Gas-phase analytical system with optical detection device

Abstract

A gas-phase analytical system (1) is proposed comprising an injection unit (12) configured to inject a sample to be analyzed comprising at least one chemical compound, a unit (14) for introducing a flow of carrier gas, a transport column (16), and a detection device (18), the chemical compound(s) being entrained by the gas in the column (16) to the device (18). The device (18) is an optical detector comprising at least one Mach-Zehnder interferometric sensor (185) powered by an optical source (183) and integrated in a microfluidic structure (181, 182), the sensor (185) comprising a sensitive arm (185-3) exposed to the chemical compound(s) and a reference arm (185-2) impermeable to the chemical compound(s), the sensor(s) (185) being adapted to optically detect the passage of the chemical compound(s) through the sensitive arm (185-3). Figure for abstract: [Fig.1]

Description

Title of the invention: Gas phase analytical system with optical detection device Technical field

[0001] The present invention relates generally to the field of gas mixture or gas sensor analysis, and in particular to a gas phase analytical system with an optical detection device.

[0002] In analytical systems of the gas chromatography type, allowing the identification and quantification of volatile chemical compounds, it is known to use conventional and / or miniaturized chromatography detectors such as, for example, mass spectroscopy devices, flame ionization detectors (denoted FID), nano-electromechanical devices or NEMS, or even technical conductivity microdetectors. Some analytical systems in the gas phase include integrated optical detection devices. Such solutions are for example described in the articles “A microfabricated optofluidic ring resonator for sensitive, high-speed detection of volatile organic compounds” by Kee Scholten et al., Lab Chip, 2014, 14, 3873, “A Portable Micro-Gas Chromatography with Integrated Photonic Crystal Slab Sensors on Chip” by Priyanka Biswas et al., Biosensors, 2021, 11, 326, or “Fabry-Pérot Cavity Sensors for Multipoint On-Column Micro Gas Chromatography Detection” by Jing Liu et al., Analytical Chemistry, 2010, 82, 11, 4370-4375. .

[0003] However, known detection devices are expensive, are limited in their ability to detect specific chemical compounds, have a high detection limit, and / or have low detection versatility.

[0004] Some optical sensing devices further require an advanced measurement environment coupled with an expensive detector. For example, some optical sensing devices use a spectrally fine and tunable laser source to spectrally align with the resonant wavelength of the optical cavity of the sensing device.

[0005] There is thus a need for an improved gas phase analytical system. Summary of the invention

[0006] The invention improves the situation by proposing a gas-phase analytical system comprising an injection unit configured to inject a sample to be analyzed comprising at least one chemical compound, a unit for introducing a flow of carrier gas, a transport column, and a detection device, the at least one chemical compound being entrained by the carrier gas in the transport column. to the detection device. The detection device is an optical detector comprising at least one Mach-Zehnder interferometric sensor powered by an optical source and integrated in a microfluidic structure, the sensor comprising a sensitive arm exposed to the at least one chemical compound and a reference arm impermeable to the at least one chemical compound, the at least one sensor being adapted to optically detect the passage of the at least one chemical compound through the sensitive arm.

[0007] Advantageously, the at least one Mach-Zehnder interferometric sensor may comprise a coating on the sensitive arm, the coating being adapted to preferentially adsorb the at least one chemical compound.

[0008] In embodiments, the microfluidic structure may comprise a primary microfluidic channel, the at least one chemical compound being transported by convection through the primary microfluidic channel, and the at least one Mach-Zehnder interferometric sensor may be positioned on the primary microfluidic channel, the detection device being adapted to determine the retention time of the at least one chemical compound at the outlet of the column from the optical detection of the passage of the at least one chemical compound through the sensor.

[0009] According to certain embodiments, the microfluidic structure may comprise at least one secondary microfluidic channel sealed at the channel end, the at least one chemical compound being transported by diffusion through the sealed secondary microfluidic channel, and the at least one Mach-Zehnder interferometric sensor may be positioned on the sealed secondary microfluidic channel, the detection device being adapted to determine the diffusion coefficient of the at least one chemical compound from the optical detection of the passage of the at least one chemical compound through the sensor.

[0010] The microfluidic structure may comprise at least one other secondary microfluidic channel sealed at the channel end, each secondary microfluidic channel having a distinct channel length L defined in the direction of movement of the at least one chemical compound.

[0011] The at least one sealed secondary microfluidic channel may comprise at least one physical obstacle arranged locally in the channel, the obstacle being adapted to minimize any convective phenomenon at the entrance to the channel and / or to slow down the diffusion phenomenon of the chemical compound to be detected.

[0012] According to some embodiments, the microfluidic structure may comprise at least one secondary microfluidic channel open at the channel end, the at least one chemical compound being transported by convection through the open secondary microfluidic channel.

[0013] The at least one open and / or sealed secondary microfluidic channel may comprise a coating comprising a physicochemical substance on the wall of the channel.

[0014] The invention also provides a method for analyzing a sample comprising at least one chemical compound, the method comprising at least the following steps: - Injecting the sample to be analyzed into the gas-phase analytical system; - Acquiring at least one optical measurement signal detected by at least one Mach-Zehnder interferometric sensor of the gas-phase analytical system; - Associate at least one optical measurement signal with a chemical compound of the sample to be analyzed.

[0015] Advantageously, the method may further comprise a step consisting of determining a retention time value and / or a diffusion time value relating to the chemical compound associated with at least one optical measurement signal.

[0016] The embodiments of the invention thus provide an improved gas-phase analytical system comprising a miniaturized detector allowing improved selectivity of chemical compounds to be analyzed, with a low detection limit, at low cost, fast, and compatible with any carrier gas.

[0017] The gas phase analytical system and the associated method, according to the embodiments of the invention, make it possible on the one hand to detect the passage of a compound or several gaseous chemical compounds previously separated spatially by a chromatography column, and on the other hand to provide specific information on the nature of the gaseous chemical compound(s).

[0018] They also allow implementation compatible with any type of carrier gas, a wide range of detection relative to the nature of the gaseous chemical compounds detected (i.e. alkanes, alcohols, acetone, esters, etc.), non-destructive detection of the gaseous compounds to be analyzed, as well as a low limit of detection of gaseous chemical compounds typically for concentrations lower than a few hundred ppbs (or "parts per billion" in English, corresponding to a ratio of I O9).

[0019] They also make it possible to provide a solution with increased compactness, compatible with high-frequency measurement acquisition (i.e. in particular between 240-1000 Hz), and to limit the effects of drift over time of the measurements associated for example with fluctuations in temperature, flow, pressure, or even laser wavelength.

[0020] The embodiments of the invention advantageously provide an affordable solution in terms of cost, the manufacture of the gas phase analytical system being in particular compatible with collective manufacture in a clean room and with the use of inexpensive detection electronics. Description of figures

[0021] Other characteristics, details and advantages of the invention will emerge from reading the description given with reference to the appended drawings given by way of example.

[0022] [Fig-1] [Fig.l] is a diagram representing an analytical system in phase gaseous, according to embodiments of the invention.

[0023] [Fig.2] [Fig.2] is a diagram showing an optical detection device, according to embodiments of the invention.

[0024] [Fig.3] [Fig.3] is a diagram showing an optical detection device, according to embodiments of the invention.

[0025] [Fig.4] [Fig.4] is a diagram showing an optical detection device, according to embodiments of the invention.

[0026] [Fig.5] [Fig.5] is a diagram showing a schematic view of a sensor Mach-Zehnder interferometric, according to embodiments of the invention.

[0027] [Fig.6] [Fig.6] is a diagram showing a sectional plane of a sensor Mach-Zehnder interferometric, according to embodiments of the invention.

[0028] [Fig.7] [Fig.7] consists of four graphs (a), (b), (c) and (d) illustrating results of analysis of chemical compounds by the gas phase analytical system, according to embodiments of the invention.

[0029] [Fig.8] [Fig.8] is a photograph taken by electron microscopy at scan illustrating a Mach-Zehnder interferometric sensor, according to embodiments of the invention.

[0030] [Fig.9] [Fig.9] is a diagram showing an optical detection device, according to embodiments of the invention.

[0031] [Fig. 10] Figure 10 consists of two graphs (a) and (b) respectively illustrating the evolution of a diffusion duration T and a detection separation time δ between two diffusion durations as a function of the length L of a secondary microfluidic channel, according to embodiments of the invention.

[0032] [Fig. 11] [Fig. 11] is a diagram showing a detection device, according to embodiments of the invention.

[0033] [Fig. 12] [Fig. 12] is a flowchart representing a method of analyzing a sample by a gas-phase analytical system, according to embodiments of the invention.

[0034] Identical references are used in the figures to designate identical or similar elements. For reasons of clarity, the elements shown are not to scale. Detailed description

[0035] [Fig.l] schematically represents a gas-phase analytical system 1 (also called “analytical system”) comprising an injection unit 12 configured to inject a sample to be analyzed, a unit 14 for introducing a flow of carrier gas, a transport column 16, the injected sample being entrained by the carrier gas in the transport column and a detection device 18, according to embodiments of the invention.

[0036] Such a sample to be analyzed comprises a chemical compound (i.e., a type of molecule, a chemical species or an analyte) or a mixture of chemical compounds to be identified and / or quantified by the analytical system 1.

[0037] The analytical system 1 can be used in various fields of gas mixture or gas sensor analysis, for example for industrial, security or defense, health, energy, or environmental applications.

[0038] The injection unit 12 can be associated for example with a manual or automatic injection micro-syringe containing the sample to be injected into the analytical system 1.

[0039] Once injected into the analytical system 1, the sample to be analyzed (in liquid phase or gas phase) is entrained by a carrier gas, through the column 16 which contains an active substance called the stationary phase. The carrier gas, constituting a mobile phase for the chemical compound(s), may be for example helium, dihydrogen, compressed air, or even nitrogen maintained at 1 bar in the introduction unit 14. The unit for introducing a carrier gas flow may therefore be configured to contain and regulate the introduction of a controlled carrier gas flow into the analytical system 1. The unit 14 may comprise for example a pressure reducer-regulator. In addition, the entrainment of the then gaseous compounds of the sample, in the column 16, may be carried out by pumping and valve units not shown in the figures.The transport column 16 may be a so-called capillary chromatography column or a silicon microchannel for example. The column 16 and at least part of the injection unit 12 may be placed in a thermostatically controlled enclosure, also not shown in the figures, the applied temperature of which is adapted to the volatility of the chemical compound(s) of the sample to be analyzed.

[0040] The column 16 is characterized by a predefined length. For example and without limitations, this length may be equal to 3 meters. The different gaseous compound(s) pass through the column 16 at a specific speed predefined by their physicochemical affinity with the stationary phase. As used herein, the term “physicochemical affinity”, also called “physicochemical compatibility” or “physicochemical similarity”, is associated with all the physicochemical interactions between analytes of the sample and elements of the analytical system 1. In particular, in relation to column 16, the term "physicochemical affinity" refers to all the physicochemical interactions between analytes passing through the transport column and the active substance of the stationary phase, thus impacting the elution rate of the analytes in the column. Thus, a gaseous compound passes through column 16 following a time defined as a function of the length of the column and the physicochemical affinity of this compound with the stationary phase of the column. This time to pass through column 16, also called "retention time" or "elution time", thus represents the time elapsed between the injection of the compound into the analytical system 1 and its exit from column 16.

[0041] In the case of a sample comprising a mixture of chemical compounds each having a distinct physicochemical affinity with the stationary phase, each compound of the mixture is associated with a distinct displacement speed in the column 16. The different chemical compounds thus separate spatially along the column 16 and exit the column 16 one after the other, according to a distinct retention time.

[0042] As shown in [Fig.2], the detection device 18 is connected to the column 16 by a device inlet 181-2, associated with a microfluidic structure, through which the chemical compound(s) to be analyzed are transferred.

[0043] The microfluidic structure may include a primary microfluidic channel 181 through which the chemical compound(s) are transported by convection from the device inlet 181-2 to a device outlet 181-4.

[0044] The detection device 18 further comprises an optical source 183, one or more Mach-Zehnder interferometric sensors 185 (also called 'measuring sensor' or 'sensor'), and an optical detection and processing unit 187. A Mach-Zehnder interferometric sensor 185 is integrated into the microfluidic structure, and optically connected and operated by the optical source 183.

[0045] In embodiments, the Mach-Zehnder interferometric sensor(s) 185 may be positioned at the primary microfluidic channel 181. For example and without limitation, the detection device 18 may comprise N measurement sensors 185n positioned at the primary microfluidic channel 181, as shown in [Fig. 2]. The number N of sensors may be, for example, a positive integer greater than or equal to 1. The parameter 'n' designates an index associated with a sensor of the detection device and is an integer between 1 and N. In this case, each Mach-Zehnder interferometric sensor 185n is configured to optically detect the passage of a compound, or several gaseous chemical compounds of the sample (previously spatially separated by a column 16), transported by convection and passing through the sensor 185n. The detection of a passage of at least one compound consists of carrying out an optical measurement of the retention time value of at least one compound of the sample transported by convection and passing through the sensor 185n. The optical detection and processing unit 187 of the detection device 18, connected to the measurement sensor(s) 185n as shown in [Fig.2], can thus be adapted to collect the optical detection (or measurement) signals, and determine the retention time of at least one compound of the sample at the outlet of the column 16 from the optical measurements of the sensors.

[0046] It should be noted that in such a primary microfluidic channel 181, the Mach-Zehnder interferometric sensors 185n can be configured to detect simultaneously (i.e. substantially at the same time) the passage of a specific compound. Thus, for such a detection device 18, the time axis associated with the numerical evaluation of the retention time value of the transported sample compound(s) is advantageously identical for each sensor 185n. The origin (i.e. the zero) of such a single time axis can in particular correspond to the instant of injection of the sample to be analyzed (at the inlet of the transport column 16). The retention time value of an analyte then corresponds to the time between the associated detection peak of any analyte and the origin relative to the single time axis of the detection device 18.

[0047] According to certain embodiments, as illustrated in [Fig. 3], the microfluidic structure may also comprise a secondary microfluidic channel 182 fluidly connected to the primary microfluidic channel 181 by an access 182-2 and which extends to a channel termination 182-4. The Mach-Zehnder interferometric sensor(s) 185 may be positioned at the secondary microfluidic channel 182. For example and without limitation, the detection device 18 comprises Q Mach-Zehnder interferometric sensors 185q positioned at the secondary microfluidic channel 182, as shown in FIGS. 3 and 4. The sensor number Q may be, for example, a positive integer greater than or equal to 1. The parameter 'q' designates an index associated with a sensor of the detection device and is an integer between 1 and Q.

[0048] Advantageously, the channel termination 182-4 may be sealed (or closed) as shown in [Fig. 3]. In this case, the chemical compound(s) to be analyzed are transported through the secondary microfluidic channel 182 by diffusion. Each Mach-Zehnder interferometric sensor 185q is thus configured to optically detect the passage of one or more gaseous chemical compounds of the sample, transported by diffusion and passing through the sensor 185q. The detection of a passage of compound(s) consists of performing an optical measurement of the “relative diffusion time” value of at least one compound of the sample transported by diffusion and passing through the sensor(s) 185q. The optical detection and processing unit 187 of the detection device 18, connected to the measurement sensor(s) 185q, can thus be adapted to collect the optical measurement signals and determine the diffusion time of at least one compound of the sample transported through the secondary microfluidic channel 182 from the optical measurements of the sensors.

[0049] It should be noted that the relative diffusion time value measured by a sensor depends on the diffusion rate of the compound

[0050] In embodiments, the diffusion coefficient of a compound (or diffusion speed in the microfluidic channel) can be determined as a function of the relative diffusion time value measured optically by a sensor 185q positioned at the end (i.e. at the end) of channel 182-4 and the position of the measurement sensor 185q in this channel. The diffusion coefficient of a compound can be adjusted by further taking into account the optical measurement of at least one sensor positioned at the primary microfluidic channel 181 (sensor 185n), i.e. by taking into account the relative retention time value by the sensor. The diffusion coefficient of a compound can also be adjusted by further taking into account the optical measurement of a sensor positioned for example at the access 182-2 at the inlet of the secondary microfluidic channel 182 (sensor 185q).

[0051] Alternatively, the termination (or end) of the channel 182-4 may be open, as shown in [Fig. 4]. In this case, as for the primary microfluidic channel 181, the chemical compound(s) to be analyzed are transported through the secondary microfluidic channel 182 (i.e. forming a so-called 'through' channel) by convection, and the Mach-Zehnder interferometric sensor(s) 185 positioned at the channel 182 are configured to optically measure the retention time value of at least one compound of the sample transported by convection and passing through the sensor(s) 185.

[0052] The detection device 18 which comprises one or more secondary microfluidic channels 182 with open termination 182-4 makes it possible in particular to increase the number of Mach-Zehnder interferometric sensors 185 in the analytical system 1, as well as to address them (i.e. to interrogate them optically) simultaneously. Such a configuration of device 18 also makes it possible to adjust (or adjust) the transport flow rate of the analytes at each sensor of the device 18. Such an adjustment can be carried out, in particular passively, by design and / or manufacture of the microfluidic channels and as a function of certain sensors, for example, to determine the optimal transport flow rate of the analytes through the different microfluidic channels (secondary and / or primary).

[0053] Furthermore, the detection device 18 may comprise a functionalization of the wall of such a secondary microfluidic channel 182 having an open and / or closed channel termination.

[0054] As used herein, the term "functionalization" refers to a coating (called a layer or deposit) comprising one or more chemical species and / or a physicochemical substance, on an element of the microfluidic structure and / or on an element of a Mach-Zehnder interferometric sensor of the detection device 18, so as to generate physicochemical properties specific to this element.

[0055] In particular, the functionalization of the wall (i.e., the internal wall) of such a secondary microfluidic channel 182, in embodiments of the invention, corresponds to a coating of a physicochemical substance (or stationary phase) on the wall of the channel. Such a substance may be adapted to retain (i.e., adsorb) certain specific analytes depending on its physicochemical affinity with the chemical compounds to be analyzed. The analytes said to be 'retained' by the physicochemical substance of the wall are then associated with a retention time value, in the functionalized secondary microfluidic channel 182, which is greater than the retention time values ​​of the 'non-retained' analytes.

[0056] It should be noted that the active substance (i.e. stationary phase) of the transport column 16 corresponds to a type of functionalization of the internal wall of this chromatography column.

[0057] Advantageously, the functionalization of the wall of the secondary microfluidic channel 182 may be different from the functionalization of the transport column 16, thus generating a chromatography dimension distinct from the chromatography dimension relating to the chromatography column.

[0058] For example and without limitation, the secondary microfluidic channel 182 having an open channel termination can then correspond to a chromatographic measurement channel. Such a so-called 2D (i.e. two-dimensional or two-dimensional) chromatography system resulting from the coupling of the results of two chromatographic separations of different nature (transport column 16 and secondary microfluidic channel 182) makes it possible to improve the analysis of complex mixtures of chemical compounds to be separated having substantially similar physicochemical affinities. In particular, such a 2D chromatography system makes it possible to separate compounds through the secondary microfluidic channel 182 which have not previously been separated through the chromatography transport column 16.A 2D chromatography system using at least two stationary phase chromatographic separations with opposite physicochemical properties makes it possible in particular to verify or control possible crossings (or overlaps) between detection peaks. For example and without . limitations, the analytical system 1 may comprise a transport column 16 called “polar” and a secondary microfluidic channel 182 called “apolar”. In this case, a “polar” compound may be associated with a retention time value, obtained at the outlet of the polar column 16, which is greater than the retention time value of an “apolar” compound. The same polar compound may then be associated with a retention time value, obtained at the end of the apolar channel 182, which is smaller or similar compared to the retention time value of the apolar compound. The use of channels comprising Mach-Zehnder interferometric sensors 185 for a 2D chromatography system allows for rapid measurement and optimized real-time monitoring of the detection measurements, even on small channel dimensions 181 and 182.

[0059] [Fig.5] and [Fig.6] respectively represent a schematic view and a sectional view of a Mach-Zehnder interferometric sensor 185 (i.e. sensor 185n or 185q). The Mach-Zehnder interferometric sensor 185 is powered (or implemented) by the optical source 183 adapted to produce electromagnetic radiation (also called 'optical signal'). For example and without limitation, the optical source 183 may be a laser or a visible or near infrared diode configured to emit a beam at a wavelength of 800nm, 1310nm or 1550nm. The emission wavelength of the optical source 183 may alternatively be greater than 3pm for example.

[0060] The initial optical signal from the optical source 183 initially propagates in free space or in an optical fiber coupled to a first coupling waveguide 185-1 of the Mach-Zehnder interferometric sensor 185. The initial optical signal is thus directed towards a directional beam splitter, as shown in [Fig. 5]. Such a splitter may be a symmetrical optical coupler of the 50 / 50 type (for example in fibered Y).

[0061] The directional splitter is configured to separate the initial optical signal transmitted by the optical source 183 via the first coupling waveguide 185-1 into a reference component of the signal and a measurement component of the signal, propagating respectively towards a reference waveguide 185-2 (also called 'reference arm') and a measurement waveguide 185-3 (also called 'sensitive arm').

[0062] The two components of the signal transmitted through the reference arm 185-2 and the sensitive arm 185-3 are then directed towards a directional beam combiner configured to recombine them on a second coupling waveguide 185-4 (i.e. on a single optical path) into a measurement optical signal. Such a combiner can also be a symmetrical Y-fiber optical coupler of the 50 / 50 type.

[0063] The optical measurement signal is thus directed towards the optical detection and processing unit 187, via a waveguide, a coupling in an optical fiber or according to propagation in free space. In particular, the optical detection and processing unit 187 is adapted to detect the optical measurement signal so as to generate a signal representative of the evolution over time of the detected light intensity resulting from the interference between the reference component of the signal and the measurement component of the signal. For example and without limitation, the unit 187 may comprise at least one photodiode.

[0064] While the sensitive arm 185-3 of the Mach-Zehnder interferometric sensor 185 is exposed to the chemical compound(s) to be analyzed transported in the exposure medium 185-5, the reference arm 185-2 of the Mach-Zehnder interferometric sensor 185 is encapsulated using an encapsulation layer 185-6 impermeable to the chemical compound(s) to be analyzed.

[0065] The exposure medium 185-5 corresponds to the primary microfluidic channel 181 or to the secondary microfluidic channel 182 at the sensor 185. In other words, the microfluidic channel 181 or 182 passes through the Mach-Zehnder interferometric sensor(s) 185. For example and without limitation, the first coupling waveguide 185-1, the reference arm 185-2 encapsulated in the encapsulation layer 185-6, the sensitive arm 185-3 and the second coupling waveguide 185-4 may be positioned in the microfluidic channel 181 or 182, as shown in FIGS. 5 and 6. In other examples, only the sensitive arm 185-3 may be positioned in the microfluidic channel 181 or 182 then narrower than the sensor 185.

[0066] During their passage by convection or by diffusion through the exposure medium 185-5 (i.e. through the microfluidic channel 181 or 182), the chemical compound(s) to be analyzed induce a modification of the local refractive index perceived by the evanescent part of the electromagnetic field of the measurement component of the signal propagating in the measurement waveguide 185-3, inducing a temporary modification of its effective optical index. At the same time, the encapsulation layer 185-6 is configured so that the reference waveguide 185-2 does not undergo any modification of its effective index, in particular during the passage of the sensor 185 by an analytical, not affecting the propagation of the reference component of the signal. The encapsulation layer 185-6 may for example be a silicon dioxide coating.

[0067] Those skilled in the art will understand that the hardware design and manufacturing of the Mach-Zehnder interferometric sensor 185 depends on the nature and wavelength of the beam used, emitted by the optical source 183, to implement the photonic-optical sensor. Similarly, the optical detection and processing unit 187 can be chosen and adapted to collect the optical measurement signals at the output of the sensors 185 (i.e. in particular as a function of the wavelength, the power of the signals, the frequency, etc.).

[0068] It should be noted that the change in effective optical index which occurs in the sensitive arm 185-3 results in a phase shift between the reference component of the signal and the measurement component of the signal, which induces the interference signal measurable by the optical detection and processing unit 187. The modification of the effective optical index of the measurement waveguide 185-3 being determined in particular as a function of the quantity of adsorbed molecules, the amplitude of such an index modification can be, as a first approximation, proportional to the concentration of the same chemical compound to be analyzed passing through the exposure medium 185-5.

[0069] [Fig.7] represents examples of graphs illustrating results of analysis of chemical compounds by the optical detection and processing unit 187 of the analytical system 1. In particular, [Fig.7] represents so-called chromatographic detection peaks corresponding to the detection of specific chemical compounds by one or more Mach-Zehnder interferometric sensors 185. These detection peaks are associated on the abscissa with determined retention times for the chemical compounds detected: a heptane compound (C7, peak no. 1 in [Fig.7]), a toluene compound (peak no. 2) and an octane compound (C8, peak no. 3), initially prepared in a solution of 1 1 / 2 L of mineral oil solvent, separately (graphs (a), (b) and (c) of [Fig.7]) or in a mixture (graph (d) of [Fig.7]).

[0070] All of the waveguides of the Mach-Zehnder interferometric sensor 185, forming the integrated optical circuit of the sensor, may be positioned on a support layer (or substrate layer) 183-7 consisting, for example, of a silicon layer (or 'silicon wafer') and a silicon dioxide layer, also called 'thermal SiO2 BOX'. Such an integrated optical circuit also comprises a cap layer 183-8 as shown in [Fig. 6]. For example and without limitation, the cap layer 183-8 may be made of a silicon layer or a glass layer, etched to form the microfluidic channel passing through the sensor 185, and bonded by a bonding process such as a screen printing process or an anodic sealing process.

[0071] In embodiments, the sensitive arm 185-3 and the reference arm 185-2 may consist of a straight waveguide as shown in [Fig.5], or else consist of several segments of straight waveguides defined along the axis of the channel and connected by segments of curved waveguides (or elbows) not shown in the figures.

[0072] In other embodiments, the sensitive arm 185-3 and the reference arm 185-2 may be square-shell spiral waveguides such as shown in [Fig.8], of circular or elliptical envelope, or of rectangular envelope defined along the axis of the channel (not shown in the figures).

[0073] A spiral arm configuration or one comprising several straight waveguide segments allows for a long arm length and therefore high sensitivity associated with the sensitive arm 185-3. Furthermore, a square envelope spiral configuration can be advantageously used in a Mach-Zehnder interferometric sensor 185 positioned at a secondary microfluidic channel 182 since it allows for a compact sensor suitable for the point measurement of diffusion time.

[0074] Advantageously, a Mach-Zehnder interferometric sensor 185 may comprise a functionalization of the sensitive arm 185-3 so as to modulate the sensitivity of the arm as a function of the physicochemical properties of the chemical compounds to be analyzed.

[0075] In particular, the functionalization (or functionalization layer) of the sensitive arm 185-3 of a Mach-Zehnder interferometric sensor (185n and / or 185q), in embodiments of the invention, corresponds to a coating of one or more chemical species on (i.e. covering) the surface of the waveguide of the sensitive measurement arm. Such a functionalization layer can be adapted to preferentially adsorb one or more of the specific chemical compounds passing through the exposure medium 185-5, which allows better detection of the targeted compound(s). In particular, the functionalization layer makes it possible to obtain specific information additional to that already obtained using the chromatography column. The functionalization layer notably increases the capacity of the system to specifically identify compounds, even if the latter are only slightly separated by the chromatography column.

[0076] Advantageously, a large number N and / or Q of Mach-Zehnder interferometric sensors (185n and / or 185q), comprising different functionalizations in particular, makes it possible to determine a large number of different pieces of information relating to each detected compound of the sample to be analyzed. For example and without limitation, for each compound noted C; of the sample to be analyzed, the detection of the compound by a sensor (185n and / or 185q) is associated with a score value (i.e. parameter or weight) determined from one or more quantities relating to the detection peak (i.e. the measurement signal) of the sensor considered for this compound. Such a score value, noted sin and / or s; q, can be determined from the height of the peak (i.e. value of the peak along the ordinate axis in [Fig.7] for example), and / or the width of the peak at half-height, area of ​​the peak, the shape of the peak, etc., or more generally any measurement associated with the peak of the measurement signal from the sensor 185. relating to the adsorption and / or desorption of the analyte by this sensor. Each determined score value (sin and / or siq) then corresponds to additional information of a compound Ci of the sample to be analyzed (relating to a given retention time provided by the column 16 and / or a diffusion time) given by a sensor (185n and / or 185q) precise and characteristic of specific physicochemical property. Thus, the set noted S; of the score values ​​of a compound Ci forms the physicochemical signature of this compound through the detection device 18. The signature S;, unique for each compound Ci to be analyzed, can therefore be written according to the expression (01) below:

[0077] S- {sn, ..., siNet / or (01)

[0078] The evaluation of a signature Si thus makes it possible to effectively determine the nature of the compound C;. Such an evaluation can be carried out from the comparison of the different score values ​​of the compound Ci for example, and in particular by taking into account a comparison with other score values ​​relating to other compounds or an analysis according to such values.

[0079] The use of S signatures allows more robust identification of the compounds in the sample compared to a simple estimation from diffusion times and / or retention times, these times being able to prove similar for several compounds to be differentiated.

[0080] By way of example, the functionalization (or functionalization layer) of the sensitive arm 185-3 of a Mach-Zehnder interferometric sensor (185n and / or 185q) may correspond to a “polar” functionalization adapted to increase the detection sensitivity of the sensitive arm 185-3 to polar compounds and reduce the sensitivity to apolar compounds. Chemistries of more or less significant polarities associated with distinct measurement sensors 185 induce a more or less significant physicochemical affinity with such specific gaseous analytes depending on their polarity. This induces variations in intensity / optical phase at the sensitive arm 185-3 that are more or less significant depending on the sensor 185n or 185q involved. The variations in optical response between a plurality of differently functionalized sensors are quantifiable and make it possible to position the specific analyte on a polarity scale.

[0081] For example and without limitations, a functionalization layer deposited on the measurement waveguide 185-3 may consist of a thin film deposition by cathodic sputtering, one or more chemical vapor depositions which may be associated with a plasma treatment, a layer obtained by grafting used for example in chromatography for the functionalization of stationary phases, or even a layer obtained by liquid phase grafting of biomolecules by deposition of microdrops as described for example in the articles “A Silicon photonic olfactory sensor based on an array of 64 biofunctionalized Mach-Zehnder interferometers” by Laplatine, L. et al., Optics Express 30(19), 33955-33968 (2022).

[0082] In addition, each Mach-Zehnder interferometric sensor 185 (i.e. sensor 185n and / or 185q) may comprise a particular functionalization associated with one of the different chemical compounds to be detected by convection and / or by diffusion. The chromatographic peaks obtained at the unit 187 may make it possible to characterize the ratio of the responses of the sensors 185 associated with different polarity chemistries.

[0083] It should be noted that the primary microfluidic channel 181 and / or the secondary microfluidic channel 182 of the detection device 18 may be characterized by a sufficiently small fluidic cavity volume in order to avoid broadening of the detection peaks obtained at the unit 187. Typically, such a fluidic cavity volume may be less than one microliter (pL). A microfluidic channel may for example be represented by a cavity having a height of 200 pm and a width of 400 pm, in the section plane of the cavity perpendicular to the direction of propagation (i.e. convection) of the compounds. The microfluidic channel can also be represented by a cavity having a height of 200 pm and a width of 200 pm, in the mode where only the sensitive arm 185-3 can be positioned in the microfluidic channel 181 or 182 which is in this case narrower than the sensor 185.

[0084] It should be noted that at the transition between the transport column 16 and the primary microfluidic channel 181, i.e. at the device inlet 181-2, the chemical compounds to be detected may undergo a reduction in transport volume by convection, called 'dead volume'.

[0085] Furthermore, a primary microfluidic channel 181 can be sized for a channel length of 1 mm, in the direction of movement of the compounds.

[0086] Advantageously, the detection device 18, and in particular the microfluidic structure, can comprise a plurality of secondary microfluidic channels 182, each channel comprising a sensor 185q positioned at the end of channel 182-4 and characterized by a separate channel length, for example and without limitation between 1 and 10 mm.

[0087] Such channel lengths (181 and / or 182) are compatible with the incorporation of several Mach-Zehnder interferometric sensors (185n and / or 185q) of typical unit area of ​​sensitive arm 185-3 of 200pm by 200pm.

[0088] In embodiments, two measurement sensors 185q positioned respectively at the inlet (access 182-2) and at the outlet (termination 182-4) of the secondary microfluidic channel 182, as shown in FIG. 9, make it possible to determine the diffusion time T necessary for one or more chemical compounds to travel by diffusion the length L of this channel 182. Figure 10(a) illustrates the evolution of the diffusion time T as a function of the length L of a secondary microfluidic channel 182, obtained from equation (02) described below:

[0089] lyLi(02)

[0090] In equation (02), the parameter D corresponds to the diffusion coefficient of a chemical compound to be detected. The value of D used in equation (02) can be calculated (from the Chapman-Enskog equation for example) or extracted from tables. For example and without limitations, the coefficient D can be equal to 0.1 cm2.s ', as in the example of figure 10(a). For an example of channel length L of 3 mm, the diffusion time T required for a chemical compound having such a diffusion coefficient is 150 ms. For an example of length L of 10 mm, the diffusion time T is 1.6 s. Such an architecture of a detection device 18 comprising one or more secondary microfluidic channels 182 therefore allows a chemical compound to have time to diffuse into the secondary microfluidic channel 182 over a period of time less than the time required for this compound to cross the primary microfluidic channel 181, typically several seconds.By using several secondary microfluidic channels 182 of different lengths L and / or different functionalizations, it is possible to address a wide range of diffusion coefficients of the chemical compounds to be analyzed.

[0091] A detection separation time 5t corresponds to the difference between diffusion times of two compounds detected for example by a sensor 185q. For example, as shown in FIG. 10(b), for a channel length L 182 of 5 mm, the detection separation δ between the detection of a benzene compound (with a diffusion coefficient value Di “ 0.089 cm2.s ') and the detection of a formaldehyde compound (with a diffusion coefficient value D2 “ 0.176 cm2.s ') is approximately 200 ms. Such a detection device architecture 18 comprising at least one secondary microfluidic channel 182 also makes it possible to detect two chemical compounds having relatively similar diffusion coefficients.

[0092] As a result, the optical detection and processing unit 187 of the detection device 18 can thus be adapted to determine specific information on the diffusivity (represented by the diffusion coefficient) of at least one compound of the sample transported through a secondary microfluidic channel 182 from the determined compound diffusion time values ​​and the geometry of the channel.

[0093] Advantageously, a secondary microfluidic channel 182 of the detection device 18 may comprise one or more so-called physical micro-obstacles and / or nano-obstacles, arranged locally in the channel, as shown in FIG. 9. Such obstacles may be, for example, pillars 182-6 positioned at the access 182-2 of the channel so as to minimize any convective phenomenon at the inlet of the channel 182 and optimize the transport of chemical compounds by diffusion specifically. Such obstacles may also be any other physical obstacle 182-8 positioned in the channel to slow down the diffusion phenomenon of certain chemical compounds. Such slowing down of diffusion possibly makes it possible to address a wider range of diffusion coefficients of chemical compounds otherwise requiring a length L of diffusion channel 182 that is too long, or even to increase the detection separation time δr between two chemical compounds with very close diffusion coefficients. Channel obstacles may consist, for example and without limitations, of a silicon layer comprising a porous membrane.Channel obstacles may also be comprised of a thin layer of porous silica, such as a porous silica matrix obtained by a sol-gel manufacturing process generated directly in the secondary microfluidic channel 182 during its manufacture or mechanically inserted post-manufacturing.

[0094] In embodiments, the detection device 18, and in particular the microfluidic structure, may comprise at least one secondary microfluidic channel 182 whose channel termination 182-4 is sealed so that the chemical compound(s) to be analyzed are transported by diffusion through the channel. The channel comprises one or more physical sensors 189 connected to the optical detection and processing unit 187. Advantageously, the channel 182 comprises a physical sensor 189 positioned at the termination (i.e. at the end) of the channel 182-4, as shown in [Fig. 11].Such physical sensors 189 may be Mach-Zehnder interferometric sensors 185, and / or other types of physical sensors, such as for example technical micro-conductivity detectors (denoted pTCD), capacitive micro-machined ultrasonic transducers (denoted cMUT), piezoelectric micro-machined ultrasonic transducers (denoted pMUT), resonant rings, Lamb wave pressure detectors, etc.

[0095] In embodiments, the detection device 18 may comprise one or more reference sensors (not shown in the figures) configured to adjust, by calibration, the measurement values ​​obtained by the optical detection and processing unit 187 from the optical measurement signals generated by the measurement sensors 185. Such a calibration makes it possible in particular to compensate for certain parameter variations due to physical and environmental fluctuations that may be experienced by the gas-phase analytical system 1, such as temperature fluctuations, pressure fluctuations during the injection of the sample to be analyzed, or even laser wavelength fluctuations during data acquisition.

[0096] A reference sensor may, for example, correspond to a Mach-Zehnder interferometric sensor type sensor, the two interferometric arms (or interferometric waveguides) of which are either reference arms (impermeable to the chemical compound(s) to be analyzed), or sensitive arms (exposed to the chemical compound(s) to be analyzed).

[0097] [Fig. 12] represents the method for analyzing a sample comprising at least one chemical compound and implementing a gas-phase analytical system 1, according to embodiments of the invention.

[0098] The method comprises an initial step 1210 consisting of injecting the sample to be analyzed into the analytical system 1.

[0099] The chemical compound(s) transported in the column 16 then pass through the measurement sensor(s) 185, generating an optical measurement signal for each sensor and each chemical compound detected.

[0100] The method thus comprises an initial step 1230 consisting of acquiring by the optical detection and processing unit 187 each optical measurement signal coming from the measurement sensor(s) 185.

[0101] In step 1290, each detected optical measurement signal originating from the measurement sensor(s) 185 is associated with a chemical compound of the sample to be analyzed.

[0102] Advantageously, the method may further comprise a step 1250 consisting of determining the retention time value and / or the diffusion time value relating to the chemical compound associated with each optical measurement signal is determined.

[0103] In the case where the detection device 18 comprises a plurality of measurement sensors (185n and / or 185q) functionalized differently, the method may also comprise a step 1270 consisting of determining for each optical measurement signal detected (corresponding to a specific chemical compound Ci and a particular sensor n and / or q) a score value (sin and / or siq) relating to complementary information to form the signature Si of the compound. At this step, the evaluation of the signature Si of the chemical compound(s) C; to be analyzed may be carried out to determine the nature of these compounds.

[0104] In embodiments, the method may comprise an additional step of calibrating the sensors with respect to potential variations in environmental parameters from reference sensors positioned in the detection device 18.

[0105] Those skilled in the art will readily understand that certain steps of the method of [Fig. 12] (in particular steps 1250 and 1270) can be carried out in a manner simultaneous, sequential, independent or not, and / or in a different order, for example in an order defined by system 1 or unit 187.

[0106] It should be noted that certain features of the invention may have advantages when considered separately.

[0107] The device and methods described above according to the embodiments of the invention or sub-elements of this system can be implemented in various ways by hardware, software, or a combination of hardware and software, in particular in the form of program code which can be distributed in the form of a program product, in various forms.

[0108] The invention is not limited to the embodiments described above by way of non-limiting example. It encompasses all the variant embodiments that may be envisaged by those skilled in the art. In particular, those skilled in the art will understand that the invention is not limited to the different microfluidic channels, the different measurement sensors, or the different configurations of the detection device described by way of non-limiting example. In particular, certain embodiments of the invention may be combined.

Claims

Claims

1. Gas phase analytical system (1) comprising an injection unit (12) configured to inject a sample to be analyzed comprising at least one chemical compound, a unit (14) for introducing a flow of carrier gas, a transport column (16), and a detection device (18), said at least one chemical compound being entrained by the carrier gas in the transport column to the detection device (18), characterized in that said detection device (18) is an optical detector comprising at least one Mach-Zehnder interferometric sensor (185) powered by an optical source (183) and integrated in a microfluidic structure (181; 182), said sensor (185) comprising a sensitive arm (185-3) exposed to said at least one chemical compound and a reference arm (185-2) impermeable to said at least one chemical compound,said at least one sensor (185) being adapted to optically detect the passage of said at least one chemical compound through said sensitive arm (185-3), said microfluidic structure comprising a primary microfluidic channel (181) and / or at least one secondary microfluidic channel (182) sealed at the channel end (182-4), said at least one chemical compound being transported by convection through the primary channel (181) and / or by diffusion through the sealed secondary channel (182), said at least one sensor (185) being positioned on said primary channel (181) and / or said sealed secondary channel (182), said detection device (18) being adapted to determine the retention time and / or the diffusion coefficient of said at least one chemical compound at the outlet of the column (16) from the optical detection of the passage of said at least one chemical compound through said sensor (185).

2. Analytical system (1) according to claim 1, wherein said at least one Mach-Zehnder interferometric sensor (185) comprises a coating on said sensitive arm (185-3), said coating being adapted to preferentially adsorb said at least one chemical compound.

3. Analytical system (1) according to one of the preceding claims, wherein each sealed secondary microfluidic channel (182) has a distinct channel length L defined in the direction of movement of said at least one chemical compound.

4. Analytical system (1) according to one of the preceding claims, wherein said at least one sealed secondary microfluidic channel (182) comprises at least one physical obstacle (182-6 or 182-8) arranged locally in said channel (182), said obstacle (182-6 or 182-8) being adapted to minimize any convective phenomenon at the inlet of said channel (182) and / or to slow down the diffusion phenomenon of said chemical compound to be detected.

5. Analytical system (1) according to one of the preceding claims, wherein the microfluidic structure further comprises at least one secondary microfluidic channel (182) open at the channel end (182-4), said at least one chemical compound being transported by convection through the open secondary microfluidic channel (182).

6. Analytical system (1) according to one of the preceding claims, wherein said at least one open and / or sealed secondary microfluidic channel (182) comprises a coating comprising a physicochemical substance on the wall of the channel (182).

7. Method for analyzing a sample comprising at least one chemical compound, the method comprising at least the following steps: - Injecting (1210) the sample to be analyzed into the gas-phase analytical system (1) according to one of the preceding claims 1 to 6; - Acquiring (1230) at least one optical measurement signal detected by at least one Mach-Zehnder interferometric sensor (185) of said gas-phase analytical system (1); - Associating (1290) with said at least one optical measurement signal, a chemical compound of the sample to be analyzed. the method further comprising a step of determining (1250) a retention time value and / or a diffusion time value relating to the chemical compound associated with said at least one optical measurement signal.

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