Compact, calibrated interferometric characterization system

Abstract

The present invention relates to an interferometry system for characterizing an analyte present in a fluid medium, comprising at least one light source (11) suitable for emitting an optical signal with a predetermined power, an array of photodetectors (16), and an array of N Mach-Zehnder interferometers (12(n)), including an input splitter (13) coupled to the light source, two waveguides forming a sensitive arm (14s) and a reference arm (14r), and a multimode output coupler (15) having a plurality of outputs, only two of which are phase shifted by π / 2 and referred to as useful outputs (15u), each coupled to a photodetector and connected to the Mach-Zehnder interferometers (12(n)). (n) ) is a processing unit for each of the optical signals input to the input splitter (13) according to a predetermined power of the optical signal emitted by the light source (11). jn(n) and an optical power offset O associated with each useful output (15u) and defined when the light source (11) is in a stopped state. 1(n) , O 2(n) and a predetermined calibration parameter value formed from:

Description

[Technical Field]

[0001] The field of the invention is the characterization of analytes present in gaseous or liquid media by means of interferometry systems. [Background technology]

[0002] The ability to analyze and characterize analytes present in a fluid medium, such as odor molecules or volatile organic compounds, or even compounds present in solution or suspension in a liquid medium, is becoming an increasingly important issue, especially in the health sector, the food industry, the fragrance industry (fragrances), and the olfactory comfort industry in enclosed public or private spaces (cars, hotels, communal areas, etc.). The characterization of such analytes present can be performed by a characterization system.

[0003] A variety of characterization techniques are available, which differ from one another in particular by whether the analyte or receptor needs to be previously "tagged" with a reagent. For example, unlike fluorescence detection, which requires the use of such markers, detection using surface plasmon resonance imaging (SPRi) and interferometry, such as Mach-Zehnder interferometers (MZI), are so-called label-free techniques.

[0004] In such characterization systems, analytes present in a fluid medium interact by adsorption / desorption with receptors located at one or more sensitive sites on a functionalized surface. The goal is to detect in real time an optical signal associated with each sensitive site, which represents the time variation of the local refractive index due to the adsorption / desorption interaction of the analyte with the receptor. The intensity or power of each optical signal detected by the optical sensor is directly correlated to the adsorption / desorption interaction of the analyte with the receptor.

[0005] FIG. 1A illustrates a Mach-Zehnder interferometer 12 in the characterization system described in EP 3754326 A1. This characterization system includes a functionalized surface on which a receptor is located, a light source (here, a diffraction grating provides coupling between the light source and the interferometer 12), an array of Mach-Zehnder interferometers 12 within a photonic integrated circuit (ΦIC) on a photonic chip, a photodetector (here, a diffraction grating provides coupling to a remote photodetector), and a processing unit (also not shown). Each interferometer 12 includes two waveguides, one of which forms a reference arm 14r and the other of which forms a sensitive arm 14s, on whose surface a receptor is located. The presence of an analyte adsorbed on the surface of the sensitive arm 14s alters the properties of the optical signal passing through the sensitive arm 14s, more specifically, resulting in a change in the phase of the optical signal, while the phase of the optical signal passing through the reference arm 14r remains unchanged. The phase difference Φ(t) between these optical signals results in constructive or destructive interference, modulating the power of the optical output signal detected by the photodetector.

[0006] FIG. 1B illustrates a signal (or sensorgram) obtained by the characterization system during the analyte characterization process. A sensorgram herein refers to a signal obtained at a reference phase Ph where no analyte is present. ref , followed by a characterization phase Ph in which the analyte is present and interacts with the receptor. carac Then, the reference phase Ph ref and characterization phase Ph carac The value of the phase shift Φ(t) associated with each i and Φ f From this, the analyte can be characterized.

[0007] However, because the power of the optical signal received by the photodetector is a sinusoidal function of the phase shift Φ(t), it may be necessary to be able to determine the direction of variation of the phase shift Φ(t). To this end, in one approach, a Mach-Zehnder interferometer includes 2 × 3 multimode output couplers (MMI, for Multimode Interferometer). The multimode coupler therefore includes three outputs, each phase-shifted by 2π / 3, referred to as useful outputs because each is coupled to a photodetector. Figure 1C illustrates such a Mach-Zehnder interferometer 12, as described in Halir et al., "Direct and Sensitive Phase Readout for Integrated Waveguide Sensors," IEEE Photonics J., Vol. 5, No. 4, 6800906, August 2013, and includes a multimode coupler 15 coupled to three photodetectors 16. Also, for an array of N Mach-Zehnder interferometers 12, it is necessary to provide an array of 3 × N photodetectors 16, which translates into a significant footprint on the surface of the photonic chip. This footprint can be due to the presence of an array of 3 × N diffraction gratings on the photonic chip to provide coupling with a remote array photodetector (camera), or the presence of the array of 3 × N photodetectors if integrated into the photonic chip.

[0008] Characterization systems using Mach-Zehnder interferometers are described, inter alia, in the article by Laplatine et al. entitled "Silicon photonic olfactory sensor based on an array of 64 biofunctionalized Mach-Zehnder interferometers," Optics Express, Vol. 30, No. 19, pages 33955-33968, 2022; the article by Milvich et al. entitled "Integrated phase-sensitive photonic sensors: a System design tutorial," Advances in Optics and Photonics, Vol. 13, No. 3, pages 584-642, 2021; and the article by Schweikert et al. entitled "Improved Phase Detection in On-Chip Refractometers," 2021 International Conference on Numerical Simulation of Optoelectronic Devices (NUSOD), pages 113-114, 2021. Summary of the Invention

[0009] It is an object of the present invention to at least partially remedy the drawbacks of the background art, and more particularly to provide an interferometric characterization system that has a reduced footprint while still being able to determine the phase shift Φ(t) and its direction of variation.

[0010] To this end, the subject of the present invention is a characterization system suitable for characterizing an analyte present in a fluid medium, comprising a measurement device, the measurement device comprising: at least one light source suitable for emitting an optical signal having a predetermined power; an array of N Mach-Zehnder interferometers, N>1, each including an input splitter coupled to a light source, two waveguides forming a sensitive arm and a reference arm, the sensitive arm having a receptor located on its surface with which the analyte can interact by adsorption / desorption, and a multimode output coupler coupled to the two waveguides; an array of photodetectors suitable for measuring the power of an optical signal transmitted by the multimode coupler.

[0011] The characterization system also includes a processing unit for calculating, for each Mach-Zehnder interferometer with a refractive index n ranging from 1 to N, a phase shift Φ between the optical signals circulating in the waveguide from the measured power. (n) (t) and the phase shift Φ (n) (t) to determine the values ​​Φ associated with the reference phase where the analyte is not present and the characterization phase where the analyte is present and interacting with the receptor, respectively. i(n) and Φ f(n) and then determine the value Φ i(n) and Φ f(n) a processing unit suitable for characterizing the analyte from the sample.

[0012] According to the present invention, each of the multimode couplers has a plurality of outputs, only two of which, called useful outputs phase-shifted by π / 2, are coupled to photodetectors, which in turn form an array of 2 × N photodetectors, each of which detects the power P of the optical signal transmitted by the useful output of each Mach-Zehnder interferometer. 1(n) (t) and P 2(n) Measure (t).

[0013] In addition, the processing unit calculates, for each of the Mach-Zehnder interferometers, the input power P of the optical signal incident on the input divider according to the predetermined power of the optical signal emitted by the light source. in(n) and an optical power offset o associated with each useful output and defined when the light source is in a stopped state. 1(n) , o 2(n)Additionally, it contains predetermined values ​​of the calibration parameters, which consist of the measured optical power P 1(n) (t) and P 2(n) (t), and the calibration parameter P in(n) , o 1(n) , and o 2(n) A phase shift Φ from a given value (n) (t) is suitable for determining

[0014] Some preferred, but non-limiting aspects of this characterization system are as follows:

[0015] Each output coupler may include an output that is not coupled to the photodetector array, referred to as the "non-useful" output, and that includes a tapered end.

[0016] The characterization system may include a photonic chip containing an array of N Mach-Zehnder interferometers and an array of 2×N photodetector elements coupled to the N interferometers by integrated waveguides, where the photodetector elements are either photodetectors or diffraction gratings coupled to the array photodetectors.

[0017] The measurement apparatus may include an array of at least four Mach-Zehnder interferometers.

[0018] Each multimode coupler can be a 2x4 coupler.

[0019] The characterization system, together with the processing unit, calculates the calibration parameter P in(n) , o 1(n) , and o 2(n) A suitable calibration device may be provided to determine the value of .

[0020] The calibration device may include a so-called calibration analyte reservoir in fluid communication with the measurement device to allow the calibration analyte to interact with the receptor, such that a predetermined concentration of the calibration analyte, when interacting with the receptor, causes a phase shift Φ of each of the Mach-Zehnder interferometers. (n) The default minimum variation ΔΦ of (t)min induces.

[0021] The calibration device may include a Mach-Zehnder interferometer, also called a calibration interferometer, coupled to at least one so-called calibration photodetector.

[0022] The calibration interferometer may include a reference arm and a discontinuity arm.

[0023] The present invention also relates to a process for calibrating a characterization system according to an embodiment in which the calibration device includes a reservoir of calibration analyte. The process then comprises the following steps: -activating the light source to emit an optical signal at a predetermined power; - placing a calibration analyte in contact with the receptor; - the calibration analyte interacts with the receptor and has a specified minimum value ΔΦ min A phase shift Φ at least equal to (n) (t) During the induction of fluctuations, the power P of the optical signal transmitted by each Mach-Zehnder interferometer is measured by the photodetector. 1(n) (t), P 2(n) (t) measuring the -The processing unit measures the power P 1(n) (t), P 2(n) (t) to the calibration parameter P in(n) , o 1(n) , and o 2(n) and determining the value of a calibration parameter P in the processing unit. in(n) , o 1(n) , and o 2(n) and storing the determined value of

[0024] Calibration parameter P in(n) , o 1(n) , and o 2(n) is the measured power P 1(n) (t), P 2(n) It can be determined from the minimum and maximum values ​​of (t).

[0025] The present invention also relates to a process for calibrating a characterization system according to an embodiment in which the calibration device comprises a calibration interferometer and at least one calibration photodetector. The process then comprises the following steps: - measuring, by means of a calibration photodetector, the power of the optical signal transmitted by the calibration interferometer while the light source is activated; - the input power P of the optical signal incident on the input splitter of the calibration interferometer in,calib determining the value of -Decision value P in,calib From the above, for each interferometer in the measurement system, the input value P in(n) and determining:

[0026] The process comprises the following steps: measuring the power P of the optical signal transmitted by each interferometer of the measurement device by a photodetector of the measurement device while the light source is turned off; 1(n) (t), P 2(n) (t) and then measuring the measured power P 1(n) (t), P 2(n) (t) to offset value o 1(n) and o 2(n) and determining:

[0027] The present invention also provides a process for characterizing an analyte by means of a characterization system according to any one of the preceding features, comprising the following steps: - the power P of the optical signal transmitted by each Mach-Zehnder interferometer during a reference phase in which no analyte is present, and during a characterization phase in which the analyte is present and interacting with the receptor, as measured by the photodetector of the measurement device. 1(n) (t), P 2(n) (t) measuring the - the processing unit measures, for each Mach-Zehnder interferometer, the power P 1(n) (t), P 2(n) (t) and the calibration parameter P in(n) , o 1(n) , and o 2(n) and the phase shift Φ between the optical signals circulating in the arms. (n) determining (t); - phase shift Φ relative to the reference phase and the characterization phase, respectively (n) From (t), the value Φ i(n) and Φ f(n) determining -value Φ i(n) and Φ f(n) and characterizing the analyte from the

[0028] Phase shift Φ (n) The process of determining (t) is referred to as the extracted phase shift and the measured power P 1(n) (t), P 2(n) (t), and the calibration parameter P in(n) , o 1(n) , and o 2(n) From a given value of , the phase shift Φ whose value is between 0 and 2π (n) (t) and then the extracted phase shift Φ, which is called the unfolded phase shift. (n) (t) and adding a positive or negative integer multiple of 2π to it, resulting in a phase shift Φ (n) (t) and determining [Brief explanation of the drawings]

[0029] Other aspects, objects, advantages and features of the present invention will become apparent from the following detailed description of preferred embodiments of the invention, given by way of non-limiting example and made with reference to the accompanying drawings, in which: [Figure 1A] FIG. 1 is a schematic partial perspective view of a Mach-Zehnder interferometer of a characterization system according to another example of the background art, previously described; [Figure 1B] Illustrates the time evolution of the phase shift Φ(t) between optical signals circulating in the two waveguides of a Mach-Zehnder interferometer between the reference phase Phref and then the characterization phase Phcarac, as already described. [Figure 1C] 1 is a schematic partial view of a Mach-Zehnder interferometer of another example of a characterization system according to the background art, including a 2×3 multimode output coupler, as previously described. [Figure 2A]FIG. 1 is a partial schematic diagram of a compact calibrated characterization system according to one embodiment. [Figure 2B] FIG. 10 is a schematic partial view of another example of a Mach-Zehnder interferometer of a measurement device of a calibrated characterization system in accordance with an embodiment. [Figure 3A] 2A or 2B, illustrating the time evolution of the extracted phase shift Φ(t) and the unfolded phase shift Φ(t), associated with an optical signal circulating in the arms of the Mach-Zehnder interferometer, where the phase evolution is highlighted. [Figure 3B] 1 illustrates a flow chart of a calibration process and an analyte characterization process according to one embodiment. [Figure 4A] 1 is a schematic partial view of a compact characterization system to be calibrated, in which the calibration device includes a reservoir of calibration analyte. [Figure 4B] 4B is a schematic partial view of the calibrated characterization system of FIG. 4A illustrating the fluid connections between a reservoir of calibration analyte and a measurement device of the characterization system. [Figure 5A] 10 illustrates the time evolution of the powers P1(n)(t) and P2(n)(t) of the optical signals transmitted by a multimode coupler of a Mach-Zehnder interferometer of a characterization system according to one embodiment for determining the calibration parameters P1(n), o1(n), and o2(n). [Figure 5B] For the purpose of also determining the calibration parameters P(n), o1(n), and o2(n), we further illustrate the time evolution of the extracted phase shift Φ(n)(t), which is in the form of an ellipse in the complex plane (x,y). [Figure 6A] FIG. 10 is a schematic partial view of a compact characterization system to be calibrated according to another embodiment, in which the calibration device includes a calibration Mach-Zehnder interferometer coupled to a calibration photodetector. [Figure 6B] FIG. 10 is a schematic partial view of another example of a calibrated Mach-Zehnder interferometer. DETAILED DESCRIPTION OF THE INVENTION

[0030] In the drawings and the rest of the description, the same reference symbols represent the same or similar elements. Additionally, various elements are not drawn to scale for clarity. Furthermore, various embodiments and variations are not mutually exclusive and can be combined with each other. Unless otherwise indicated, the terms "substantially," "approximately," and "to the extent" mean within 10%, preferably within 5%. Furthermore, the words "between" and "and" and equivalents mean that the boundary values ​​are included unless otherwise specified.

[0031] The present invention generally relates to the characterization of analytes present in a fluid medium (gas or liquid). In general, characterization refers to obtaining information representative of the interaction of analytes contained in the fluid medium with receptors at sensitive sites on the functionalized surface of a characterization system. The interactions in question here are adsorption and / or desorption events of analytes with receptors. This information also forms an interaction pattern, or analyte "signature," which can be shown, for example, as a histogram or radar diagram. More precisely, if the characterization system comprises N distinct sensitive sites, the interaction pattern consists of N representative items of scalar or vector information.

[0032] The invention more precisely relates to a calibrated characterization system, i.e. a system in which the processing unit contains, for each of the Mach-Zehnder interferometers of the measurement device, predetermined values ​​of calibration parameters, so that these values ​​are used to calculate the phase shift Φ between the optical signals circulating in the arms of each Mach-Zehnder interferometer. (n) The present invention relates to a system that allows for determining the value of the calibration parameters (t) and their direction of variation. The present invention also relates to a characterization system to be calibrated, comprising a calibration device that determines these values ​​of the calibration parameters by means of a processing unit. Finally, the present invention relates to a process for calibrating such a characterization system (to be calibrated), and to a process for characterizing an analyte using such a calibrated characterization system.

[0033] For each Mach-Zehnder interferometer with refractive index n ranging from 1 to N, where N>1, the calibration parameter is the input power P of the optical signal incident on the input splitter due to the given power of the optical signal launched by the light source of the characterization system. in(n) and an optical power offset o associated with each useful output and defined when the light source is in a stopped state (and therefore the input power of the optical signal entering the input splitter is 0). 1(n) , o 2(n) It is noted herein that the term "offset" is synonymous with bias, offset, offset error, zero error, and the like.

[0034] The characterization of the analyte is performed by an interferometric characterization system comprising at least: A measuring device, at least one light source suitable for emitting an optical signal having a predetermined power; an array of N Mach-Zehnder interferometers, N>1, each including an input splitter coupled to a light source, two waveguides forming a sensitive arm and a reference arm, and an output coupler of the MMI type (multimode coupler) having a plurality of outputs, only two of which are useful outputs phase shifted by π / 2; ●A measurement device comprising: an array of 2xN photodetectors coupled to the useful output either directly (the photodetectors are then placed on or within the photonic chip) or indirectly (via an array of 2xN diffraction gratings fabricated on or within the photonic chip). a processing unit, for each of the Mach-Zehnder interferometers of the measurement device, including predetermined values ​​of calibration parameters; For each of the interferometers, the measured optical power P associated with the useful output 1(n) (t) and P 2(n) (t), and the predetermined values ​​of the calibration parameters (input power P in(n) and offset o 1(n) , o 2(n) ) gives the phase shift Φ between the optical signals circulating in the arms.(n) and then Reference process Ph where the interferometer is not exposed to the analyte ref , and a characterization step Ph in which the interferometer is exposed to the analyte. carac and the phase shift Φ associated with (n) (t) value Φ i(n) and Φ f(n) a processing unit suitable for characterizing an analyte from the

[0035] According to the present invention, the output coupler of each Mach-Zehnder interferometer is a multimode coupler with two inputs and multiple outputs (preferably four outputs) coupled to its arms. Of these outputs, only two, phase-shifted by π / 2, are coupled to the photodetectors and are therefore said to be useful. The other outputs are not used to characterize the analyte (i.e., are not coupled to the photodetectors of the measurement device). This configuration therefore significantly reduces the footprint on the photonic chip, since only 2 × N photodetectors are required instead of 3 × N, as previously mentioned in Halir et al.'s 2013 paper. The footprint associated with the waveguides connecting the output couplers to the photodetectors (if integrated on the photonic chip) or diffraction gratings (if the photodetectors are remote) is also significantly reduced. In addition, the predetermined values ​​of the calibration parameters are determined by the phase shift Φ n This makes it possible to determine (t) and also to know the direction of its fluctuation.

[0036] As will be described in more detail below, the characterization system may further comprise a calibration device suitable for determining in the processing unit the values ​​in question of the calibration parameters during the calibration process.

[0037] 2A is a schematic partial view of a calibrated characterization system 1 according to one embodiment. FIG. 2B further illustrates the Mach-Zehnder interferometer 12 of the characterization system 1 of FIG. 2A. (n) is illustrated in more detail.

[0038] Generally, the characterization system 1 includes a measurement device 10 and a set of calibration parameters Paramcalib and a processing unit 3 containing the predetermined values ​​of . The characterization system 1 is then calibrated. (n) are integrated into a photonic chip, which may be of the silicon photonic chip type.

[0039] Analytes are elements present in the fluid medium (gas or liquid) being analyzed and intended to be detected and characterized by the characterization system 1. Examples include bacteria, viruses, proteins, lipids, volatile organic molecules, and inorganic compounds. Furthermore, receptors 2 (ligands) are elements that coat one of the waveguides (sensor arms 14s) of the Mach-Zehnder interferometer 12 and have the ability to interact with analytes, although the chemical and / or physical affinity between the analyte and receptor 2 is not necessarily known. Receptors 2 on different sensing surfaces preferably have different physicochemical properties that affect their ability to interact with analytes. Examples include amino acids, peptides, nucleotides, polypeptides, proteins, organic polymers, and oligo- or polysaccharides, among others.

[0040] Mach-Zehnder Interferometer 12 (n) are fabricated within a photonic chip containing, for example, silicon-based integrated photonic circuits. The light source 11 and photodetector 16 can be located on or within the photonic chip, or can be offset and linked by an optical coupler (such as a diffraction grating 17), as illustrated in FIG. 2B. Similarly, the processing unit 3 can be located within or on the photonic chip, or can be located remotely.

[0041] The measurement device 10 includes at least one light source 11 and N Mach-Zehnder interferometers 12. (n) and an array of 2×N photodetectors 16.

[0042] The light source 11 is preferably a coherent or non-coherent optical source with a continuous or pulsed monochromatic signal, a reduced spectral width (e.g., less than 30 nm, or even less than 15 nm, or even less than 2 nm, or even less than 1 nm), and a predetermined central wavelength, for example in the near infrared. It can be a Vertical Cavity Surface Emitting Laser (VCSEL) source, a III-V / Si hybrid laser source, a laser diode, or any other type of laser source. It can also be a light-emitting diode.

[0043] The measurement device 10 of the characterization system 1 includes an array of N Mach-Zehnder interferometers (12(n)), referenced by refractive indices n in the range 1 to N, where N>1, preferably at least 4, e.g., 64 or more. (n) Each of the waveguides 14r, 14s comprises an input splitter 13 (for example of the MMI type) and two waveguides 14r, 14s coupled to the input splitter 13, one of which forms a sensitive arm 14s that is sensitive to the amount of analyte adsorbed on the receptor 2, and the other of which forms a reference arm 14r that is not sensitive to the analyte present, so that the optical signals circulating in the two arms 14r, 14s have an effective phase shift denoted Φ(t). The two waveguides 14r, 14s are then coupled to a multimode coupler 15 having multiple outputs (here four outputs) that are phase shifted by π / 2, of which only the two outputs phase shifted by π / 2 are useful and are coupled to a photodetector 16.

[0044] In the example shown in Figure 2A, arms 14r, 14s extend helically in the sense that they wrap around themselves between input splitter 13 and multimode coupler 15. They may also extend in a coiled manner, or even linearly (optionally with coil and / or helical portions) as illustrated in Figure 2B. Other shapes of waveguides are possible.

[0045] The receptors 2 thus form N sensitive sites of the so-called functionalized surface of the photonic chip, which functionalized surface is intended to be exposed to a fluid medium containing the analyte. In other words, the sensitive sites contain the receptors 2 and are connected to the interferometer 12. (n) The zones are located in the sensing arms 14s of the sensor. They may contain receptors 2 which differ from one sensing site to another in terms of their physicochemical affinity with the analyte. The sensing sites may be identical, for example, to detect any measurement drift.

[0046] Interferometer 12 (n) Each of the sensing arms 14s includes a sensing arm 14s on whose surface a receptor 2 is disposed to form a sensing site, while the other arm does not include a receptor 2 and forms a reference arm 14r. The waveguide (a material with a high refractive index) of the sensing arm 14s is located at a certain depth from the receptor 2 so that the optical signal propagating therein (the guided mode) has an effective refractive index that depends on the amount of analyte bound to the receptor 2 of the sensing site. Therefore, a notch (see, for example, French Patent Application Publication No. 2106153, filed June 10, 2021) can be made in the sheath covering the sensing arm 14s to allow the guided mode to be affected by the presence of adsorbed analyte.

[0047] Note that the effective refractive index of a guided mode is defined as the product of the propagation constant β and λ / 2π, where λ is the wavelength of the optical signal. The propagation constant β depends on the wavelength λ and the mode of the optical signal, as well as the properties of the waveguide (refractive index and geometry). The effective refractive index of a mode corresponds, in a sense, to the refractive index of the waveguide as "seen" by the optical mode. It is usually between the refractive index of the core and the sheath of the waveguide. It is therefore understood that the amount of analyte adsorbed on the sensitive sites modifies the optical mode and / or the properties of the waveguide, in particular the phase of the guided mode.

[0048] As a result, the presence of adsorbed analyte on the sensitive sites of the sensitive arm 14s results in a change in the phase of the guided mode, while the phase of the guided mode passing through the reference arm 14r remains substantially unchanged. The phase shift Φ(t) between the optical signals passing through the arms and then received by the multimode coupler 15 results in a change in the power of the optical signal that is recombined and detected by the photodetector 16 due to constructive or destructive interference between the optical signals circulating in the two arms.

[0049] The output coupler 15 is a 2x4 multimode coupler (MMI) in this example, although the number of inputs may vary. It includes at least two outputs, referred to herein as useful outputs 15u, that are phase-shifted by π / 2 and each coupled to a photodetector 16. The other outputs 15nu are referred to as non-useful outputs unless they are coupled to a photodetector 16. These may each include tapered ends to allow the optical signal to leak into the substrate of the photonic chip, significantly reducing retroreflection back toward the multimode coupler 15.

[0050] The measurement device 10 includes an array of 2×N photodetectors 16, each of which is connected to an interferometer 12. (n) The photodetector 16 is coupled to the useful outputs 15u of the multimode coupler 15. The photodetector 16 measures the value of the power (or equivalently the intensity) of the optical signal transmitted by each useful output 15u at each measurement time and transmits this information to the processing unit 3. The power of the optical signal at the useful output 15u is expressed as P 1(n) and P 2(n) On the photonic chip, the array of interferometers 12 is coupled to an array of 2×N detector elements, which can either be a diffraction grating 17 (in the form of a camera with 2×N sensitive detection zones, each sensitive zone optionally comprising at least one detector pixel) if the photodetector is remote from the photonic chip, or the photodetector 16 itself if the photodetector 16 is integrated on the photonic chip.

[0051] The processing unit 3 enables the processing operations of the analyte characterization process to be carried out. For this purpose, it is connected to the photodetector 16 of the measurement device 10. It includes at least one microprocessor and at least one memory. It therefore includes a programmable processor capable of carrying out instructions stored in an information storage medium. It further includes at least one memory containing the instructions necessary to carry out the characterization process. The memory is also suitable for storing the information calculated at each measurement time point.

[0052] In particular, the processing unit 3 controls the interferometer 12 of the measuring device 10. (n) For each of the calibration parameters Param calib a predetermined value of, i.e., more precisely, the power P in(n) and offset o 1(n) and o 2(n) Contains Power P in(n) is a function of the predetermined power of the optical signal emitted by the light source 11, and in fact, the value P in(n) depends on the higher or lower power of the signal emitted by the light source 11. Furthermore, the offset (n) and / or may be related to the photodetectors of the measurement device 10 and may result from residual light present in the characterization system 1 or may even be related to the dark current of the photodetectors 16 .

[0053] The processing unit 3 controls each interferometer 12 (n) The "extracted" phase shift Φ, which represents the phase shift between the optical signals circulating in the arms of (n) (t) is measured by interferometer 12. (n) The optical power P measured by the photodetector 16 for each 1(n) (t) and P 2(n) (t) and the calibration parameters Param calib and a predetermined value of . It is also suitable to determine the so-called "unfolded" phase shift Φ (n) (t) and then the reference phase Ph ref (Absence of analyte) and characterization phase Ph carac(presence of analyte) i(n) and Φ f(n) These values ​​Φ i(n) and Φ f(n) For example, S={Φ f(n) -Φ i(n)} n=1;N This allows the determination of the signature of the analyte, such as

[0054] As illustrated in FIG. 2A, the characterization system 1 has a small footprint on the photonic chip insofar as the detection array includes only 2×N detection elements (diffraction gratings 17 or photodetectors 16). The footprint associated with the waveguides providing the coupling between the multimode coupler 15 and the detection array is also reduced. In the case of a remote camera, the reduced number of sensitive detection surfaces, 2×N, allows for the use of a less expensive camera. In addition, calibration parameters Param can be obtained via the calibration device 20. calib By determining n By determining t, it is possible to know the direction of its fluctuation. Finally, a Mach-Zehnder interferometer 12 with two useful outputs 15u that are phase-shifted by π / 2 is obtained. (n) In the case of , the phase shift Φ is larger than in the case of three useful outputs phase shifted by 2π / 3. (n) It can be shown that the error in determining (t) can be smaller.

[0055] Figure 3A shows the extracted phase shift Φ (n) (t) and the unfolded phase shift Φ (n) The time evolution of (t) is illustrated below.

[0056] As mentioned above, the powers P1(t) and P2(t) of the optical signals output by the Mach-Zehnder interferometer 12 vary periodically, or more precisely sinusoidally, according to the phase shift between the optical signals passing through the arms of the interferometer 12. Phase extraction methods generally use inverse trigonometric functions such as the arctangent, so that the calculated phase shift has a value modulo 2π, which is the extracted phase shift Φ(t).

[0057] Thus, when an analyte binds to the receptor 2 in the sensitive arm 14s, the phase shift between the optical signals passing through the two arms of the interferometer increases. The extracted phase shift Φ(t) also increases by exhibiting a discontinuity of about 2π each time it reaches one of the boundaries of the interval of width 2π, here ]-π;+π]. It therefore increases until it reaches +π, then exhibits a discontinuity of -2π value before returning to the value of -π, and then resumes growth. The unfolded phase shift Φ(t), representing the effective phase shift between the optical signals passing through the interferometer arms, continuously increases without remaining contained within the interval ]-π;+π].

[0058] 3B illustrates a flow chart of a process 200 for characterizing an analyte by the calibrated characterization system 1 of FIG. 2A. The characterization process 200 follows the calibration process 100.

[0059] During a prior calibration process 100, described in detail below, the calibration parameters Param calib The value of the input power P in(n) and offset o 1(n) and o 2(n) The Mach-Zehnder interferometer 12 of the measurement device 10 (n) is determined for each of the sigma and stored in the processing unit 3. This process 100 is described in more detail below in connection with two different embodiments described below.

[0060] The characterization process 200 measures the interferometer 12 at each successive measurement time ti by the photodetector 16. (n) The power P of the optical signal transmitted by each of 1(n) (t i ) and P 2(n) (t i ) are transmitted to the processing unit 3. These powers P 1(n) (t i ) and P 2(n) (t i) corresponds to the optical signals transmitted by the two useful outputs 15u of each multimode coupler 15. This step is performed with a reference phase Ph, where the functionalized surface is not exposed to the analyte. ref and the characterization phase Ph during which the functionalized surface is exposed to the analyte. carac It is executed between

[0061] In step 220, the processing unit 3 calculates the calibration parameters Param calib :P in(n) , o 1(n) and o 2(n) and optical power P 1(n) (t i ) and P 2(n) (t i ) and the extracted phase shift Φ n :(t i This step is performed as exemplified herein, at each measurement time t i or power P 1(n) (t i ) and P 2(n) (t i ) can be performed after the time evolution of

[0062] For this purpose, the optical power P 1(n) (t i ) and P 2(n) (t i ) can be expressed by the following formula:

[0063]

number

[0064]

number

[0065]

number

[0066] In the phase-unfolding step 230, the extracted phase shift Φ n (t i The time evolution of m(t) is then corrected by adding positive or negative integer multiples of 2π in the interval [-π;+π], i )x2π, and m(t i ) is a positive or negative integer. The latter is the extracted phase shift Φ (n) (t i ) increments by one unit +1 or -1 at each discontinuity. This process is usually called phase unfolding or phase unwrapping. This is because the unfolded phase shift Φ (n) which value is no longer modulo 2π and then effectively represents the effective phase shift.

[0067] Different approaches are possible. In this example, the extracted phase shift Φ between two successive measurement times (n) Instantaneous fluctuation of ΔΦ (n) (t i )=Φ (n) (t i )-Φ (n) (t i-1 ) is calculated (substep 231), and then the increment m(t i ) is determined (substep 232). In this step, the instantaneous fluctuation ΔΦ n (t i ) is the value of the previous increment m(t i-i ) is compared with a predetermined threshold S1, for example about n, so as to optionally add a positive or negative unit to the unfolded phase shift Φ (n) (t i ) is the extracted phase shift Φ(n) (t i ) to a multiple of 2π, that is, m(t i )x2π (substep 233).

[0068] Finally, in a characterization step 240, the processing unit 3 calculates the reference phase Ph ref (absence of analyte) (n) (t i ) steady-state value Φ i(n) and the characterization phase Ph carac A steady-state value Φ representing the presence of analyte f(n) The signature S of the analyte is then determined, for example, by the formula: S={Φ f(n) -Φ i(n)} n=1;N can be determined from

[0069] 4A and 4B show that the calibration device 20 contains a reservoir of so-called calibration analytes 21, the concentration of which is determined by the unfolded phase shift Φ (n) FIG. 1 is a schematic partial view of a calibrated characterization system 1 according to an alternative embodiment suitable for inducing a predetermined minimum variation in (t).

[0070] The characterization system 1 comprises a measurement device 10 and a processing unit 3 identical to those of the characterization system 1 of Fig. 2A. It further comprises a calibration device 20, which together with the processing unit 3 calibrates each Mach-Zehnder interferometer 12. (n) The value of the calibration parameter (power P in(n) , and offset o 1(n) and o 2(n) ) can be determined.

[0071] The characterization system 1 may comprise a reservoir 4 of an analyte-free reference fluid, which is intended to come into contact with the functionalized surface during the reference phase. This may be a reservoir or controlled access to the analyte-free environment of the characterization system 1. It may also comprise a reservoir 5 for a fluid containing the analyte to be characterized, which is intended to come into contact with the functionalized surface during the characterization phase. Here, too, this may be a reservoir or controlled access to the analyte-containing environment of the characterization system 1. Finally, it comprises a reservoir 21 of a fluid containing a calibration analyte.

[0072] Thus, during the preceding calibration process 100, the calibration reservoir 21 is placed in fluid communication with the measurement device 10, and a fluid having an analyte is delivered onto the functionalized surface. The analyte concentration is measured as a calibration parameter P in(n) , o 1(n) , and o 2(n) A predetermined minimum value ΔΦ depends on the method used to determine min The unfolded phase shift Φ is at least equal to (n) It is designed to cause a fluctuation of (t).

[0073] Power P 1(n) and P 2(n) 5A, which illustrates the time evolution of ΔΦ, the “min-max” method described in European Patent Application No. 21172910.8, filed May 8, 2021, can be used. In this case, the minimum value ΔΦ min is preferably at least equal to 2π.

[0074] In this step, the functionalized surface is exposed to a calibration analyte and the photodetector 16 measures the power P of at least one interferometer. 1(n) and P 2(n) Measure the calibration parameter P in(n) , o 1(n) , and o 2(n) is assumed to be the same for all interferometers 12), preferably as described herein, (n)Therefore, the calibration analyte measures the power of each of the unfolded phase shifts Φ (n) This caused a variation of at least 2π in (t).

[0075] The previously shown P 1(n) According to the definition of (Φ), P 1(n) (Φ=π), so o 1(n) The minimum value min(P 1(n) (t)) is measured. In addition, P 1(n) (Φ=0), and therefore 2×(P in(n) / 4)+o 1(n) Equal to the maximum value max(P 1(n) (t)) is measured. Therefore, P in(n) can then be estimated. 2(n) The procedure is carried out for the time evolution of (t), which results in o 2(n) It is therefore possible to estimate the calibration parameters Param calib It is then possible to determine the value of P in1(n) and P in2(n) can be used to determine the values ​​of , if they are not equal for the two useful outputs 15u of the multimode coupler 15.

[0076] FIG. 5B shows the extracted phase shift Φ in the complex plane (x;y), where x and y are the parameters defined above. (n) (t i ) is used as part of the elliptic method, specifically described in the aforementioned paper by Halir et al. (2013). In this case, the minimum value of ΔΦ min is advantageously equal to 2π, but may be less than 2π if enough values ​​are obtained so that the entire ellipse can be reconstructed by curve fitting.

[0077] Calibration parameters Param calib can be estimated from the position and shape of the ellipse. In fact, the half length of the minor axis, "a", is in1(n)The half length of the major axis "b" is equal to P in2(n) In addition, the coordinates of the center of the ellipse (x0; y0) are given by the following formula: x0 = P in1(n) +o 1(n) ;y0=P in2(n) +o 2(n) It is then possible to estimate the value of the offset due to

[0078] There are other ways to determine the calibration parameters, for example, by using the observation matrix P as a function of the measured optical power P 1(n) and P 2(n) where M depends on the calibration parameters and X depends only on the phase shift Φ.

[0079] This alternative embodiment, in which the calibration device 20 includes the analyte reservoir 21, also keeps the footprint of the photonic chip small, since it does not include additional interferometers and photodetectors. calib Once the value of the calibration parameter Param has been defined and stored in the processing unit 3, the reservoir 21 of calibration analyte can be removed, resulting in a calibrated characterization system 1. It should be noted that this reservoir 21 can be retained in the calibrated characterization system 1, for example, so that the characterization system 1 can be periodically recalibrated. Finally, the method includes the step of removing the calibration parameter Param calib Mach-Zehnder Interferometer 12 (n) Note that this allows for accurate determination of each of

[0080] Figure 6A is a schematic partial view of a calibrated characterization system 1 according to another alternative embodiment in which the calibration apparatus 20 includes a Mach-Zehnder interferometer 22, referred to as a calibration interferometer, associated with at least one calibration photodetector 26. Figure 6B further illustrates the calibration interferometer 22 of the characterization system 1 of Figure 6A in more detail.

[0081] The characterization system 1 herein comprises the same measurement device 10 and processing unit 3 as those of the characterization system 1 of Fig. 2A. It further comprises a calibration device 20, which together with the processing unit 3 calibrates each Mach-Zehnder interferometer 12. (n) The value of the calibration parameter (power P in(n) , and offset o 1(n) and o 2(n) ) can be determined.

[0082] The calibration interferometer 22 does not include a sensitive arm and is therefore not affected by the presence of the analyte in the fluid medium. Its shape is preferably similar to that of the interferometer 12 of the measurement device 10. It may therefore include two arms extending continuously between the input splitter 13 and the multimode coupler 15 and optically isolated from the external environment, or, as exemplified herein, a continuous arm 24r and a discontinuous arm 24d.

[0083] In this example, where calibration interferometer 22 includes discontinuous arm 24d, a zone of the functionalized surface in this discontinuous arm 24d may have a notch similar to that of interferometer 12 and is intended to receive analytes. In this zone, analytes may still be deposited. Alternatively, they may not be deposited, but the notch may allow the external environment to affect the waveguide mode. For this reason, waveguide 24d is discontinuous herein. If both arms were continuous, the sheath would be locally thick enough to avoid the influence of the external environment on the waveguide mode.

[0084] Furthermore, in this example, the outputs of the multimode coupler 25 each have a power P in,calib / 2 / 4, i.e. P in,calib 8 optical signal. The four outputs of the multimode coupler 25 can each be coupled to a calibration photodetector. To avoid duplication of information, only one output (useful output 25u) of the multimode coupler 25 is coupled to the calibration photodetector 26.

[0085] The processing unit 3 then calculates at least one calibration parameter P associated with this calibration interferometer 22. in.calib can then be determined by the interferometer 12 of the measurement device 10. (n) The following parameters may be defined:

[0086] Therefore, in the first step of the calibration process 100, each interferometer 12 of the measurement device 10 (n) Offset of 1(n) and o 2(n) To this end, the photodetector 16 of the measuring device 10 can measure the optical power while the light source 11 is not emitting an optical signal, which determines the offset o 1(n) and o 2(n) Alternatively, the offset o relative to the calibration photodetector 26 corresponds to calib and measures only the offset o of the photodetector 16 of the measuring device 10. 1(n) , o 2(n) is the measured value calib can be considered to be identical to

[0087] The light source 11 is then activated to emit a light signal. This second step of the calibration process 100 is the reference phase Ph of the measurement step 210. ref The calibration photodetector 26 then measures the optical power P transmitted by the useful output 25u of the calibration interferometer 22. in,calib Then, the processing unit 3 measures the measured value P in,calib / 8 to each interferometer 12 of the measuring device 10 (n) The value of P in(n) Determine.

[0088] While particular embodiments have been described above, many variations and modifications will be apparent to those skilled in the art.

Claims

1. A characterization system (1) suitable for characterizing an analyte present in a fluid medium, ○ Measuring device (10), ●At least one light source (11) suitable for emitting an optical signal having a predetermined power, ●N Mach-Zehnder interferometers (12) where N > 1 （ｎ） An array of N Mach-Zehnder interferometers (12) each comprising an input divider (13) connected to the light source (11), a sensitive arm (14s) on which a receiver capable of interacting with the analyte by adsorption / desorption is located, a reference arm (14r), two waveguides forming a reference arm, and a multimode output coupler (15) connected to the two waveguides. （ｎ） ) array and ● A measuring device (10) comprising an array of photodetectors (16) suitable for measuring the power of the optical signal transmitted by the multimode coupler (15), ○ a processing unit (3), configured for, with respect to each Mach-Zehnder interferometer (12 （ｎ） ) having a refractive index n in a range from 1 to N, determining, from the measured power, a phase shift Φ （ｎ） (t) between said optical signals circulating in said waveguide, and values Φ （ｎ） respectively associated with a reference phase in the absence of an analyte and a characterization phase when the analyte is present and interacts with a receptor, from said phase shift Φ ｉ（ｎ） and Φ ｆ（ｎ） , and then characterizing said analyte from said values Φ ｉ（ｎ） and Φ ｆ（ｎ） ; and a processing unit (3) suitable for said characterization, comprising: ○Features are, ●Each of the multimode couplers (15) has multiple outputs, and only two of these, which are called useful outputs (15u) with a phase shift of π / 2, are connected to the photodetector (16). ● The photodetector (16) forms an array of 2 × N photodetectors, each of which is a Mach-Zehnder interferometer (12 （ｎ） The power P of the optical signal transmitted by the useful output (15u) of ) １（ｎ） (t) and P ２（ｎ） (t) is measured, ●The processing unit (3) uses the Mach-Zehnder interferometer (12 （ｎ） For each of the above, the input power P of the optical signal incident on the input divider (13) is the predetermined power of the optical signal transmitted by the light source (11). ｉｎ（ｎ） And, in relation to each useful output (15u), the optical power offset o defined when the light source (11) is in a stopped state. １（ｎ） , o ２（ｎ） A predetermined value of a calibration parameter consisting of the following: ●The processing unit (3) measures the optical power P related to the useful output (15u). １（ｎ） (t) and P ２（ｎ） (t), and the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） From a predetermined value, the phase shift Φ （ｎ） A characteristic evaluation system (1) having features suitable for determining (t).

2. The characterization system (1) according to claim 1, wherein each output coupler (15) includes an output (15nu) that is referred to as a "useless" output and has a tapered end, and is not connected to the array of photodetectors (16).

3. N Mach-Zehnder interferometers (12 （ｎ） The above arrangement of ) and the N interferometers (12 （ｎ） Characterization system (1) according to claim 1 or 2, comprising a photonic chip containing an array of 2 × N photodetectors (16, 17) connected to a photodetector, wherein the photodetectors are either photodetectors or diffraction gratings connected to array photodetectors.

4. The measuring device (10) has at least four Mach-Zehnder interferometers (12 （ｎ） The characterization system (1) according to claim 1 or 2, comprising an array of ).

5. The characteristic evaluation system (1) according to claim 1 or 2, wherein each multimode coupler (15) is a 2 x 4 coupler.

6. Using the processing unit (3), the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） The characteristic evaluation system (1) according to claim 1 or 2, comprising a calibration device (20) suitable for determining the aforementioned value.

7. The calibration device (20) is arranged in fluid communication with the measuring device (10) and includes a reservoir for the calibration analyte (21), which allows the calibration analyte to interact with the receptor, and when a predetermined concentration of the calibration analyte interacts with the receptor, the Mach-Zehnder interferometer (12 （ｎ） ) each of the aforementioned phase shift Φ （ｎ） (t) default minimum variation ΔΦ ｍｉｎ A characteristic evaluation system (1) according to claim 6 that induces the following.

8. The characterization system (1) according to claim 6, wherein the calibration device (20) includes a Mach-Zehnder interferometer (22) referred to as a calibration interferometer, which is connected to at least one so-called calibration photodetector (26).

9. The characteristic evaluation system (1) according to claim 8, wherein the calibration interferometer (22) includes a reference arm (24r) and a discontinuous arm (24d).

10. A process for calibrating the characteristic evaluation system (1) described in claim 7, comprising the following steps: ○The process of activating the light source (11) and transmitting the optical signal at the predetermined power, ○ A step of placing the calibration analyte in contact with the receptor, ○The calibration analyte interacts with the receptor and the predetermined minimum value ΔΦ ｍｉｎ The phase shift Φ is at least equal to the above. （ｎ） While inducing fluctuations in (t), the photodetector (16) detects each Mach-Zehnder interferometer (12 （ｎ） The power P of the optical signal transmitted by ) １（ｎ） (t), P ２（ｎ） The process of measuring (t), ○The processing unit (3) then processes the measured power P １（ｎ） (t), P ２（ｎ） (t) from the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） A step of determining the aforementioned value and the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） A calibration process comprising the step of storing the determined value in the processing unit (3).

11. The calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） However, the measured power P １（ｎ） (t), P ２（ｎ） The calibration process according to claim 10, determined from the minimum and maximum values ​​of (t).

12. A process for calibrating the characteristic evaluation system (1) described in claim 8, comprising the following steps: ○The calibration photodetector (26) measures the power of the optical signal transmitted by the calibration interferometer (22) while the light source (11) is in operation, ○ The input power P of the optical signal incident on the input divider (23) of the calibration interferometer (22) ｉｎ，ｃａｌｉｂ The process of determining the value, and then, ○Determined value P ｉｎ，ｃａｌｉｂ From the measuring device (10), the interferometer (12 （ｎ） For each of the above, input value P ｊｎ（ｎ） A process for calibration, including the process of determining [something].

13. The following steps: ○While the light source (11) is in a stopped state, the photodetector (16) of the measuring device (10) detects each interferometer (12) of the measuring device (10). （ｎ） The power P of the optical signal transmitted by ) １（ｎ） (t), P ２（ｎ） The process of measuring (t), and then, ○The measured power P １（ｎ） (t), P ２（ｎ） (t) Offset value o １（ｎ） and o ２（ｎ） The calibration process according to claim 12, comprising the step of determining a.

14. A process for characterizing an analyte using the characterization system (1) described in claim 1 or 2, comprising the following steps: ○The photodetector (16) of the measuring device (10) measures each Mach-Zehnder interferometer (12) between the reference phase in which the analyte is absent and the characterization phase in which the analyte is present and interacts with the receptor. （ｎ） The power P of the optical signal transmitted by ) １（ｎ） (t), P ２（ｎ） The process of measuring (t), ○The processing unit (3) processes each Mach-Zehnder interferometer (12 ｎ） In contrast, the measured power P １（ｎ） (t), P ２（ｎ） (t) and the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） The phase shift Φ between the optical signals circulating within the arm, from the predetermined value of the above. （ｎ） The process of determining (t), ○The phase shift Φ related to the reference phase and the characteristic evaluation phase, respectively. （ｎ） (t) gives the value Φ ｉ（ｎ） and Φ ｆ（ｎ） The process of determining, ○The aforementioned value Φ ｉ（ｎ） and Φ ｆ（ｎ） A process for characterization, comprising the step of characterizing the analyte from the said analyte.

15. The phase shift Φ ｎ The step of determining (t) is ○The extracted phase shift is referred to as the measured power P １（ｎ） (t), P ２（ｎ） (t), and the calibration parameter P ｉｎ（ｎ） , o １（ｎ） , and o ２（ｎ） From the predetermined value, the phase shift Φ whose value is between 0 and 2π （ｎ） (t) and then, ○This is referred to as the expanded phase shift, and the extracted phase shift Φ （ｎ） The phase shift Φ obtained by expanding (t) and adding a positive or negative integer multiple of 2π to it. （ｎ） The characteristic evaluation process according to claim 14, comprising determining (t) and .

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