CUTANEOUS BODY VOLATOLOME SAMPLING SYSTEM

Abstract

The invention relates to a novel system for sampling cutaneous volatile organic compounds (VOCs) and its use in implementing a method for sampling cutaneous VOCs. The invention also relates to a method for sampling cutaneous VOCs as such. Figure 1

Description

Title of the invention: CUTANEOUS BODY VOLATOLOME SAMPLING SYSTEM FIELD OF INVENTION

[0001] The invention relates to a novel system for sampling cutaneous volatile organic compounds (VOCs) and its use in implementing a method for sampling cutaneous VOCs. The invention also relates to a method for sampling cutaneous VOCs as such. PREVIOUS ART

[0002] The human body emits more than 500 different volatile organic compounds (VOCs), called the body volatolome, from various sources and contributing to body odor (B. de L. Costello et al. A review of the volatiles from the healthy human body, J. Breath Res. 8 (2014) 014001). To better understand the information contained in these compounds, body odor can be divided into 3 categories (V. Cuzuel et al. Origin, Analytical Characterization, and Use of Human Odor in Forensics, J. Forensic Sci. 62 (2017) 330-350): • The primary odor, which is linked to genetic factors, stable over time. • Secondary odor, which is endogenous but variable since it is influenced by environmental factors and metabolism, the variations of which may indicate the presence of a pathology. • Tertiary odor, which comes from exogenous sources such as cosmetics.

[0003] Since Hippocrates, around 400 BC, the sense of smell has been used to detect diseases through secondary odors. Nowadays, thanks to their keen sense of smell, dogs can be trained to detect diseases (C. Angle et al. Canine Detection of the Volatilome: A Review of Implications for Pathogen and Disease Detection, Front. Vet. Sci. 3 (2016)). Furthermore, thanks to advanced analytical techniques, it is possible to obtain the detailed composition of the body's volatilome for health monitoring purposes, as shown by Shirasu et al. (M. Shirasu et al. The scent of disease: volatile organic compounds of the human body related to disease and disorder, J. Biochem. (Tokyo) 150 (2011) 257-266).

[0004] The preferred analytical technique for the analysis of volatile compounds is gas chromatography coupled to mass spectrometry (GC-MS). In this case, a sampling method is required prior to GC-MS. Generally, this involves trapping the VOCs on a sorbent. Only and While sampling should be possible from any area of ​​the body, in any location (hospital, at home, in the laboratory, etc.) and by any person, there is no standardized procedure. Furthermore, the sources of sample contamination are numerous (environment, handling, transport, etc.) and often overlooked, even though bodily VOCs are present in extremely low concentrations ( <ppm). Leur signal est donc très vite masqué par celui d’un contaminant ce qui fausse l’analyse et son interprétation.

[0005] It is ultimately observed that, to date, these problems limit the understanding of cutaneous body volatoloma and its use, particularly for diagnostic purposes. BRIEF OVERVIEW OF THE INVENTION

[0006] Faced with the challenge of having a means of capturing cutaneous body volatolome in the purest possible form and free from contamination, the inventors developed the missing tool. Therefore, a primary objective of the invention is to make available to the relevant public a new system for sampling cutaneous volatile organic compounds (VOCs).

[0007] A second object of the invention is to provide a kit for collecting cutaneous volatile organic compounds (VOCs).

[0008] Another object of the invention relates to the use of this new system- or kit for sampling cutaneous volatile organic compounds (VOCs) in particular to implement a method for sampling cutaneous VOCs on an individual, and said method for sampling cutaneous VOCs on an individual.

[0009] Another object of the invention is to offer a method for determining an olfactory signature of a pathology for possible diagnostic purposes. DETAILED DESCRIPTION

[0010] In its most general aspect, the invention relates to a system for collecting cutaneous volatile organic compounds (VOCs) comprising: • a housing suitable for receiving a support for at least one adsorbent (3) comprising: • a receptacle (5) comprising a first opening at its upper end, • a first removable lid (1) and • a first removable sealing cover (2),

[0011] the opening and closing of said orifice of said receptacle (5) being ensured by means of said first removable cover (1) in combination with said first removable sealing cap (2) to form said housing,

[0012] said first removable cover (1) allowing, in the closed position of said housing, to maintain pressure on said first removable sealing cap (2), in in particular by means of a screw system, to ensure the airtightness of said casing and to isolate said support from any external contamination for at least one adsorbent (3); and • a support for at least one adsorbent (3) comprising: • a gripping zone (3a); and • a cutaneous VOC sampling zone (3b) comprising a cavity into which said at least one adsorbent (4) can be inserted at the upper part of said cavity,

[0013] into which: • the respective materials of said receptacle (5), said first removable lid (1) and said support for at least one adsorbent (3) are inert and selected from: • aluminium and one of these alloys, in particular ZAMAK [or ZAMAC]; • stainless steel, in particular 304L and 316L stainless steel; and • a metal and a metallic alloy emitting less than 10% VOCs, in particular from 0% to 3%, compared to an average sample of VOCs from the body volatolome, and • said first removable sealing cover (2) comprises two layers: • a first silicone layer (which supports said pressure from said first removable cover (1)) opposite the inside of said first removable cover (1); and • a second layer of polytetrafluoroethylene (PTFE) opposite the inside of said receptacle (5).

[0014] The invention therefore implements a particular casing, which serves to store under optimal conditions a support for at least one adsorbent (3), into which said at least one adsorbent (4) can be inserted. The latter is necessarily present when the sampling of cutaneous volatile organic compounds (VOCs) is carried out since it is the adsorbent whose function is: • to capture cutaneous VOCs; and • to restore them at the times of their analysis.

[0015] Also, and assuming that the skin volatile organic compound (VOC) sampling system as described above does not include said at least one adsorbent (4), said at least one adsorbent (4), which is capable of capturing said skin VOCs and returning them, may be provided by means of a kit as illustrated below.

[0016] The term “volatile organic compounds (VOCs)” refers to substances characterized by their high volatility. These are most often chemical molecules formed primarily, but not exclusively, from bonds between carbon and hydrogen atoms. hydrogen, oxygen, and nitrogen atoms. They are referred to as "cutaneous" in the Invention to signify that the sampling system of the invention is designed to specifically capture VOCs emitted by an individual's skin, ensuring they are as pure and free from contamination as possible. Thus, the body's volatile organic compounds (VOCs) can be studied, understood, and used for purposes including diagnostics.

[0017] As mentioned above, the skin VOC sampling system according to the invention (Figures 1-5) comprises several parts: a housing and a holder for at least one adsorbent (3). In the invention, said holder for at least one adsorbent (3) corresponds to a device for collecting (or sampling) skin VOCs, which is stored in said housing. The role of said holder for at least one adsorbent (3) is twofold. It allows its user to manipulate it without touching said at least one adsorbent (4) by means of a gripping area (3a) (e.g., a handle) designed for this purpose. It also allows at least one adsorbent (4) to be held in place to prevent it from falling and to keep it close to the skin without necessarily making contact with it.To this end, a skin VOC sampling zone (3b) was designed, which includes a cavity (or notch) into which at least one adsorbent (4) can be inserted at the top of said cavity. As illustrated in [Fig. 8], this insertion can be made at the level of slots (or notches), and although 4 slots were provided, it is possible either not to use all of them (for example, inserting 2 of the 4 possible adsorbents), or to adapt the geometry of said skin VOC sampling zone (3b) to correspond to the exact number of adsorbents used (for example: 1, 2, 3, 4, 5 or 6).

[0018] The container serves to store said support for at least one adsorbent (3) under optimal preservation conditions, protecting said at least one adsorbent (4) before and after a sample has been taken. To this end, it consists of an assembly comprising at least: a receptacle (5), a first removable lid (1), and a first removable sealing flap (2), the role of which is to ensure a good seal so that said at least one adsorbent (4) is isolated from the external environment. This prevents external VOC contamination while avoiding the loss of VOCs from the sample during storage. Advantageously, this seal is ensured by the first removable sealing flap (2), which is pressed against the upper edges of the container by means, for example, of a system for screwing the first removable lid (1) onto the container.They are described as "removable" because the said first removable cover (1) and the said first removable sealing cap (2) are parts that can be removed or replaced at will on the said receptacle (5) to ensure its opening or closing.

[0019] Said first removable sealing cover (2) is further described as a “sealing” because its bilayer composition means that it does not allow either the passage of It is impervious to fluids (gas and / or liquid) and solids in the form of fine particles (dust, etc.), and it does not leak. Thus, when the first removable sealing cap (2) is positioned on the receptacle and reversibly secured with the first removable cover (1), a hermetically sealed container is obtained. The terms "hermetic," "hermitic," and "hermetically" therefore describe the creation of a container with the most perfect seal possible in order to prevent any external contamination of its contents.

[0020] If the inventive geometry of said support for at least one adsorbent (3) makes it possible to capture the cutaneous body volatolome in the purest possible form and free from contamination, it should be emphasized that what preserves its quality [i.e., that of the captured cutaneous body volatolome] is the storage of said support for at least one adsorbent (3) in a container specifically designed for this purpose. To achieve this, the inventors optimized the arrangement of the materials with particular attention to ensuring that they are "inert," that is, that they do not emit more than 10% of VOCs (i.e., from 0% to 10%) compared to an average VOC sample of the body volatolome. To arrive at this measurement, the quantities of VOCs emitted were calculated by summing the areas found on the chromatograms for the materials of interest.The final quantities obtained were determined by calculating the arithmetic means over the different chromatograms of each material (between 3 and 30 chromatograms per material). These quantities were then compared to the sum of the areas of an average chromatogram of a body volatoloma sample, which average chromatogram was obtained by calculating the arithmetic mean over the sums of the areas obtained from 51 chromatograms. These 51 chromatograms correspond to body volatoloma samples collected from 26 individuals of different ages and sexes, and of these 51 samples, 39 were collected from the axilla, 6 from the inguinal region, and 6 from the hand.

[0021] Advantageously, the inert materials used are: • aluminum and one of these alloys, in particular ZAMAK [or ZAMAC] (i.e., a zinc-based alloy to which aluminum, magnesium, and copper are bonded), and stainless steel (such as 304L or 316L stainless steel) for said receptacle (5), said first removable cover (1), and said support for at least one adsorbent (3); and • polytetrafluoroethylene (PTFE) for the layer (or face) of said first removable sealing cover (2) opposite the inside of said receptacle (5).

[0022] With regard to said receptacle (5), said first removable cover (1) and said support for at least one adsorbent (3), it is therefore possible to have some parts made of one material and other parts made of a different material, as well as it is possible to have all the parts made of the same material.

[0023] According to another embodiment, the invention therefore relates to the skin VOC sampling system as described above, in which the respective materials of said receptacle (5), of said first removable cover (1) and of said support for at least one adsorbent (3): • emit 0% to 10% of VOCs, specifically 0% to 3%, compared to an average VOC sample from the body volatolome; and • are different.

[0024] According to another embodiment, the invention also relates to the skin VOC sampling system as described above, in which the respective materials of said receptacle (5), said first removable cover (1) and said support for at least one adsorbent (3): • emit 0% to 10% of VOCs, specifically 0% to 3%, compared to an average VOC sample from the body volatolome; and • are identical.

[0025] In particular, the invention relates to the skin VOC sampling system as described above, in which the respective materials of said receptacle (5), said first removable cover (1) and said support for at least one adsorbent (3) are 304L stainless steel or 316L stainless steel, the VOC emission of which, relative to an average VOC sample from the body volatolome, is between 0% and 10%, in particular between 0% and 3%, in particular between 1% and 2% and is advantageously 1.5%.

[0026] In particular, the invention also relates to the skin VOC sampling system as described above, in which the respective materials of said receptacle (5), said first removable cover (1) and said support for at least one adsorbent (3) are aluminium or one of these alloys (in particular ZAMAK [or ZAMAC]) the emission of VOCs relative to an average VOC sample of the body volatolome is between 0% and 10%, in particular between 0% and 3%, in particular between 1% and 2% and is advantageously 1.5%.

[0027] In particular, the invention also relates to the skin VOC sampling system as described above, in which the respective materials of said receptacle (5), said first removable cover (1) and said support for at least one adsorbent (3) are a metal or a metal alloy whose VOC emission relative to an average VOC sample from the body volatolome is between 0% and 10%, in particular between 0% and 3%, in particular between 1% and 2% and is advantageously 1.5%.

[0028] In view of the foregoing, one embodiment of the invention therefore relates to the skin volatile organic compound (VOC) sampling system as described above, comprising: • a housing suitable for receiving a support for at least one adsorbent (3) comprising: • a receptacle (5) comprising a first opening at its upper end, • a first removable lid (1) and • a first removable sealing cover (2),

[0029] the opening and closing of said orifice of said receptacle (5) being ensured by means of said first removable cover (1) in combination with said first removable sealing cap (2) to form said housing,

[0030] said first removable cover (1) allowing, in the closed position of said housing, pressure to be maintained on said first removable sealing cap (2), in particular by means of a screw system, to ensure the airtightness of said housing and to isolate said support from any external contamination for at least one adsorbent (3); and • a support for at least one adsorbent (3) comprising: • a gripping zone (3a); and • a cutaneous VOC sampling area (3b) comprising a cavity into which said at least one adsorbent (4) can be inserted at the upper part of said cavity,

[0031] in which: • the respective materials of said receptacle (5), said first removable lid (1) and said support for at least one adsorbent (3) are inert, identical or different, and chosen from: • aluminum and one of its alloys, in particular ZAMAK [or ZAMAC]; and • stainless steel, in particular 304L and 316L stainless steel, and • said first removable sealing cover (2) comprises two layers: • a first silicone layer (which supports said pressure from said first removable cover (1)) opposite the inside of said first removable cover (1); and • a second layer of polytetrafluoroethylene (PTFE) opposite the inside of said receptacle (5).

[0032] With regard to said first removable sealing cover (2), if one of its layers is made of polytetrafluoroethylene (PTFE), the other must be able to withstand the pressure of said first removable cover (1) when the housing is closed. Among the possible materials, silicone was selected. It should be noted that the orientation of said first removable sealing cover (2) is important to ensure the airtightness of said housing. As already mentioned, the layer opposite the inside of said The first removable cover (1) is made of silicone and the one opposite the inside of said receptacle (5) is made of polytetrafluoroethylene (PTFE) whose VOC emission relative to an average sample of VOCs from the body volatolome is between 0% and 3%, in particular between 1.5% and 2.5% and is in particular 2.1%.

[0033] According to another embodiment, the invention relates to the skin VOC sampling system as described above, in which said support for at least one adsorbent (3) further comprises said at least one adsorbent (4),

[0034] said at least one adsorbent (4): • comprising an inert polymer, resistant to a temperature of at least 220°C (i.e., between 220°C and 260°C), particularly for a period of at least 4 hours (i.e., between 1 hour and 4 hours), and capable of capturing cutaneous VOCs and releasing at least 80% of said captured cutaneous VOCs, and • having in particular a dimension allowing it to be inserted into a thermal desorption tube.

[0035] Here, said at least one adsorbent (4) allows for the capture and subsequent release of VOCs from the body volatolome. To this end, it is made of a polymer that must be "inert" and emit no VOCs or only a small, well-defined, and identifiable quantity. After measurement, this quantity is between 0% and 10% relative to an average sample of VOCs from the body volatolome. It should also be noted that the quantity of VOCs potentially emitted by said at least one adsorbent (4) is easily distinguishable from the compounds of the body volatolome because it is primarily composed of compounds containing silica atoms. However, this type of atom is not emitted by the body volatolome.

[0036] The expression "resistant to a temperature of at least 220°C" indicates the requirement that said at least one adsorbent (4) must withstand a minimum temperature of 220°C to be inserted into a thermal desorption tube and analyzed. In other words, said at least one adsorbent (4) is resistant to a temperature between 220°C and 260°C. This also means that said at least one adsorbent (4) is resistant to a temperature of at least 220°C, 230°C, 240°C, 250°C, or 260°C. Advantageously, this resistance to a temperature of at least 220°C is maintained for a period of at least 4 hours. According to another embodiment, said at least one adsorbent (4) is therefore resistant to a temperature of 220°C to 260°C for a period of 1h to 4h, in particular from 3h to 4h.

[0037] The expression "capable of capturing cutaneous VOCs and releasing at least 80% of said captured cutaneous VOCs" indicates that said inert polymer allows, on the one hand, sampling by capturing bodily VOCs and, on the other hand, their release at the time of analysis for study. Advantageously, said inert polymer is capable of releasing at least 80% of said captured cutaneous VOCs, i.e. a release of said captured cutaneous VOCs of between 80% and 100%. Note that here, the expression "at least 80%" also means at least 85%, at least 90%, at least 95% and at least 99%, and the expression "from 80% to 100%" also means from 85% to 100%, from 90% to 100% and from 95% to 100%.

[0038] The expression "having in particular a dimension enabling it to be inserted into a thermal desorption tube" refers to the fact that, in order to perform the analysis of said cutaneous VOCs captured using, for example, thermal desorption followed by fully two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (TD-GCxGC / ToFMS), it is preferable that said at least one adsorbent (4) be ready for use. This means that it can be unclipped from said support for at least one adsorbent (3) and easily inserted into a thermal desorption tube. Also, and in particular, the invention relates to the cutaneous VOC sampling system as described above, in which said at least one adsorbent (4) has a dimension enabling it to be inserted into a thermal desorption tube.For example, given that a thermal desorption tube is 8.9 cm long and 0.6 cm wide (3.5 inches x 1 / 4 inch) with an internal diameter of 0.5 cm, the dimensions of at least one adsorbent (4) must be less than these dimensions, i.e., less than 8.9 cm in length (i.e., from 20 mm to 700 mm) and less than 0.4 cm in diameter (i.e., from 1 mm to 3 mm). Advantageously, at least one adsorbent (4) is 20 mm long and has a diameter of 2 mm.

[0039] According to another embodiment, the invention relates to the skin VOC sampling system as described above, in which the material of said at least one adsorbent (4) is: • self-supporting and in the form of a rod (e.g., polydimethylsiloxane); or • in powder form and arranged in a gas-porous tube (e.g., resin) 2,6-diphenylene-oxide polymer trapped in a porous polytetrafluoroethylene membrane).

[0040] The term "self-supporting material" refers to a material that can support its own weight without requiring external support, unlike a powder. In other words, a self-supporting material is capable of maintaining its shape and resisting forces applied to it without collapsing or deforming significantly.

[0041] According to another embodiment, the invention relates to the skin VOC sampling system as described above, in which the material of said at least one adsorbent (4) is selected from: • Polydimethylsiloxane (PDMS); and • a 2,6-diphenylene-oxide polymer resin (e.g. Tenax® TA 200 pm sold by Sigma-Aldrich for example) trapped in a porous polytetrafluoroethylene (PTFE) membrane.

[0042] According to another embodiment, the invention relates to the skin VOC sampling system as described above, in which the material of said at least one adsorbent (4) is self-supporting and is PowerSorb® (sold by Action Europe®) whose VOC emission relative to an average VOC sample from the body volatolome is between 0% and 10%, in particular between 8% and 10% and is in particular 8.6%.

[0043] According to another embodiment, the invention relates to the skin VOC sampling system as described above, wherein the material of said at least one adsorbent (4) is reusable. That is to say, after the skin VOCs have been collected and analyzed (for example, by TD-GCxGC / ToFMS), said at least one adsorbent (4) can be repackaged for reintroduction into the kit of the invention or directly into said support for at least one adsorbent (3).

[0044] According to another embodiment, the invention relates to the skin VOC collection system as described above, in which said receptacle (5) further comprises at its lower end a base (6) in which said support is housed for at least one adsorbent (3),

[0045] the material of said base (6) being inert and chosen from: • aluminum and one of its alloys, in particular ZAMAK [or ZAMAC]; • stainless steel, in particular 304L stainless steel and 316L stainless steel; and • a metal and a metallic alloy emitting less than 10% VOCs, in particular from 0% to 3%, compared to an average sample of VOCs from the body volatolome.

[0046] According to another embodiment, the invention relates to the skin VOC sampling system as described above, wherein said base (6) is an integral part of said receptacle (5). In other words, and in this configuration, the receptacle (5) has been machined so as to include said base (6) from its manufacture. It is therefore not a part added and welded to said receptacle (5), and said base (6) is made of the same material as that of the receptacle (5). In particular, the invention therefore relates to the skin VOC sampling system as described above, wherein the material of said base (6) is identical to that of said receptacle and is identical to the respective materials of said receptacle (5), said first removable cover (1), and said support for at least one adsorbent (3). Advantageously, this is aluminum or one of its alloys (e.g.ZAMAK (or ZAMAC), or stainless steel (especially 304L or 316L stainless steel) which emits . VOCs compared to an average sample of VOCs from the body volatolome is between 0% and 3%, notably between 1% and 2% and is in particular 1.5%.

[0047] According to another embodiment, the invention relates to the cutaneous VOC sampling system as described above: • the surface of said base (6) at the level of said cavity of said cutaneous VOC sampling zone (3b) of said support for at least one adsorbent (3) has the shape of a grid; and • said receptacle (5) further includes a second opening at its lower end, the opening and closing of which are effected by means of a second removable cover (1') in combination with a second removable sealing cap (2'),

[0048] the material of said second removable cover (1') being inert and chosen from: • aluminium and one of these alloys, in particular ZAMAK [or ZAMAC]; • stainless steel, in particular 304L and 316L stainless steel; and • a metal and a metallic alloy emitting less than 10% VOCs, specifically from 0% to 3%, compared to an average sample of VOCs from the body volatolome,

[0049] said second removable sealing cover (2') comprising two layers: • a first silicone layer on the inside of said second removable cover (1'); and • a second layer of polytetrafluoroethylene (PTFE) directly above said base (6), and

[0050] said second removable cover (1') allowing in closed position said housing to maintain pressure on said second removable sealing cover (2'), in particular by means of a screwing system, to ensure the airtightness of said housing and to isolate said support from any external contamination for at least one adsorbent (3).

[0051] This embodiment corresponds to that shown in Figures 4 and 5, and is designed in particular for the purpose of training dogs to recognize body odor. The aim is that, from the upper opening, said support for at least one adsorbent (3) can be removed from the housing to collect skin VOCs and then placed back inside; and that, from the lower opening, the odor captured on said at least one adsorbent (4) can be presented to the dog without handling the collected sample. With the invention, the preservation of the sample is ensured, as is the control of contamination risks, since once collected, the sample does not leave the housing unless an analysis (TD-GCxGC / ToFMS) is necessary, and is protected from the dog's nose by said grid.

[0052] It should be noted that insofar as there is a parallel between the orifice at the upper end and the orifice at the lower end of said receptacle (5), the latter being opened or closed by the same means, what applies to said first removable cover (1) and said first removable sealing cover (2) also applies to said second removable cover (1') and said second removable sealing cover (2'). Advantageously, the material of said second removable cover (1') is therefore identical to that of said first removable cover (1). Advantageously, the material of said second removable cover (1') is also identical to the respective materials of said receptacle (5) and said support for at least one adsorbent (3). This is in particular aluminum or one of its alloys (e.g.ZAMAK (or ZAMAC), or stainless steel (in particular 304L or 316L stainless steel) whose VOC emission relative to an average VOC sample of body volatolome is between 0% and 3%, in particular between 1% and 2% and is in particular 1.5%.

[0053] Regarding the dimensions of the object of the invention, it should be noted that the skin VOC sampling system according to the invention fits in the palm of one's hand. According to one embodiment (see Figures 2-4), the invention therefore relates to the skin VOC sampling system as described above, in which: • said housing adapted to receive a support for at least one adsorbent (3) has an outside diameter (I) of 50 mm and a height (II) of 24 mm, and comprises: • said receptacle (5) having: • a height (n) of 21.4 mm; • an outside diameter (o) of 50 mm; • an inner diameter (p) of 37 mm; and • a depth (s) of 17.4 mm,

[0054] and comprising said base having a length (q) of 28 mm and a width (r) of 14 mm, • said first removable cover (1) having: • an outside diameter (a) of 50 mm; • a height (b) of 9 mm; and • an inner diameter (c) of 42 mm, and • said first removable sealing cap (2) having: • a diameter (d) of 42 mm; and • a thickness (e) of 1 mm,

[0055] and • said support for at least one adsorbent (3) has a length (i) of 27.8 mm and a height (j) of 19.4 mm, and comprises: • said cutaneous VOC sampling area (3b) having: • a height (f) of 7 mm; and • a width (g) of 13.8 mm,

[0056] and comprising a cavity whose length (k) is 25 mm in which is disposed at least one slot (or notch) [suitable to accommodate said at least one adsorbent (4) whose diameter (l) is in particular 2 mm and whose length (m) is in particular 20 mm] whose width (h) is 2 mm.

[0057] According to another embodiment (see Figures 5-7), the invention also relates to the skin VOC sampling system as described above, in which: • said housing adapted to receive a support for at least one adsorbent (3) has an outer diameter (III) of 50 mm and a height (IV) of 24 mm, and comprises: • said receptacle (5) having: • a height (n) of 21.4 mm; • an outside diameter (o) of 50 mm; • an inner diameter (p) of 37 mm; and • a depth (s) of 17.4 mm,

[0058] and comprising said base having a length (q) of 28 mm and a width (r) of 14 mm, • said first removable cover (1) having: • an outside diameter (a) of 50 mm; • a height (b) of 9 mm; and • an inner diameter (c) of 42 mm, • said first removable sealing cap (2) having: • a diameter (d) of 42 mm; and • a thickness (e) of 1 mm, • said second removable cover (1') having: • an outside diameter (a') of 50 mm; • a height (b') of 9 mm; and • an inner diameter (c') of 42 mm, and • said second removable sealing cover (2') having: • a diameter (d') of 42 mm; and • a thickness (e') of 1 mm,

[0059] and • said support for at least one adsorbent (3) has a length (i) of 27.8 mm and a height (j) of 19.4 mm, and comprises: • said cutaneous VOC sampling area (3b) having: • a height (f) of 7 mm; and • a width (g) of 13.8 mm,

[0060] and comprising a cavity whose length (k) is 25 mm in which is disposed at least one slot (or notch) [suitable to accommodate said at least one adsorbent (4) whose diameter (l) is in particular 2 mm and whose length (m) is in particular 20 mm] whose width (h) is 2 mm.

[0061] In its second aspect, the invention relates to a cutaneous VOC sampling kit comprising a cutaneous VOC sampling system as described above and a dressing (7),

[0062] said dressing (7) comprising: • at its center an inert material (i.e., emitting no more than 10% of VOCs relative to an average VOC sample from the body volatolome) such as aluminum in which a slot is cut to allow passage of said gripping zone (3a); and • around its perimeter an adhesive material suitable for being placed on an individual's skin.

[0063] The expression "inert material [...] in which a slit is cut to allow passage of said gripping zone (3a)" refers to the fact that it is possible to insert said gripping zone (3a) of said support for at least one adsorbent (3) into the dressing. This allows, once said support for at least one adsorbent (3) has been positioned on the area to be sampled, said support for at least one adsorbent (3) to be properly secured during the sampling procedure. An illustration is shown in [Fig. 8]. Interestingly, the assembly comprising said support for at least one adsorbent (3), said at least one adsorbent (4), and said dressing (7) has VOC emissions of less than 10% (i.e., from 0% to 10%) compared to an average VOC sample of body volatolome.

[0064] According to another embodiment, the invention relates to the skin VOC sampling kit as described above, in which the material of said dressing (7) in its center is aluminum, the emission of VOCs relative to an average sample of VOCs from the body volatolome is between 0% and 3%, in particular between 1% and 2%, and is in particular 1.9%.

[0065] According to another embodiment, the invention relates to the skin VOC sampling kit as described above, in which the adhesive material of said dressing (7) around its perimeter is a polyurethane film coated with a silicone adhesive (for example, Safetac® sold by Molnlycke).

[0066] According to another embodiment, the invention relates to the skin VOC sampling kit as described above, in which said dressing is a Mepitel® dressing (sold by Molnlycke).

[0067] According to another embodiment, the invention relates to the skin VOC sampling kit as described above, further comprising: • an unscented cleansing wipe; and • a pair of gloves.

[0068] The expression "odorless cleansing wipe" refers to a wipe that does not leave VOC residues on the skin and does not itself emit any. For example, it could be a wipe sold by Ront® Medical composed of Aqua and Benzalkonium chloride for gentle, no-rinse cleansing.

[0069] In the event that said at least one adsorbent (4) is not already inserted into said sampling zone (3b) of said support for at least one adsorbent (3), the kit also includes said at least one adsorbent (4). According to another embodiment, the invention therefore relates to the skin VOC sampling kit as described above, further including said at least one adsorbent (4). In this case, an additional step is required to perform the sampling of said skin VOCs, which consists of loading said support for at least one adsorbent (3) with at least one adsorbent (4) provided in the kit of the invention.

[0070] In another aspect, the invention relates to the use of a skin VOC sampling system as described above or a skin VOC sampling kit as described above to implement a method of skin VOC sampling on an individual.

[0071] The expression "method for sampling cutaneous VOCs on an individual" refers to the sampling or capture of VOCs emitted by the skin of an individual using said support for at least one adsorbent (3) comprising at least one adsorbent (4). This implies that the area where this sampling is carried out is suitable for the application of said support for at least one adsorbent (3) comprising at least one adsorbent (4) and its retention by means of said dressing (7).

[0072] According to another embodiment, the invention relates to the use as described above, in which said method of collecting cutaneous VOCs from an individual is carried out on an area of ​​said individual's body, said body area being flat and having a minimum surface area of ​​2 x 3 cm (6 cm², i.e., the surface area of ​​said support for at least one adsorbent (3) with respect to the skin). Such a surface area may be found, for example, on: the scalp, face, neck, armpits, back, chest, abdomen, arms, hands, groin, buttocks, legs, or feet.

[0073] In other words, and according to another embodiment, the invention relates to the use, as described above, of a skin VOC sampling system as described above or of a skin VOC sampling kit as described above to implement a method of skin VOC sampling on an individual,

[0074] in particular said sampling method being carried out at the level of an area of ​​the body of said individual, said area of ​​the body being flat and having a surface of 2x3 cm.

[0075] According to another embodiment, the invention relates to the use as described above, in which said method of collecting cutaneous VOCs from an individual is carried out at the level of: the scalp, face, neck, armpits, back, chest, belly, arms, hands, groin, buttocks, legs or feet.

[0076] In another aspect, the invention relates to a method for collecting cutaneous VOCs from an individual comprising at least the following steps:

[0077] i. clean the area to be sampled with an odorless cleaning wipe to obtain a cleaned area to be sampled;

[0078] ii. collect said cutaneous VOCs using a cutaneous VOC collection system as described above or a cutaneous VOC collection kit as described above,

[0079] the sampling of said cutaneous VOCs being carried out by means of said support for at least one adsorbent (3) which is exited from the casing by its upper end and comprises at least one adsorbent (4) and is then: • placed on the cleaned area to be sampled; and • is maintained on said area to be sampled, cleaned with a dressing, for a period of 45 to 75 minutes to obtain a support for at least one adsorbent (3) comprising at least one adsorbent (4) containing said cutaneous VOCs; and

[0080] iii. arrange said support for at least one adsorbent (3) comprising at least one adsorbent (4) containing said cutaneous VOCs in said receptacle (5) which is then hermetically sealed.

[0081] As mentioned above, it is possible that said at least one adsorbent (4) may not be inserted into said sampling area (3b) of said support for at least one adsorbent (3). Also, when said support for at least one adsorbent (3) is removed from the housing by its upper end, it is possible that a preparation step for said support for at least one adsorbent (3) may be necessary. This step consists of inserting said at least one adsorbent (4), which may be supplied via the kit, into the sampling area (3b) of said support for at least one adsorbent (3). According to another embodiment, the invention therefore relates to the method of sampling cutaneous VOCs from an individual as described above, which further includes in step ii.a preliminary step of introducing at least one adsorbent (4) into said sampling area (3b) of said support for at least one adsorbent (3), said preliminary step being carried out before said support for at least one adsorbent (3) is placed on the cleaned sampling area for a sampling time of 45 min to 75 min.

[0082] The expression "duration [...] from 45 min to 75 min" indicates that the sampling can last from 45 min to 75 min, but also from 50 min, 55 min, 60 min, 65 min or 70 min. It also means that the duration of the sampling can be from 50 min to 70 min or from 55 min to 65 min. Advantageously, the sampling lasts 60 min (1 hour).

[0083] Interestingly, during the sampling period, the container is hermetically sealed to prevent its contents from being contaminated by ambient air and is advantageously placed under refrigerated conditions (temperature between 4°C and 8°C). It is then reopened when storing the support for at least one adsorbent (3) comprising at least one adsorbent (4) containing the cutaneous VOCs in the receptacle (5), which is again hermetically sealed and advantageously placed under refrigerated conditions (temperature between 4°C and 8°C).

[0084] Advantageously, once: • the sample is taken; and • said support for at least one adsorbent (3) comprising at least one adsorbent (4) containing said cutaneous VOCs is stored in said receptacle (5),

[0085] The skin volatile organic compound (VOC) sampling system is placed under refrigerated conditions (temperature between 4°C and 8°C). It should be noted that this improves the preservation of the collected skin VOCs and reduces the risk of potential contamination.

[0086] In so doing, it is understood that the advantageous use of these refrigerated conditions (temperature between 4°C and 8°C) can be implemented to store the skin volatile organic compound (VOC) sampling system of the invention: • before using it; • during its transport to the collection site; • during / after its use; and • during its transport to the site of analysis of said VOCs, where refrigerated storage upstream of the analysis may also be implemented.

[0087] A more complete illustration of the method for collecting cutaneous VOCs from an individual as described above may be the following:

[0088] 1- The sampling kit is sent by mail or courier to the user. The sampling can be carried out directly by the individual being sampled from themselves or by another person (caregiver or healthcare staff for example).

[0089] 2- The sampled area is cleaned using an odorless cleansing wipe (Ront® Medical) then left to air dry for 5 min.

[0090] 3- The user puts on the gloves provided in the sampling kit.

[0091] 4- The housing containing the support for at least one adsorbent (3) is opened by the user.

[0092] 5- The dressing (7) has been removed from its packaging and the protective film over the adhesive area is withdrawn.

[0093] 6- The support for at least one adsorbent (3), which contains at least 2 sticks The adsorbent (4) is inserted into the central slit of the dressing (7) as shown in [Fig. 8]. The loop (i.e., the gripping area (3a)) allows the support to be held securely for at least one adsorbent (3) and facilitates its placement.

[0094] 7- The removable cover (1) and the removable sealing cap (2) are placed back on the receptacle (5) for closing the case.

[0095] 8- The assembly, a support for at least one adsorbent (3) and a dressing (7), is applied to the area of ​​the individual to be sampled. A chamber is thus formed by the pressure of the contours of the support for at least one adsorbent (3) against the skin. The cutaneous VOCs emitted by the area in question can then migrate towards the adsorbent phase during the hour (duration between 45 and 75 min) corresponding to the duration of the sampling.

[0096] 9- After the sampling, the user peels the dressing (7) off the skin of The sample is taken from the individual. He retrieves the support for at least one adsorbent (3), which he immediately places back in its container and seals tightly. The dressing (7) is discarded.

[0097] 10- The skin VOC sampling system according to the invention is then stored in a refrigerator (temperature between 4 and 8°C) until it is sent to the analysis laboratory. The airtight container protects the integrity of the sample during storage and transport.

[0098] 11- Once the skin VOC sampling system according to the invention has arrived at In the laboratory, the person performing the analyses removes the adsorbent (4) from the support for at least one adsorbent (3) using forceps (e.g., metal tweezers) while wearing gloves. This operation is carried out in a suitable location to avoid contaminating the samples. This could be a cleanroom or another environment with a low potential for contamination. The adsorbent (4), in the form of a rod, is then placed in a thermal desorption tube and analyzed.

[0099] 12- Once analyzed, the adsorbent (4) which can be reused is either discarded, or reconditioned; and the skin VOC sampling system according to the invention can be reused after cleaning. New adsorbents (4) or reconditioned adsorbents (4) can be inserted into the holder for at least one adsorbent (3) or supplied separately before the skin VOC sampling system according to the invention is (re)sent to the sampling centers.

[0100] In light of the foregoing, it is understood that, according to another embodiment, the invention relates to the method for collecting cutaneous VOCs from an individual as described above, which further comprises, in step i, a drying step of said area to be sampled after cleaning said area to be sampled to obtain a cleaned and dried area. Advantageously, this drying step is carried out in air for a period of 3 to 5 minutes. It is also understood that an advantage of the invention is the reuse of the cutaneous VOC sampling system according to the invention, except with regard to said at least one adsorbent (4), which must be changed between each use.

[0101] According to another embodiment, the invention relates to the method for collecting cutaneous VOCs from an individual as described above, which further includes a step of analyzing said cutaneous VOCs. For this purpose, it may be necessary to implement a transport step (advantageously refrigerated at a temperature between 4°C and 8°C) of said cutaneous VOC collection system as described above, comprising said support for at least one adsorbent (3) comprising at least one adsorbent (4) containing said cutaneous VOCs, between the collection site and the analysis site. Regarding the analysis itself, conventional methods are used, such as TD-GC / MS or TD-GCxGC / ToFMS technology.

[0102] Regarding the cleaning of the skin VOC sampling system according to the invention (excluding the adsorbent (4)) mentioned above, this can be carried out before and / or after its use. By way of example, this cleaning consists of immersing the various components (receptacle (5), lid (1), seal (2) and support for at least one adsorbent (3)) in a solvent bath and placing them in an ultrasonic bath for a period of 5 to 30 minutes before drying them for a period of 30 minutes to 3 hours in an oven at a temperature of 40°C to 100°C. "Solvent" refers to an organic solvent, in particular, selected from: isopropanol, acetone, ethanol, acetonitrile and mixtures thereof. The term "duration of 5 to 30 min in the ultrasonic bath" includes, in particular, a duration of 5 min, 10 min, 15 min, 20 min, 25 min or 30 min, and also a duration of 5 min to 25 min or 10 min to 20 min.The term "to be dried for a period of 30 minutes to 3 hours in an oven" includes, in particular, periods of 30 minutes, 60 minutes (1 hour), 90 minutes (1 hour 30 minutes), 120 minutes (2 hours), 150 minutes (2 hours 30 minutes), or 180 minutes (3 hours), and also periods of 45 to 75 minutes or 60 to 90 minutes. The term "to be dried [...] at a temperature of 40°C to 100°C" includes, in particular, temperatures of 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, or 100°C, and also temperatures of 70°C to 100°C or 60°C to 90°C. Advantageously, the method of collecting cutaneous VOCs from an individual as described above includes this cleaning step before and / or. after using the skin VOC sampling system according to the invention (excluding adsorbent (4)).

[0103] Regarding the conditioning and / or reconditioning of said at least one adsorbent (4) mentioned above, this is advantageously implemented. For example, it may consist of heating said at least one adsorbent (4) to a temperature of 200°C to 300°C under a flow of high-quality inert gas at a flow rate of 10 mL / min to 75 mL / min for a period of 1 to 6 hours. The term "temperature between 200°C and 300°C" specifically includes temperatures of 200°C, 210°C, 220°C, 230°C, 240°C, 250°C, 260°C, 270°C, 280°C, 290°C, or 300°C, as well as temperatures between 240°C and 300°C or between 220°C and 280°C. "Inert gas" specifically refers to helium and nitrogen, and they are described as "high quality" due to their purity, which can be graded 1.0, 2.0, 3.0, 4.0, or 5.0.The term “a flow rate of 10 mL / min to 75 mL / min” includes, in particular, a flow rate of 10 mL / min, 15 mL / min, 20 mL / min, 25 mL / min, 30 mL / min, 35 mL / min, 40 mL / min, 45 mL / min, 50 mL / min, 55 mL / min, 60 mL / min, 65 mL / min, 70 mL / min or 75 mL / min, and also a flow rate of 20 mL / min to 70 mL / min or 30 mL / min to 50 mL / min. Advantageously, the method for collecting cutaneous VOCs from an individual as described above includes this conditioning step and / or the reconditioning of said at least one adsorbent (4).

[0104] In another aspect, the invention relates to a method for determining an olfactory signature of a pathology, said method implementing a method for collecting cutaneous VOCs as described above on at least one healthy individual and at least one individual suffering from said pathology followed by a comparative analysis method by gas chromatography coupled with mass spectrometry of said cutaneous VOCs collected.

[0105] The expression "at least one healthy individual" refers to a cohort of healthy subjects, that is, subjects not suffering from the pathology whose olfactory signature is being sought. Ideally, this cohort of healthy subjects does not suffer from any pathology and consists of a number of subjects ranging from 1 to 100.

[0106] The expression "at least one individual suffering from said pathology" refers to a cohort of patients suffering from said pathology, that is, suffering from the pathology whose olfactory signature is being sought. Ideally, this cohort of patients suffering from said pathology consists of a number of patients ranging from 1 to 100.

[0107] The expression "comparative analysis method by gas chromatography coupled with mass spectrometry of said cutaneous VOCs collected" refers to: • on the one hand, the analysis by gas chromatography coupled with mass spectrometry (for example, TD-GCxGC / ToFMS technology) of cutaneous VOC profiles of the healthy subject cohort and those of the patient cohort; and • On the other hand, a comparative step is carried out between these profiles (cutaneous VOCs from healthy subjects versus cutaneous VOCs from patients) to determine if a difference in VOCs exists. If so, an olfactory signature of the pathology is then determined, which can be used for its diagnosis.

[0108] According to another embodiment, the invention relates to the method for determining an olfactory signature of a pathology as described above, said pathology being chosen from among any pathology likely to have an olfactory signature. For example, one might mention: diabetes, epilepsy, cancer, a bacterial infection, or even COVID-19.

[0109] The ability of dogs to detect numerous odors, even the faintest, is well established, given its widespread use in various applications. The best-known examples are the detection of explosives and / or drugs, and the detection of victims during accidents (avalanches, collapses). More recently, dogs have been trained to recognize the specific odors emitted by people suffering from a disease. They can thus participate in or confirm the diagnosis, even before the appearance of clinical signs. Since this ability comes from training, it is necessary to have tools for training dogs. In this context, another aspect of the invention relates to a method for training a dog to recognize an olfactory signature of a disease, said method implementing the cutaneous VOC sampling system as described above. This includes, in particular, the embodiment with two orifices and the grid-shaped base (6).

[0110] In all respects, it should be noted that the various aspects of the invention, as well as the various embodiments thereof, are interdependent. These can therefore be combined as necessary to obtain preferred aspects and / or embodiments of the invention not explicitly described. This also applies to all the definitions provided in this description, which apply to all aspects of the invention and its embodiments.

[0111] In addition, the present invention is illustrated, but not limited to, by the following figures and examples. LIST OF FIGURES [Fig 1]

[0112] Figure 1 is a general illustration of the skin VOC sampling system according to the invention, showing: a removable cover (1), a removable sealing cap (2), a support for at least one adsorbent (3) comprising a zone of gripping (3a) and a cutaneous VOC sampling area (3b), four adsorbent sticks (4) and a receptacle (5). [Fig 2]

[0113] Figure 2 illustrates a first embodiment of the skin VOC sampling system according to the invention, where the following are visible:

[0114] Left (exploded view): a removable lid (1), a removable sealing cap (2), a support for at least one adsorbent (3) comprising a gripping area (3a) and a skin VOC sampling area (3b), four adsorbent sticks (4) and a receptacle (5) comprising a base (6);

[0115] Right (closed view): the closed case whose outer diameter I is 50 mm and height II is 24 mm. [Fig 3]

[0116] Fig. 3 is an illustration of different views of the first embodiment of the skin VOC sampling system shown in Fig. 2. In detail are visible: a removable cover (1), a removable sealing cap (2), a holder for at least one adsorbent (3) comprising a gripping area (3a) and a skin VOC sampling area (3b), four adsorbent sticks (4) and a receptacle (5) comprising a base (6). [Fig 4]

[0117] Figure 4 is a manufacturing drawing of the first embodiment of the skin VOC sampling system shown in Figures 2 and 3. In detail, the dimensions indicated are:

[0118] a. Outer diameter of the removable cover (1) (50 mm)

[0119] b. Height of removable cover (1) (9 mm)

[0120] c. Inner diameter of removable cover (1) (42 mm)

[0121] d. Diameter of the removable sealing cap (2) (42 mm)

[0122] e. Thickness of the removable sealing cap (2) (1 mm)

[0123] f. Height of the cutaneous VOC sampling area (3b) (7 mm)

[0124] g. Width of skin VOC sampling area (3b) (13.8 mm)

[0125] h. Width of a slit (or notch) arranged in the cavity of the cutaneous VOC sampling area (3b) (2 mm)

[0126] i. Length of support for at least one adsorbent (3) (27.8 mm)

[0127] j. Height of the support for at least one adsorbent (3) (19.4 mm)

[0128] k. Length of the cavity in the cutaneous VOC sampling area (3b) (25 mm)

[0129] 1. Diameter of at least one adsorbent (4) (2 mm)

[0130] m. Length of at least one adsorbent (4) (20 mm)

[0131] n. Height of receptacle (5) (21.4 mm)

[0132] o. Outer diameter of the receptacle (5) (50 mm)

[0133] p. Inner diameter of receptacle (5) (37 mm)

[0134] q. Base length (6) (28 mm)

[0135] r. Base width (6) (14 mm)

[0136] s. Depth of receptacle (5) (17.4 mm) [Fig 5]

[0137] Figure 5 illustrates a second embodiment of the skin VOC sampling system according to the invention, where the following are visible:

[0138] On the left (exploded view): a first removable lid (1), a first removable sealing cover (2), a support for at least one adsorbent (3) comprising a gripping area (3a) and a cutaneous VOC sampling area (3b), four adsorbent sticks (4), a receptacle (5) comprising a base (6), a second removable sealing cover (2') and a second removable lid (1');

[0139] Right (closed view): the closed case whose outer diameter III is 50 mm and height IV is 26.6 mm. [Fig 6]

[0140] Fig. 6 is an illustration of different views of the second embodiment of the skin VOC sampling system seen in Fig. 5. In detail are visible: a first removable cover (1), a first removable sealing cap (2), a support for at least one adsorbent (3) comprising a gripping area (3a) and a skin VOC sampling area (3b), four adsorbent sticks (4), a receptacle (5) comprising a base (6), a second removable sealing cap (2') and a second removable cover (1'). [Fig 7]

[0141] Figure 7 is a manufacturing drawing of the second embodiment of the skin VOC sampling system shown in Figures 5 and 6. In detail, the dimensions indicated are:

[0142] In detail, the dimensions indicated are:

[0143] a. Outer diameter of the removable cover (1) (50 mm)

[0144] b. Height of removable cover (1) (9 mm)

[0145] c. Inner diameter of removable cover (1) (42 mm)

[0146] d. Diameter of the removable sealing cap (2) (42 mm)

[0147] e. Thickness of the removable sealing cap (2) (1 mm)

[0148] f. Height of the cutaneous VOC sampling area (3b) (7 mm)

[0149] g. Width of skin VOC sampling area (3b) (13.8 mm)

[0150] h. Width of a slit (or notch) arranged in the cavity of the cutaneous VOC sampling area (3b) (2 mm)

[0151] i. Length of support for at least one adsorbent (3) (27.8 mm)

[0152] j. Height of the support for at least one adsorbent (3) (19.4 mm)

[0153] k. Length of the cavity in the cutaneous VOC sampling area (3b) (25 mm)

[0154] 1. Diameter of at least one adsorbent (4) (2 mm)

[0155] m. Length of at least one adsorbent (4) (20 mm)

[0156] n. Height of receptacle (5) (21.4 mm)

[0157] o. Outer diameter of the receptacle (5) (50 mm)

[0158] p. Inner diameter of receptacle (5) (37 mm)

[0159] q. Base length (6) (28 mm)

[0160] r. Base width (6) (14 mm)

[0161] s. Depth of receptacle (5) (17.4 mm)

[0162] a'. Outer diameter of the second removable cover (1') (50 mm)

[0163] b'. Height of the second removable cover (1') (9 mm)

[0164] c'. Inner diameter of the second removable cover (1') (42 mm)

[0165] d'. Diameter of the second removable sealing cap (2') (42 mm)

[0166] e'. Thickness of the second removable sealing cover (2') (1 mm) [Fig 8]

[0167] Fig. 8 is a pair of photographs illustrating how the support for at least one adsorbent (3) is inserted into the dressing (7) and how the assembly is handled by the user. [Fig 9]

[0168] The [Fig.9] is a 2D chromatogram of a healthy body odor sample taken from the axillary area. [Fig 10]

[0169] Figure 10 shows the box plot of the areas obtained in the samples taken for 2-ethylhexanoic acid (above) and nonanoic acid (below) after converting the data to log10. Each point represents one sample. EXAMPLES

[0170] Example No. 1 - Manufacture of the skin VOC sampling system according to the invention

[0171] A housing (receptacle (5) + removable lid (1)) was obtained by machining a piece of stainless steel. The support for at least one adsorbent (3) was also obtained by machining a piece of stainless steel. A removable sealing disc (2) made of PTFE and silicone was cut to the diameter corresponding to the inside of the removable lid (1) of the housing. The aforementioned components were immersed in a solvent bath and placed in an ultrasonic bath for 5 to 30 minutes before being dried in an oven for 30 minutes to 3 hours. at a temperature of 40°C to 100°C. Two PowerSorb® brand adsorbent sticks (4) (sold by Action Europe®) were conditioned for a period of 1h to 6h at a temperature of 200°C to 300°C under a flow of high quality inert gas at a flow rate of 10 mL / min to 75 mL / min.

[0172] Once the various elements constituting the skin volatile organic compound (VOC) sampling system of the invention have been cleaned or conditioned, they were assembled as follows ([Fig.1]): • the removable sealing cap (2) made of PTFE / silicone has been inserted into the removable lid (1) so that the PTFE face is oriented towards the inside of the receptacle (5) and the silicone face towards the removable lid (1); • the adsorbent sticks (4) were inserted into the notches of the skin VOC sampling area (3b) of said support for at least one adsorbent (3) using metal tweezers; and • the support for at least one adsorbent (3) was then placed in the receptacle (5) which was hermetically sealed using the removable lid (1) and the removable sealing cap (2) made of PTFE / silicone.

[0173] Example No. 2 - Determination of the olfactory signature of COVID-19

[0174] Body odor is greatly influenced by internal physiological processes, thus providing potential information about health status. To investigate this aspect, a clinical study was conducted with the aim of identifying volatile organic compounds (VOCs) from the body's volatolome that could be linked to COVID-19 infection. MATERIALS & METHODS

[0175] 13 healthy individuals and 40 hospitalized patients with COVID-19 were Samples were collected. The status of each individual was confirmed by PCR or antigen test. Samples were collected using the skin volatile organic compound (VOC) sampling system according to the invention. Patients who tested positive for COVID-19 were sampled from the axilla, inguinal region, and hand, while healthy individuals who tested negative for COVID-19 were sampled only from the axilla. Before each sample was taken, the area was cleaned with an odorless wipe from Ront® medical. The area was then left to air dry for a few minutes (2 to 5 minutes), after which the skin volatile organic compound (VOC) sampling system was attached. The skin volatile organic compound (VOC) sampling system was left in place for 1 hour, which corresponds to the sampling time during which the VOCs emitted by the individual / patient can migrate and be trapped on the PowerSorb® adsorbent phase. 。

[0176] Following collection, the samples were stored in a refrigerated chamber (at approximately 4°C) and / or transported to the analytical laboratory in a refrigerated container (also at approximately 4°C). Upon receipt, the samples, i.e., the PowerSorb® sticks, were retrieved using metal tweezers and placed in a thermal desorption tube. Each thermal desorption tube contained one sample, i.e., the two PowerSorb® sticks used for collection, for one hour. The sample was then analyzed by thermal desorption followed by fully two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (TD-GCxGC / ToFMS). The thermal desorber used was a TD 100-xr (Markes® International, Bridgend, UK) and the GCxGC / ToFMS system was a LECO Pegasus BT4D (LECO®, Villepinte, France).Following an analysis, the results obtained for a sample are presented in the form of a chromatogram like the one shown in [Fig. 9]. On this chromatogram, the axes correspond to the retention times in the first and second dimensions (abscissa and ordinate), each visible spot corresponds to a compound, and the black and white scale indicates the intensity of the signal, thus related to the quantity of compound initially trapped on the PowerSorb® rod.

[0177] In total, 130 samples were collected, resulting in 130 chromatograms, each containing over 1,000 chromatographic peaks, i.e., 1,000 detected compounds. To analyze this dense data, a research methodology was developed using computational and chemometric tools. Initially, the chromatograms were compared using ChromaToF Tile (LECO®) software to identify significantly different compounds between the COVID (+) and COVID (-) groups by calculating the F-ratio using Fisher's exact statistic. Compounds with a p-value < 0.0001 were retained. Fold change calculations were then performed to determine whether the compounds were under- or over-expressed in the infected individuals, while also verifying that they were not associated with VOCs emitted by the sampling system itself and thus not linked to bias. RESULTS

[0178] These sorting and verification steps made it possible to identify 24 compounds that allowed differentiation of the body volatolome from hospitalized patients and that from healthy individuals. Having acquired more knowledge about the body volatolome through ancillary studies, it was possible to eliminate 19 of these compounds: 12 were eliminated because they were overexpressed in healthy individuals and linked to the use of cosmetic products, and 7 others were eliminated because they were overexpressed only in healthy individuals sampled from an urban environment and therefore potentially linked to the pollution. Of the 5 remaining compounds, the nature of 2 could be assigned and validated: 2-ethylhexanoic acid and nonanoic acid. These molecules made it possible to differentiate the body volatolome of hospitalized patients from that of healthy individuals, as shown in [Fig. 10] with the box plots representing the median and quartiles associated with the areas of the compounds in the samples of the COVID (+) and COVID (-) groups. • CONCLUSION

[0179] In conclusion, the use of the skin volatile organic compound (VOC) sampling system according to the invention in the context of the clinical study on COVID-19 made it possible to highlight 2 molecules (2-ethylhexanoic acid and nonanoic acid) which make it possible to distinctly differentiate the body odor of a sick patient from that of a healthy individual.

[0180] Finally, this work confirmed that the cutaneous volatile organic compound (VOC) sampling system according to the invention makes it possible to identify the olfactory signature of a pathology and thus to have biomarkers of an infection (bacterial, viral or other) available for diagnosis.

Claims

Demands

1. A skin volatile organic compound (VOC) sampling system comprising: • a housing suitable for receiving a support for at least one adsorbent (3) comprising: • a receptacle (5) comprising a first opening at its upper end, • a first removable lid (1) and • a first removable sealing cover (2), the opening and closing of said orifice of said receptacle (5) being ensured by means of said first removable cover (1) in combination with said first removable sealing cap (2) to form said housing, said first removable cover (1) allowing, in the closed position of said housing, pressure to be maintained on said first removable sealing cap (2), in particular by means of a screw system, to ensure the airtightness of said housing and to isolate said support from any external contamination for at least one adsorbent (3); and • a support for at least one adsorbent (3) comprising: • a gripping zone (3a); and • a cutaneous VOC sampling area (3b) co comprising a cavity into which said at least one adsorbent (4) can be inserted at the level of the upper part of said cavity, in which: • the respective materials of said receptacle (5), said first removable lid (1) and said support for at least one adsorbent (3) are inert and selected from: • aluminium and one of these alloys, in particular ZAMAK; • stainless steel, in particular 304L and 316L stainless steel; and • a metal and a metallic alloy emitting less than 10% VOCs, in particular from 0% to 3%, compared rt to an average sample of VOCs from the body volatolome, and • said first removable sealing lid (2) comprises two layers: • a first silicone layer on the inside of said first removable lid (1); and • a second polytetrafluoroethylene (PTFE) layer on the inside of said receptacle (5).

2. Skin VOC sampling system according to claim 1, wherein said support for at least one adsorbent (3) further comprises said at least one adsorbent (4), said at least one adsorbent (4): • comprising an inert polymer, resistant to a temperature of at least 220°C in particular for a period of at least 4h, and being capable of capturing skin VOCs and releasing at least 80% of said captured skin VOCs, and • having in particular a dimension enabling it to be inserted into a thermal desorption tube.

3. Skin VOC sampling system according to claim 1 to or 2, wherein the material of said at least one adsorbent (4) is selected from: • Polydimethylsiloxane (PDMS); and • a 2,6-diphenylene-oxide polymer resin trapped in a porous polytetrafluoroethylene (PTFE) membrane.

4. A skin VOC sampling system according to any one of claims 1 to 3, wherein said receptacle (5) further comprises at its lower end a base (6) in which said support is housed for at least one adsorbent (3), the material of said base (6) being inert and selected from: • aluminum and one of its alloys, in particular ZAMAC; • stainless steel, in particular 304L stainless steel and 316L stainless steel; and • a metal and a metal alloy emitting less than 10% of VOCs, specifically 0% to 3%, compared to an average VOC sample from the body volatolome.

5. A skin VOC sampling system according to claim 4, wherein: • the surface of said base (6) opposite said cavity of said skin VOC sampling zone (3b) of said support for at least one adsorbent (3) is grid-shaped; and • said receptacle (5) further comprises a second orifice at its lower end, the opening and closing of which are effected by means of a second removable cover (1') in combination with a second removable sealing cap (2'), the material of said second removable cover (1') being inert and selected from: • aluminum and one of its alloys, in particular ZAMAC • stainless steel, in particular 304L and 316L stainless steel; and • a metal and a metallic alloy emitting less than 10% of VOCs, specifically 0% to 3%, compared to an average VOC sample from the body volatolome, said second removable sealing cover (2') comprising two layers: • a first silicone layer on the inside of said second removable cover (1'); and • a second layer of polytetrafluoroethylene (PTFE) to the right of said base (6), and said second removable cover (1') allowing in closed position said case to maintain pressure on said second removable sealing cover (2'), in particular by means of a screwing system, to ensure the airtightness of said case and to isolate said support from any external contamination for at least one adsorbent (3).

6. Skin VOC sampling kit comprising a skin VOC sampling system according to any one of claims 1 to 5 and a dressing (7), said dressing (7) comprising: • in its center an inert material such as aluminum in which is cut a slit adapted to allow passage of said gripping zone (3a); and • around its perimeter an adhesive material adapted to be placed on the skin of an individual.

7. Skin VOC sampling kit according to claim 6 further comprising: • an odorless cleansing wipe; and • a pair of gloves.

8. Use of a skin VOC sampling system according to any one of claims 1 to 5 or of a skin VOC sampling kit according to claim 6 or 7 to implement a method of skin VOC sampling on an individual, in particular said sampling method being carried out on an area of ​​the body of said individual, said body area being flat and having a surface area of ​​2x3 cm.

9. A method for collecting cutaneous VOCs from an individual comprising at least the following steps: i. cleaning the sampling area with an odorless cleansing wipe to obtain a clean sampling area; ii. collecting said cutaneous VOCs using a cutaneous VOC sampling system according to any one of claims 1 to 5 or a cutaneous VOC sampling kit according to claim 6 or 7, the collection of said cutaneous VOCs being carried out using said support for at least one adsorbent (3) which is extended from the casing by its upper end and comprises at least one adsorbent (4) and is then: • placed on the cleaned sampling area; and • held on said cleaned sampling area using a dressing for a period of 45 min to 75 min to obtain a support for at least one adsorbent (3). comprising at least one adsorbent (4) containing said cutaneous VOCs; and iii. arranging said support for at least one adsorbent (3) comprising at least one adsorbent (4) containing said cutaneous VOCs in said receptacle (5) which is then hermetically sealed.

10. Method for determining an olfactory signature of a pathology, said method implementing a method for sampling cutaneous VOCs according to claim 9 on at least one healthy individual and at least one individual suffering from said pathology followed by a comparative analysis method by gas chromatography coupled with mass spectrometry of said cutaneous VOCs sampled.

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