Photoacoustic detection device having a protective film

Abstract

To provide a photoacoustic detection device including a transducer, configured to solve the following problem: water vapor emanating from the skin may condense and form droplets, which may damage the transducer, moreover, dust or other undesirable elements may accumulate in the device.SOLUTION: A photoacoustic detection device includes: a pulsed or amplitude-modulated light source 10 configured to emit an incident light beam toward a medium 2 to be analyzed trough a contact surface 3, through a cavity 20, to a contact aperture; an acoustic transducer 28 connected to the cavity, and configured to detect a photoacoustic wave 12 extending through the cavity. Under the effect of an illumination of the medium by the incident light beam, the acoustic transducer detects an acoustic wave produced by heating of the medium 2. The cavity comprises a membrane extending through the cavity, facing the contact face. The membrane is bounded by a lower face and an upper face. The membrane comprises through-apertures produced between the lower face and the upper face 2.SELECTED DRAWING: Figure 1A

Description

Technical Field

[0001] The technical field of the present invention is the detection of analytes by photoacoustic detection.

Background Art

[0002] Photoacoustic detection is based on the detection of acoustic waves generated by the effect of absorption of an incident electromagnetic wave, which is pulse-modulated or amplitude-modulated, by a medium to be analyzed. The acoustic waves are formed following the heating of molecules of interest present in the analyzed medium by the effect of absorption of the incident wave. The heating results in a modulated thermal expansion of the medium, and the expansion generates acoustic waves.

[0003] Photoacoustic detection can be made specific to one particular analyte by adjusting the wavelength of the incident electromagnetic wave to the absorption wavelength of the analyte. Photoacoustic detection has been applied to the detection of gas species in gases and the detection of the presence of specific molecules in biological tissues. The wavelength of the incident wave is often in the infrared.

[0004] Photoacoustic detection is a non-invasive analytical technique and can be applied to scattering media and opaque media.

[0005] The application of photoacoustic detection to biological tissues is described in the following publications.

Prior Art Documents

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] In these publications, an aptitude-modulated laser light source activated at a frequency between several tens of Hz and several tens of kHz is used. It aims to estimate the glucose concentration in the interstitial bodily fluid at a depth of 10 μm to 100 μm under the user's skin surface. To do this, a photoacoustic detection device is placed and used against the user's skin.

[0008] The photoacoustic detection device includes a transducer configured to detect an acoustical wave amplitude-modulated by the effect of periodic heating induced by a modulated light wave. More specifically, the photoacoustic detection device is configured to detect a periodic pressure modulation at a period corresponding to the modulation frequency of the light wave. The response function of the photoacoustic device can be calibrated to establish the correlation between the measured pressure modulation and the amount of analyte present in the analysis medium.

[0009] Sweating may make it difficult for water vapor to be released from the skin. The water vapor may condense to form droplets, which may damage the transducer. Further, during use of the device, dust or other undesirable elements, such as skin fragments, may accumulate within the device. The object of the present invention is to solve this problem.

Means for Solving the Problem

[0010] A first problem of the present invention is a photoacoustic detection device applied to a medium to be analyzed through a contact surface, - a hollow cavity communicating with a contact opening formed in the contact surface; - a light source modulated in pulse or amplitude, which is configured to emit an incident light beam in a radiation spectral band through the cavity to the contact opening when activated; - an acoustic transducer connected to the cavity and configured to detect an acoustic wave propagating through the cavity; comprising the acoustic transducer detects an acoustic wave generated by heating of the medium by the effect of illumination of the medium by the incident light beam; the device - the cavity faces the contact surface and includes a film extending through the cavity; - the film is surrounded by a lower surface and an upper surface and includes a through hole formed between the lower surface and the upper surface, characterized in that.

[0011] The through hole means a hole that allows air to pass through the hole between the lower surface and the upper surface of the film.

[0012] The device may include any of the following-described features alone or in a technically achievable combination. - The radius of each through hole is 5 μm to 25 μm. - The membrane defines an aperture ratio corresponding to the ratio of the cumulative area of each through-hole to the total area of the lower surface or the upper surface of the membrane, and the aperture ratio is, for example, 0.05 to 0.3. - The thickness of the membrane is 100 μm to 1 mm.

[0013] - The membrane is within the cavity at a non-zero distance from the contact surface.

[0014] Preferably: - The membrane is arranged such that when the light source is activated, the incident light beam passes through the membrane before reaching the contact opening; - The membrane includes an intersection segment corresponding to the portion of the membrane through which the light beam passes; - At least in the intersection segment, the membrane is made of a transparent material having a transmittance higher than 0.4, preferably higher than 0.8, in the emission spectral band.

[0015] The membrane may not be open in the intersection segment. Not being open means having no through-holes.

[0016] The transparent material may be made of at least one material selected from Si, Ge, AlN, ZnSe, BaF2, CaF2, KBr, ZnS, and sapphire.

[0017] At least in the intersection segment, the upper surface of the membrane may be provided with an anti-reflection coating.

[0018] The anti-reflection coating may be applied to the entire upper surface, and optionally, may be applied to the entire or a part of the lower surface.

[0019] According to one possibility, the membrane is monolithic. The membrane is manufactured from a single material (excluding any hydrophobic coating or anti-reflection coating).

[0020] As one possibility, the membrane is - A first material outside the intersection segment; - An auxiliary material that forms the transparent material in the intersection segment, Consisting of.

[0021] The film may particularly have a hydrophobic coating on the lower surface.

[0022] According to one embodiment, - The cavity is surrounded by a transverse wall and side walls, and the side walls extend between the transverse wall and the contact surface; - The film extends between two opposing surfaces of the side walls.

[0023] The transverse wall may be parallel to the contact surface.

[0024] According to one embodiment, the film is removably disposed within the cavity.

[0025] The light source may be a laser light source.

[0026] The volume of the cavity may be less than 50 μL.

[0027] The present invention will be better understood by reading the description of the examples of the embodiments presented in the following part with reference to the figures listed below.

Brief Description of the Drawings

[0028]

Figure 1A

Figure 1B

Figure 1C

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 4C

Figure 5A

Figure 5B

[0029] Figure 1A schematically shows an apparatus 1 that enables the implementation of the present invention. The apparatus 1 is configured to be applied to a medium 2 to be analyzed. The apparatus includes a contact surface 3 intended to be applied to the medium to be analyzed. The contact surface is designed to conform to the medium to which it is pressed. For example, it is planar. In this example, the medium 2 is the skin of a user. The apparatus includes a light source 10 configured to emit a light beam 11 that propagates in the medium to be analyzed. The light source 10 is pulse-modulated or amplitude-modulated. The light beam 11 is emitted in a radiation spectral band Δλ including the absorption wavelength λ of the analyte 4 present in the medium. One objective of the apparatus 1 is to detect the presence of the analyte 4 and optionally estimate its concentration. a

[0030] The analyte 4 may be a molecule present in a body fluid. It may be, for example, glucose, or a problem of a body analyte such as cholesterol, triglyceride, urea, albumin, alcohol (e.g., ethanol), tetrahydrocannabinol, etc.

[0031] The radiation spectral band is preferably visible or infrared, for example, wavelengths from 3 μm to 15 μm. Preferably, the radiation spectral band Δλ is narrow enough so that the device 1 is specific to a single analyte. When the analyte is glucose, the radiation spectral band is centered on the absorption wavelength of glucose, for example, at a wavenumber of 1034 cm -1 corresponding thereto. The light source 10 may in particular be a pulsed laser light source, for example, a wavelength tunable quantum cascade laser (QCL). Thus, the radiation spectral band Δλ is within the infrared.

[0032] According to other embodiments, the light source may be a filament-based source or a light emitting diode. According to these embodiments, it is preferable to associate the light source with a bandpass filter in order to define a sufficiently narrow radiation spectral band centered on the absorption wavelength in question. However, the use of a laser light source is preferred.

[0033] In the embodiment shown in FIG. 1A, the device 1 comprises optical components 15 configured to control the light beam 11 emitted by the light source to be directed towards the medium 2 to be analyzed.

[0034] The device 1 is intended to be applied to the medium 2 to be analyzed. It includes a confining jacket 21 that is placed in contact with the medium and surrounds the cavity 20. The cavity 20 communicates with a contact opening 22 formed in the contact surface 3 and is open to the medium 2. The light beam 11 propagates through the cavity 20 and the contact opening 22 to the medium 2 after being reflected by the optical components 15. The device includes a transparent window 17 configured to transmit the incident light beam 11.

[0035] In the apparatus shown in FIG. 1A, the optical component 15 is a reflector in the form of a reflecting prism. Preferably, the incident light beam 11 reaches the medium 2 at normal incidence or substantially normal incidence. Substantially normal means normal within an angular tolerance of ±30°.

[0036] Due to the presence of the analyte 4 in the medium 2, a sound wave called the photoacoustic wave 12 is generated. The photoacoustic wave 12 is an acoustic wave generated by the medium being periodically heated by the incident light beam, and the incident light beam 11 is pulse - modulated or amplitude - modulated. A part of the photoacoustic wave 12 propagates through the cavity 20 to be detected by the acoustic transducer 28. The acoustic transducer 28 is connected to the cavity 20 by an acoustic channel 25. The acoustic transducer may be a microphone having a detection spectral range including the frequency of the photoacoustic wave. The photoacoustic wave is amplitude - modulated at the pulse frequency or amplitude - modulation frequency of the light source. Thus, at the transducer, the pressure is amplitude - modulated.

[0037] The restriction jacket 21 - Preferably, a lateral component 211 extending parallel to the axis Z perpendicular to the contact surface 3. The lateral component 211 forms a lateral wall surrounding the cavity. - A transverse component 212 extending parallel or substantially parallel to the contact surface 3 and facing the contact surface 3. The transverse component 212 extends parallel or substantially parallel to the contact opening 22. In the embodiment shown in FIG. 1A, the transverse component 212 includes the window 17. The transverse component 212 forms a transverse wall surrounding the cavity. comprises.

[0038] Substantially parallel means parallel within an angular tolerance of ±30° or ±20°.

[0039] The side wall 211 extends between the contact surface 3 and the transverse wall 212.

[0040] The device includes a protective cover 30 that encapsulates the above-described components. The light source is disposed on a carrier 13 connected to the cover 30.

[0041] As described in the publication Kottmann, “Mid-infrared photoacoustic detection of glucose in human skin: towards non-invasive diagnostics”, Sensors, 2016, 16, 1663, the following relationship can be established between the modulation amplitude A of the photoacoustic wave at the modulation frequency f and the volume V of the cavity 20.

Equation

[0042] Assuming the frequency of the light beam is f and the intensity of the light beam is I 11 (λ), the modulation amplitude A of the photoacoustic wave detected by the acoustic transducer is proportional to the absorption coefficient α(λ) of the medium. However, the latter is considered to be proportional to the concentration of the analyte in the medium. Therefore, by measuring the modulation amplitude A using the acoustic transducer 28 in consideration of the absorption coefficient α(λ) of the medium, the concentration of the analyte 4 in the medium can be estimated.

[0043] The device includes a membrane 23 located within the cavity 20 between the contact surface 3 and the transducer 28. As shown in Figure 1B, the membrane 23 can divide the cavity as follows. - A lower cavity 20 that extends between the contact surface 3 and the membrane 23i ; - The upper cavity 20 extending between the membrane 23 and the transducer 28 s 。

[0044] Therefore, the membrane forms a protective screen intervening between the lower cavity 20 i and the upper cavity 20 s As a result, the upper cavity 20 s is separated from water droplets or dust, or other undesirable elements that may enter the lower cavity 20 i through the contact opening 22

[0045] The membrane 23 is within the cavity 20 at a non-zero distance d from the contact opening 22. Specifically, during operation of the device, the membrane 23 preferably does not contact the skin 2 so as not to impede the heating of the surface layer of the gas in contact with the skin 2. By disposing the membrane at a distance, an air layer can be maintained between the contact opening 22 and the membrane. The distance between the membrane and the contact opening is preferably greater than 200 μm or 500 μm

[0046] Preferably, the membrane extends to the right through the cavity facing the contact surface 3. The membrane extends between points on opposite sides facing each other. The membrane is preferably disposed parallel or substantially parallel to the contact surface

[0047] The membrane 23 is held within the cavity 20 by the holder 24. In this example, the membrane is inserted into the holder 24. The membrane 23 is removable, whereby the membrane 23 can be exchanged and / or cleaned

[0048] When the light source 10 is activated, the light beam 11 passes through the membrane 23 before reaching the contact opening 22. The membrane includes an intersection segment 23 int corresponding to the portion of the membrane through which the light beam 11 passes

[0049] At least the intersection segment 23 intIn this case, the membrane is formed of a material having a high transmittance in the spectral band Δλ of the emitted beam 11. High transmittance means that the transmittance of the material is preferably higher than 0.4, or is uniform, preferably higher than 0.8, and is on the order of 0.9 or higher, for example. The material may be, for example, silicon. Transmittance means a part of the light intensity transmitted by the membrane 23. The membrane may be formed partially or entirely of Si or another material transparent in the infrared, such as porous Si, Ge, AlN, ZnSe, BaF2, CaF2, KBr, ZnS, or sapphire.

[0050] Figure 2 shows the transmittance (y-axis) of a Si membrane with a thickness of 300 μm as a function of wavelength (x-axis - unit μm). The transmittance is particularly affected by the reflection by the upper surface 23 s The transmittance is particularly affected by the reflection by the upper surface 23 s , preferably the upper surface 23 s and the lower surface 23 i can be improved to achieve a value close to 1 by applying an antireflection coating to the upper surface (and preferably the lower surface). The antireflection coating can take the form of a non-open "quarter-wave" layer deposited in the form of a thin layer. Since the thickness of the thin layer is thin, it can be deposited on all or part of the upper surface (and preferably the lower surface) without risking blocking the through-holes.

[0051] The membrane may also be a composite material including a material that is considered to be sufficiently transparent in the infrared in the intersecting segment 23 int and another material outside the intersecting segment. An example of the composite membrane will be described below with reference to FIG. 5B.

[0052] To enable the pressure modulation to be transmitted through the cavity 20 to the transducer 28, the membrane includes through-holes 23 o extending directly through the thickness of the membrane. The through-holes are shown in FIG. 1C. The through-holes are dimensioned to transmit the pressure modulation through the membrane 23 while blocking liquid or dust droplets. These through-holes 23 oallows for air communication between the lower cavity 20 i and the upper cavity 20 s and enables it.

[0053] Figure 3 shows droplets deposited on the lower surface 23 of the membrane 23 i The wetting angle θ of the droplets on the lower surface of the membrane and the wetting angle θ of the droplets in the through-hole 23 R and the through-hole 23 o are respectively shown. Here, we consider the micro-droplets formed by the condensation of water vapor due to sweating. The droplets are assumed to be microscopic, and capillary forces are dominant over gravity. The droplets are subjected to pressure differences, i.e., different pressures on both sides of the membrane, due to the antagonistic capillary forces that interact with the droplets through the lower surface 23 A and the through-hole 23 i and the through-hole 23 o These capillary forces induce a pressure difference Δp on the droplets, which can be expressed as follows.

Equation

[0054] Equation (2) is derived from Cho, H.-Y., Kim, J. Y., Kang, J. Y., & Kim, T. S. (2007). How the capillary burst microvalve works. Journal of Colloid and Interface Science, 306(2), 379 - 385. Equation (2) defines the condition for a droplet to penetrate a through-hole with a circular cross-section. The membrane blocks the droplet when Δp > 0.

[0055] The droplet forms a meniscus, and the meniscus engages with the through-hole 23 o and is subject to a capillary force that advances the droplet into the interior of the capillary tube formed by the through-hole. The resulting pressure is

Number

Number

[0056] Contact angle θ R To increase the contact angle θ, the lower surface 23 of the membrane i may be subjected to a hydrophobic surface treatment. Specifically, when the material forming the membrane is hydrophilic Si, the contact angle of water is 5°. Considering droplets of biological buffer, this better approximates the conditions encountered when the device is applied to the user's skin, and the contact angle is on the order of 20° to 40°. By applying a hydrophobic surface treatment, such as a silane treatment (grafting of a hydrophobic silane function), the contact angle can be increased to 110° for water and 80° for biological buffer. Therefore, the hydrophobic surface treatment enhances the ability to hold droplets on the lower surface of the membrane. Also, the hydrophobic treatment may be applied to the inner surface of the through-hole by "overflow".

[0057] Apart from the wettability of the liquid, the surface tension γ is also an important parameter. When the diameter of the through-hole 23 o is 20 μm (r = 10 μm) and the liquid is water (γ = 0.073 N / m) or biological liquid (γ = 0.03 N / m), applying Equation (1) gives Δp = 0.14 bar and Δp = 0.06 bar respectively. Therefore, a pressure higher than the pressure Δp when the droplet passes through the membrane by capillary action needs to be applied. This estimate was made considering R = 20 μm.

[0058] The radius of the through-hole is preferably 5 μm to 25 μm, more preferably 5 μm to 15 μm. As the radius increases, the transmission of pressure modulation is optimal, but the value Δp decreases, and the ability of the membrane to prevent the passage of droplets through the through-hole deteriorates. This drawback can be overcome to some extent by subjecting the lower surface 23 i to a hydrophobic surface treatment.

[0059] The film thickness ε of the membrane 23 is preferably 100 μm to 1 mm, more preferably 150 μm to 750 μm.

[0060] Also, the radius of each through-hole depends on the film thickness ε. The through-holes can be formed in the Si substrate by photolithography and subsequent wet etching. In this case, it is considered that through-holes with a diameter of about 1 / 10 of the thickness ε or less may be formed if necessary.

[0061] The membrane is sized to allow pressure modulation to be transmitted between the lower and upper parts of the cavity. The number of through-holes must be determined such that the influence of the membrane on the photoacoustic wave can be ignored in the frequency range corresponding to the pulse frequency of the light source.

[0062] The aperture factor of the membrane corresponds to the ratio of the cumulative area of each through-hole to the total area of the lower surface (or upper surface). The aperture factor may be 0.01 to 0.3. The inventors modeled the transmission of amplitude modulation of the photoacoustic wave 12 for two aperture factors. A model was created considering a membrane that forms an acoustic impedance similar to electrical impedance. FIG. 4A shows a model of the cavity 20 (left figure), where the membrane 23 is arranged at an intermediate height and forms an acoustic impedance represented by the electrical impedance Z (right figure). The acoustic impedance was modeled by an RLC circuit as shown in FIG. 4B. The membrane is the lower cavity 20 i and the upper cavity 20 s and the circuit R between them M 、L M 、C M shown by.

[0063] The volume of the modeled cavity was 4.45 mm 3 , and the height h was 1.5 mm. The following two different aperture ratios were considered. - The first aperture ratio corresponding to 1000 through-holes with a radius of 10 μm: The value of the first aperture ratio was 0.1; - The second aperture ratio corresponding to 100 through-holes with a radius of 10 μm: The value of the second aperture ratio was 0.01.

[0064] The thickness of the model film was 200 μm.

[0065] Figure 4C shows the amplitude of the pressure modulation (y-axis - arbitrary unit) as a function of the modulation frequency (x-axis - Hz). - Lower cavity 20 i (Curve a - solid black line) and upper cavity 20 s for the first aperture ratio; - Lower cavity 20 i (Curve c - dashed black line) and upper cavity 20 s for the second aperture ratio.

[0066] Figure 4C shows the influence of the aperture ratio on the transmission of the pressure modulation from one side of the film to the other. It can be seen that the lower second aperture ratio results in attenuation of the pressure modulation transmitted by the film, especially at high frequencies.

[0067] To prevent the transmission of the light beam 11 from being affected by the diffraction effect, as shown in Figure 5A, the intersecting segments 23 of the film int do not have to be open. The non-open segments may be provided with an anti-reflection coating applied to the upper surface 23 s , preferably the lower surface 23 i as well. The anti-reflection coating may be a thin layer or a photonic crystal. The non-open segments mean segments that do not contain through-holes.

[0068] The membrane may be monolithic, i.e., formed from a single material, except for any anti-reflection treatment or any hydrophobic treatment. FIG. 5B shows one variant where the membrane is a composite membrane. The membrane is composed of a standard first material 231 that is not necessarily transparent in the infrared outside the intersecting segments. In the intersecting segments, the membrane includes an auxiliary material 23 that is transparent in the infrared. a The first material 231 may be a material of a standard porous membrane, for example, a material such as GoreTex®. The auxiliary material 23 a is different from the first material 231.

Claims

1. A photoacoustic detection device (1) applied to a medium (2) to be analyzed via a contact surface (3), - a hollow cavity (20) leading to a contact opening (22) formed in the contact surface; - a light source (10) modulated in pulse or amplitude, which is configured to emit an incident light beam (11) in a radiation spectral band (Δλ) through the cavity (20) to the contact opening when activated; - an acoustic transducer (28) connected to the cavity and configured to detect an acoustic wave (12) propagating through the cavity; comprising due to the effect of illumination of the medium by the incident light beam, the acoustic transducer detects an acoustic wave generated by heating of the medium (2); The device is - the cavity faces the contact surface and comprises a film extending through the cavity; - The film is surrounded by a lower surface (23 ｉ ) and an upper surface (23 ｓ ), and includes a through-hole (23 ｏ ) formed between the lower surface and the upper surface; - the film is within the cavity at a non-zero distance (d) from the contact surface (3) A photoacoustic detection device, characterized in that.

2. The radius of each through-hole (23 ｏ ) is 5 μm to 25 μm. The photoacoustic detection device according to claim 1.

3. - the film defines an aperture ratio corresponding to the ratio of the cumulative area of each through-hole to the total area of the lower surface or the upper surface of the film; - the aperture ratio is 0.05 to 0.3, The photoacoustic detection device according to claim 1 or 2.

4. The thickness of the film is 100 μm to 1 mm, and the photoacoustic detection device according to any one of claims 1 to 3.

5. - the film is arranged such that the incident light beam passes through the film before reaching the contact opening (22) when the light source is activated; - The film includes an intersection segment (23 ｉｎｔ ) corresponding to the portion of the film through which the light beam passes; - at least in the intersection segment, the film is made of a transparent material with a transmittance higher than 0.4 in the radiation spectral band, The photoacoustic detection device according to any one of claims 1 to 4.

6. The photoacoustic detection device according to claim 5, wherein the film is not open in the intersection segment.

7. wherein the transparent material is at least one material selected from Si, Ge, AlN, ZnSe, BaF ２ , CaF ２ , KBr, ZnS, sapphire, the photoacoustic detection device according to claim 5 or 6.

8. At least in the intersection segment (23 ｉｎｔ ), the upper surface (23 ｓ ) of the film is provided with an antireflection coating, and the photoacoustic detection device according to any one of claims 5 to 7.

9. The film is - The first material (23) outside the cross segment １ ) - In the cross segment, an auxiliary material (23) for forming the transparent material ａ ) made of, and the photoacoustic detection device according to any one of claims 5 to 8.

10. The photoacoustic detection device according to any one of claims 1 to 9, wherein the film is provided with a hydrophobic coating on the lower surface.

11. - The cavity is surrounded by a transverse wall (21 ２ ), and side walls (21 １ ), and the side walls extend between the transverse wall and the contact surface; - the film extends between two opposing surfaces of the side wall, The photoacoustic detection device according to any one of claims 1 to 10.

12. The photoacoustic detection device according to any one of claims 1 to 11, wherein the membrane is removably disposed within the cavity. **Claim 13** The photoacoustic detection device according to any one of claims 1 to 12, wherein the light source is a laser light source. **Claim 14** The photoacoustic detection device according to any one of claims 1 to 13, wherein the volume of the cavity is less than 50 μL.

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