Apparatus for detecting an analyte by photoacoustic detection

Abstract

A photoacoustic detection device (1) intended to be applied to a medium to be analyzed through a contact face (3), the device comprising: - a hollow cavity (20) comprising a first opening (22) arranged in the contact face, the cavity being delimited by a containment casing (21) extending around the first opening, the containment casing comprising a transversal wall (231) and lateral walls (232) extending between the transversal wall and the contact face; - a pulsed or amplitude-modulated light source (10) configured to emit incident light waves (11) in an emission spectral band (Δλ) through the cavity (20) up to the first opening; - an acoustic transducer (28) connected to the cavity and configured to detect photoacoustic waves (12) extending through the cavity. The photoacoustic detection device is optimized to increase the amplitude of the photoacoustic waves detected by the acoustic transducer.

Description

Technical Field

[0001] The technical field of this invention is the detection and analysis of analytes based on the photoacoustic detection principle. Background Technology

[0002] Photoacoustic detection is based on detecting sound waves generated by the absorption of pulsed or amplitude-modulated electromagnetic incident waves by the analyzed medium. Sound waves are formed after absorbing molecules present in the analyzed medium are heated, resulting in the absorption of the incident wave. Heating causes regulated thermal expansion of the medium, which is the origin of the sound waves.

[0003] By tuning the wavelength of the incident electromagnetic wave to the absorption wavelength of the analyte, photoacoustic detection can be specialized for specific analytes. Therefore, photoacoustic detection has been applied to detect gaseous species in gases or to detect the presence of specific molecules in biological tissues. The incident wave wavelength is often in the infrared range.

[0004] Then, photoacoustic detection constitutes a non-invasive analytical technique that can be implemented in diffuse or opaque media.

[0005] The application of photoacoustic detection to biological tissues is described, for example, in the following disclosures:

[0006] -Bauer AJ. "IR-spectroscopy for skin in vivo: Optimal skin sites and properties for non-invasive glucose measurement by photoacoustic and photothermal spectroscopy"; Journal of biopohtonics 11 (2018);

[0007] - "Windowless ultrasound photoacoustic cell for in-vivo mid-IRspectroscopy of human epidermis: Low interference by changes of air pressure, temperature, and humidity caused by skin contact opens the possibility for anon-invasive monitoring of glucose in the interstitial fluid", Rev.Sci.Instrum.84,084901(2013).

[0008] In these disclosures, pulsed laser light sources activated at frequencies ranging from tens of Hz to tens of kHz are used. The aim is to estimate the glucose concentration in bodily fluids at a depth of 10 μm to 50 μm below the user's skin. For this purpose, a photoacoustic detection device positioned against the user's skin is used.

[0009] The inventors sought to improve existing equipment to address greater depths and increase the amplitude of detected sound waves. Summary of the Invention

[0010] The first subject of this invention is a photoacoustic detection device designed to apply a contact surface to a medium to be analyzed, the device comprising:

[0011] - A hollow cavity leading to a first opening, the first opening being disposed in the contact surface;

[0012] - A pulsed or amplitude-modulated light source, configured to emit incident light waves in the emission spectrum that pass through the cavity until the first opening;

[0013] - An acoustic transducer, which is connected to the cavity and configured to detect photoacoustic waves extending through the cavity.

[0014] This allows the acoustic transducer to detect sound waves generated by heating the medium under the effect of illumination of the medium by incident light waves.

[0015] The device may include any of the following features individually or in combination, depending on the technology.

[0016] - The light source is a laser source.

[0017] - The volume of the cavity is less than 50 μL or 30 μL. The volume of the cavity can be from 5 μL to 30 μL.

[0018] - The device includes an open tube extending in length from 1 to 20 mm between the cavity and the air located outside the cavity, the diameter of which is as follows:

[0019] • When the volume of the cavity is less than or equal to 15 μL, the diameter of the tube is 150 μm to 300 μm;

[0020] • When the volume of the cavity is 15 μL to 30 μL, the diameter of the tube is 200 μm to 350 μm;

[0021] • When the volume of the cavity is greater than 30 μL, the diameter of the tube is 250 μm to 500 μm.

[0022] - The cavity is defined by a transverse wall and a lateral wall, with the lateral wall extending between the transverse wall and the contact surface.

[0023] - The pipe extends through the transverse wall or through the lateral wall.

[0024] - The device includes an acoustic channel extending between the acoustic transducer and the cavity.

[0025] - The device includes an optical component configured to guide incident light waves emitted by a light source toward a first opening, the optical component being a reflector.

[0026] - The light source is a laser source, and the device may include a support extending from the contact surface to the light source, the support being configured to conduct heat emitted by the analyzed medium to the light source.

[0027] The device includes a support extending from the contact surface to the light source, the support being configured to conduct heat emitted by the analyzed medium to the light source. The support comprises a thermally conductive metal, such as copper or aluminum.

[0028] - The volume of the cavity is less than 20 μL.

[0029] The second subject of this invention is a method for estimating the concentration of an analyte in a medium, the method comprising the following steps:

[0030] a) Apply the device according to the first subject of the invention to the medium such that the contact surface is held against the medium;

[0031] b) Activate the light source, which emits a pulsed or amplitude-modulated incident light wave at a wavelength corresponding to the absorption wavelength of the analyte, according to the activation or modulation frequency.

[0032] c) Detect the sound waves emitted by the medium under the effect of the incident light wave based on the sound frequency, which is equal to the activation frequency of the light source;

[0033] d) Measure the amplitude of the sound wave;

[0034] e) Based on the amplitude measured during step d), detect the analyte and / or estimate the concentration of the analyte in the medium.

[0035] The invention will be better understood by referring to the accompanying drawings and the description of the illustrated embodiments below. Attached Figure Description

[0036] Figure 1A and 1B Two embodiments of the device according to the invention are shown.

[0037] Figure 2A The cavity that has been modeled is shown.

[0038] Figure 2B schematically shown Figure 2A The equivalent circuit of the cavity modeled in the model.

[0039] Figure 3A The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the relative changes in the amplitude of the sound waves in the cavity described in the paper.

[0040] Figure 3B The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the normalized average amplitude of the sound waves in the cavity described in the paper.

[0041] Figure 3C Showing separate considerations Figure 2A The diagram is schematically shown and is composed of Figure 2B The schematic diagram illustrates different configurations of the cavity opening tube in the circuit model, such as in Figure 2A The amplitude (vertical axis) of the sound waves in the cavity described herein varies according to the frequency (horizontal axis).

[0042] exist Figure 3A , 3B In 3C, the cavity volume is equal to 5 μL.

[0043] Figure 4A The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the relative changes in the amplitude of the sound waves in the cavity described in the paper.

[0044] Figure 4B The following diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening tube. Figure 2A The modeling results of the normalized average amplitude of the sound waves in the cavity described in the paper.

[0045] Figure 4C Showing separate considerations Figure 2A The diagram is schematically shown and is composed of Figure 2B The schematic diagram illustrates different configurations of the cavity opening tube in the circuit model, such as in Figure 2A The amplitude (vertical axis) of the sound waves in the cavity described herein varies according to the frequency (horizontal axis).

[0046] exist Figure 4A , 4B In 4C, the cavity volume is equal to 10 μL.

[0047] Figure 5A The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2AThe modeling results of the relative changes in the amplitude of the sound waves in the cavity described in the paper.

[0048] Figure 5B The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the normalized average amplitude of the sound waves in the cavity described in the paper.

[0049] Figure 5C Showing separate considerations Figure 2A The diagram is schematically shown and is composed of Figure 2B The schematic diagram illustrates different configurations of the cavity opening tube in the circuit model, such as in Figure 2A The amplitude (vertical axis) of the sound waves in the cavity described herein varies according to the frequency (horizontal axis).

[0050] exist Figure 5A , 5B In 5C, the cavity volume is equal to 20 μL.

[0051] Figure 6A The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the relative changes in the amplitude of the sound waves in the cavity described in the paper.

[0052] Figure 6B The diagram shows the spectral bands from 100 Hz to 1 kHz based on the length (horizontal axis - mm) and diameter (vertical axis - μm) of the cavity opening. Figure 2A The modeling results of the normalized average amplitude of the sound waves in the cavity described in the paper.

[0053] Figure 6C and 6D Showing separate considerations Figure 2A The diagram is schematically shown and is composed of Figure 2B The schematic diagram illustrates different configurations of the cavity opening tube in the circuit model, such as in Figure 2A The amplitude (vertical axis) of the sound waves in the cavity described herein varies according to the frequency (horizontal axis).

[0054] exist Figure 6A , 6B In 6C and 6D, the cavity volume is equal to 50 μL.

[0055] Figure 7A , 7B 7C, 7D, 7E, 7F, 7G, and 7H are respectively similar to Figure 3A , 3B 4A, 4B, 5A, 5B, 6A, and 6B, which cover a larger range of tube lengths from 0mm to 20mm.

[0056] Figure 7I Showing separate considerations Figure 2A The diagram is schematically shown and is composed of Figure 2B The schematic diagram illustrates different configurations of the cavity opening tube in the circuit model, with a volume of 50 μL, as shown in... Figure 2A The amplitude (vertical axis) of the sound waves in the cavity described herein varies according to the frequency (horizontal axis). Figure 7I The tube has a height of 19 mm and a cavity volume of 50 μL. Detailed Implementation

[0057] exist Figure 1A The diagram schematically illustrates a device 1 that allows for the implementation of the invention. Device 1 is configured to be applied to a medium 2 to be analyzed. The device includes a contact surface 3 intended for application to the medium. The contact surface is designed to conform to the medium intended to be placed thereon. The contact surface is, for example, flat. In this example, the medium 2 is the user's skin. The device includes a light source 10 configured to emit light waves 11 that propagate to the medium 2 to be analyzed. The light source 10 is pulsed or amplitude modulated. The light waves 11 are absorbed at wavelengths λ including the analyte 4 present in the medium. a It emits in the emission band Δλ. The purpose of device 1 is to detect the presence of analyte 4 and, if possible, estimate its concentration.

[0058] Analyte 4 can be a molecule present in bodily fluids. It may, for example, involve glucose, or bodily analytes of the type such as cholesterol, triglycerides, urea, albumin, alcohols (e.g., ethanol), or tetrahydrocannabinol.

[0059] The emission band is preferably extended in visible or infrared light, for example, at wavelengths from 3 μm to 15 μm. Preferably, the emission band Δλ is narrow enough that device 1 is dedicated to a single analyte. For example, the width of the emission band is approximately 0.1 μm. When the analyte is glucose, the emission band is concentrated at the absorption wavelength of glucose, for example, corresponding to 1034 cm⁻¹. -1 The wavenumber. The light source 10 can be, in particular, a pulsed laser source, such as a wavelength-tunable quantum cascade laser (QCL). The emission band Δλ is located in the infrared.

[0060] According to other embodiments, the light source can be a wire-type source or a light-emitting diode. According to these embodiments, the light source is preferably associated with a bandpass filter to define an emission band that is sufficiently narrow and focused on the absorption wavelength in question. However, using a laser source is preferred.

[0061] exist Figure 1A In the embodiment shown, device 1 includes an optical component 15 configured to deflect light waves 11 emitted by a light source toward the medium 2 to be analyzed.

[0062] Apparatus 1 is intended to be applied to a medium 2 to be analyzed. The apparatus includes a constraint cover 21 arranged to contact the medium and define a cavity 20. The cavity 20 opens to a first opening 22 disposed in the contact surface 3 to access the medium 2. Incident light waves 11, after being reflected by optical components 15, propagate through the cavity 20 and through the first opening 22 to the medium 2. The apparatus includes a transparent window 17 configured to transmit the incident light waves 11.

[0063] exist Figure 1A In the device shown, the optical component 15 is a reflector, which takes the form of a reflecting prism. The optical component is connected to the device's cover 31 via a support 15'. In other embodiments, the optical component 15 may be a curved optical fiber such that the incident light wave 11 reaches the medium 2 with orthogonal or approximately orthogonal incidence. "Approximately orthogonal" means orthogonal considering an angular error of ±30°.

[0064] Based on the effect of the presence of analyte 4 in medium 2, a photoacoustic wave 12 is formed. The photoacoustic wave 12 is an acoustic wave formed by the periodic heating of the medium by a pulsed or amplitude-modulated incident light wave 11. A portion of the photoacoustic wave 12 extends through cavity 20 to be detected by acoustic transducer 28. Acoustic transducer 28 is connected to cavity 20 via acoustic channel 25. The acoustic transducer may be a microphone with a detection spectrum range that includes the frequencies of the photoacoustic wave.

[0065] As mentioned in Kottmann's publication "Mid-infrared photoacoustic detection of glucose inhuma skin: towards non-invasive diagnostics", Sensors 2016, 16, 1663 (hereinafter referred to as "Kottmann 2016"), a relationship can be established between the amplitude A of the photoacoustic wave at frequency f and the volume V of cavity 20, such that:

[0066]

[0067] in:

[0068] -∝ is the proportional operator;

[0069] -I 10 (λ) is the intensity of the incident light wave at wavelength λ;

[0070] -α(λ) is the absorption coefficient of the analyzed medium at wavelength λ;

[0071] -V is the volume of the cavity, which may include the acoustic passage;

[0072] -f represents the frequency of the sound wave.

[0073] When the intensity I of the light wave 10 When α(λ) and frequency f are fixed, the amplitude A of the photoacoustic wave detected by the acoustic transducer is proportional to the absorption coefficient α(λ) of the medium. This absorption coefficient is considered to be proportional to the concentration of the analyte in the medium. Therefore, the measurement of amplitude A by the acoustic transducer 28 allows the estimation of the concentration of the analyte in the medium by estimating the absorption coefficient α(λ).

[0074] Expression (1) assumes the following thickness of medium 2:

[0075] L>>μ a (λ)>μ s (λ) (2)

[0076] in:

[0077] -μ a (λ) is the optical penetration depth, μ a (λ) makes:

[0078]

[0079] -μ s (λ) is the thermal diffusion length, such that:

[0080]

[0081] In expression (4), D is the thermal diffusivity, such that:

[0082]

[0083] in:

[0084] -ρ is the density of the medium;

[0085] -C is the heat capacity of the medium;

[0086] -k is the thermal conductivity of the medium.

[0087] It should be noted that μ a (λ) does not depend on the frequency f, while μ s (λ) then changes according to the reciprocal of the square root of the frequency f. In "Kottman 2016", it was determined that when the medium is biological tissue (e.g., skin), the condition L >> μ is met as long as the frequency is above 50 Hz. a (λ)>μ s (λ).

[0088] Expression (1) shows that using a low frequency allows for an increase in the amplitude of the photoacoustic wave 12. Furthermore, the inventors considered that when the medium 2 is biological tissue, it is advantageous for the frequency of the photoacoustic wave to be below 1 kHz, preferably below 500 Hz. The frequency is advantageously between 50 Hz and 500 Hz.

[0089] According to expression (4), it can be concluded that decreasing the frequency f also allows for an increase in the thermal diffusion length μ. s (λ). This allows for further querying of the medium at a deeper level.

[0090] When analyte 4 is glucose or other nutrients transported by the blood, the increased depth at which its concentration is determined constitutes an advantage. In practice, photoacoustic detection does not allow for large depths, such as several millimeters. Capillaries extend to these depths. The glucose concentration estimated by photoacoustic detection is determined indirectly by estimating the glucose concentration in the interstitial fluid extending between the capillaries and epidermal cells. The determined glucose concentration in the interstitial fluid corresponds to the glucose concentration in the blood, with a time difference of approximately 20 minutes. By increasing the depth at which the analyte 2 is examined, the time difference between the glucose concentration in the blood and the concentration estimated using expression (1) is reduced.

[0091] According to expression (1), the volume of cavity 20 must be small to increase the amplitude of the photoacoustic wave. However, the smaller the volume of the cavity, the higher the frequency f.

[0092] Considering expression (1), a compromise is needed to reduce the volume while controlling the frequency f, with the aim of increasing the photoacoustic amplitude to improve the sensitivity of the method.

[0093] The inventors have achieved a satisfactory compromise by designing a cavity 20 with a small volume of 1 to 50 μL, preferably 5 to 30 μL. The constraint cover 21 includes a solid inner wall 23 defining the cavity 20. The inner wall includes:

[0094] - Lateral member 231, which preferably extends parallel to the axis Z orthogonal to the contact surface 3;

[0095] - A transverse member 232 extends parallel to or substantially parallel to the contact surface 3. The transverse member 232 extends parallel to or substantially parallel to the first opening 22. Figure 1A and 1B In the embodiment shown, the lateral member 232 includes a window 17.

[0096] "Approximately parallel" means parallel, while allowing for an angular tolerance of ±30° or ±20°. The lateral member 231 extends between the contact surface 3 and the transverse member 232.

[0097] The device includes a tube 26 extending from a cavity 20 and opening to air outside the cavity 20. The tube 26 forms an opening through which the cavity 20 contacts air at atmospheric pressure outside the cavity. The tube 26 extends with a length l and a cross-section of diameter Φ. Figure 1A In the middle, pipe 26 extends through transverse member 232 of the inner wall. Figure 1B In the middle, the tube 26 extends through the lateral member 231 of the inner wall.

[0098] exist Figure 1A In the configuration shown, the tube 26 leads to a space 30 defined by a cover 31. The cover 31 includes at least one hole 32 allowing communication with air 5 outside the device 1. Figure 1B In the configuration shown, pipe 26 is directly connected to the air outside the device 1. Thus, pipe 26 is directly or indirectly connected to the external air 5.

[0099] A key element of this invention is the inventor's observation that the spectral response of cavity 20 changes by altering the geometry of tube 26. The inventor's objective is to obtain a spectral response that is as uniform as possible between 100 Hz and 1000 Hz. "Spectral response" refers to the amplitude of the sound pressure level in the cavity according to frequency.

[0100] The inventors considered the following: Figure 2A The cavity shown. Figure 2A The dimensions l, ε, and h are shown to be 2.6 mm, 1.2 mm, and 1.5 mm, respectively.

[0101] It is known that such cavities can be modeled using equivalent electrical models. As described in the publication by Dehé A. et al., “The Infineon Silicon MEMS microphone,” AMA conferences 2013-Sensor 2013, Opto 2013, this allows for the simulation of pressure within the cavity in the presence of sound wave effects.

[0102] exist Figure 2B It shows Figure 2A The equivalent electrical model of the cavity is shown. It is modeled using an amplitude-modulated current source I0 at the excitation frequency, induced by the excitation sound wave. The cavity response, i.e., the amplitude of the sound wave within the cavity, corresponds to an amplitude-modulated voltage U at the excitation frequency.

[0103] According to the following expression, if P0 is the pressure of the acoustic wave in the cavity, the intensity I0 depends on the power of the laser:

[0104]

[0105] Where γ is the adiabatic coefficient of air, P laser That is the power of the laser.

[0106] μs It is the thermal diffusion length described in conjunction with expression (4);

[0107] α is the absorption coefficient per unit length.

[0108] The cavity effect is modeled by the capacitance C2, therefore:

[0109]

[0110] Where V is the volume of cavity 20, which may include acoustic channel 25.

[0111] The effect of tube 26 is modeled by capacitor C1 connected in parallel with capacitor C2 and inductor L1 connected in series with resistor R1. Therefore,

[0112]

[0113] Where l and S correspond to the length and cross-sectional area of ​​tube 26, respectively.

[0114]

[0115] Where ρ0 corresponds to the volume density of air.

[0116]

[0117] Here, μ corresponds to the viscosity of air.

[0118] The inventor used Figure 2B The model shown schematically considers 10 2 Hz to 10 4 A laser modulation frequency of Hz and a laser power P equal to 1mW. laser The inventors estimated the amplitude of the voltage U modulated to the modulation frequency of the laser. This amplitude is considered to characterize the pressure in the cavity. Calculations of the voltage U considering different excitation frequencies allow for the determination of the spectral response of cavity 20.

[0119] The inventors subsequently considered four different cavity volumes of 5 μL, 10 μL, 20 μL, and 50 μL. For each volume, the inventors investigated the effects of variations in the tube diameter and length on the cavity's spectral response. The performance of each modeled construct was examined while taking into account the following:

[0120] - The relative change in pressure ΔP0 in the spectral band from 100 Hz to 1 kHz: It corresponds to the following expression:

[0121]

[0122] Among them, P 0,max P 0,min and These represent the maximum, minimum, and average pressures within the 100Hz to 1kHz spectral band. The aim is to obtain the smallest possible relative pressure variation.

[0123] - The average pressure normalized by using the average pressure obtained through a closed cavity (i.e., without tube 26). The normalized average pressure is denoted as... It is as follows:

[0124]

[0125] in, and These are the average pressure in a modeled cavity within the 100Hz to 1kHz spectral band, and the average pressure in a closed cavity with the same dimensions within the same spectral band. The normalized average pressure represents the intensity of the detected signal and corresponds to an index regarding measurement sensitivity. Preferably, this normalized average pressure is as high as possible.

[0126] To determine ΔP0 and The inventors modeled such a combination Figure 2A The cavity described. The inventors considered different volumes, and for each volume, different dimensions of the tube: particularly a diameter varying between 50 μm and 500 μm, and a length varying between 1 mm and 10 mm. The inventors, based on the combination... Figure 2B The electrical model described above models the cavity. The inventors estimated the voltage U characterizing the pressure P0 for different frequencies from 100 Hz to 10 kHz. Based on these modelings, the inventors estimated the quantity ΔP0 and the quantity described in expressions (11) and (12). These quantities are considered performance indicators.

[0127] Figure 3A and 3B The relative pressure variation ΔP0 and normalized average pressure based on the length (horizontal axis - in mm) and diameter (vertical axis - in μm) of tube 26 are shown respectively. The cavity volume is 5 μL. In each figure, the numerical values ​​of the quantities considered correspond to grayscale. Figure 3C The modeled spectral response is shown for different tube diameters of 110 μm, 220 μm, and 440 μm, considering a cavity volume of 5 μL with a tube length of 10 mm. The results show that optimal performance (low ΔP0 value and high...) is obtained when the tube length is greater than 3 mm or 5 mm and the tube diameter is between 150 μm and 300 μm. value)

[0128] Figure 3CAnalysis shows that when the tube diameter is small (110 μm), the spectral response is close to that of a closed cavity. When the diameter increases to 220 μm, the spectral response can be considered relatively "flat," i.e., uniform across the 100 Hz to 1000 Hz band, which corresponds to the desired outcome. The pressure P0 is high enough for easy measurement. When the diameter increases further (360 μm), the cavity's spectral response approaches that of a resonant cavity, exhibiting a resonance peak. The pressure P0 decreases, making it more difficult to measure.

[0129] Figure 4A , 4B Similar to 4C Figure 3A , 3B And 3C, they are considered to have a cavity volume equal to 10 μL. In Figure 4C In this study, the diameters of the tubes considered were 120 μm, 240 μm, and 360 μm, with a length of 9.4 mm. It was deduced that optimal performance (low ΔP0 value and high...) was achieved when the tube length was greater than 3 mm or 5 mm and the tube diameter was between 150 μm and 300 μm. value).

[0130] Figure 5A , 5B And 5C are similar to Figure 3A , 3B And 3C, they are considered to have a cavity volume equal to 20 μL. In Figure 5C In this study, the diameters of the tubes considered were 140 μm, 280 μm, and 560 μm, with a length of 9.6 mm. It was deduced that optimal performance (low ΔP0 value and high...) was achieved when the tube length was greater than 2 mm or 5 mm and the diameter was between 200 μm and 350 μm. value).

[0131] Figure 6A , 6B And 6C are similar to Figure 3A , 3B And 3C, they are considered to have a cavity volume equal to 50 μL. In Figure 6C In this study, the diameters of the tubes considered were 170μm, 340μm, and 680μm, and the length was 9.4mm. Figure 6D The modeled spectral response is shown for different tube diameters of 160 μm, 320 μm and 640 μm, respectively, with a tube length of 5 mm and a cavity volume of 50 μL.

[0132] Depend on Figures 6A to 6D It was deduced that optimal performance (low ΔP0 value and high efficiency) is obtained when the tube length is greater than 1 mm or 5 mm and the tube diameter is between 250 μm and 500 μm. value).

[0133] Figure 7A ,7B 7C, 7D, 7E, 7F, 7G, and 7H are respectively similar to Figure 3A , 3B Figures 4A, 4B, 5A, 5B, 6A, and 6B represent a larger range of pipe lengths varying from 0 mm to 20 mm in diameter. These figures illustrate that the pipe diameter ranges defined above apply at least to pipe lengths up to 20 mm. Figure 7I The modeled spectral response is shown for different tube diameters of 200 μm, 400 μm, and 800 μm, respectively, considering a cavity volume of 50 μL with a tube length of 19 mm. (Combined with...) Figure 6C and 6D Similarly, it was observed that optimal performance (low ΔP0 value and high efficiency) was obtained when the tube length reached 19 mm and the tube diameter was between 250 μm and 500 μm. value).

[0134] Generally, regardless of the volume considered, when the tube diameter is small, the spectral response approximates that of a closed cavity. When the tube diameter is large, the spectral response of the cavity approximates that of a resonant cavity, exhibiting a resonance peak. The aforementioned length and diameter ranges correspond to relatively flat spectral responses characterizing the closed cavity and resonant cavity.

[0135] Based on the implemented modeling, the inventors determined the optimal dimensions of the tube for different cavity volume ranges:

[0136] - When the volume of the cavity is less than or equal to 15 μL, the diameter of the tube can be from 150 μm to 300 μm;

[0137] - When the volume of the cavity is 15 μL to 30 μL, the diameter of the tube can be 200 μm to 350 μm;

[0138] - When the volume of the cavity is greater than 30 μL, the diameter of the tube can be from 250 μm to 500 μm.

[0139] Regardless of volume, the length of the tube is preferably greater than 1 mm or 3 mm. The length of the tube is preferably less than 20 mm.

[0140] exist Figure 1A and 1B In the illustrated embodiment, the light source 10 is a QCL-type laser source formed on a substrate. For design simplicity, it is preferable that the light waves emitted by the light source extend parallel to the plane of the substrate on which the light source is formed. The device includes an optical component 15 for guiding all or part of the incident light wave 11 toward the first opening 22. The optical component may be a reflector or an optical fiber.

[0141] The optimal operating temperature for QCL-type laser sources is generally between 30°C and 40°C. When the device is applied to the skin of a living user, the user's body temperature can serve as a heat source for the QCL laser source. The device includes a support 16 on which the laser source 10 is disposed. The support 16 is configured to contact the user's skin. The support is made of a material with good thermal conductivity (e.g., metal, especially copper or aluminum). The support 16 extends between the contact surface 3 and the light source 10. The thickness of the support 16 along the Z-axis is, for example, 1 mm to 10 mm. The support 16 thus acts as a thermal buffer between the user's skin and the light source.

[0142] The present invention can be implemented to detect the presence of an analyte in a medium, which may be a user's skin. To this end, the following steps are performed:

[0143] - To apply the device to the medium such that the contact surface remains against the medium;

[0144] - Activate the light source according to the activation frequency or modulation frequency;

[0145] - Detect photoacoustic waves emitted by the medium under the effect of incident light waves, based on the audio frequency equal to the activation or modulation frequency of the light source.

[0146] -Measure the amplitude of the sound wave, which is equivalent to estimating the amplitude A as described in the combined expression (1);

[0147] - Based on the measured amplitude, the presence of the analyte is detected and / or the concentration of the analyte in the medium is estimated. This step is carried out by estimating the absorption α as described in expression (1), where the relationship between the analyte concentration and absorption is known.

Claims

1. A photoacoustic detection device (1) intended to be applied to a medium to be analyzed through a contact face (3), the device comprising: - a hollow cavity (20) opening onto a first opening (22) provided in the contact face; - a pulsed or amplitude-modulated light source (10) configured to emit an incident light wave (11) in an emission spectral band (Δλ) through the cavity (20) up to the first opening; - an acoustic transducer (28) connected to the cavity and configured to detect a photoacoustic wave (12) extending through the cavity, so that, under the effect of the illumination of the medium by the incident light wave, the acoustic transducer detects an acoustic wave resulting from the heating of the medium (2); the device being characterized in that: - the volume of the cavity (20) is less than 50 μL; - the device comprises an open tube (26) extending between the cavity (20) and the air outside the cavity according to a length of 1 to 20 mm, the diameter of the tube being as follows: • from 150 μm to 300 μm when the volume of the cavity is less than or equal to 15 μL; • from 200 μm to 350 μm when the volume of the cavity is from 15 μL to 30 μL; • from 250 μm to 500 μm when the volume of the cavity is greater than 30 μL.

2. The device according to claim 1, wherein: - the cavity is delimited by a transverse wall (231) and by a lateral wall (232) extending between the transverse wall and the contact face; - the tube extends through the transverse wall or through the lateral wall.

3. The device according to claim 1, comprising an acoustic channel (25) extending between the acoustic transducer (28) and the cavity (20).

4. The device according to claim 1, comprising optical means (15) configured to direct the incident light wave (11) emitted by the light source (10) towards the first opening (22).

5. The apparatus of claim 4, wherein, The optical means are reflectors.

6. The apparatus of claim 4, wherein, The light source is a laser source.

7. The apparatus of claim 6, wherein, The light source is a laser source, the device comprising a support (16) extending from the contact face (3) up to the light source (10), the support being configured to conduct the heat emitted by the analyzed medium towards the light source.

8. The apparatus of claim 7, wherein, The support comprises a heat-conducting metal.

9. The apparatus of claim 1, wherein, The volume of the cavity is less than 20 μL.

10. The apparatus of claim 8, wherein, The heat-conducting metal is copper or aluminum.

11. A method for estimating the concentration of an analyte in a medium, the method comprising the following steps: a) applying the device (1) according to claim 1 to the medium (2) so that the contact face (3) is held against the medium; b) activating the light source (10) which emits pulsed or amplitude-modulated incident light waves according to an activation or modulation frequency in a wavelength corresponding to the absorption wavelength of the analyte; c) detecting, according to an acoustic frequency equal to the activation or modulation frequency of the light source, an acoustic wave (12) emitted by the medium under the effect of the incident light wave; d) measuring the amplitude of the acoustic wave; e) detecting the presence of the analyte and / or estimating the concentration of the analyte in the medium on the basis of the amplitude measured during step d).

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