FR3144867A1 - Device and method for characterizing a fluid - Google Patents

Abstract

This electronic device (30) for characterizing a fluid comprises at least one sensor (38i) comprising a first reactive site (40i) on which identical first reactive components are grafted, a transducer (44) designed to provide, in interaction with said at least one sensor (38i), a sequence of measurement signals (S), and a processor (48) for processing the sequence of measurement signals (S) to provide at least one temporal signal (ΔSGi) representative of an interaction of the fluid with each sensor (38i). Each sensor (38i) comprises a second reactive site (42i) onto which are grafted second identical reactive components consisting respectively of first reactive portions identical to the first reactive components of the first reactive site (40i) and of distinctive reactive extensions. Said at least one temporal signal (ΔSGi) results, for each sensor, from a comparison of the interactions of the fluid with the two reactive sites (40i, 42i). Figure for abstract: Fig. 3

Description

Device and method for characterizing a fluid

The present invention relates to an electronic device for characterizing a liquid or gaseous fluid. It also relates to a characterization method implemented by such a device.

• au moins un capteur conçu pour interagir avec le fluide, chaque capteur comportant un site réactif sur lequel sont greffés des composants réactifs identiques aptes à interagir avec des composés susceptibles d’être présents dans le fluide ;
• un transducteur conçu pour fournir, en interaction avec ledit au moins un capteur, une séquence de signaux de mesure ; et
• un processeur de traitement de la séquence de signaux de mesure pour fournir au moins un signal temporel représentatif d’une interaction du fluide avec chaque capteur.

The invention applies more particularly to an electronic device for characterizing a fluid, comprising:

• at least one sensor designed to interact with the fluid, each sensor comprising a reactive site onto which are grafted identical reactive components capable of interacting with compounds likely to be present in the fluid;
• a transducer adapted to provide, in interaction with said at least one sensor, a sequence of measurement signals; and
• a processor for processing the sequence of measurement signals to provide at least one time signal representative of an interaction of the fluid with each sensor.

It is understood that the interaction with the fluid, the provision of the measurement signal sequence and its processing are operations that can be carried out in parallel over time. Alternatively, the processing can be carried out a posteriori .

• l’industrie du parfum, par exemple pour comparer, étudier ou concevoir des compositions olfactives pures ou mélangées,
• la protection de l’environnement, en particulier pour détecter les pollutions odorantes ou la surveillance de la qualité d’environnements plus ou moins confinés,
• la surveillance de sites industriels présentant un risque de contamination par des matériaux volatils ou solubles dans un solvant potentiellement dangereux ou odorants,
• la santé, par exemple pour proposer un substitut d’odorat à des personnes souffrant d’anosmie ou pour détecter des marqueurs biologiques volatils tels que les émanations d’une activité microbiologique infectieuse,
• l’industrie alimentaire, par exemple pour détecter des contaminations dans une chaîne de fabrication et/ou distribution de nourriture,
• n’importe quel autre domaine industriel dans lequel le contrôle d’un produit odorant quelconque peut s’avérer utile.

This type of device is sometimes called a multivariate sensor. It can be considered for various olfactory estimation applications and is generally, in this case, referred to as an "electronic nose" (in a gaseous medium) or "electronic tongue" (in a liquid medium). It is then used to detect, discriminate, identify and quantify volatile organic compounds in a gaseous fluid to be analyzed, or compounds present in a liquid. It can be used in different industrial fields such as:

• the perfume industry, for example to compare, study or design pure or mixed olfactory compositions,
• environmental protection, in particular to detect odorous pollution or monitor the quality of more or less confined environments,
• monitoring of industrial sites presenting a risk of contamination by volatile or solvent-soluble materials that are potentially dangerous or odorous,
• health, for example to provide a substitute for smell to people suffering from anosmia or to detect volatile biological markers such as emanations of infectious microbiological activity,
• the food industry, for example to detect contamination in a food manufacturing and/or distribution chain,
• any other industrial field in which the control of any odorous product may be useful.

An example is known and described in patent documents WO 2018/158458 A1 and WO 2019/053366 A1. This example, called NeOse Pro (registered trademark), was marketed by the company Aryballe in 2018. It is based on surface plasmon resonance detection technology, i.e. an SPR (Surface Plasmon Resonance) type imaging system and includes a processor capable of providing a vector digital signature with M components from the measurement signals provided by the transducer, each signature being specific to a detected odor and which can be described as an olfactory signature. In general, M is less than or equal to the number of sensors. By learning carried out on several fluid samples and under different conditions, it is potentially possible to identify all odors. Alternatively, as taught in the article by Bernini et al, entitled “Generalized Mach-Zehnder interferometers for sensing applications”, published in Sensors and Actuators B 100 (2004), pages 72-74, or as envisaged in patent document WO 2022/238812 A1, the SPR imaging system can be replaced by a system for amplification of optical index variation by Mach-Zehnder interferometry, i.e. an MZI (Mach-Zehnder Interferometer) type imaging system. For example, an electronic olfactory characterization device with an MZI system, called NeOse Advance (registered trademark), is also marketed by the company Aryballe. Also alternatively, it can also be replaced by a NEMS or MEMS (nano- or micro-electromechanical system).

According to a good use of such a device, it is generally advantageous to control the moments of contact with the fluid to be analyzed and those of contact with a reference medium. We thus obtain exploitable time signals called "sensorgrams" characteristic of a kinetics of interactions between target compounds of the fluid and the reactive sites of the sensors of the device, from which it is possible to characterize the fluid and its composition. These sensorgrams, an example of which is illustrated on the in the form of a time diagram obtained using MZI technology, thus generally comprise a first portion PH1 corresponding to a first reference state of exposure of the sensors to a reference fluid environment with a carrier fluid without the presence of the target compounds, i.e. without the presence of the fluid to be characterized, followed by a second portion PH2 corresponding to a second analytical state of exposure of the sensors to the fluid to be analyzed, called adsorption and equilibrium, followed by a third portion PH3 corresponding to a third final state, called desorption, of re-exposure of the reactive sites to the reference fluid environment.

In practice and as illustrated in the also, each sensor 10 comprises reactive components 12, such as polymers of limited sizes, for example chemical polymers other than biomolecular with a molar mass of less than 2000 g/mol, peptides, DNA fragments (for DeoxyriboNucleic Acid), oligosaccharides, or more generally oligomers, advantageously identical, which are specific to it and of which certain reactive endings 14, in particular the residues or side chains of amino acids when they are peptides, interact specifically by adsorption with certain compounds 16 likely to be present in the fluid to be characterized. The different sensors of the electronic characterization device also differ from each other by their reactive components, that is to say by the reactive endings which characterize them, in particular the amino acids which compose them when they are peptides, and their resulting capacities to adsorb such or such compound. It will be noted that the more specifically illustrates the non-limiting case of reactive components formed from peptides with six peptide bonds.

Thus, all the time signals, or sensorgrams, that can be obtained by interaction of a fluid to be characterized with all the sensors of the same electronic characterization device form as such a raw signature of the fluid. In particular, two fluids of different compositions cannot theoretically present the same sensorgram when they interact with a given sensor.

But the reactive site of each sensor 10 has a substrate 18, generally based on silicon or gold compounds, and possible elements 20 for grafting the reactive components, generally silane groups fixed to the substrate 18 when it is based on silicon compounds. Now it turns out that the compounds 16 of the fluid to be characterized can interact, not only in a discriminatory manner with the reactive components 12, but also in an inopportune manner with the substrate 18 and the grafting elements 20 when these are present and accessible, in particular when they are not completely covered or requested for the grafting of reactive components, which is inevitable.

More generally, the interactions between the fluid and the reactive endings 14 carried by the reactive components 12 of a sensor 10 are discriminating. But the interactions also possible between the fluid and the substrate 18, the grafting elements 20 or the bonds 22 internal to the reactive components 12, in particular the peptide bonds when they are peptides, the phosphodiester bonds when they are DNA fragments, the glycosidic bonds when they are oligosaccharides or other chemical bonds when they are polymers, are not. They are therefore a source of measurement noise. Furthermore, it may happen that, depending on the physicochemical properties of the reactive components 12 grafted onto the substrate 18, reactive endings 14 are in reality not accessible for an interaction, which is also a source of noise. The characterization of the fluid is therefore noisy by these inopportune interactions, so that it can even happen that two different fluids interact differently with the same sensor while producing two sensorgrams that are difficult to distinguish, one resulting for example from more inopportune interactions than the other. As a non-limiting example, based on peptide reactive components, the shows by illustration that two fluids F1 and F2 of respective compounds C1 and C2 produce two very similar sensorgrams by interacting differently with the same sensor 10. The compounds C1 of the fluid F1 interact more with the amino acid residues specific to the sensor 10, while the compounds C2 of the fluid F2 interact more with its substrate and its grafting elements, for a relatively similar overall adsorption dynamic as shown by the resulting sensorgrams S1 and S2.

To overcome this difficulty in characterizing the fluid, it is known to provide a reference sensor on the reactive site of which no reactive component is grafted, for example a reactive site with a silica substrate and silane groups alone, and to subtract the resulting reference sensorgram from each other sensorgram. But it turns out that the silane itself constitutes a sensor, so that it is likely to react specifically with certain compounds, which puts the interest of the reference sensor into perspective quite singularly.

It may thus be desirable to provide an electronic device for characterizing a fluid which makes it possible to overcome at least some of the aforementioned problems and constraints, in particular by making it possible to obtain representative time signals which are much less sensitive to the aforementioned sources of measurement noise.

• au moins un capteur conçu pour interagir avec le fluide, chaque capteur comportant un premier site réactif sur lequel sont greffés des premiers composants réactifs identiques aptes à interagir avec des composés susceptibles d’être présents dans le fluide ;
• un transducteur conçu pour fournir, en interaction avec ledit au moins un capteur, une séquence de signaux de mesure ; et
• un processeur de traitement de la séquence de signaux de mesure pour fournir au moins un signal temporel représentatif d’une interaction du fluide avec chaque capteur ;

dans lequel :

• chaque capteur comporte un deuxième site réactif sur lequel sont greffés des deuxièmes composants réactifs identiques constitués respectivement de premières portions réactives, greffées sur le deuxième site réactif et identiques aux premiers composants réactifs du premier site réactif de ce capteur, et d’extensions réactives qui les distinguent des premiers composants réactifs du premier site réactif de ce capteur ; et
• le processeur est configuré pour fournir ledit au moins un signal temporel, pour chaque capteur, sur la base d’une comparaison des interactions du fluide avec les deux sites réactifs de ce capteur.

An electronic device for characterizing a fluid is therefore proposed, comprising:

• at least one sensor designed to interact with the fluid, each sensor comprising a first reactive site onto which are grafted first identical reactive components capable of interacting with compounds likely to be present in the fluid;
• a transducer adapted to provide, in interaction with said at least one sensor, a sequence of measurement signals; and
• a processor for processing the sequence of measurement signals to provide at least one time signal representative of an interaction of the fluid with each sensor;

in which:

• each sensor comprises a second reactive site onto which are grafted second identical reactive components consisting respectively of first reactive portions, grafted onto the second reactive site and identical to the first reactive components of the first reactive site of this sensor, and of reactive extensions which distinguish them from the first reactive components of the first reactive site of this sensor; and
• the processor is configured to provide said at least one time signal, for each sensor, on the basis of a comparison of the interactions of the fluid with the two reactive sites of this sensor.

Thus, the largest contribution to the measurement noise is removed by comparison, since it is statistically intended to occur in approximately the same way on the first and second reactive sites of each sensor, namely the interactions between the fluid compounds and the substrate, the possible grafting elements and the internal bonds of the first common reactive portions.

• un substrat à base de composé du silicium, notamment à base de silice ou de nitrure de silicium, des groupes de silanes fixés au substrat et des composants réactifs identiques greffés aux groupes de silanes ; ou
• un substrat à base d’or et des composants réactifs identiques greffés au substrat.

Optionally, each reactive site of each sensor includes:

• a substrate based on a silicon compound, in particular based on silica or silicon nitride, silane groups attached to the substrate and identical reactive components grafted to the silane groups; or
• a gold-based substrate and identical reactive components grafted to the substrate.

Optionally also, the reactive components of the same sensor are homo-oligomers, that is to say all made up of monomeric units which are themselves identical, for example homopeptides all made up of a peptide chain of one or more occurrences of the same amino acid.

Also optionally, each first reactive component of the first reactive site of each sensor is an oligomer that comprises between one and five monomeric units.

Also optionally, each second reactive component of the second reactive site of each sensor is an oligomer that has between six and eighteen monomeric units.

• un premier signal temporel représentatif d’une interaction du fluide avec le premier site réactif de ce capteur ;
• un deuxième signal temporel représentatif d’une interaction du fluide avec le deuxième site réactif de ce capteur ; et
• un signal temporel différentiel résultant d’une comparaison, par exemple par soustraction, des premier et deuxième signaux temporels.

Also optionally, for each sensor, the processor is designed to provide:

• a first time signal representative of an interaction of the fluid with the first reactive site of this sensor;
• a second time signal representative of an interaction of the fluid with the second reactive site of this sensor; and
• a differential time signal resulting from a comparison, for example by subtraction, of the first and second time signals.

Optionally also, the processor is configured to provide said at least one time signal representative of an interaction of the fluid with each sensor from each differential time signal.

Also optionally, the first reactive components of the first reactive site of the same sensor are hetero-oligomers, that is to say all consisting of monomeric units of which at least two are different, for example heteropeptides all consisting of a peptide chain of several occurrences from at least two different amino acids, and each reactive extension of each second reactive component of the second reactive site of this same sensor comprises at least one repetition of its first reactive portion identical to the first reactive components of the first reactive site, for example at least one repetition of the heteropeptide chain of its first peptide portion identical to the first peptides of the first reactive site.

Also optionally, the processor is designed to obtain a characterization of the fluid, in particular an identifying signature of the fluid, by extracting a predetermined characteristic of said at least one representative temporal signal.

• approcher le dispositif électronique du fluide de manière à obtenir une interaction du fluide avec chaque capteur ;
• fournir, à l’aide du transducteur et en interaction avec ledit au moins un capteur, une séquence de signaux (S) de mesure ; et
• fournir, à l’aide du processeur, au moins un signal temporel représentatif d’une interaction du fluide avec chaque capteur ;

dans lequel :

• l’approche du dispositif électronique est réalisée de manière à obtenir une interaction du fluide avec les premier et deuxième sites réactifs de chaque capteur ; et
• le processeur procède, pour chaque capteur, à une comparaison des interactions du fluide avec les deux sites réactifs de ce capteur pour fournir ledit au moins un signal temporel comme résultant de cette comparaison.

A method for characterizing a fluid is also proposed, using an electronic device as defined above, comprising the following steps:

• approach the electronic device to the fluid so as to obtain an interaction of the fluid with each sensor;
• providing, using the transducer and in interaction with said at least one sensor, a sequence of measurement signals (S); and
• providing, using the processor, at least one time signal representative of an interaction of the fluid with each sensor;

in which:

• the approach of the electronic device is carried out so as to obtain an interaction of the fluid with the first and second reactive sites of each sensor; and
• the processor proceeds, for each sensor, to a comparison of the interactions of the fluid with the two reactive sites of this sensor to provide said at least one temporal signal as resulting from this comparison.

• la , déjà décrite, illustre un exemple de diagramme temporel de signal représentatif d’une interaction d’un fluide avec un capteur de l’état de la technique, ou sensorgramme, pouvant être obtenu dans des conditions maîtrisées de mesure multivariée,
• la , déjà décrite, illustre un autre exemple de diagramme temporel dans lequel se superposent deux signaux respectivement représentatifs d’une interaction de deux fluides différents avec un même capteur de l’état de la technique, ou sensorgrammes, pouvant être obtenus dans des conditions maîtrisées de mesure multivariée,
• La représente schématiquement la structure générale d’un dispositif électronique de caractérisation d’un fluide, selon un mode de réalisation de l’invention,
• la illustre un exemple de diagramme temporel dans lequel se superposent plusieurs signaux de réponse, ou sensorgrammes, pouvant être obtenus par le dispositif électronique de la , dans des conditions maîtrisées de mesure multivariée,
• la illustre, sous la forme d’un diagramme circulaire, un exemple de signature normée pouvant être calculée par le dispositif électronique de la à partir de sensorgrammes tels que ceux de la ,
• la illustre un exemple de diagramme temporel dans lequel se superposent deux signaux représentatifs d’une interaction d’un fluide avec un capteur du dispositif électronique de la , ou sensorgrammes, pouvant être obtenus dans des conditions maîtrisées de mesure multivariée,
• la représente schématiquement la structure générale d’un capteur du dispositif de la , dans un mode de réalisation en technologie MZI,
• la illustre les étapes successives d’un procédé de caractérisation d’un fluide pouvant être mis en œuvre par le dispositif électronique de la .

The invention will be better understood with the aid of the following description, given solely by way of example and with reference to the appended drawings in which:

• there , already described, illustrates an example of a signal time diagram representative of an interaction of a fluid with a state-of-the-art sensor, or sensorgram, which can be obtained under controlled multivariate measurement conditions,
• there , already described, illustrates another example of a time diagram in which two signals respectively representative of an interaction of two different fluids with the same state-of-the-art sensor, or sensorgrams, are superimposed, which can be obtained under controlled multivariate measurement conditions,
• There schematically represents the general structure of an electronic device for characterizing a fluid, according to one embodiment of the invention,
• there illustrates an example of a timing diagram in which several response signals, or sensorgrams, which can be obtained by the electronic device of the , under controlled multivariate measurement conditions,
• there illustrates, in the form of a circular diagram, an example of a standardized signature that can be calculated by the electronic device of the from sensorgrams such as those of the ,
• there illustrates an example of a time diagram in which two signals representative of an interaction of a fluid with a sensor of the electronic device of the , or sensorgrams, which can be obtained under controlled multivariate measurement conditions,
• there schematically represents the general structure of a sensor of the device of the , in an embodiment using MZI technology,
• there illustrates the successive steps of a process for characterizing a fluid that can be implemented by the electronic device of the .

The electronic device 30 for olfactory characterization of a fluid shown schematically in the is a non-limiting example of a fluid characterization device according to a possible embodiment of the present invention for a non-limiting olfactory application of odor identification. It comprises a measuring chamber 32 intended to receive a fluid, for example a gas such as ambient air. To do this, it comprises a suction device 34 designed to suck in the air located inside the measuring chamber 32 and to release it to the outside. It further comprises an air inlet 36 which can be selectively closed to keep the ambient air in the measuring chamber 32 or opened to allow the evacuation of the ambient air from the measuring chamber 32 and its renewal by activating the suction device 34. It is thus provided with means for controlling the incoming and outgoing flows.

In its measuring chamber 32, the electronic olfactory characterization device 30 comprises several olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M , for example around thirty, designed to interact with compounds likely to be present in the measuring chamber 32 when the device 30 is placed near a fluid to be analyzed emitting these compounds, in particular when the air inlet 36 is near the fluid considered. The compounds emitted are generally volatile organic compounds but the present invention is not limited to such compounds.

Each olfactory sensor 38 _i , 1≤i≤M, is itself for example a biosensor designed to interact with the compounds of a particular family of volatile organic compounds. In accordance with the general principles of the present invention, each olfactory sensor 38 _i , 1≤i≤M, comprises two distinct reactive sites 40 _i and 42 _i on which are grafted reactive components capable of interacting with compounds likely to be present in the fluid, more precisely the compounds of the family associated with this olfactory sensor 38 _i . On the first reactive site 40 _i , first identical reactive components are grafted onto a first substrate possibly using first grafting elements. On the second reactive site 42 _i , second identical reactive components are grafted onto a second substrate possibly using second grafting elements. The second identical reactive components are respectively composed of first reactive portions, grafted onto the second substrate and identical to the first reactive components of the first reactive site 40 _i of this olfactory sensor 38 _i , and of reactive extensions which distinguish them from the first reactive components of the first reactive site 40 _i of this olfactory sensor 38 _i . On the other hand, the first and second substrates of this olfactory sensor 38 _i are identical. For example, they are two substrates based on silica, silicon nitride, or gold. Similarly, all the first and second possible grafting elements of this olfactory sensor 38 _i are identical. For example, they are silane groups to which the reactive components are grafted when the two substrates are based on silicon compounds.

Optionally but preferably, the reactive components of the same olfactory sensor are homo-oligomers, that is to say all consisting of monomeric units which are themselves identical, for example homopeptides all consisting of a peptide chain of one or more occurrences of the same amino acid.

Alternatively, however, the reactive components of the same olfactory sensor may be hetero-oligomers, i.e. all consisting of monomeric units of which at least two are different, for example heteropeptides all consisting of a peptide chain of several occurrences derived from at least two different amino acids. In this case, more precisely, the first reactive components of the first reactive site of the same sensor are hetero-oligomers comprising, for example, between two and twenty monomeric units and each reactive extension of each second reactive component of the second reactive site of this same sensor may be a homo-oligomer or a hetero-oligomer. In the case where each aforementioned reactive extension is a hetero-oligomer, it may advantageously comprise at least one repetition, in particular between two and ten repetitions, of its first reactive portion identical to the first reactive components of the first reactive site, for example at least one repetition of the heteropeptide chain of its first peptide portion identical to the first peptides of the first reactive site. In this variant also, the first reactive components of the first reactive site of the same sensor may be homo-oligomers, only the reactive extensions of the second reactive components of the corresponding second reactive site being of hetero-oligomeric nature.

Alternatively, the olfactory characterization device 30 could be adapted to be placed in contact with any other fluid, liquid or gas, than ambient air. It could also, according to a particularly simple version, not include the suction device 34 and the air inlet 36, or even the measuring chamber 32. In this simple version, the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M are then likely to be placed directly in contact with the fluid to be analyzed without flow control.

The olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M are associated with at least one transducer 44 with which they interact. This transducer 44 is arranged and configured to measure any change in physical property caused by an interaction of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M with the fluid to be analyzed. It provides a sequence of electrical measurement signals S which characterizes this fluid since it is representative of the volatile organic compounds with which the olfactory sensors can interact in the measurement chamber 32.

More specifically, the transducer 44 may be a surface plasmon resonance imaging system, i.e. an SPR (Surface Plasmonic Resonance) imaging system configured to measure any change in a refractive index due to an interaction of the fluid studied with at least one of the olfactory sensors using a plasmonic effect. Such a transducer comprises: a metal layer, a first face with reactive sites of which serves as a support for the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M ; an optical prism arranged against a second face, opposite the first, of the metal layer; a device for illuminating this second face of the metal layer with collimated and polarized light via a light entry face of the optical prism; and a camera arranged at the light output of the optical prism for providing the sequence of measurement signals S in the form of a sequence of grayscale images of the reactive sites on which the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M are arranged. The reactive sites of the first face of the metal layer are for example organized in a positioning matrix grid.

Alternatively, the transducer 44 may be a system for amplifying optical index variation by Mach-Zehnder interferometry, for example according to a technology with a matrix of Mach-Zehnder interferometers, called MZI technology (from the English "Mach-Zehnder Interferometer"), or more precisely a MZI technology with multimodal interferences, called MZI/MMI technology (from the English "Multi Mode Interference"). Such a system is configured to measure any change in a refractive index due to an interaction of the fluid studied with at least any one of the reactive sites of each olfactory sensor thanks to a detectable phase shift between a reference arm of the interferometer and a detection arm on which this reactive site is arranged. The resulting transducer provides the measurement signal sequence S which is presented in the form of a sequence of phase shift images, expressed in Radians, of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M .

According to another variant, the transducer 44 could be a nano- or micro-electromechanical NEMS (Nano Electro-Mechanical System) or MEMS (Micro Electro-Mechanical System) amplification system. Such a system is configured to measure any change in the resonant frequency of a vibrating membrane on which any of the olfactory sensors is arranged. The reactive sites on which the olfactory sensors are placed are for example arranged in a matrix of NEMS or MEMS vibrating membranes for providing the sequence of measurement signals S which is in the form of a sequence of signals of resonant frequency shifts of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M . We can thus cite the CMUT (Capacitive Micromachined Ultrasonic Transducer) technology which uses MEMS type capacitive ultrasonic transducers.

Other variants are conceivable by implementing any other equivalent physical transduction device (i.e. optical, mechanical, etc.), i.e. with probes connectable to reactive sites grafted with reactive components, by operating a simple adaptation of the electronic olfactory characterization device 30 which will not be described because it is within the reach of those skilled in the art. Whatever the choice of the transducer 44, the general idea remains to functionalize reactive sites of olfactory sensors 38₁, …, 38_i, …, 38_Msuch that they adsorb and desorb volatile organic compounds in a differentiated manner, to form a differentiated molecular interaction response of the olfactory sensors, and to amplify the response in the form of a sequence of electrical measurement signals S using a physical transduction device.

The electronic olfactory characterization device 30 further comprises several functional modules. which will be described below. In the example described, these modules are of a software nature. Thus, the device 30 comprises a computer-type element 46 comprising a processing unit 48 and an associated memory area 50 in which several computer programs or several functions of the same computer program are recorded. These computer programs comprise instructions designed to be executed by the processing unit 48 in order to perform the functions of the software modules. They are presented as distinct, but this distinction is purely functional. They could just as well be grouped according to all possible combinations in one or more software programs. Their functions could also be at least partly microprogrammed or microwired in dedicated integrated circuits, such as digital circuits. Thus, as a variant, the computer 46 could be replaced by an electronic device composed solely of digital circuits (without a computer program) for performing the same functions.

The electronic olfactory characterization device 30 thus firstly comprises a software module 52, intended to be executed by the processing unit 48, for controlling the suction device 34 (if it is provided in the device 30), the air inlet 36 (if it is also provided in the device 30) and the transducer 44.

It further comprises, optionally but advantageously, a software module 54, intended to be executed by the processing unit 48, for selecting, from among the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M of the electronic olfactory characterization device 30, a subset of sensors sensitive to volatile components characteristic of a sought-after olfactory imprint. These characteristic volatile components may vary from one application or fluid studied to another so that the selection of olfactory sensors carried out by the software module 54 may also vary and be parameterized. The selected subset comprises, for example, at least one olfactory sensor, in particular advantageously several olfactory sensors, or even all of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M with M≥3.

In the remainder of the presentation, all olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M will be considered as selected for the sake of simplification in the notations. All reactive components will further be considered as homopeptides for the sake of simplification in the illustrations, although everything that will be described in relation to these homopeptides can be adapted in particular to heteropeptides, DNA fragments, oligosaccharides, or generalized to homo-/hetero-oligomers and homo-/hetero-polymers.

The electronic olfactory characterization device 30 further comprises a software module 56, intended to be executed by the processing unit 48, to extract 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} respectively representative of the interactions of the 2M reactive sites of the M selected olfactory sensors with the volatile organic compounds concerned from the values specific to these M olfactory sensors in the sequence of measurement signals S provided by the transducer 44. These sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} are for example reflectance signals expressed as a percentage according to a ratio of luminance values obtained with transversely polarized light to luminance values obtained with the same 90-degree polarized light for each of the 2M reactive sites of the M selected olfactory sensors when the transducer 44 is an SPR type imaging system. They take the form of phase shift signals and are expressed in Radians when the transducer is an MZI or MZI/MMI amplification system. They take the form of frequency shift signals and are expressed in Hertz when the transducer is a NEMS or MEMS amplification system. They can take other forms when the transducer is of another compatible type.

• les sites réactifs 40₁, …, 40_i, …, 40_Met 42₁, …, 42_i, …, 42_Mdes capteurs olfactifs 38₁, …, 38_i, …, 38_Msont tout d’abord exposés à un environnement fluidique de référence à fluide porteur sans présence des composés cibles d’un fluide à analyser au cours d’un premier état de référence identifiable par une première portion PH1 des sensorgrammes,
• ils sont ensuite exposés au fluide à analyser au cours d’un deuxième état analytique d’adsorption déclenché par une injection maîtrisée de ce fluide dans la chambre de mesure 32, ce deuxième état étant identifiable par une deuxième portion PH2 des sensorgrammes, et
• ils sont finalement exposés de nouveau à l’environnement fluidique de référence au cours d’un troisième état final de désorption par une évacuation maîtrisée du fluide à analyser hors de la chambre de mesure 32, ce troisième état étant identifiable par une troisième portion PH3 des sensorgrammes.

There thus illustrates the time diagram of a superposition of around sixty sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} obtained using an MZI or MZI/MMI amplification system over a period of around 190 seconds according to a well-controlled measurement protocol, involving control of the suction device 34 and the air inlet 36, in which:

• the reactive sites 40 ₁ , …, 40 _i , …, 40 _M and 42 ₁ , …, 42 _i , …, 42 _M of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M are first exposed to a reference fluid environment with a carrier fluid without the presence of the target compounds of a fluid to be analyzed during a first reference state identifiable by a first portion PH1 of the sensorgrams,
• they are then exposed to the fluid to be analyzed during a second analytical adsorption state triggered by a controlled injection of this fluid into the measuring chamber 32, this second state being identifiable by a second portion PH2 of the sensorgrams, and
• they are finally exposed again to the reference fluid environment during a third final desorption state by a controlled evacuation of the fluid to be analyzed out of the measuring chamber 32, this third state being identifiable by a third portion PH3 of the sensorgrams.

The emergence of two distinct groups of sensorgrams SG1 _i , i∈{1, …, M} and SG2 _i , i∈{1, …, M} arising respectively from the first 40 ₁ , …, 40 _i , …, 40 _M and second 42 ₁ , …, 42 _i , …, 42 _M reactive sites of the olfactory sensors 38 ₁ , …, 38 _i , …, 38 _M will be explained later with reference to the .

Back to the , the electronic olfactory characterization device 30 further comprises an optional software module 58, intended to be executed by the processing unit 48, to carry out possible prior processing on the 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} provided by the software module 56.

This pre-processing includes, for example, low-pass filtering implemented in the form of a digital filter with finite or infinite impulse response. This involves filtering out high-frequency measurement noise in the raw signals as provided by software module 56. A Butterworth filter with a first-order finite impulse response and a cut-off frequency normalized to 0.45 (i.e. the value of the ratio between the cut-off frequency and the sampling frequency equal to 0.45) is suitable.

This preliminary processing also includes, for example, a calculation of a norm within the meaning of patent document WO 2020/141281 A1 on the 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} filtered or not to obtain 2M filtered and/or normalized sensorgrams SG1' _i , SG2' _i , i∈{1, …, M}.

The electronic olfactory characterization device 30 further comprises several software modules 60 to 64, intended to be executed by the processing unit 48, to obtain a SIG characterization of the composition of the fluid to be analyzed from the 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} or SG1' _i , SG2' _i , i∈{1, …, M}. This SIG characterization can take the form of a standardized olfactory signature as mentioned previously and as illustrated in the in the form of a pie chart.

In accordance with the general principles of the present invention, the software modules 60 to 64 are designed to obtain a SIG characterization of the composition of a fluid to be analyzed from the 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} or SG1' _i , SG2' _i , i∈{1, …, M} which is clearly more discriminating than in the state of the art.

For this purpose, the software module 60, intended to be executed by the processing unit 48, performs a comparison of the interactions of the fluid with the two reactive sites of each olfactory sensor, for example in the form of a comparison of the two sensorgrams SG1 _i and SG2 _i , or SG1' _i and SG2' _i , from each olfactory sensor 38 _i , 1≤i≤M. This comparison can even more precisely take the form of a simple subtraction, to obtain M differential sensorgrams ΔSG _i , i∈{1, …, M}.

This comparison is illustrated in the . We see two reactive sites 40 _i and 42 _i of the same olfactory sensor 38 _i , 1≤i≤M. These two reactive sites comprise substrates 66 and identical grafting elements 68. The first reactive site 40 _i comprises homopeptides 70 all identical with two peptide bonds 72 and two amino acid residues 74 each. The second reactive site 42 _i comprises homopeptides 76 all identical with twelve peptide bonds 72 and twelve amino acid residues 74 each. Thus, the homopeptides 76 of the second reactive site 42 _i each comprise a first peptide portion with two peptide bonds 72 and two amino acid residues 74 grafted onto the grafting elements 68. This first peptide portion is identical to the homopeptides 70 of the first reactive site 40 _i . On the other hand, the homopeptides 76 of the second reactive site 42 _i each further comprise a peptide extension 78 with ten peptide bonds 72 and ten amino acid residues 74 to form in total the twelve peptide bonds 72 and the twelve amino acid residues 74.

It will be noted that, more generally, it is advantageous to provide between one and five peptide bond(s) for each peptide 70 of the first reactive site 40 _i and between six and eighteen peptide bonds for each peptide 76 of the second reactive site 42 _i .

The interactions of a fluid with the first reactive site 40 _i produce the sensorgram SG1 _i , while those of the same fluid with the second reactive site 42 _i produce the sensorgram SG2 _i whose amplitude at each instant is greater due to the greater number of peptide bonds. By subtracting at each instant the sensorgram SG1 _i from the sensorgram SG2 _i as illustrated by the operation Δ in the , we obtain the aforementioned differential sensorgram ΔSG _i which results statistically only from the interactions of the fluid with the peptide extensions 78. We have therefore gotten rid of the inopportune interactions of the fluid with the substrates 66 and the grafting elements 68, or even with the first two peptide bonds of each peptide 70 or 76, so that the differential sensorgram ΔSG _i is much more relevant than each of the sensorgrams SG1 _i and SG2 _i for characterizing the fluid.

A concrete example of the realization of each 38 _i olfactory sensor in MZI technology is illustrated on the . The transducer 44 is in this case a system for amplifying the variation of optical index by Mach-Zehnder interferometry. The olfactory sensor 38 _i comprises a first arm (i.e. in the form of an optical fiber) 80 _i for detection on which the first reactive site 40 _i is arranged and a first reference arm 82 _i for measuring the variation of optical index generated by this first reactive site 40 _i . It further comprises a second detection arm 84 _i on which the second reactive site 42 _i is arranged and a second reference arm 86 _i for measuring the variation of optical index generated by this second reactive site 42 _i .

Back to the , the software module 62, intended to be executed by the processing unit 48, takes each of the M differential sensorgrams ΔSG _i , i∈{1, …, M} and performs for each of them the calculation of at least one descriptive value DSCR _i . There are many known ways of determining such a descriptive value, in particular by statistical calculation, so that the operation of the software module 62 will not be detailed.

Finally, the software module 64, intended to be executed by the processing unit 48, obtains the characterization of the composition of the fluid on the basis of the descriptive values thus calculated. This characterization is done for example by estimating an olfactory signature SIG of the M differential sensorgrams ΔSG _i , i∈{1, …, M}. In the simplest variant, it is for example simply a matter of defining the olfactory signature SIG as a vector whose M components are the M descriptive values DSCR _i , i∈{1, …, M}, calculated by the software module 62. As mentioned previously, this vector can then be normalized to make the olfactory signature more generic.

The method of olfactory characterization of a fluid corresponding to the execution of software modules 52 to 64 will now be detailed in accordance with the succession of steps of the .

During a first step 100, the electronic olfactory characterization device 30 is brought close to a fluid so as to obtain an interaction of the fluid with each of the two reactive sites 40 _i , 42 _i of each olfactory sensor 38 _i , 1≤i≤M. On this occasion, the software module 52 is executed.

During a following step 102, the transducer 44 provides a sequence S of measurement signals in interaction with the olfactory sensors 38 _i , 1≤i≤M.

During a following step 104 carried out by executing the software module 56, the processor 48 provides the 2M sensorgrams SG1 _i , SG2 _i , i∈{1, …, M} representative of an interaction of the fluid with each reactive site of the olfactory sensor.

During a following optional step 106 performed by executing the software module 58, the processor 48 provides the 2M sensorgrams SG1' _i , SG2' _i , i∈{1, …, M}.

During a following step 108 performed by executing the software module 60, the processor 48 performs, for each olfactory sensor 38 _i , a comparison of the interactions of the fluid with the two reactive sites 40 _i and 42 _i of this olfactory sensor to provide the M differential sensorgrams ΔSG _i , i∈{1, …, M}, for example resulting from a simple subtraction of the M sensorgrams SG1 _i , i∈{1, …, M} from the M sensorgrams SG2 _i , i∈{1, …, M}, or of the M sensorgrams SG1' _i , i∈{1, …, M} from the M sensorgrams SG2' _i , i∈{1, …, M}. These M differential sensorgrams are for example directly used as representative of an interaction of the fluid with the M olfactory sensors considered as a whole.

During a following step 110 carried out by executing the software module 62, M descriptive values DSCRi, i∈{1, …, M}, of the M differential sensorgrams ΔSG _i , i∈{1, …, M}, are extracted in a manner known per se.

Finally, during a last step 112 carried out by executing the software module 64, a standardized olfactory signature SIG is obtained from the M descriptive values DSCRi, i∈{1, …, M}.

It is clear that an electronic device for characterizing a fluid such as that of the allows to significantly improve the discriminatory property of this characterization by cleverly getting rid of the measurement noise linked to the inappropriate interactions between the fluid and certain components of the sensors, such as the substrates and the possible peptide grafting elements.

It should also be noted that the invention is not limited to the embodiment described above. It will indeed appear to those skilled in the art that various modifications can be made to the embodiment described above, in light of the teaching that has just been disclosed to them. In the detailed presentation of the invention that is given above, the terms used should not be interpreted as limiting the invention to the embodiment set out in the present description, but should be interpreted to include all equivalents that can be foreseen by those skilled in the art by applying their general knowledge to the implementation of the teaching that has just been disclosed to them.

Claims (10)

Electronic device (30) for characterizing a fluid, comprising:

• at least one sensor (38 ₁ , …, 38 _i , …, 38 _M ) designed to interact with the fluid, each sensor (38 ₁ , …, 38 _i , …, 38 _M ) comprising a first reactive site (40 ₁ , …, 40 _i , …, 40 _M ) onto which are grafted first identical reactive components (70) capable of interacting with compounds (16) likely to be present in the fluid;
• a transducer (44) designed to provide, in interaction with said at least one sensor (38 ₁ , …, 38 _i , …, 38 _M ), a sequence of measurement signals (S); and
• a processor (48) for processing the sequence of measurement signals (S) to provide at least one time signal (ΔSG _i ) representative of an interaction of the fluid with each sensor (38 ₁ , …, 38 _i , …, 38 _M );

characterized in that:

• each sensor (38 ₁ , …, 38 _i , …, 38 _M ) comprises a second reactive site (42 ₁ , …, 42 _i , …, 42 _M ) onto which are grafted second identical reactive components (76) consisting respectively of first reactive portions, grafted onto the second reactive site (42 ₁ , …, 42 _i , …, 42 _M ) and identical to the first reactive components (70) of the first reactive site (40 ₁ , …, 40 _i , …, 40 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M ), and of reactive extensions (78) which distinguish them from the first reactive components (70) of the first reactive site (40 ₁ , …, 40 _i , …, 40 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M ); and
• the processor (48) is configured to provide said at least one time signal (ΔSG _i ), for each sensor (38 ₁ , …, 38 _i , …, 38 _M ), on the basis of a comparison of the interactions of the fluid with the two reactive sites (40 ₁ , …, 40 _i , …, 40 _M , 42 ₁ , …, 42 _i , …, 42 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M ).

Electronic device (30) for characterizing a fluid according to claim 1, in which each reactive site (40₁, …, 40_i, …, 40_M, 42₁, …, 42_i, …, 42_M) of each sensor (38₁, …, 38_i, …, 38_M) includes:

• a substrate (66) based on a silicon compound, in particular based on silica or silicon nitride, silane groups (68) fixed to the substrate (66) and identical reactive components (70, 76) grafted to the silane groups (68); or
• a gold-based substrate (66) and identical reactive components (70, 76) grafted to the substrate (66).

Electronic device (30) for characterizing a fluid according to claim 1 or 2, in which the reactive components (70, 76) of the same sensor (38 ₁ , …, 38 _i , …, 38 _M ) are homo-oligomers, that is to say all consisting of monomeric units which are themselves identical, for example homopeptides all consisting of a peptide chain of one or more occurrences of the same amino acid (74). Electronic device (30) for characterizing a fluid according to any one of claims 1 to 3, in which each first reactive component (70) of the first reactive site (40 ₁ , …, 40 _i , …, 40 _M ) of each sensor (38 ₁ , …, 38 _i , …, 38 _M ) is an oligomer which comprises between one and five monomer units. Electronic device (30) for characterizing a fluid according to any one of claims 1 to 4, in which each second reactive component of the second reactive site (42 ₁ , …, 42 _i , …, 42 _M ) of each sensor (38 ₁ , …, 38 _i , …, 38 _M ) is an oligomer which comprises between six and eighteen monomer units. Electronic device (30) for characterizing a fluid according to any one of claims 1 to 5, in which, for each sensor (38₁, …, 38_i, …, 38_M), the processor (48) is designed to provide:

• a first time signal (SG1 _i ) representative of an interaction of the fluid with the first reactive site (40 ₁ , …, 40 _i , …, 40 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M );
• a second time signal (SG2 _i ) representative of an interaction of the fluid with the second reactive site (42 ₁ , …, 42 _i , …, 42 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M ); and
• a differential time signal (ΔSG _i ) resulting from a comparison, for example by subtraction, of the first (SG1 _i ) and second (SG2 _i ) time signals.

Electronic device (30) for characterizing a fluid according to claim 6, in which the processor (48) is designed to provide said at least one temporal signal (ΔSG _i ) representative of an interaction of the fluid with each sensor (38 ₁ , …, 38 _i , …, 38 _M ) from each differential temporal signal (ΔSG _i ). Electronic device (30) for characterizing a fluid according to any one of claims 1 to 7, in which the first reactive components (70) of the first reactive site of the same sensor (38 ₁ , …, 38 _i , …, 38 _M ) are hetero-oligomers, that is to say all consisting of monomeric units of which at least two are different, for example heteropeptides all consisting of a peptide chain of several occurrences from at least two different amino acids, and each reactive extension (78) of each second reactive component (76) of the second reactive site of this same sensor (38 ₁ , …, 38 _i , …, 38 _M ) comprises at least one repetition of its first reactive portion identical to the first reactive components (70) of the first reactive site, for example at least one repetition of the heteropeptide chain of its first peptide portion identical to the first peptides (70) of the first reactive site. Electronic device (30) for characterizing a fluid according to any one of claims 1 to 8, in which the processor (48) is designed to obtain a characterization of the fluid, in particular an identifying signature (SIG) of the fluid, by extracting a predetermined characteristic (DSCR _i ) from said at least one representative time signal (ΔSG _i ). Method for characterizing a fluid, using an electronic device (30) according to any one of claims 1 to 9, comprising the following steps:

• approaching the electronic device (30) to the fluid so as to obtain an interaction of the fluid with each sensor (38 ₁ , …, 38 _i , …, 38 _M );
• providing, using the transducer (44) and in interaction with said at least one sensor (38 ₁ , …, 38 _i , …, 38 _M ), a sequence of measurement signals (S); and
• providing, using the processor (48), at least one time signal (ΔSG _i ) representative of an interaction of the fluid with each sensor (38 ₁ , …, 38 _i , …, 38 _M );

characterized in that:

• the approach of the electronic device (30) is carried out so as to obtain an interaction of the fluid with the first (40 ₁ , …, 40 _i , …, 40 _M ) and second (42 ₁ , …, 42 _i , …, 42 _M ) reactive sites of each sensor (38 ₁ , …, 38 _i , …, 38 _M ); and
• the processor (48) performs, for each sensor (38 ₁ , …, 38 _i , …, 38 _M ), a comparison of the interactions of the fluid with the two reactive sites (40 ₁ , …, 40 _i , …, 40 _M , 42 ₁ , …, 42 _i , …, 42 _M ) of this sensor (38 ₁ , …, 38 _i , …, 38 _M ) to provide said at least one time signal (ΔSG _i ) as resulting from this comparison.