity. Fig. 2

[0050] [Fig.2] shows a diagram of a second system where desorption and ionization are carried out in the same place or in the immediate vicinity. Fig. 3

[0051] [Fig.3] shows a diagram of a third system where desorption and ionization are carried out at the same location or in close proximity. Fig. 4

[0052] [Fig.4] shows a diagram of a first system where desorption and ionization are carried out remotely. Fig. 5

[0053] [Fig.5] shows a diagram of a second system where desorption and ionization are carried out remotely. Fig. 6

[0054] [Fig.6] shows a diagram of a third system where desorption and ionization are carried out remotely. Fig. 7

[0055] [Fig.7] shows a diagram of a usable barrel-shaped membrane support in the system of [Fig.6]. Fig. 8

[0056] [Fig.8] shows a diagram of a translational plate-shaped membrane support usable in the system of [Fig.6]. Fig. 9

[0057] [Fig.9] shows a schematic of a single electrode LTP ionizer. Fig. 10

[0058] [Fig. 10] shows a schematic of a two-electrode LTP ionizer. Fig. 11

[0059] [Fig. 11] is a graph illustrating the minimum size (in angstroms) of the pores of an adsorbent membrane to allow a molecule of a given size (in daltons) to pass through. Fig. 12

[0060] [Fig. 12] shows four spectra obtained using the method and system according to the invention: PI and P2 are spectra obtained from two patients suffering from breast cancer and SI and S2 are spectra obtained from two healthy people, with the left breast. Fig. 13

[0061] [Fig. 13] shows two spectra obtained from a single patient using the method and system according to the invention: B1 is the spectrum corresponding to the right breast and B2 to the left breast. Description of the embodiments

[0062] The drawings and the description below contain, for the most part, elements of a certain character. They may therefore not only serve to better understand the present disclosure, but also contribute to its definition, if necessary. System

[0063] With reference to the drawings, a system for analyzing VOCs adsorbed on an adsorbent membrane by LTP-MS will be described below. Such a system, which can be on-board, comprises a receptacle 1 for receiving the adsorbent membrane M, a low-temperature plasma ionizer 2 (LTP ionizer) and adapted to emit a plasma flow P along a plasma emission direction thus ionizing the VOCs adsorbed by the membrane M and a mass spectrometer (MS) 3 configured to analyze the gas mixture comprising the ionized VOCs such as cyclohexanol C6H ii-OH, dodecan-2-one CH3-CO-(CH2)9-CH3, nonan-2-one CH3-CO-(CH2)6-CH3 and 4-methylheptan-2-one CH3-CO-CH2-CH(CH3)-(CH2)2-CH3. These VOCs are present in particular in samples taken from patients suffering from breast cancer.The system may further include an ion mobility cell (not shown in the figures) for LTP-IMS (ion mobility spectrometry)-MS analysis. This ion mobility cell may be provided separately from the MS between it and the LTP ionizer or may be an integral part of the MS.

[0064] Throughout this disclosure, reference is made to ionized species, as ionized gas or ionized VOCs. Of course, this does not necessarily mean that all molecules of the ionized species have been ionized by the plasma, but that at least some of the gas or VOCs have been ionized.

[0065] The system may further comprise a power supply 4 for powering the LTP ionizer 2, in particular at a voltage of between 1 and 30 kV (preferably 7 to 18 kV) and / or at a frequency of between 0.8 and 30 kHz (preferably 2 to 10 kHz). The combination of preferred ranges is particularly suitable for one of the many applications envisaged, which is the detection of breast cancer. The power supply may be continuous or alternating. In the latter case, the following combinations are particularly interesting: (4 kV; 24 kHz) to (6 kV; 20 kHz); (5.5 kV; 25 kHz) to (7 kV; 21 kHz); (6.5 kV, 25 kHz) to (10 kV; 23.5 kHz). The ionizer may be configured to produce a plasma continuously or by pulses.

[0066] The LTP 2 ionizer can be of two types: a first type with a single electrode ([Fig.9]) and a second type with two electrodes ([Fig. 10]). In the figures representing the system, only the LTP 2 ionizer with two electrodes is shown, but this can be replaced by a LTP 2 ionizer with a single electrode.

[0067] Regardless of the type, the LTP ionizer 2 typically comprises a T-connector 24 with two coaxial arms 241, 242 and a transverse arm 243, a dielectric barrier 22 connected to one of the two coaxial arms, an electrode extending through the T-connector 24 via the two coaxial arms 241, 242 and the dielectric barrier 22 to a position close to and upstream of the plasma outlet 28. The electrode 26 may be connected to the power supply 4 in operation. The electrode 26 may be made of copper. Preferably, the electrode 26 is a metal wire, for example 1.5 mm in diameter.

[0068] The inert gas of the LTP, for which the transverse arm 243 of the T-connector 24 serves as an injection inlet, can be nitrogen, water vapor or a rare gas. In the case where the inert gas is a rare gas, this rare gas can be argon, helium or neon. A mixture of these mentioned gases is also possible. The LTP ionizer 2 can be configured for an injection of inert gas at a flow rate between 50 and 1000 mL / min.

[0069] The single-electrode LTP 2 ionizer ([Fig.9]) typically further comprises three glass tubes 21, 22, 23 connected end to end: i.e. the second tube 22 is connected by one of its ends to the first tube 21 and by the other of its ends to the third tube 23. It also comprises a flexible tube 25. The two coaxial arms 241, 242 of the T-connector 24 connect the first tube 21 to the second tube 22. The flexible tube 25 connects the second tube 22 and the third tube 23 to each other. The electrode 26 extends inside the first and second tubes 21, 22, in particular from the end of the first tube 21 not connected to the second tube 22, up to the end of the second tube 22 connected to the third tube 23 without exceeding the second tube 22. The second tube 22 forms the dielectric discharge barrier and the third tube 23 forms a capillary extension.

[0070] The two-electrode LTP 2 ionizer ([Fig. 10]) typically further comprises a glass tube 22 forming the dielectric barrier and extending through the T-connector 24 from the first coaxial arm 241 thereof and to the plasma outlet 28 formed by one end of the glass tube 22. The first electrode 26 extends through the glass tube 22 to the position downstream of the plasma outlet 28. The LTP 2 ionizer comprises a second electrode 29 arranged around the second tube 22 so as to also surround the first electrode 26 and not to extend beyond the end thereof. Thus, the second electrode 29 has an annular shape. The second electrode 29 is preferably made of copper and connected to ground to serve as a reference electrode.

[0071] This disclosure also covers LTP 2 ionizers having the same structure as the single-electrode ionizer described above but with two electrodes, the second electrode serving as a reference; as well as LTP 2 ionizers having the same structure as the two-electrode ionizer described above but with a single electrode, the ground of the power supply serving as a reference.

[0072] Two embodiments are possible. These two embodiments differ from each other by the location of the ionization, which can be at the location of the desorption of the VOCs or at a distance from it. Figures 1 to 3 show variants in which the ionization is carried out at the location or at least close to the desorption of the VOCs and Figures 4 to 5 illustrate variants in which the ionization is carried out at a distance from the desorption of the VOCs.

[0073] Thus, Figures 1 to 3 show systems in which the receptacle 1 is arranged under the plasma flow P so that the plasma flow P is directed towards the membrane M when the latter is received in the receptacle 1. In this embodiment, the receptacle 1 and the LTP ionizer 2 are arranged so that the plasma plume P touches or is flush with the upper surface of the membrane M when the latter is positioned on the receptacle 1. Still in this embodiment, a heater 4 (preferably homogeneous) may further be provided in the system for heating the membrane M and thus assisting in the desorption of the VOCs. Typically, this heater 4 is arranged below the receptacle 1 which transmits the heat generated by the heater 4 to the membrane M.The heater 4 is configured to allow heating between 0 and 500°C (preferably between 0 and 400°C, in particular between 200 and 300°C or even between 225 and 275°C; for example 50°C, 100°C, 150°C, 200°C, 250°C, 300°C, 350°C, 400°C, 450°C) and to assist in the desorption of VOCs.

[0074] More particularly, [Fig.l] shows a system in which the receptacle 1 is arranged just below the LTP ionizer 2 and close to the inlet 31 of the MS 3. Thus, the receptacle 1 is arranged so that the plasma plume P formed is directed towards the adsorbent membrane M. For example, the receptacle 1 can be arranged so that a front edge M1 of the adsorbent membrane M when the latter is received by the receptacle, is located between 0 and 20 mm from the inlet 31 of the MS. Alternatively or in addition the receptacle 1 and the LTP ionizer 2 can be arranged so that the outlet 28 of the plasma plume and the surface of the adsorbent membrane M when the latter is in place, are spaced 0 to 20 mm apart. The LTP 2 ionizer can also be arranged to rotate so that the angle a formed by the plasma plume P and the surface of the adsorbent membrane when the latter is in place is between 0 and 90°, preferably between 35 and 75°, thus forcing the gas towards the MS.The rotation axis being horizontal is perpendicular to the axis of the inlet 31 of the MS; the angle a being acute when the LTP 2 ionizer is moved away from the MS 3. Thus, in this variant of the first embodiment, the plasma plume P generated by the LTP 2 ionizer has two functions: that of desorbing the VOCs and that of ionizing them.

[0075] [Fig. 2] shows a system similar to that of [Fig. 1]. The difference lies in the receptacle 1 comprising a carrier gas inlet 11 on a lower surface thereof. Thus, a carrier gas can be injected under the lower surface of the adsorbent membrane M. The carrier gas can be in particular an inert gas, for example nitrogen, helium, argon or a mixture thereof. Preferably, the cross-section of the carrier gas inlet 11 has substantially the same dimension as the membrane M. In order for the membrane M to be able to be supported, a grid is provided at the carrier gas inlet. The gas source is preferably adapted to emit a carrier gas flow rate of between 0.5 and 7 L / min. The gas source can be the same as that of the MS; above 7 L / min, there is a risk of disturbing the plasma. This carrier gas inlet can be extended by an injection tube connected to a carrier gas source.Preferably, heating is provided around the injection tube.

[0076] [Fig. 3] shows a system in which the receptacle 1 is a resealable container so as to form a confined environment with the exception of a gas inlet and outlet as well as a plasma inlet. The container 1 is therefore closed and can be made airtight. Thus, the container comprises a carrier gas inlet 11 for the arrival of a carrier gas inside the container 1, a plasma inlet 13, and a gas outlet 12 for the outlet of an ionized gas loaded with VOCs comprising the carrier gas and potentially ionized VOCs. The carrier gas may in particular be an inert gas, for example nitrogen, helium, argon or a mixture thereof.

[0077] The container 1 may have a cylindrical geometry with a lower support surface and an upper surface parallel to each other and a lateral surface connecting the lower and upper surfaces.

[0078] Furthermore, the gas inlet 11 may be an injection tube connected at its free end to a source of inert gas. The axis of the injection tube and the upper surface of the container may form an angle p of between 30 and 75° or even between 35 and 75°, making it possible to force the gas towards the gas outlet 12. The internal diameter of the injection tube may be between 2 and 10 mm. The gas source is preferably adapted to emit a flow rate of inert gas of between 0.5 and 7 L / min. The gas source may be the same as that of the MS; above 7 L / min, there is a risk of disturbing the plasma.

[0079] The plasma inlet 13 may be an orifice made on the upper surface of the container 1. Alternatively, the plasma inlet 13 may be a short tube extending from the upper surface of the container 1. In both cases, the plasma inlet 13 may be connected to the plasma outlet orifice of the LTP ionizer. This connection may be direct with the plasma outlet orifice of the LTP ionizer in contact with the plasma inlet 13, or via a connector (not shown). This connection may be hermetic or non-hermetic.

[0080] The outlet 12 may be a guide tube for guiding the ionized gas to the inlet 31 of the MS. It is preferably made on a lateral surface of the container 1. The axis of the guide tube is preferably horizontal and connects the outlet of the container 1 and the inlet 31 of the MS. The internal diameter of the guide tube may be between 2 and 12 mm. The free end of the guide tube may be arranged at a distance of between 0 and 100 mm from the inlet of the MS.

[0081] The container 1 and the LTP ionizer 3 can be arranged so that the outlet of the plasma plume P and the surface of the adsorbent membrane when it is received therein are spaced apart by 0 to 50 mm. The LTP ionizer can also be arranged to rotate so that the angle formed by the plasma plume and the surface of the adsorbent membrane when it is in place is between 30 and 90°, preferably between 35 and 75°, thus making it possible to force the gas towards the MS. The axis of rotation being horizontal is perpendicular to the axis of the inlet of the MS; the angle being acute when the LTP ionizer is moved away from the MS. Thus, in this variant of the first embodiment, the plasma plume generated by the LTP ionizer has two functions: that of desorbing the VOCs and that of ionizing them.

[0082] As indicated above, Figures 4 to 6 show systems in which the receptacle is arranged outside the plasma flow. Heating (preferably homogeneous) may also be provided for heating the container, in particular between 0 and 500°C and thus assist in the desorption of VOCs. Preferably, the heating temperature is between 0 and 400°C, in particular between 200 and 300°C or even between 225 and 275°C; for example 50°C, 100°C, 150°C, 200°C, 250°C, 300°C, 350°C, 400°C, 450°C) and to help desorb VOCs.

[0083] Figures 4 to 6 show systems in which the receptacle 1 is a resealable container so as to form a confined medium except for an inlet and an outlet, and comprises an inlet 11 for carrier gas and an outlet 12 for gas loaded with VOCs.

[0084] In these variants, the container 1 may be an Erlenmeyer flask (figures 4 and 5) provided with a stopper 14, in particular made of cork, with two through bores made in the stopper 14. The bores allow the introduction of two tubes: a first tube forming an inlet 11 for carrier gas, the end of which inserted into the container is located near the bottom of the container; and a second tube forming an outlet 12 for gas loaded with VOCs, the end of which inserted into the container is at a higher altitude than the end of the tube forming an inlet for carrier gas. Each of the first and second tubes may have an internal diameter of between 2 and 10 mm.

[0085] The carrier gas inlet 11 may be connected to a carrier gas source. The carrier gas is in particular an inert gas, for example nitrogen, helium, argon or a mixture thereof. The gas source may be configured to emit a flow rate of between 0.5 and 7 L / min. The gas source may be the same as that of the MS; above 7 L / min, there is a risk of disturbing the plasma.

[0086] The heater 4 can be arranged under the receptacle.

[0087] More particularly, [Fig. 4] shows a system which further comprises a guide tube 15. In this system, the outlet 12 of gas charged with VOCs is extended by the guide tube 15, the free end of which is close to the plasma flow P, and in particular the end of the plasma plume, when the latter is emitted so that the plasma ionizes the charged gas at the outlet of the guide tube 15 and before its entry into the MS 3. The axis of the guide tube 15 preferably forms an angle y of between 10 and 65° with the vertical. The distance between the free end of the guide tube 15 and the inlet 31 of the MS may be between 2 and 50 mm. The guide tube 15 may have an internal diameter of between 2 and 10 mm. Furthermore, the guide tube 15 and the second tube forming the outlet 12 of gas charged with VOCs may be made in a single piece.

[0088] The LTP 2 ionizer can also be arranged to rotate so that the angle formed by the plasma plume P and the horizontal is between 0 and 90°, preferably between 35 and 75°, thus making it possible to force the gas towards the MS. The axis of rotation being horizontal is perpendicular to the axis of the inlet 31 of the MS; the angle being acute when the LTP 2 ionizer is spaced from the MS 3. In this case, the LTP 2 ionizer and the MS 3 can be arranged so that the axis of the plasma plume P is coaxial with the inlet 31 of the MS when the angle is equal to 0. In this position with a zero angle, the distance between the end of the plasma plume and the inlet of the MS can be between between 1 and 70 mm.

[0089] [Fig. 5] shows a system further comprising a two-arm connector 17. A first arm is connected to the outlet 12 of the container 1, for example using a hose 16. A second arm has one end directed towards the inlet 31 of the MS. Although not necessary, preferably the axis of the second arm is coaxial with the inlet 31 of the MS. An orifice arranged between the first and second arms is used to receive the plasma plume. This orifice can be replaced by a third arm; the connector was then a three-arm connector.

[0090] The three-arm connector 17 may be a T-connector with the first arm and the second coaxial arms following the same first direction and the third arm transverse with respect to the coaxial arms and extending in a second direction different from the first direction.

[0091] The inner diameter of the first and second arms may be between 2 and 10 mm. The length between the free ends of the first and second arms may be between 2 and 20 cm. The distance between the inlet of the MS and the free end of the arm facing it may be between 0 and 70 mm. The length of the hose may be between 2 and 200 cm.

[0092] The third arm, or the orifice that replaces it, can be connected to the plasma outlet orifice of the LTP ionizer. This connection can be direct with the plasma outlet orifice of the LTP ionizer in contact with the third arm or the edge of the orifice that replaces it, or via a connector (not shown). This connection can be hermetic or non-hermetic.

[0093] [Fig. 6] shows a system which further comprises a vector gas injection tube 18 and a guide tube 15. The vector gas injection tube 18 extends along a gas injection axis and one of the ends, the outlet end, opens into the closed container 1 for the inlet 11 thereof. The closed container is configured to maintain the adsorbent membrane M in a position where its surface is perpendicular to the gas injection axis, thus allowing the vector gas to be charged with VOCs as it passes through the membrane; for example by comprising a membrane support. The guide tube 15 is used for conveying the gas charged with VOCs from the outlet 12 of the closed container to the LTP ionizer 2 and the MS 3.

[0094] The length of the vector gas injection tube 18 may be between 5 and 100 cm. The inner diameter of the vector gas injection tube may be between 2 and 10 mm.

[0095] A carrier gas source may be provided and connected to the free end of the gas injection tube for injecting an inert gas. The inert gas may be nitrogen, water vapor, or a rare gas. In the case where the inert gas is a rare gas, this rare gas may be argon or helium. A mixture of these mentioned gases is also possible. The gas source can be configured to allow a carrier gas flow rate between 0.05 and 7 L / min. The gas source can be the same as that of the MS; above 7 L / min there is a risk of disturbing the plasma

[0096] The vector gas injection tube 18 may be provided with a valve 181 and / or the inlet 11 of the closed container with a valve 111. The valve 181 makes it possible to avoid excessive pressure inside the vector gas injection tube 18; which could damage the adsorbent membrane. The valve 111 allows the gas flow rate to be controlled, in particular finer control than that of the inert gas source.

[0097] The axis of the guide tube 15 is preferably coaxial with the axis of the inlet 31 of the MS. The length of the guide tube may be between 1 and 10 cm. The internal diameter of the guide tube may be between 1 and 10 mm.

[0098] The guide tube 15 may be a three-arm connector with two arms forming the guide tube itself (the first arm being at the outlet of the container 1 and the second arm opening out in the vicinity of or connected to the inlet 31 of the MS) and a third arm for the plasma plume generated by the LTP ionizer 2 in order to carry out ionization in a confined environment. The three-arm connector may be a T-connector with the first and second coaxial arms forming the guide tube itself and the third arm transverse to the first and second arms. The three-arm connector may be a T-connector with the first and second coaxial arms and the third arm transverse to the first and second arms. The third arm may be connected to the plasma outlet orifice of the LTP ionizer. This connection may be direct with the plasma outlet orifice of the LTP ionizer in contact with the third arm or via a connector (not shown).This connection can be hermetic or non-hermetic. Just like the variant in [Fig.5], the third arm can be replaced by a simple orifice.

[0099] In this variant, the heater 4 may be provided around the injection tube 18 for heating the carrier gas, for example, using an electric heating tape wound around the carrier gas injection tube. The electric heating tape may, for example, be clamped onto the carrier gas injection tube or glued thereto.

[0100] The closed container 1 may further comprise a sampling inlet 191 for the entry of a sample gas and the loading of the adsorbent membrane M with VOCs and a sampling outlet 192 for the exit of the sample gas. Thus, it is possible, using a single element, to carry out both the loading of the membrane with a gaseous sample possibly comprising VOCs and the analysis without the need to manipulate the adsorbent membrane.

[0101] For example, the sampling inlet 191 and outlet 192 may be positioned on either side of the membrane support, in the direction of the carrier gas flow. Two versions may be provided: - the sample inlet 191 is downstream and the sample outlet 192 is upstream relative to the direction of the carrier gas flow (membrane not passing VOCs); - the sample inlet 191 is upstream and the sample outlet 192 is downstream relative to the direction of the carrier gas flow (membrane passing VOCs).

[0102] In order to simplify the container, two ports can be provided on either side of the membrane support and acting as both inlet and outlet for the sample gas depending on whether the sample gas flow is in the same direction as the carrier gas flow, or in the opposite direction.

[0103] The membrane support 9 can serve as a membrane magazine. In this case, the membrane support 9 can be adapted to be inserted by sliding into a housing for receiving it. Also, it can be configured to be put into movement, for example rotary and / or translational, and comprise a plurality of membrane housings 91. The membrane support 9 can be mounted so as to place a single housing 91, housing in analysis, between the inlet 11 and the outlet 12 of the closed container 1. Similarly, the membrane support 9 can be mounted so as to place a single housing 91, housing in charge, between the sampling inlet 191 and the sampling outlet 192. The housings 91 are preferably through orifices whose side wall is a right cylinder, preferably with a circular base. The membrane support 9 may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or even more housings.These housings 91 are preferably regularly distributed on the membrane support 9.

[0104] For example, the membrane support 9 may be a rotating barrel ([Fig.7]) with a plurality of membrane housings 91 distributed angularly around the axis of rotation of the barrel which is preferably collinear with the flow of vector gas arriving in the container 1. These housings 91 are preferably regularly distributed angularly and their center is placed on the same circle whose center is the axis of rotation of the barrel. The barrel is for example a cylinder with a circular base having the housings and being wider than it is high. The mean plane of the barrel passing through the middle of its height is perpendicular to the flow of vector gas arriving in the container 1 so that preferably its axis of rotation is perpendicular to its mean plane.

[0105] Alternatively, the membrane support 9 may be a translational plate ( [Fig.8]) with a plurality of membrane housings 91. The mean plane (passing through the thickness) of the translational plate is perpendicular to the flow of carrier gas arriving in the container 1. The translational plate is mounted in translation allowing a translation in its mean plane along a single axis or two perpendicular axes. The housings are preferably regularly distributed on the translational plate. The example illustrated in [Fig.8] is particularly particularly suitable for translational motion along two perpendicular axes. A translational plate with membrane housings 91 aligned along a line is particularly suitable for translational motion along a single axis.

[0106] Advantageously, the membrane support 9 is made of a material resistant to high temperatures, up to 300°C in particular, for example stainless steel. The material is preferably also resistant to high pressure, in particular up to 7 bar.

[0107] The connections between the membrane support 9 and the vector gas injection or sample loading and unloading elements are advantageously gas-tight. In order to ensure this sealing, a housing may be provided in which the membrane support 9 is mounted (in particular for rotation or translation). The gas inlets and outlets and / or the sampling inlets and outlets are made in this housing.

[0108] The system may comprise an electronic control configured to control the movement of the membrane support 9. The control may also control the loading of a membrane with a gas sample and / or control the injection of the carrier gas.

[0109] The LTP ionizer 1 can also be arranged to rotate so that the angle formed by the plasma plume and the axis of the guide tube is between 30 and 90°, preferably between 35 and 75°, thus making it possible to force the gas towards the MS. The axis of rotation being horizontal is perpendicular to the axis of the MS inlet; the angle being acute when the LTP ionizer is moved away from the MS.

[0110] In all the cases described above, the source of the carrier gases can be that of the MS.

[0111] The system can be used in particular with adsorbent membranes in mode passing or not. That is to say, during desorption, the VOCs pass through the adsorbent membrane or not.

[0112] Simulations were carried out to determine the minimum pore size (radius Rmin in angstroms) of a suitable adsorbent membrane as a function of the size (weight M in daltons) of the VOC molecule in gaseous form and assimilated to a sphere (see [Fig.l 1]). The graph in [Fig.l] is obtained from known calculations of the compound size in the form of a sphere:

[0113] [Math.l] Rmin =

[0114] The following table gives some points of the graph of [Fig.l 1].

[0115] [Tables 1] M(Da) Rmin (Â) 50 2.43 100 3.06 150 3.51 200 3.86 225 4.01 250 4.16 300 4.42 400 4.86 500 5.24 1000 6.60 5000 11.29 10000 14.22 20000 17.92 50000 24.31

[0116] Thus, in order to allow a molecule of 400 Da, for example, to desorb and pass through the membrane, the pore size must be at least 4.86 Å. Thus, the pore size of adsorbent membranes determines whether they can be used in pass-through mode or not.

[0117] The membranes may be of the carbon-based type, including molecular sieves or graphitized carbon black. The membranes may also be of the porous polymer type, including divinylbenzene or phenylphenylene oxide-based polymer or polydimethylsiloxane. The table below summarizes the characteristics of some types of membranes:

[0118] [T ableaux2] Type Carbon Material Surface area (m2 / g) Polarity Carbon molecular sieve 387-485 Polar Graphitized carbon black 240-250 Non-polar Porous polymer Divinylbenzene 550 Polar Phenylphenylene oxide 20-35 Bipolar PDMS 280-350 Non-polar Process

[0119] A method for analyzing VOCs adsorbed on an adsorbent membrane and using the system presented above is described below with reference to Figures 1 to 8.

[0120] This method comprises providing an adsorbent membrane onto which VOCs have been adsorbed, desorbing the VOCs adsorbed onto the adsorbent membrane, low temperature plasma ionization of the desorbed VOCs thereby forming an ionized gas, and mass spectrometric analysis of the ionized gas.

[0121] LTP ionization typically comprises injecting an inert gas into a dielectric discharge barrier in which the inert gas is charged. The inert gas may be nitrogen, water vapor, or a rare gas. In the case where the inert gas is a rare gas, this rare gas may be argon, helium, or neon. A mixture of these mentioned gases is also possible. The injection may be carried out at a flow rate between 50 and 1000 mL / min.

[0122] The discharge can be carried out at a voltage between 1 and 30 kV and / or at a frequency between 0.8 and 30 kHz. The discharge can be continuous or pulsed.

[0123] The method may further comprise a step of heating the adsorbent membrane, in particular to a temperature between 0 and 400°C.

[0124] The method may further comprise adsorbing the VOCs onto the adsorbent membrane.

[0125] Adsorption may include preconcentration of VOCs on the adsorbent membrane. Preconcentration may be achieved by static headspace sampling (SHS), dynamic headspace sampling (DHS), or solid phase microextraction (SPME).

[0126] When preconcentration is performed by static sampling in the headspace, it can be performed by aspiration (in English: aspiration dynamic headspace sampling, DHSa) or by gas sweep (in English: sweep gas dynamic headspace sampling, DHSs).

[0127] Alternatively, adsorption may be achieved by contacting the adsorbent membrane before a source of VOC potential; for example, by depositing the adsorbent membrane directly on a patient's skin, or by directing a patient's breath toward the adsorbent membrane, etc.

[0128] The analysis may include comparing the obtained spectra(s) with a database of molecular fingerprints. Each of these molecular fingerprints is a global VOC spectrum corresponding to given situations (classes), e.g. healthy person, cancer, type and subtype of cancer, stage of cancer, etc. The molecular fingerprints of the database with their class are used to construct classification models with multivariate statistical analysis tools, for example algorithms of the support vector machine (SVM) or latent Dirichlet allocation (LDA), or even by neural networks such as the convolutional neural network (CNN).

[0129] Thus, the spectrum(s) obtained are not compared to isolated VOC spectra, but it is the general appearance of the spectrum(s) obtained which is compared with the appearance of the molecular fingerprints in the database. Examples of such comparisons are given below. Alternatively, the spectra obtained can be compared to isolated VOC spectra.

[0130] Two modes of implementation are possible. In a first mode (corresponding to the systems of Figures 1 to 3), the ionization is carried out in the immediate vicinity of the desorption, in particular by the formation of a plasma flow directed towards the adsorbent membrane. In a second mode (corresponding to the systems of Figures 4 to 6), the ionization is carried out at a distance from the desorption.

[0131] In the first mode, ionization can be achieved by forming a plasma flow directed toward the adsorbent membrane. The plasma flow can be perpendicular to the upper surface of the adsorbent membrane or inclined so that the tip of the plasma plume is oriented toward the inlet of the MS by rotating the LPD, for example. The tip of the plasma plume can just be flush with the upper surface of the adsorbent membrane or touch it.

[0132] In a first variant of the first mode (corresponding to the system of [Fig.l]), the ionization can be carried out at a distance of between 0 and 20 mm from the inlet of the MS. The ionization can be carried out with an angle of the plasma plume relative to the surface of the adsorbent membrane of between 0 and 90°; the angle being acute when the plasma plume has its tip directed towards the MS. Thus, desorption and ionization are carried out concomitantly by LTP.

[0133] In a sub-variant (corresponding to the system of [Fig.2]), the method further comprises an injection of carrier gas perpendicular to the lower surface of the adsorbent membrane. The carrier gas may be in particular an inert gas, for example nitrogen, helium, argon or a mixture thereof. The flow rate of the carrier gas may be between 0.5 and 7 L / min. Preferably, the carrier gas is injected over the entire lower surface of the adsorbent membrane. The heating of the adsorbent membrane may be achieved by heating the carrier gas before it reaches the lower surface of the adsorbent membrane.

[0134] In a second variant of the first mode (corresponding to the system of [Fig. 3]), the desorption and ionization are carried out in a confined medium with the exception of a gas inlet and outlet as well as a plasma inlet. The adsorbent membrane is arranged inside the confined medium. The method then also comprises the injection of a carrier gas inside the confined medium. The injection angle of the carrier gas relative to the surface of the adsorbent membrane may be 30 to 75°. The injection of the carrier gas may be carried out at a flow rate of 0.5 to 7 L / min. The carrier gas may be in particular an inert gas, for example nitrogen, helium, argon or a mixture thereof. Inside the confined environment, the carrier gas eventually becomes loaded with VOCs if VOCs are adsorbed on the adsorbent membrane, and the VOC-loaded gas is evacuated towards the gas outlet to the MS.

[0135] The method may include conducting the carrier gas to the inlet of the MS such that the flow direction of the charged gas is coaxial with the inlet of the MS.

[0136] The formation of the plasma plume can be carried out so that the axis of the plasma plume and the surface of the adsorbent membrane when the latter is in place, is between 30 and 90°.

[0137] In a first variant of the second mode (corresponding to Figures 4 and 5), the desorption is carried out in a confined medium with the exception of a gas inlet and outlet. The adsorbent membrane is arranged in the confined medium. The method then comprises the injection of a carrier gas inside the confined medium. This carrier gas carries away any desorbed VOCs present on the adsorbent membrane, thus forming a gas loaded with VOCs which leaves the confined medium through the outlet.

[0138] The vector gas being in particular an inert gas, for example nitrogen or a rare gas such as helium and argon, or a mixture thereof. The injection of the vector gas can be carried out at a flow rate of between 0.5 and 7 L / min.

[0139] Heating may be achieved by heating the receptacle.

[0140] More particularly, in a first sub-variant (corresponding to the system of [Fig.4]), the gas loaded with VOCs is guided to the vicinity of the plasma flow, and in particular from the end of the plasma plume, when it is emitted so that the plasma ionizes the charged gas and just before its entry into the MS, for example between 2 and 50 mm before the MS entry. Thus, the ionization takes place in the open air. Preferably, the guidance of the VOC-charged gas is carried out at an angle to the vertical of between 10 and 65°.

[0141] Ionization can be carried out so that the plasma plume forms an angle between 0 and 90° with the horizontal. The angle is acute when the plasma plume is directed towards the MS. It is therefore possible to orient the plasma plume so that it is coaxial with the inlet of the MS. In this position with a zero angle, the distance between the end of the plasma plume and the inlet of the MS can be between 1 and 70 mm.

[0142] In a second sub-variant (corresponding to the system of [Fig.5]), the VOC-laden gas is guided to the vicinity of the plasma flow and ionization is carried out in a confined environment before leaving the confined place towards the entrance of the MS.

[0143] In a second variant (corresponding to the system of [Fig.6]), the injection of the vector gas is carried out perpendicular to the surface of the adsorbent membrane and the guidance of the gas loaded with VOCs is carried out coaxially with the injection of the vector gas. The vector gas is an inert gas, for example nitrogen, water vapor or a rare gas. In the case where the inert gas is a rare gas, this rare gas can be argon or helium. A mixture of these gases mentioned is also possible. The injection of the vector gas is carried out with a vector gas flow rate of between 0.5 and 7 L / min. The ionization of the gas loaded with VOCs is carried out either in the open air or in a confined environment.

[0144] In this case, the heating is carried out by heating the carrier gas during its injection.

[0145] Still in this variant, the method may comprise loading the adsorbent membrane with a gas sample when it is already in the closed container and before the injection of carrier gas, which makes it possible to avoid excessive handling of the membrane, thus limiting contamination and VOC losses. The loading may be carried out at ambient temperature or when hot. The loading temperature may in particular be lower than the heating temperature. This is particularly advantageous for adsorbent membranes used in non-passing mode, although it can also be used for the passing mode. Alternatively, the membrane may already be loaded with VOCs when it is placed in the closed container. There is then no need to load it with a gas sample.

[0146] Furthermore, in this variant, it is possible to carry out the analysis of several samples continuously. For this, the method further comprises changing the adsorbent membrane before a new loading of the new adsorbent membrane with gaseous sample and a repetition of the other steps of the method. Alterna Typically, a plurality of membranes already loaded with VOCs are arranged in the closed container. In both cases, only one membrane at a time is presented in the carrier gas flow.

[0147] Other features of the method are directly deduced from the characteristics of the system described above in these multiple variants. Furthermore, in the embodiments comprising the injection of a carrier gas, the heating of the membrane can be carried out by the introduction of hot carrier gas, in particular between 23 and 100°C, for example approximately 30°C.

[0148] The applications of this method are particularly medical. Thus, the methods described above can be part of a diagnostic aid method. In which case the VOCs come from a patient and have been adsorbed onto the adsorbent membrane, for example by physical contact with the patient or by gaseous transfer (exhalation) for gaseous samples. For bodily fluids (for example sweat, saliva, urine), the bodily fluid is first collected in a container, in particular a tube. It is then transferred onto the adsorbent membrane in particular by one of the preconcentration techniques described above (SHS or DHS). Solid samples can be transferred onto an adsorbent membrane by solid-phase microextraction.

[0149] Such a diagnostic assistance method further comprises steps of the VOC analysis method, determining the medical status of the patient based on the results of the comparison. This determination is not a diagnosis that only the doctor is authorized to make, but gives an indication to assist the doctor in his decisions. This diagnostic assistance method can be advantageously used for example for cancer and in particular cancer and in particular breast cancer.

[0150] For this, the medical status of the patient provided by the method may include information concerning at least one of the stage, grade and type of cancer from which the patient is suffering.

[0151] Conventionally, a diagnosis is made to determine the stage of the cancer, i.e. its extent. To do this, doctors use three criteria: i) the size and infiltration of the tumor, ii) whether or not the lymph nodes are involved, and iii) whether or not there are metastases. These criteria are the subject of a classification called "TNM" for "tumor, nodes, metastases" ("Tumor, Nodes, Metastasis" in English) by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC, in English). T concerns the size of the tumor, N for lymph node involvement, and M for distant metastases. For each of these criteria T, N or M, an annotation is made either by letter (“x” when the criterion cannot be evaluated, for example the information obtained is insufficient) or by numbers (from 1 to 4 for T; from 1 to 3 for N; and 0 if there is no distant metastasis or 1 if there is). These criteria are assessed during a clinical examination which can be carried out before any treatment to determine the pre-therapeutic stage (cTNM classification, c for clinical) or after surgery to determine the anatomopathological stage (pTNM classification, p for post-surgical).

[0152] Thus, when the patient's medical status includes information on the stage of the cancer, this information includes an annotation on at least one of the criteria T, N and M, preferably on all three criteria. This information then statistically indicates to which stage the molecular spectrum obtained corresponds.

[0153] Furthermore, particularly with regard to breast cancer, not all these cancers have the same aggressiveness. Only anatomopathological examination can determine this. For this, conventionally, the practitioner carefully observes, first with the naked eye and then under a microscope, tissues taken from the patient. This examination makes it possible to define the grade of the tumor, that is to say its aggressiveness. For this, three criteria are evaluated on a scale ranging from 1 to 3: i) the architecture, 1 indicating that the tumor contains many well-formed structures, 3 that the tumor contains few or no well-formed structures; ii) the nucleus, 1 indicating that the tumor nuclei are small and uniform, 3 that the nuclei are large and their size and shape vary; and iii) mitotic activity, with 1 indicating that the tumor cells are dividing slowly (low number of mitoses), and 3 indicating that the cells are dividing rapidly (high number of mitoses).The scores given for each of these criteria are then added together and an overall score is obtained. This overall score is classified from I to III, which corresponds to the Elston-Ellis histoprognostic grade. If the sum of the scores is 3, 4 or 5, the grade is I (least aggressive tumors); if the sum of the scores is 8 or 9, the grade is III (most aggressive tumors); if the sum is 6 or 7, the grade is II.

[0154] Thus, when the patient's medical status includes information on the grade of the cancer, this information includes an indication of grade I, II or III of the cancer; in addition or alternatively, the overall score ranging from 3 to 9. This information then statistically indicates to which grade the molecular spectrum obtained corresponds.

[0155] The optimal treatment for breast cancer depends in particular on the type and subtype of cancer the patient has. The type concerns the region of the breast affected while the subtype concerns the mutation causing the tumor. For example, the types of breast cancer are: ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), lobular carcinoma in situ (LCIS), invasive lobular carcinoma (ILC), and inflammatory breast cancer. For example, the subtypes of breast cancer are: hormone receptor positive (HR+, concerning estrogen receptors (ER+) and progesterone receptors (PR+)), HER2-positive (HER2+), triple negative (ER-, PR- and HER2-), and BRCA. It is possible to have a combination of these subtypes.

[0156] Thus, when the patient's medical status includes information on the type of cancer, this information includes an indication of the type (for example for breast cancer: DCIS, ICC, LCIS, CLI or inflammatory) and / or the subtype (for example for breast cancer: RH+ / -, alternatively ER+ / - and / or PR+ / -; HER2+ / -; triple negative, BRCA). This information then statistically indicates to which type and / or subtype the molecular spectrum obtained corresponds.

[0157] [Fig. 12] shows examples of spectra obtained and providing the molecular signature of the samples. The spectra obtained for four samples from four people are represented in this figure, including two patients with breast cancer and two healthy people. The samples are obtained by applying an adsorbent membrane directly to the chest of these people. PI is a patient suffering from metastatic breast cancer with involvement of the right breast and bones, her profile is RH+ and HER2-. P2 is a patient suffering from early-stage breast cancer with involvement of the left breast and underlying lymph nodes, her profile is RH+ and HER2-. SI and S2 are two healthy people, i.e. not suffering from breast cancer. The SI and S2 spectra can serve as controls.

[0158] As conventionally, the abscissa represents the mass-to-charge ratio (m / z) of the detected fragments. The four spectra are aligned with each other on this axis. The numbers shown indicate the m / z ratio at the top and the peak height at the bottom.

[0159] It is clear from the four spectra that those relating to the patients have a similar general appearance and that those relating to the healthy individuals also have a similar general appearance. Furthermore, the spectra of the patients have a different appearance from those of the healthy individuals. In particular, the two spectra of the patients have the following peaks (m / z): 83.04; 101.04; 237.09; 345.15. The spectrum of patient PI also has a peak at 119.05, and that of patient P2 a peak at 309.13. These peaks are not present on the spectra of the healthy individuals.

[0160] Thus, it is not so much the peak corresponding to a particular compound which is interesting but rather the general appearance of the spectrum obtained.

[0161] Furthermore, two spectra obtained from adsorbent membranes placed in contact with the skin of a patient on, for one, an affected breast or, for the other, a healthy breast, do not have an identical appearance.

[0162] Indeed, [Fig. 13] shows two spectra obtained from two adsorbent membranes placed on the skin of the same patient. B1 corresponds to the right breast and B2 corresponds to the left breast. The right breast is the breast with a tumor while the left breast does not have a tumor. These spectra are almost identical with the notable difference that the spectrum of the right breast includes a peak at m / z =195 while the spectrum of the left breast does not include any. Thus, in addition to allowing the detection of a sick person, it is also possible to know the affected organ.

[0163] However, other applications can be envisaged, such as the olfactory analysis of beverages (beer and wine) or other food products or even the analysis of hydrocarbons.

Claims

Claims

1. System for analyzing VOCs adsorbed on an adsorbent membrane (M) by LTP-MS, comprising: - a receptacle (1) for receiving the adsorbent membrane; - a low-temperature plasma ionizer (2) adapted to emit a plasma flow (P) along a plasma emission direction, thus ionizing the VOCs adsorbed by the membrane and forming an ionized gas loaded with VOCs; and - a mass spectrometer (3) for analyzing the ionized VOCs.

2. The system of claim 1, further comprising a heater (4) for heating the adsorbent membrane.

3. System according to claim 1 or claim 2, in which the receptacle is arranged outside the plasma flow and in which: - the receptacle is a resealable container so as to form a confined medium with the exception of an inlet and an outlet; - the container comprises a carrier gas inlet (11) for the arrival of a carrier gas inside the container and a gas outlet (12) for the exit of a gas potentially loaded with VOCs.

4. System according to claim 3, further comprising: - a vector gas injection tube (18) extending along a gas injection axis and one of the ends of which, the outlet end, opens into the closed container, the closed container being configured to maintain the adsorbent membrane so that its surface is perpendicular to the gas injection axis, thus allowing the vector gas to be charged with VOCs as it passes through the membrane; and - a guide tube (15) for conveying the vector gas charged with VOCs to the ionizer.

5. The system of claim 4, wherein the closed container comprises a membrane support for supporting a membrane, a sampling inlet (191, 192) for entering a sample gas and loading the membrane with VOCs, a sampling outlet (192, 191) for exiting the sample gas, a carrier gas inlet.

6. A system according to claim 5, wherein the membrane support is a membrane magazine (9) configured to be put into rotational and / or translational movement and comprises a plurality of membrane housings (91), the membrane magazine being mounted so as to place a single housing, housing under analysis, opposite the outlet end of the injection tube and the inlet end of the guide tube.

7. System according to claim 3, further comprising a guide tube (15) and in which: - the outlet of the container is extended by the guide tube whose free end is close to the plasma flow when the latter is emitted so that the plasma ionizes the charged gas at the outlet of the tube.

8. System according to claim 3, further comprising a connector (17) with at least two arms, and wherein: - a first arm is connected to the outlet of the container; - a second arm has one end directed towards the inlet of the mass spectrometer; - the ionizer is configured so that the plasma flow is directed towards an orifice between the first and second arms or a third arm in operation.

9. A system according to claim 1 or claim 2, wherein the receptacle is arranged under the plasma flow so that the plasma flow is directed towards the membrane when the latter is received in the receptacle.

10. System according to claim 9, wherein: - the receptacle is a resealable container so as to form a confined medium with the exception of inlets and an outlet; - the container comprises a carrier gas inlet (11) for the arrival of a carrier gas inside the container, a gas outlet (12) for the exit of the ionized gas and a plasma inlet (13); - the outlet is extended by a guide tube (15) for guiding the ionized gas towards the inlet of the mass spectrometer.

11. A system according to one of claims 1 to 10, wherein the ionizer is a single-electrode or two-electrode ionizer.

12. A method for analyzing VOCs adsorbed on an adsorbent membrane by LTP-MS, comprising: - providing an adsorbent membrane on which VOCs have been adsorbed; - desorbing the VOCs adsorbed on the adsorbent membrane; - low-temperature plasma ionization of the desorbed VOCs, thereby forming an ionized gas; and - analyzing the ionized gas by mass spectrometry.

13. The method of claim 12, wherein the analysis comprises comparing obtained spectra with a molecular fingerprint database.

14. The method of claim 13, wherein VOCs from a patient have been adsorbed onto the adsorbent membrane, the method further comprising determining the medical status of the patient based on the results of the comparison.

15. The method of claim 14, wherein the patient's medical status includes information regarding at least one of breast cancer stage, grade, and type.

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