Apparatus and method for analyte measurements with improved coupling of excitation radiation into a material including the analyte

Abstract

Device (10) for analysing a material (12) comprising at least one analyte, the device comprising a measuring body (16) having a contact surface (14) adapted for thermal or pressure transfer contact with the material (12), an excitation radiation source (26) configured for irradiating excitation radiation (18) into the material (12) to be absorbed therein, and a detection apparatus for detecting a physical response of the measuring body to thermal or pressure waves received from the material (12) upon absorption of the excitation radiation (18), and for generating a response signal indicative of the degree of absorption of the excitation radiation, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing towards the material (12) and coming into contact with the material when the material is in contact with the contact surface, and wherein the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80), wherein the protrusion (80) is formed on the contact surface (14) of the measuring body (16), or wherein the measuring body (16) forms the protrusion or a part of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least part of the front surface of the protrusion and is elevated relative to the surrounding structure.

Description

Technical Field

[0001] This application generally relates to apparatus and methods for analyzing materials, such as fluids, that include at least one analyte. In particular, this application relates to apparatus and methods for the non-invasive measurement of glucose concentration in bodily fluids, such as human skin, and especially in the interstitial fluid of human skin. Background Technology

[0002] This application relates to an apparatus and method for analyzing materials comprising at least one analyte. The apparatus includes a measuring body having a contact surface adapted for thermal or pressure-transmitting contact with the material, the thermal or pressure-transmitting contact allowing heat or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0003] The apparatus also includes an excitation radiation source configured to irradiate the material with excitation radiation for absorption therein, and a detection device for detecting the physical response of the measuring body or a component therein to thermal or pressure waves received from the material after absorption of the excitation radiation, and for generating a response signal based on the detected physical response. Herein, the response signal indicates the degree of absorption of the excitation radiation.

[0004] This application is not limited to any particular physical response to thermal or pressure waves received from the material after absorption of excitation radiation, nor is it limited to any particular manner in which such physical response is detected in a way that allows the generation of a response signal indicative of the degree of excitation radiation absorption. The applicant has previously proposed various physical responses and corresponding detection methods for these types of analyte measurement procedures, which are briefly outlined below, and each of them can be applied to this application.

[0005] For example, the detection device may include a light source for generating a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, and the physical response of the measuring body to thermal or pressure waves received from the material after absorbing the excitation radiation may be a localized change in the refractive index of the measuring body or the component. In this case, the detection device may be configured to detect either a change in the optical path or a change in the phase of the detection beam caused by the change in the refractive index of the material of the measuring body or the component included therein.

[0006] For example, in various methods and apparatuses detailed in the applicant’s two earlier applications, WO 2015 / 193310A1 and WO 2017 / 097824 A1 (both incorporated herein by reference), the measuring body is transmissible to the detection beam, and the detection beam is directed to be fully or partially reflected at the surface of the measuring body in thermal contact with the material. In this case, the detection apparatus may include a photodetector, particularly a position-sensitive photodetector, capable of detecting the degree of deflection of the detection beam, particularly the deflection angle, due to the localized change in refractive index. Thus, in this case, the physical response to the thermal or pressure wave received by the measuring body is a localized change in refractive index, and the response signal is the detected degree of deflection, which has in fact been found to indicate the degree of absorption of the excitation radiation.

[0007] In an alternative variation proposed by the applicant, such as that disclosed in International Application PCT / EP2019 / 064356 (incorporated herein by reference), the detection apparatus may include an interferometric device to allow evaluation of the phase change of the detection beam and to generate a response signal indicative of the phase change. In this case, the physical response of the measurement body (or a component thereof) to thermal or pressure waves received from the material after absorbing the excitation radiation is again a localized change in refractive index, and in this case, the response signal is an interferometric signal reflecting the phase change of the detection beam due to the localized change in refractive index.

[0008] In yet another alternative embodiment, the measuring body or a component therein may have electrical properties that change in response to localized changes in temperature or pressure associated therewith, and the detection device includes electrodes for capturing an electrical signal representing said electrical properties. Various possible configurations are disclosed in WO 2019 / 110597A2, which are incorporated herein by reference. For example, the measuring body may include portions having piezoelectric properties, and pressure changes associated with received heat result in an electrical signal that can be recorded by electrodes. In this case, the pressure change is analogous to the physical response of the measuring body or a component therein to heat received from the material after absorbing excitation radiation, which is detected using the piezoelectric properties of the measuring body and electrodes and results in an electrical signal representing the aforementioned response signal indicating the degree of absorption of the excitation radiation. In yet another variation, a very sensitive temperature sensor may be used to directly measure the temperature change caused by the received heat.

[0009] Note that the physical response of the measuring body to heat received from the material is described in detail in the following description. However, it should be understood that in various embodiments of the methods and apparatus of this application, the material is in pressure-transmitting contact with the measuring body, and the physical response of the measuring body is a response to pressure waves received from the material. In this document, the expression "pressure-transmitting contact" should include all relationships that allow pressure waves to be transmitted from the material to the measuring body, and in particular acoustic coupling relationships, where coupling can be established by a gas, liquid, or solid. All detailed explanations given in conjunction with thermal contact and the physical response to heat received by the measuring body from the material should be understood in the context of including pressure-transmitting contact and the physical response to pressure waves (where applicable), without explicit reference.

[0010] The apparatus can also be configured to perform analytical steps, wherein the analysis is performed at least in part based on the response signal. For this purpose, the apparatus may include a control system comprising one or more processors programmed to perform the analysis. If, for example, there is interest in determining the concentration of an analyte in the material, the excitation radiation can be selected to have a characteristic wavelength of the analyte's absorption spectrum, for example, correlated with its absorption peak. Since the response signal indicates the degree of absorption of the excitation radiation, in this case, the response signal is directly related to the concentration of the analyte in the material. Therefore, the analytical step can be based at least in part on a measurement of the concentration of the analyte in the material, and in some non-limiting applications, it can practically be equivalent to determining that concentration.

[0011] For example, the applicant has used devices of the type described above to non-invasively measure a user's glucose levels. In this particular application, the "analyte" is formed from glucose, and the "material" is the user's skin. It has previously been demonstrated that this method allows for very precise measurement of glucose concentration in the interstitial fluid within human skin, which has been found to be directly correlated with and therefore representative of the glucose levels in the patient's blood. This application's... Figure 4 The results of Clark error grid analysis taken from WO2017 / 097824A1 are shown, indicating that the above-mentioned device and analysis method allow for very accurate prediction of a person's actual glucose concentration.

[0012] However, we hope to further improve the accuracy and reliability of the analysis results. Invention Overview

[0014] The purpose of this application is to provide an apparatus and method for analyzing the above-mentioned materials, which allows for improved accuracy or reliability of the analytical results.

[0015] According to one aspect of this application, the solution to the problem lies in providing a protrusion having a front surface facing the material and contacting the material when the material contacts the contact surface, and the excitation radiation irradiating the material through the front surface of the protrusion.

[0016] In this paper, protrusions may be formed on the contact surface of the measuring body.

[0017] In an alternative embodiment, the measuring body itself may form a protrusion, or form a portion of said protrusion. In this case, the contact surface of the measuring body simultaneously forms the front surface of said protrusion, or at least a portion of said front surface of said protrusion, and is raised relative to the surrounding structure. The surrounding structure may be, for example, a wall portion of the device housing.

[0018] The inventors have noted that a key aspect of the measurement procedure performed by the device is the reliable and consistent transmission of excitation radiation into the material. In some devices described by the applicant in the aforementioned prior application, the excitation radiation is directed through the measuring body, such as to enter the material at the interface between the contact surface of the measuring body and the material, and it has been observed that at this interface, the excitation radiation can generally be coupled very well into the material. This has been found to be particularly true in applications where the material is formed by the user's fingertip, and in applications where the device is used to measure glucose levels in the skin. In this case, the fingertip is firmly placed on the contact surface of the measuring body, thereby establishing sufficient optical coupling to allow the excitation radiation to enter the material through the contact surface of the measuring body.

[0019] However, extensive research has shown that imperfect and particularly unstable optical coupling can be a source of measurement inaccuracies. In particular, the inventors have noted that optical coupling can change during a single measurement, i.e., without intentionally moving a fingertip to or even away from the contact surface. If optical coupling changes during measurement, this results in a change in the intensity of the excitation radiation actually absorbed by the analyte, and thus a change in the response signal, independent of the analyte's absorbance at the excitation wavelength or analyte concentration. In other words, a loss of optical coupling during a portion of the measurement can be misinterpreted as a decrease in absorbance at a given excitation wavelength. Evaluating an analyte spectrum typically involves measuring multiple characteristic wavelengths, such as the wavelengths corresponding to the peaks or local absorption minima of the analyte's absorption spectrum, and also involves mathematical combinations of response signals associated with different wavelengths, such as subtracting the response signal obtained at the local minima of the absorption spectrum from the response signal at the absorption peak. Therefore, it is understandable that artifacts and inaccuracies can occur in the measurement results when the optical coupling in the material, and thus the effective intensity of the excitation radiation, changes between measurements at different wavelengths, or even during measurements at a specific wavelength.

[0020] For the inventors, the significant source of error from unstable optical coupling is not readily apparent, and it is even less clear why the optical coupling between the contact surface and the material changes significantly during measurement, since the fingertip was not intentionally moved during the measurement. One possible reason could be that the user unintentionally failed to maintain a constant contact pressure between the finger and the contact surface. Another possible reason could be that the user unintentionally moved the fingertip slightly on the contact surface, and even a very small movement could have an unexpectedly large effect. For example, this could be a situation where the fingertip moves between a position where the excitation radiation enters the skin at the ridge of the fingertip and a position where the excitation radiation enters the skin between the two ridges, where a decrease in optical coupling may occur.

[0021] Regardless of the exact underlying cause, the inventors have observed that forming protrusions on a contact surface having a front surface facing the material improves optical contact and its consistency. These protrusions contact the material when it comes into contact with the contact surface, and if excitation radiation irradiates the material through the front surface of the protrusion. Specifically, at the front surface of the protrusion, if a finger applies the same total force to the contact surface, a significantly higher local contact pressure is found compared to a flat contact surface. This local increase in contact pressure allows for better optical coupling, and particularly more consistent optical coupling during measurement.

[0022] Note that the protrusion not only allows for improved optical coupling but also for improved thermal or pressure transmission coupling. Therefore, in many cases, the protrusion will also facilitate improved transmission of thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body. While not an embodiment of the currently claimed invention, the use of such a protrusion is also contemplated herein, even if the excitation radiation does not irradiate into the material through its front surface.

[0023] In a preferred embodiment, the front surface is flat. However, this application is not limited to this, and a curved front surface may also be advantageous, particularly in cases where detection relies on a reflected detection beam, as will be described below.

[0024] In a preferred embodiment, the protrusion has a diameter of less than 0.3 cm. 2 Preferably less than 0.2cm 2 More preferably less than 0.1cm 2 Even more preferred is less than 0.05cm. 2 And the optimal value is less than 0.02cm. 2 The area of ​​the footprint.

[0025] In a preferred embodiment, the protrusion has a tapered shape, wherein one or more sidewalls gradually narrow toward the front surface. This tapered shape means that the front surface can be smaller than the footprint area, thus resulting in even higher local contact pressure. The tapered sidewalls also increase the stability of the protrusion. Furthermore, in some embodiments, in the case of detecting a detection beam that depends on reflection, the tapered sidewalls make it easier for the detection beam to enter the protrusion while keeping the contact surface small, as will become apparent from the following detailed description of the embodiments.

[0026] In some embodiments, the protrusion has a circular, oval, or square footprint shape.

[0027] In a particularly preferred embodiment, the protrusion is ridge-shaped, having a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, wherein the longer extension exceeds the shorter extension by at least 1.5 times, preferably at least 2.0 times, more preferably at least 2.5 times, and most preferably at least 3.0 times. In this document, expressing "the longer extension exceeds the shorter extension by at least 1.5 times" means that if the shorter extension is 2 mm, then the longer extension will be at least 3 mm.

[0028] In a preferred embodiment, the measuring body forming the protrusion or a portion thereof is received in a frame or container, wherein the contact surface of the measuring body protrudes from the frame or container, or wherein the frame or container protrudes from a surrounding structure.

[0029] In a preferred embodiment, a pressure sensor is provided for measuring the contact pressure between the material and the measuring body. Preferably, the apparatus also includes a control system configured to receive a signal from the pressure sensor indicating the contact pressure between the material and the measuring body, wherein the control system is configured to check whether the contact pressure is below a predetermined threshold. If the contact pressure is found to be below the threshold, the control system is configured to perform one or more of the following:

[0030] Inform the user of the lack of contact pressure.

[0031] To prevent the analyte measurement process from starting, and

[0032] Interrupt the current analyte measurement process.

[0033] In other words, while protrusions help to precisely establish high contact pressure where needed, i.e., at the front surface where excitation radiation couples into the material, reliability can be further improved by monitoring the contact pressure and indicating to the user if insufficient contact pressure is present, allowing for correction. Furthermore, by preventing the analyte measurement process from starting or interrupting an already performed analyte measurement, incorrect measurement results can be avoided in the event of insufficient contact pressure.

[0034] In a preferred embodiment, the device further includes a clamping device comprising a clamping member movable between an open position and a closed position. In the open position, the clamping member moves away from the contact surface of the measuring body, and in the closed position, it moves closer to the contact surface, the clamping member being biased toward the closed position. When the clamping member is in the open position, material can be placed on the contact surface, and due to the biasing force toward the closed position, the clamping member is adapted to press the material onto the contact surface. In this way, a predetermined contact pressure can be ensured.

[0035] In a preferred embodiment, the pressure sensor described above is arranged on the clamping device. Although in the preferred embodiment the clamping device is engaged with / at least partially formed by the measuring body on the contact surface, the clamping device can also be used in embodiments without such a protrusion.

[0036] In other embodiments, the apparatus further includes a strap for securing the material to the contact surface of the measuring body.

[0037] In a preferred embodiment, the measuring body is permeable to the excitation radiation, wherein the excitation radiation source is configured to provide the excitation radiation as an excitation beam. Furthermore, the excitation radiation source is arranged such that the excitation beam is irradiated into the measuring body at its incident surface, propagates through a portion of the measuring body, and exits the measuring body at the contact surface. In previous devices, the applicant ensured that the excitation radiation beam struck the incident surface at a 90° angle, such as to avoid refraction and excessive reflection of the excitation radiation beam at the incident surface. However, extensive research has shown that another reason for unexpected variations in the excitation radiation actually reaching the material is the possible interference between the excitation radiation emitted from the excitation radiation source and the excitation radiation reflected back from the incident surface of the measuring body. This interference has been found to indeed cause fluctuations in the intensity of the excitation radiation in the material, and thus immediately result in changes in the response signal independent of the analyte concentration. Furthermore, the inventors have found that this effect can be suppressed by slightly tilting the incident angle of the excitation beam, thereby improving the accuracy and reliability of the measurement. Therefore, in this embodiment, the excitation beam is directed to strike the incident surface at an angle of 89.0° or less, preferably 88.0° or less, and most preferably 87.5° or less. In this way, accidental interference can be reliably prevented. Another advantageous effect of doing so is that the excitation radiation can be prevented from being reflected back into the excitation radiation source, which could be damaged by it. On the other hand, the incident angle should not deviate too much from 90°, such as to avoid losses due to excessive reflection. Therefore, in this embodiment, the incident angle should be 82.0° or greater, preferably 84.0° or greater, and most preferably 85.0° or greater. While this embodiment is advantageously used with / at least partially formed by the measuring body on the contact surface, it can also be used in embodiments without such a protrusion.

[0038] In a preferred embodiment, the excitation beam strikes the contact surface of the measuring body at an angle of 90°±1.5° to minimize losses due to reflections at the contact surface.

[0039] In a preferred embodiment, the incident surface and the contact surface are tilted relative to each other at angles of 1.0° or greater, preferably 2.0° or greater, and most preferably 2.5° or greater, and 8.0° or less, preferably 6.0° or less, and most preferably 5.0° or less, at their respective entry and exit points of the excitation beam from the measuring body. Graphically, the measuring body according to this embodiment can have a slightly “wedge-shaped” shape, which allows for a slight tilt of the excitation beam at the incident surface and its orthogonal orientation at the contact surface.

[0040] In a preferred embodiment, the detection device includes a light source for generating a detection beam that travels through at least a portion of the measuring body or components included in the measuring body. Hereinafter, the physical response of the measuring body to thermal or pressure waves received from the material after absorbing the excitation radiation is a localized change in the refractive index of the measuring body or the components, and the detection device is configured to detect one of the changes in the optical path or the change in the phase of the detection beam due to the change in refractive index.

[0041] In a preferred embodiment, the detection device is configured such that the detection beam is irradiated into the measuring body at the incident surface, wherein the detection beam strikes the incident surface at an angle of incidence of 89° or less, preferably 88° or less, and most preferably 87.5° or less, and 80° or greater, preferably 82° or greater, more preferably 84° or greater, and most preferably 85° or greater, relative to the incident surface. In this way, the detection beam is prevented from being reflected back onto itself, which could lead to interference and undesirable interference phenomena. Another advantageous effect is that the detection beam is prevented from being reflected back into the detection light source, which could potentially be damaged.

[0042] In a preferred embodiment, the measuring body is received within a frame or container to allow rotation of the measuring body, such as to adjust the angle of incidence of the detection beam when it strikes the incident surface of the measuring body. In this way, adjusting the appropriate angle of incidence of the detection beam onto the measuring body is greatly facilitated compared to, for example, adjusting any optical element such as a mirror in the optical path of the detection light source or the detection beam. Preferably, the frame or container allows rotation of the measuring body about an axis parallel to the excitation beam, or deviating from parallel by less than 10°, preferably less than 5°. In the most preferred embodiment, the axis of rotation of the measuring body is aligned with the position of the excitation beam.

[0043] In relevant embodiments, the measuring body is transmissible to the detection beam, which is directed to be fully or partially reflected at the surface of the measuring body in thermal or pressure-transmitting contact with the material. The detection device includes a detector for detecting the degree of deflection, particularly the deflection angle, of the detection beam after reflection at the contact surface due to the localized change in refractive index. Preferably, the detection device includes a photodetector, particularly a position-sensitive photodetector.

[0044] In this embodiment, the detection beam is preferably oriented to be fully or partially reflected at the front surface of the protrusion that is in thermal or pressure transmission contact with the material. In other words, in this embodiment, the detection beam is reflected at the same surface where the excitation radiation leaves the measuring body and enters the material. This means that the detection beam is reflected in a region where a relatively large local change in refractive index can be expected due to the thermal or pressure waves received from the material after absorbing the excitation radiation, which in turn means that a relatively large deflection of the detection beam due to the local change in refractive index is expected.

[0045] Note that the concept of "deflection" of the detection beam relates to the total change in angle at the detector or the change in the impact position, or in other words, how the detection position of the detection beam differs from its position in the absence of excitation and material absorption. Therefore, this "deflection" is the cumulative effect of local variations in refractive index on the detection beam along its optical path. Closer examination reveals that in many cases, a portion of the beam deflection due to local variations in refractive index occurs before the detection beam is reflected at the surface of the measuring body in contact with the material for thermal or pressure transmission, in this case, a surface formed by a protruding front surface. Therefore, local variations in refractive index often also cause a shift in the precise position at which the detection beam is reflected on the surface.

[0046] Given this understanding, in a preferred embodiment, the protruding front surface is curved in at least one principal direction. This curvature means that the change in the position where the detection beam is reflected is also accompanied by a change in the angle of incidence, and thus also results in a corresponding change in the angle of reflection. Therefore, by using a curved reflective surface, the total deflection evaluated by the detection device, such as the positional offset detected by a position-sensitive detector, can be increased.

[0047] In a preferred embodiment, the bend in at least one main direction corresponds to a radius bend of 5-30 mm, preferably 10-20 mm.

[0048] In a preferred embodiment, the bend in at least one main direction is either concave or convex.

[0049] In a preferred embodiment, the detection beams before and after reflection from the front surface define a detection light plane, and the at least one principal direction lies within the detection light plane, or forms an angle of less than 30°, preferably less than 20°, with the detection light plane. In this way, it is ensured that the primary effect of bending on deflection lies within the detection light plane.

[0050] Note that, in cases where the detection beam will be reflected at the front surface of the protrusion, the geometry of the protrusion typically limits the possible tilt angle of the detection beam relative to the contact surface. For example, if the protrusion has a circular footprint with height h and radius r, the tilt angle α of the detection beam relative to the contact surface must satisfy the condition tan(α) > h / r to "fit" into the protrusion. From different perspectives, given the desired protrusion height h and the desired angle α, the lower boundary of the radius r must be faced, or in other words, the lower boundary of the footprint size. As explained above, by using one or more tapered sidewalls, the size of the front surface of the protrusion can be reduced relative to the footprint size, thus allowing for a smaller front surface and therefore allowing for higher contact pressure even for larger footprint areas.

[0051] In a preferred embodiment, further improvements can be made, wherein the protrusion is ridge-shaped, having a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, wherein the longer extension is at least 1.5 times, preferably at least 2.0 times, more preferably at least 2.5 times, and most preferably at least 3.0 times, greater than the shorter extension, and the first direction is parallel to or forms an angle of less than 30°, preferably less than 20° with the detection light plane. In other words, according to this embodiment, the detection light plane at least substantially corresponds to the long direction of the ridge-shaped protrusion, meaning that at a given height of the protrusion, the tilt angle of the detection beam on the front surface of the protrusion can be smaller. Simultaneously, utilizing this orientation of the detection light plane, the extension of the ridge-shaped protrusion in the second short direction is generally independent of the tilt angle and can therefore be selected to be relatively small, thereby reducing the size of the front surface and allowing for higher contact pressure at the front surface.

[0052] In a preferred embodiment, the detection light source is arranged such that the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface, wherein the detection beam – in the absence of any deflection due to local variations in the refractive index – strikes the exit surface at an angle of 5° or greater, preferably 10° or greater, and most preferably 15° or greater, relative to the normal of the exit surface, such that the detection beam is refracted after exiting the exit surface of the measuring body, wherein the orientation of the exit surface relative to the detection beam causes the detection beam to increase the angle of the detection beam relative to the normal of the exit surface in response to the deflection of the thermal or pressure wave transmitted to the measuring body.

[0053] In the applicant's previous designs, the shape of the measuring body was typically chosen such that the detection beam was perpendicular to both the entrance and exit surfaces to avoid losses due to reflection and to avoid refraction, which at first glance only complicates the optical setup. However, according to this embodiment, the detection light source is arranged such that the detection beam is intentionally refracted at least at the exit surface in the manner described above. Since the refractive index of the measuring body is typically higher than that of the surrounding area, an increase in the angle of the detection beam perpendicular to the exit surface will result in an even greater increase in the angle of the refracted beam, further increasing the deflection of the beam detected at the detection device, thus leading to a larger response signal. In this way, the signal-to-noise ratio can be improved. The greater the angle of incidence of the detection beam deviates from the normal of the exit surface, the greater this effect generally is. However, it is, of course, necessary to avoid reaching the "critical" angle of total internal reflection. Furthermore, for angles close to this critical angle, the proportion of the detection beam reflected at the exit surface will increase, thereby attenuating the intensity of the refracted detection beam that actually reaches the detection device, such as a photodetector. Therefore, the optimal choice of the angle of incidence can be a trade-off between a large refractive index and sufficient intensity of the refracted detection beam. In any case, the angle of incidence deviation from the normal to the axial surface should be at least 5°, preferably at least 10°, and most preferably at least 15°. Although this embodiment is advantageously used with a protrusion on the contact surface / at least partially formed by the measuring body, it can also be used in embodiments without such a protrusion.

[0054] In a preferred embodiment, the detection light source is arranged such that the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface, wherein a focusing lens is attached to or integrally formed with the incident surface for focusing the detection beam into the measuring body in at least one dimension, and / or a collimating lens is attached to or integrally formed with the exit surface for collimating the detection beam in at least one dimension.

[0055] The inventors have noted that measurement quality is improved when the detection beam is focused upon reflection at a contact surface, which is also the region where it will interact with thermal lenses formed within the measurement body. For clear feature deflection, it is advantageous if the diameter of the detection beam in this region is relatively small, which can be achieved using the focusing lens. In other words, the purpose of the focusing lens is not necessarily to actually focus the detection beam at a focal point, but rather to reduce its diameter, at least in the region where it interacts with the thermal lens. However, this focusing means that the detection beam spreads out along its path toward the detection device. This is generally less important if the detection device, such as a position-sensitive detector, is arranged directly adjacent to or at least close to the exit surface of the detection beam. However, the inventors have found that if the distance between the exit surface and the detector increases, the signal-to-noise ratio of the measurement can be further increased, as this will result in a greater degree of deflection, manifested, for example, by a greater change in position of the detection beam striking the position-sensitive detector. Note that in this document, "greater degree of deflection" is not related to a larger deflection angle, which is one possible meaning of "degree of deflection," but rather to a greater effect of the deflection detected by the detection device. For example, the distance between the reflection at the contact surface of the measuring object and the detection at the detection device can be at least 4 cm, and in some embodiments even 9 cm or more, thereby introducing a certain leverage effect on the deflection detected by the detection device. However, when the detection device is located at a considerable distance from the exit surface, it is advantageous to maintain a constant diameter of the detection beam if it is collimated after leaving the measuring object. However, it should be emphasized that focusing and collimation in two dimensions are not always necessary; in many practical applications, even an extension in one direction may be desired, as will be explained below. Therefore, the focusing lens and / or other collimating lens must be effective only in at least one dimension. In fact, in a preferred embodiment, at least one of the focusing lens and the collimating lens is a cylindrical lens that focuses and collimates the detection beam at least primarily in one dimension.

[0056] Furthermore, by attaching the focusing lens and / or collimating lens to the measuring body, or even more preferably forming them integrally with the measuring body, separate adjustments to these lenses are not required during device assembly or even during use. While this embodiment is advantageously used with / at least partially formed by the measuring body on the contact surface, it can also be employed in embodiments without such protrusions.

[0057] In a preferred embodiment, the detector includes a position-sensitive detector that detects changes in the position of the detection beam impacting it in at least one sensing direction. Furthermore, the position-sensitive detector is arranged such that the deflection of the detection beam results in a change in the position of the detection beam impacting it in the at least one sensing direction. Finally, a cylindrical lens is provided in the optical path of the detection beam to shape the profile of the detection beam such that the diameter of the detection beam impacting the position-sensitive detector in the sensing direction is at least 1.5 times larger, preferably at least 2.0 times larger, than the diameter of the detection beam in the direction perpendicular to the sensing direction. The inventors note that when using a position-sensitive detector that is sensitive to changes in the position of the detection beam impacting it in at least one sensing direction, if the beam profile causes the spot formed on the position-sensitive detector to elongate in the sensing direction as described above, the signal-to-noise ratio can be increased, and in some embodiments, the linearity of the sensor output can be increased. This is particularly true for position-sensitive detectors that measure the current difference at their respective ends. Such a cylindrical lens is used to create an elongated shape of the spot according to this aspect of the application. While this implementation is advantageously used with protrusions on the contact surface / at least partially formed by the measuring body, it can also be used in implementations without such protrusions.

[0058] In a preferred embodiment, the cylindrical lens is a collimating lens in the optical path of the detection beam disposed between its reflection at the contact surface and the position-sensitive detector, wherein the cylindrical lens is arranged to collimate the detection beam at least primarily (but possibly proprietaryly) in a dimension perpendicular to the sensing direction of the position-sensitive detector, wherein the cylindrical collimating lens is preferably integrally formed with the exit surface of the measuring body from which the detection beam exits the measuring body.

[0059] Alternatively, the position-sensitive detector can be arranged at an angle 90° away from the detection beam, such that due to this angle, an elongated spot is formed on the position-sensitive detector, which has a greater extension in the sensing direction.

[0060] In a preferred embodiment, the apparatus further includes a beam splitter that splits the light source beam into the detection beam and a reference beam, wherein the reference beam is also oriented to be fully or partially reflected at the surface of the measuring body in thermal or pressure transmission contact with the material, but in a region where any effect of the thermal or pressure waves received from the material after absorption of excitation radiation is negligible. Furthermore, the apparatus includes additional detection equipment for detecting the degree of deflection of the reference beam after reflection at the contact surface, particularly the deflection angle, wherein the detection equipment preferably includes a photodetector, particularly a position-sensitive photodetector.

[0061] The reference beam is exposed to the same type of external influences as the detection beam, except for thermal or pressure waves generated due to absorbed excitation radiation. Therefore, by measuring the possible deflection of the reference beam, these external influences can be taken into account and eliminated from the measurement results obtained using the detection beam. While in the preferred embodiment, the additional reference beam is combined with / at least partially formed by the measuring body on a protrusion on the contact surface, it can also be employed in embodiments without such a protrusion.

[0062] In an optional preferred embodiment, the detection device includes an interferometric measuring device that allows for the evaluation of the phase change of the detection beam and the generation of a response signal indicating the phase change.

[0063] In yet another alternative embodiment, the measuring body or a component therein has electrical properties that change in response to local variations in temperature or pressure associated therewith, wherein the detection device includes electrodes for capturing electrical signals representing the electrical properties.

[0064] In another embodiment, the apparatus includes a fiber embedded in the measuring body, a detection light source disposed at one end of the fiber for coupling detection light into the fiber, and a pattern detector disposed at the other end of the fiber. The pattern detector is adapted to detect changes in the optical pattern of the detection light in response to heat and pressure waves received by the measuring body from the material. For example, the pattern detector may include a camera adapted to visualize the pattern, typically an interferometric pattern of several patterns, and a processor configured for detecting changes in the pattern based on image analysis of the camera image. The processor may be a dedicated processor associated with the pattern detector, or it may be provided by the control system of the aforementioned apparatus. Detectable changes in the optical pattern may include a shift or rotation of the interferometric pattern of the optical pattern at the pattern detector. Thus, the shift distance or rotation angle is a quantitative parameter associated with the intensity of the heat or pressure waves received from the material, and therefore ultimately indicates the amount of excitation light absorbed by the material. Note that such changes in the interferometric pattern of the pattern can be easily detected using a camera or image sensor, but other devices are also possible, such as sensors or detectors that allow measurement of a spatially resolved intensity value without necessarily providing a complete image. In this embodiment, the "physical response" will be the instantaneous change in the fiber optic properties caused by the received thermal or pressure waves, and the "response signal" will be a detectable change in the optical mode, such as a change in the interference mode of several modes. Although in the preferred embodiment this type of mode detection is combined with / at least partially formed by the measuring body on the contact surface, it can also be used in embodiments without such protrusions.

[0065] In a preferred embodiment, the material is human tissue, particularly human skin, and the analyte is glucose present in the skin, particularly glucose in the interstitial fluid of the skin.

[0066] In a preferred embodiment, the excitation radiation is generated using a laser array, particularly a quantum cascade laser, with each laser having a dedicated wavelength.

[0067] In an alternative preferred embodiment, at least one tunable laser, particularly at least one tunable quantum cascade laser, is used to generate the excitation radiation.

[0068] In a preferred embodiment, some or all of the excitation wavelengths are in the range of 5 μm-13 μm, preferably 8 μm-11 μm. In an optional embodiment, some or all of the excitation wavelengths are in the range of 3 μm-5 μm. This wavelength range can be used, for example, to detect the absorption of CH2 and CH3 vibrations in fatty acids.

[0069] Another aspect of this application relates to a method for analyzing materials comprising at least one analyte, the method comprising:

[0070] The measuring body with a contact surface is brought into thermal or pressure-transmitting contact with the material, which allows thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0071] Excitation radiation is irradiated into the material for absorption therein, and

[0072] The detection measures the physical response of a measuring body or its components to a thermal or pressure wave received from the material after absorption of the excitation radiation, and generates a response signal based on the detected physical response, the response signal indicating the degree of absorption of the excitation radiation.

[0073] The feature is that a protrusion is provided, the protrusion having a front surface facing the material and contacting the material when the material contacts a contact surface, and the excitation radiation is irradiated into the material through the front surface of the protrusion, wherein the protrusion is formed on the contact surface of the measuring body, or

[0074] The measuring body forms the protrusion or a portion of the protrusion, wherein the contact surface of the measuring body forms the front surface of the protrusion and is raised relative to the surrounding structure.

[0075] In a preferred embodiment of the method, the front surface is flat.

[0076] In a preferred embodiment of the method, the protrusion has a diameter of less than 0.3 cm. 2 Preferably less than 0.2cm 2More preferably less than 0.1cm 2 Even more preferred is less than 0.05cm. 2 And the optimal value is less than 0.02cm. 2 The area of ​​the footprint.

[0077] In a preferred embodiment of the method, the protrusion has a tapered shape, wherein one or more sidewalls gradually narrow toward the front surface.

[0078] In a preferred embodiment of the method, the protrusion has a circular, elliptical, or square footprint.

[0079] In a preferred embodiment of the method, the protrusion is ridge-shaped, having a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, wherein the longer extension exceeds the shorter extension by at least 1.5 times, preferably at least 2.0 times, more preferably at least 2.5 times, and most preferably at least 3.0 times.

[0080] In a preferred embodiment of the method, the contact pressure between the measuring material and the measuring body is measured.

[0081] Preferably, the method further includes a step of checking whether the contact pressure is lower than a predetermined threshold, and if the contact pressure is found to be lower than the threshold, performing one or more of the following steps:

[0082] Inform the user of the lack of contact pressure.

[0083] To prevent the analyte measurement process from starting, and

[0084] Interrupt the current analyte measurement process.

[0085] Preferably, the method further includes the step of securing the material to a contact surface using a clamping device, the clamping device including a clamping member movable between an open position and a closed position, wherein in the open position the clamping member moves away from the contact surface of the measuring body, and in the closed position it moves closer to the contact surface, the clamping member being biased toward the closed position, wherein when the clamping member is in the open position the material is placed on the contact surface, and wherein the clamping member presses the material onto the contact surface due to the biasing force toward the closed position.

[0086] In a preferred embodiment of the method, the pressure sensor is arranged on the clamping device.

[0087] In a preferred embodiment, the method includes the step of securing the material to the contact surface using a strap.

[0088] In a preferred embodiment of the method, the measuring body is transmissible to the excitation radiation, wherein the excitation radiation source provides the excitation radiation as an excitation beam, and

[0089] The excitation beam is irradiated into the measuring body at its incident surface, propagates through a portion of the measuring body, and exits the measuring body at the contact surface.

[0090] The excitation beam strikes the incident surface at an angle of 89.0° or less, preferably 88.0° or less, and most preferably 87.5° or less, and 82.0° or greater, preferably 84.0° or greater, and most preferably 85.0° or greater.

[0091] In a preferred embodiment of the method, the excitation beam strikes the contact surface of the measuring body at an angle of 90° ± 1.5°.

[0092] In a preferred embodiment of the method, the incident surface and the contact surface are tilted relative to each other at an angle of 1.0° or greater, preferably 2.0° or greater, and most preferably 2.5° or greater, and 8.0° or less, preferably 6.0° or less, and most preferably 5.0° or less, at their respective points where the excitation beam enters and exits the measuring body.

[0093] In a preferred embodiment of the method, the detection includes generating a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body.

[0094] The physical response of the measuring body to the thermal or pressure waves received from the material after absorbing the excitation radiation is a localized change in the refractive index of the measuring body or the component, and

[0095] The detection includes detecting one of the changes in the optical path or the changes in the phase of the detection beam caused by the change in refractive index.

[0096] In a preferred embodiment of the method, the detection beam is irradiated into the measuring body at the incident surface such that the detection beam impacts the incident surface at an incident angle of 89° or less, preferably 88° or less, and most preferably 87.5° or less, and 80° or greater, preferably 82° or greater, more preferably 84° or greater, and most preferably 85° or greater, relative to the incident surface.

[0097] In a related embodiment of the method, the measuring body is received in a frame or container that allows rotation of the measuring body, such as when impacted on the incident surface of the measuring body, to adjust the incident angle of the detection beam. In particular, the frame or container allows rotation of the measuring body about an axis parallel to the excitation beam, deviating from parallel by less than 10°, preferably less than 5°. Most preferably, the axis of rotation of the measuring body is aligned with the position of the excitation beam.

[0098] In a preferred embodiment of the method, the measuring body is transmissible to the detection beam, which is directed to be fully or partially reflected at the surface of the measuring body in contact with the material for thermal or pressure transmission, and wherein the detection includes detecting the degree of deflection, particularly the deflection angle, of the detection beam after reflection at the contact surface due to the local variation in refractive index, wherein the detection is preferably performed using a photodetector, particularly a position-sensitive photodetector.

[0099] In a preferred embodiment of the method, the detection beam is directed to be fully or partially reflected at the front surface of the protrusion in contact with the material for thermal or pressure transmission.

[0100] In a preferred embodiment of the method, the front surface of the protrusion is curved in at least one principal direction. In this document, the curvature in said at least one principal direction corresponds to a radius curvature of 5-30 mm, preferably 10-20 mm. The curvature in said at least one principal direction is either concave or convex.

[0101] In a preferred embodiment of the method, the detection beams before and after reflection at the front surface define a detection light plane, and the at least one principal direction lies within the detection light plane or forms an angle of less than 30°, preferably less than 20°, with the detection light plane.

[0102] In a preferred embodiment of the method, the detection beams before and after reflection at the front surface define a detection light plane, and the first direction is parallel to the detection light plane or forms an angle of less than 30°, preferably less than 20°, with the detection light plane.

[0103] In a preferred embodiment of the method, the detection light source is arranged such that the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface, wherein the detection beam impacts—in the absence of any deflection due to the local variation in refractive index—at an angle of 5° or greater, preferably 10° or greater, and most preferably 15° or greater, relative to the normal of the exit surface, such that the detection beam is refracted after exiting the exit surface of the measuring body, wherein the direction of the exit surface relative to the detection beam causes the detection beam transmitted to the measuring body to increase the angle between the detection beam and the normal of the exit surface in response to the deflection of the thermal or pressure wave.

[0104] In a preferred embodiment of the method, the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface, wherein a focusing lens is integrally formed with the incident surface to focus the detection beam entering the measuring body in at least one dimension, and / or a collimating lens is integrally formed with the exit surface to collimate the detection beam in at least one dimension. In this document, at least one of the focusing lens and the collimating lens is preferably a cylindrical lens that focuses and collimates the detection beam, respectively, in at least one dimension.

[0105] In a preferred embodiment of the method, the detector includes a position-sensitive detector of the impact of the detection beam, wherein the position-sensitive detector detects changes in the position of the impacting detection beam in at least one sensing direction.

[0106] The arrangement of the position-sensitive detectors such that the deflection of the detection beam causes a change in the position of the detection beam striking it in the at least one sensing direction, and

[0107] The cylindrical lens is disposed in the optical path of the detection beam to shape the profile of the detection beam, and / or the position sensitive detector is arranged at an angle 90° away from the detection beam, such that the diameter of the detection beam striking the position sensitive detector in the sensing direction is at least 1.5 times larger than the diameter of the detection beam in the direction perpendicular to the sensing direction, preferably at least 2.0 times larger.

[0108] In a preferred embodiment of the method, the cylindrical lens is a collimating lens in the optical path of the detection beam between its reflection at the contact surface and the position-sensitive detector, wherein the cylindrical lens collimates the detection beam at least primarily in a dimension perpendicular to the sensing direction of the position-sensitive detector, wherein the cylindrical collimating lens is preferably integrally formed with the exit surface of the measuring body, at which the detection beam exits from the measuring body.

[0109] In a preferred embodiment of the method, the light source beam is split into a detection beam and a reference beam, wherein the reference beam is also oriented at the surface of the measuring body in thermal or pressure-transmitting contact with the material, but is completely or partially reflected in a region where any effect of the heat or pressure wave received from the material upon absorption of excitation radiation is negligible, and wherein the degree of deflection of the reference beam after reflection at the contact surface is detected, particularly the deflection angle, preferably using a photodetector, particularly a position-sensitive photodetector.

[0110] In a preferred embodiment of the method, the detection includes using an interferometric measuring device that allows evaluation of the change in the phase of the detection beam and generation of a response signal indicating the change in phase.

[0111] In a preferred embodiment of the method, the measuring body or a component therein has electrical properties that change in response to local variations in temperature or pressure associated therewith, and the detection device includes electrodes for capturing electrical signals representing the electrical properties.

[0112] In a preferred embodiment of the method, an optical fiber is embedded in the measuring body, a detection light source is disposed at one end of the fiber for coupling detection light into the optical fiber, and a mode detector is disposed at the other end of the fiber, wherein the mode detector is used to detect changes in the optical mode of the detection light in response to thermal or pressure waves received by the measuring body from the material, wherein the changes in the optical mode preferably include a shift or rotation of the interference mode of the optical mode at the mode detector.

[0113] In a preferred embodiment of the method, the material is human tissue, particularly human skin, and the analyte is glucose present in the skin, particularly glucose present in the interstitial fluid of the skin.

[0114] Preferably, the method further includes the step of generating the excitation radiation using an array of lasers, particularly a quantum cascade laser, each of which has a dedicated wavelength.

[0115] Preferably, the method further includes the step of generating the excitation radiation using at least one tunable laser, particularly at least one tunable quantum cascade laser.

[0116] In a preferred embodiment of the method, some or all of the excitation wavelengths are in the range of 5 μm-13 μm, preferably 8 μm-11 μm.

[0117] Brief description of the attached figures

[0118] Figure 1 This is a schematic diagram illustrating the measurement principle according to some embodiments of this application.

[0119] Figure 2 The absorption spectrum of glucose in water after removing the water background is shown.

[0120] Figure 3 It is a schematic cross-sectional view of a device for analyzing materials that relies on a response signal based on the deflection of a detection beam.

[0121] Figure 4 Showing the use of Figure 3 Clarke error grid analysis results obtained from the device of the type shown.

[0122] Figure 5 This is a schematic diagram of a device for analyzing materials, which relies on a response signal based on a piezoelectric response to thermal and pressure waves received by the material being analyzed.

[0123] Figure 6 This is a schematic diagram of a device for analyzing materials, which relies on a response signal based on phase changes detected by interferometry in a detection beam.

[0124] Figure 7 This is a schematic cross-sectional side view of an apparatus according to one embodiment of this application.

[0125] Figure 8 yes Figure 7 A schematic diagram of the front view of the device in cross-section.

[0126] Figure 9 This is a schematic diagram showing a device for detecting the deflection of a light beam.

[0127] Figure 10 Is with Figure 9 Similarly, but with a schematic diagram of a device for detecting the refraction of the beam at the exit surface of the measuring body.

[0128] Figure 11 This is a schematic diagram illustrating the increased deflection using a curved reflective surface for detecting the beam.

[0129] Figure 12 Is with Figure 7 A schematic diagram of a similar device, wherein the position-sensitive detector is arranged at an angle relative to the detection beam.

[0130] Figure 13 Is with Figure 7 A schematic top view of a similar device, in which a reference beam is used in addition to the detection beam.

[0131] Figure 14 yes Figure 13 A perspective view of the device.

[0132] Figure 15 This is a schematic diagram of other devices, wherein the response signal corresponds to a change in optical mode formed in fibers contained in the measuring body.

[0133] Figure 16 This shows the relationship between the two when a thermal gradient is formed in the measurement volume and... Figure 15 The same device.

[0134] Figure 17 The device shown includes a clamping mechanism.

[0135] Figure 18 This is a top view of another apparatus used for measuring and analyzing interference signals based on two parts of a detection beam.

[0136] Figure 19 yes Figure 18 A perspective view of the device.

[0137] Figure 20 This is a schematic diagram of an apparatus in cross-sectional view according to an embodiment of the present application, wherein the protrusion is formed by a measuring body.

[0138] Figure 21 It is a perspective view of the supporting structure with the protrusion as part of the measuring body.

[0139] Figure 22 yes Figure 21 A top view of the supporting structure.

[0140] Figure 23 yes Figure 21 A cross-sectional view of a portion of the supporting structure.

[0141] Description of preferred implementation scheme

[0142] It should be understood that the foregoing general description and the following description are exemplary and illustrative only, and do not limit the methods and apparatus described herein. In this application, the use of the singular may include the plural unless expressly stated otherwise. Furthermore, the use of “or” means “and / or”, as applicable or otherwise specified. Those skilled in the art will recognize that the following description is illustrative only and is not intended to be limiting in any way. Other embodiments will readily inform such those skilled in the art who benefit from this disclosure. Various implementations of exemplary embodiments, as illustrated in the accompanying drawings, will now be referenced in detail. Throughout the drawings and the following description, the same reference numerals will be used to denote the same or similar items whenever possible.

[0143] Figure 1 This is a schematic diagram illustrating the measurement principle of the analyte measurement procedure outlined above, and is described in detail below. While the methods and apparatus of this application are applicable to the analysis of various materials including at least one analyte, the following description will focus on a specific embodiment where the material is a patient's skin and the analyte is glucose in interstitial fluid. It should be understood that all details and explanations given below specifically with reference to glucose measurement are also considered relevant to other materials and analytes (where applicable) that are not explicitly mentioned below.

[0144] exist Figure 1 In the illustration, the user's fingertip 12 is in thermal contact with the contact surface 14 of the measuring body 16. The fingertip can be acoustically coupled to the measuring body via an acoustic unit, which may include a hollow space filled with a liquid or gas that allows pressure waves to be transmitted to the measuring body. To determine the concentration of glucose in the skin, particularly in the interstitial fluid, various wavelengths of excitation radiation 18 are selected one after another, or at least partially, during absorption measurements, so that the glucose concentration can be determined from the measured absorption values. Figure 2 The image shows the absorption spectra of glucose at different concentrations in water, after subtracting the contribution from water absorption. As can be seen, glucose molecules exhibit several characteristic absorption peaks in the mid-infrared region, with wavenumbers ranging from 993 cm⁻¹. -1 and 1202cm -1 The values ​​between these two peaks correspond to wavelengths ranging from 10.07 μm to 8.32 μm. Local absorption minima can be observed between adjacent absorption peaks. Figure 2 The middle is indicated by a vertical arrow without wavenumber. From Figure 2It is evident that absorption differences, particularly at absorption peaks and local absorption minima, are characteristic of glucose concentration. Therefore, to determine glucose concentration, it is preferable to measure the absorption at some or all absorption peaks and some or all local absorption minima, and possibly also at a point between the maximum and minimum values. These wavelengths are referred to herein as “analyte (glucose) characteristic wavelengths.” While wavelengths precisely at absorption peaks or local absorption minima are preferred for glucose characteristic wavelengths, wavelengths close to the peaks / local minima but at separately defined distances can also be used. Thus, as understood herein, “analyte characteristic wavelengths” are also those where the absorption difference between the absorption at the closest absorption peak or closest local absorption minima is less than 30% of the absorption difference between the closest absorption peak and the closest local absorption minima, preferably less than 20%.

[0145] The intensity of the excitation beam 18 is time-modulated at a specific frequency f, such that the excitation radiation (in this case, the excitation light) has alternating intervals of high and low intensities, or even fading intensities. It is not desirable to restrict the modulation to any particular waveform; the high-intensity intervals are referred to hereinafter as "excitation light pulses." During the excitation light pulse, the excitation light, having the characteristic wavelength of glucose, is absorbed, and thus the radiant energy is converted into heat. Since glucose molecules relax from the excited state in approximately 10⁻¹² s, the generation of the corresponding thermal pulse and / or pressure wave can be considered instantaneous for all practical purposes.

[0146] Therefore, along with the excitation light pulse, a localized thermal pulse is generated at the absorption site, resulting in a temperature field that varies as a function of space and time, and can be termed a thermal wave. As explained above, the term "thermal wave" is somewhat misleading because the propagation of heat through the material is governed by a diffusion equation, not a wave equation. However, the concept of a "thermal wave" is correct at least to the extent that the thermal pulse propagates from within the skin to the surface 14 of the measuring body 16 and enters the measuring body 16, similar to what is used from wave propagation. The thermal gradient 20 induced by this thermal pulse in… Figure 1 It is shown schematically in the diagram.

[0147] The heat received by the measuring body 16 from the skin of the finger 12 causes a physical response, which can be detected by one of a variety of possible detection devices designed to generate a response signal based on the physical response, wherein the response signal indicates the degree of absorption of the excitation light. Various methods for detecting the physical response and generating an appropriate response signal will be described below.

[0148] However, regardless of the precise method of detecting the physical response, it is noteworthy that the maximum depth of absorption beneath the skin surface, which can be detected by means of a thermal pulse traveling to the measuring body 16, is found to be limited to the skin's thermal diffusion length μ. t A good approximation of , which is defined as

[0149]

[0150] And it depends on density ρ and specific heat capacity C. p and the thermal conductivity k of the material t And the modulation frequency f of the excitation light. In other words, by selecting the modulation frequency f, the depth to which any absorption of the excitation light is reflected in the thermal pulse received at the measuring body 16 can be defined.

[0151] Refer again Figure 1 In the illustrated embodiment, the physical response to absorbed heat received from the skin is a change in refractive index in a region near the surface 14 of the measuring body 16, where a thermal gradient 20 is temporarily formed. This localized change in refractive index creates something that can be considered a thermal lens, which can be detected by a detection beam 22. The detection beam 22 passes through the thermal lens or thermal gradient region 20 and is then reflected at the interface between the measuring body 16 and the skin of the finger 12. Whenever a thermal pulse is received from the skin, a localized change in refractive index occurs, and this causes the detection beam 22 to be deflected due to its interaction with the measuring body material in the thermal lens region. Figure 1 In this text, reference numeral 22b corresponds to the undeflected detection beam 22, while reference numeral 22a corresponds to the detection beam when it is deflected due to a thermal lens formed in the thermal gradient region 20. This deflection can be measured and forms an example of the response signal described above. The degree of deflection indicates the amount of heat received, and therefore also represents the degree of absorption of the excitation light 18 in the skin of the finger 12. In this document, "degree of deflection" may refer to a deflection angle, but more generally corresponds to any deviation between detection beams detectable by the corresponding detection device.

[0152] Figure 3 It shows dependence on references Figure 1 A more detailed cross-sectional view of the apparatus 10 illustrating the measurement principle is shown. The apparatus 10 includes a housing 24, which includes a measuring body 16 having a top surface (contact surface) 14 on which a finger 12 rests. Within the housing 24, an excitation source 26 is provided, which generates an excitation beam 18. In the illustrated embodiment, the excitation source 26 comprises a quantum cascade laser array, each quantum cascade laser having a dedicated wavelength. For example, the quantum cascade laser array may comprise a single quantum cascade laser element whose wavelength corresponds to... Figure 2The absorption peaks and local minima shown (i.e., characteristic wavelengths of glucose), as well as other wavelengths that can be used for reference measurements or for detecting other substances that may interfere with glucose measurements, such as lactate or albumin. The laser array can directly illuminate the measurement body 16 with an excitation beam that passes through it; however, it can also illuminate an optical waveguide (not shown) that couples the laser array to the measurement body and guides the excitation beam to the measurement body 16 in a bent or unbent manner. An optical waveguide can also be used when the excitation beam is generated by a single tunable laser.

[0153] The apparatus 10 also includes a light source 28, such as a laser, for emitting the detection beam 22, and a position-sensitive detector 30 that allows the detection beam 22 to be deflected. Note that, as understood herein, the term "beam" is not limited to light in the visible light range, although in a preferred embodiment, the detection beam 22 will indeed be in the visible spectrum. In this case, the measuring body 16 is able to transmit light through both the excitation beam 18 and the detection beam 22. Additionally, a camera 32 or other imaging device is provided, which allows the acquisition of an image of the contact surface 14 of the light medium 16 in a direction from inside the measuring body 16 to the finger 12, thereby recording the fingerprint of the finger 12 placed on the contact surface 14. This fingerprint can be processed by a control unit 34, such as for user identification via his or her fingerprint. The control unit 34 is also used to control the light sources 26 and 28 of the excitation and detection beams, and the sensor 30, respectively. The control unit 34 is also wirelessly connected to an external data processing device 36 to exchange data. For example, via wireless connection, the control unit 34 can retrieve user-specific calibration data via fingerprint identification. The control unit 34 and the external data processing device 36 together form an example of a "control system" as described herein. The control system can consist of one or more processors, microcontrollers, computers, ASICs, FPGAs, etc. Figure 3 As shown, the control system can be distributed, with various components communicating data with each other, or it can be formed by a single control unit, such as control unit 34, which will be designed for all the control functions described herein. The control system can typically be implemented in hardware, software, or a combination of both.

[0154] like Figure 3 As can be further seen, the excitation source 26, the detection source 28, and the position-sensitive detector 30 are all attached to the common carrier structure 38. This means that these components can be precisely pre-assembled on this structure 38, thus eliminating the need for separate adjustments or calibrations during the assembly of the device 10. One or more of the excitation source 26 and / or the detection source 28, as well as the position-sensitive detector 30, can also be directly mounted on the measuring body 16 to avoid additional adjustments or calibrations.

[0155] Additionally, device 10 includes a corneal measurement device 40, which allows for the measurement of skin moisture content. Corneal measurement devices for measuring the moisture content in the upper layer of skin are known in the art and need not be described in detail herein. For example, known corneal measurement devices use two interdigital electrodes to measure impedance, particularly the capacitive impedance of the skin, using an applied AC voltage. When the fingertip 12 rests against the contact surface 14 of the measuring body 16, Figure 3 The corneal measurement device 40 is in contact with the fingertip 12.

[0156] The device also includes a pH sensor 42 for measuring the pH value of the skin. pH sensors for measuring the pH value of surfaces, including the skin, are known in the prior art and do not require detailed description herein. pH sensors for measuring skin pH values ​​are commercially available for medical purposes but can also be used for cosmetic purposes.

[0157] Figure 4 Showing the use of Figure 3 The results of Clarke error grid analysis obtained by the device of the type shown illustrate that by referring to Figures 1-3 The measurement procedure described can indeed measure blood glucose concentration in a completely non-invasive manner with high reliability. Figure 4 The data shown is taken from WO 2017 / 09782A1 and does not yet reflect the improvements of this application. This application allows for, and even further improves, the reliability of the method, as described below.

[0158] Figure 5 The device 10 is schematically shown, which depends on and Figure 1 and Figure 3 The same general principle applies to absorbing the thermal pulses received by the measuring body 16 from the material 12, but the difference lies in the physical response utilized and the manner in which the corresponding response signal is generated. Such a device 10 and its numerous variations are described in detail in WO 2019 / 11059782, which is incorporated herein by reference, so that a detailed description may be omitted herein. As previously described, the device includes a measuring body 16 having a contact surface 14 that contacts or couples with the skin of the finger 12. Furthermore, a source 26 is provided for an excitation beam 18 with modulated intensity, which is irradiated into and absorbed in a region 44 below the surface of the skin 12. In this embodiment, the excitation beam 18 passes through an aperture 46 in the measuring body 16, indicated by a dashed line passing through the measuring body 16, such that the material of the measuring body 16 itself does not need to be permeable to it.

[0159] A control unit 48 is provided for modulating the intensity of the excitation beam 18. This can typically be achieved in various ways, including using a mechanical chopper or an element with electronically controllable transmittance or reflectivity. However, in a preferred embodiment, the intensity is modulated by modulating the on / off time of the excitation source 26 and the operating current during its on time.

[0160] A thermal wave (symbolically represented by arrow 50) caused by the time-varying absorption of the intensity-modulated excitation beam 18 in region 44 of the skin 12 enters the measuring body 16, where it can be detected in a detection region 52 with piezoelectric properties. The pressure change associated with the received heat 50 or pressure wave results in an electrical signal in the form of a voltage change, which can be recorded by electrodes 6a-6d connected via conductive leads 54 to an evaluation device 56 for analyzing the material (skin of finger 12). The evaluation device 56 can be a digital processing device, such as a microcontroller, processor, or computer. In this case, the pressure change is analogous to the physical response of the measuring body 16 or other components therein to heat received from the material 12 after absorbing excitation radiation, which is detected using the piezoelectric properties of the measuring body 16 or a portion thereof or embedded in the measuring body, and results in an electrical signal that generates a response signal indicating the degree of absorption of the excitation radiation 18.

[0161] In an alternative variation proposed by the applicant, such as by reference, to international application PCT / EP2019 / 064356 included herein, the detection device may include an interferometric apparatus that may be embedded in a measuring body, and which allows evaluation of the phase change of a first portion of the detection beam relative to a second portion of the detected beam, wherein only a portion of the detection beam through the measuring arm is affected by the effects of thermal or pressure waves in the measuring body, and a response signal indicative of the phase change in the measuring arm is generated on the output side of the interferometric apparatus. In this case, the physical response of the measuring body 16 (or components thereof) to the heat received from the material 12 after absorbing the excitation radiation 18 is again a localized change in refractive index, and in this case, the response signal is an interferometric signal reflecting the phase change of a portion of the detection beam due to the localized change in refractive index. This is in Figure 6 The diagram illustrates the measuring element 16 (such as a finger) that will come into contact with the material. Figure 6(Not shown in the image). In this case, the measuring body 16 may be a silicon substrate in which a light guide structure 58 is provided, which forms an interferometric measuring device 60. The interferometric measuring device 60 forms a Mach-Zehnder interferometer having a measuring arm 60a and a reference arm 60b. The detection light 22 generated by the detection light source 28 is fed into the light guide structure 58 and split by a beam splitter 60c into a portion or part of the detection beam traveling along the measuring arm 60a and a portion or part of the detection beam traveling along the reference arm 60b, which are then combined by a beam combiner 60d. The measuring body 16 is used or arranged such that the reference arm 60a is exposed to heat received from the skin after absorbing the excitation light, rather than, or at least to a much smaller extent, the reference arm 60b. Due to the received heat, the refractive index in the measuring arm 60a will change, which in turn causes a phase shift in the detection light 22 traveling along the measuring arm 60a. Since the light traveling along reference arm 60b is unaffected by the received heat, the relative phase of the two parts of the light combined by beam combiner 60d will change, resulting in an interference mode that can be detected using detector 62. It should be noted that... Figure 3 The camera shown for detecting and analyzing fingerprints can also be used with... Figure 5 and 6 The measuring body 16 and the device shown are combined.

[0162] Figure 7 A schematic diagram of the apparatus 10 according to an embodiment of this application is shown in a side sectional view. Figure 8 A front sectional view of the same device 10 is shown. Figure 7 and 8 In the illustrated embodiment, the material is also the skin of the user's finger 12, and the analyte to be evaluated is the glucose content in the skin, and in particular the glucose content in the interstitial fluid therein. Figure 7 and Figure 8 The implementation scheme allows for ensuring that the excitation radiation 18 is reliably and consistently delivered to the skin of the finger 12. Figure 7 and 8 The measuring body 16 shown is transparent to excitation radiation 18 and, in addition to the contact surface 14, has an incident surface 70 for excitation radiation 18. Figure 7 and 8 The bottom surface shown.

[0163] The measuring body 16 also has an incident surface 72 for detecting the beam 22. Figure 7In the illustration, the incident surface 72 corresponds to the left side wall, and the exit surface 74 corresponds to the right side wall. A focusing lens 76 and a collimating lens 78 are integrally formed with the incident surface 72 and exit surface 74, respectively. In the illustrated embodiment, the focusing and collimating lenses 76 and 78 are integrally formed with the rest of the measuring body 16. In other embodiments, the focusing and collimating lenses 76 and 78 may be formed separately from the measuring body 16, but may be attached to the incident surface 70 and exit surface 74 respectively, so that they do not require separate adjustment.

[0164] Furthermore, a protrusion 80 is formed on the contact surface 14 of the measuring body 16. The protrusion 80 has a front surface 82 that contacts the skin of the finger 12, and through this front surface 82, excitation radiation 18 formed by an excitation beam 18 in the mid-infrared range is radiated into the skin. The protrusion 80 has four sidewalls 84, each gradually narrowing towards the front surface 82. In this way, the area of ​​the front surface 82 is smaller than the area of ​​the footprint of the protrusion 80 on the contact surface 14. (As from...) Figure 7 and 8 The comparison shows that protrusion 80 is ridge-shaped, in the first direction, that is, located... Figure 7 It has a longer extension in the x-direction of the paper, and in the second direction perpendicular to the first direction, i.e., located in... Figure 8 There is a shorter extension in the y direction on the paper.

[0165] Finally, a pressure sensor 86 is disposed on the contact surface 14, which measures the contact pressure between the finger 12 and the contact surface 14. The pressure sensor 86 is connected to the control system, such as... Figure 3 Control unit 34 (not shown).

[0166] Next, we will explain Figure 7 and 8 The functions of the various features shown. For example... Figure 7 As shown, the incident surface 70 of the excitation radiation 18 is not parallel to the contact surface 14 or the front surface 82 of the protrusion 80. Instead, the measuring body is slightly wedge-shaped. Furthermore, the excitation source 26 is arranged such that the excitation beam 18 strikes the incident surface at an angle deviating from 90°.

[0167] This is similar to, for example Figure 3 The arrangements shown are different. Figure 3The excitation beam is intentionally struck at a 90° angle onto the incident surface to avoid refraction and excessive reflection of the excitation radiation beam at the incident surface. However, as explained above, with this arrangement, some of the excitation radiation 18 will be reflected from the incident surface 70, potentially interfering with the excitation radiation 18 emitted from the excitation radiation source 26. The inventors have found that this interference can cause fluctuations in the intensity of the excitation radiation 18 in the skin of the finger 12, resulting in artificial variations in the response signal that are completely unrelated to the analyte concentration. However, this can be suppressed by avoiding perpendicular incidence of the excitation beam 18 onto the incident surface 70. Figure 7 The interference between the incident radiation 18 and the reflected radiation 18' shown can be reduced, and the overall accuracy and reliability of the measurement can be improved.

[0168] In a preferred embodiment, the angle of incidence should deviate from 90° by only a few degrees (if any). A favorable angle of incidence may be 89.0° or less, preferably 88.0° or less, and more preferably 87.5° or less. The optimal choice of angle will also depend on the distance between the excitation radiation source 26 and the incident surface 70. The deviation from 90° should not be chosen to be greater than the deviation required to reliably avoid undesirable interference effects. In a preferred embodiment, the angle of incidence is therefore 82.0° or greater, preferably 84.0° or greater, and most preferably 85.0° or greater.

[0169] The protrusion 80 has the special technical effect of increasing the local contact pressure between the finger 12 and the measuring body 16. More precisely, the increased contact pressure occurs at the front surface 82 of the protrusion 80, which is where the excitation beam 18 is coupled from the measuring body 16 into the skin of the finger 12. This increased contact pressure allows for good and reliable optical coupling between the measuring body 14 and the skin.

[0170] The inventors were surprised by the significant improvement that can be obtained using the protrusion 80, because usually, sufficient optical coupling with a completely flat contact surface 14 is obtained in the applicant's previous device, making the additional manufacturing cost and increased complexity involved in providing the protrusion 80 not obviously worthwhile.

[0171] However, the inventors have found that while optical coupling with a perfectly flat contact surface 14 generally appears satisfactory, particularly inconsistent or unstable optical coupling can be a source of measurement inaccuracies. As explained in the overview above, the inventors note that optical coupling can change during a single measurement, i.e., without intentionally moving a fingertip to or even away from the contact surface. In some cases, this has been found to lead to variations in the intensity of the excitation radiation actually absorbed by the analyte, and thus to variations in the response signal that are independent of the analyte's absorbance at the excitation wavelength or analyte concentration. In other words, a loss of optical coupling during a portion of the measurement can be misinterpreted as a decrease in absorbance at a given excitation wavelength. As explained above, evaluating an analyte spectrum typically involves measuring absorption at multiple characteristic wavelengths, such as wavelengths corresponding to peaks or local absorption minima in the analyte absorption spectrum, and also involves mathematical combinations of response signals associated with different wavelengths. For example, the response signal obtained at a local minimum in the absorption spectrum can be subtracted from the response signal at the absorption peak to give a value representing the glucose concentration in the skin. Clearly, between measurements at different wavelengths, or even during measurements at a specific wavelength, any variation in optical coupling in the material and therefore the effective intensity of the excitation radiation can lead to artifacts or inaccuracies in the measurement results.

[0172] As explained in the overview of this application, it is not entirely clear why the optical coupling between the contact surface and the material should change during measurement, for example, whether it is because the user fails to maintain a constant contact pressure between their finger and the contact surface, or because the user inadvertently moves their fingertip on the contact surface. Regardless of the specific underlying cause, the inventors note that using methods such as Figure 7 and 8 The protrusion 80 shown has its front surface 82 in contact with the skin of the finger 12, where increased local contact pressure significantly stabilizes optical contact. The front surface can have a size of less than 5 mm. 2 Especially less than 3mm 2 It can be flat or curved in a concave or convex manner.

[0173] To further ensure constant contact pressure during measurement, a pressure sensor 86 is provided. The pressure sensor 86 generates a signal indicating the contact pressure between the finger 12 and the contact surface 14 of the measuring body 16. This signal is transmitted to a control system (not shown), which is configured to check if the sensed contact pressure is below a predetermined threshold. If this is found, it is indicated to the user via an appropriate output device, such as a display, light signal, sound signal, etc., prompting the user to increase the contact pressure. Furthermore, the control system is configured to prevent the analyte measurement process from starting when the contact pressure is below the threshold, thereby avoiding measurements of questionable quality that may have to be repeated, potentially causing user impatience or frustration. Additionally, if the contact pressure is found to drop below the threshold during measurement, the analyte measurement process is interrupted, giving the user another opportunity to restore the original contact pressure so that the measurement can be completed. The pressure sensor may also be located below a protrusion 80 in the measuring body 16 and implemented as a piezoelectric element (not shown) through which an excitation beam can pass.

[0174] Note that, so far, references Figure 7 Each feature and function explained relates to reliably coupling a consistent amount of excitation radiation into the skin of the finger 12, and is therefore independent of the specific type of physical response of the measuring body (or its components) to the thermal or pressure waves received from the skin of the finger 12 or the detection device that generates the corresponding response signal. Thus, these features can be associated with... Figure 1 , 3 Any of the variations shown in 5 and 6 can be used in combination.

[0175] exist Figure 7 In one embodiment, the physical response of the measuring body 16 to a thermal or pressure wave is a localized change in refractive index, and this physical response is detected by deflection of the detection beam 22 reflected at the front surface 82 of the protrusion 84. Figure 7 As shown, the detection beam 22 is generated by the detection light source 28, and the deflection of the detection beam 22 is detected using a position-sensitive detector (PSD) 30 (which may also be called a position-sensitive device). As understood herein, "deflection of the detection beam 22" refers to the total deviation of the detection beam at the corresponding detection device, and specifically refers to... Figure 7 The implementation scheme represents the positional deviation of the detection beam 22 on the PSD30. This deviation is a combined effect of all changes in the propagation of the detection beam 22 along its optical path caused by local variations in the refractive index.

[0176] Figure 7 and Figure 8 The specific ridge geometry of the protrusion 80 shown is adapted to this detection setup. The detection beam 22, reflected before and after the protrusion 80's front surface 82, defines a detection light plane. Figure 7 and Figure 8 In the implementation scheme, the detection light plane corresponds to the xz plane, i.e. Figure 7 The paper surface, and the position of the detection surface is aligned with the first elongated direction of the ridge protrusion 80. In fact, as from... Figure 7 Clearly visible, this significant extension of the protrusion 80 in the detection light plane is necessary to allow the incident and reflected detection beam 22 to conform into the protrusion 80. Conversely, as from... Figure 8 It is clearly visible that, in the direction perpendicular to the detection light plane, i.e., in the "second direction" of the ridge protrusion 80, the extension can be made much smaller, thereby keeping the surface area of ​​the front surface 82 as a whole smaller and thus increasing the local contact pressure.

[0177] Furthermore, the focusing lens 76 at the incident surface 72 of the detection beam 22 allows the detection beam diameter 22 to remain narrow in the area reflected on the front surface 82 of the protrusion 80, which is also the area where a thermal lens will form. Figure 7 (Not shown in the image). The narrow beam diameter facilitates the clarity and characteristic deflection of the detection beam 22 at the thermal lens, which itself has a relatively small size.

[0178] The collimating lens 78 at the exit surface 74 of the detection beam 22 allows the diameter of the detection beam 22 to remain at least nearly constant during its travel between the exit surface 72 and the PSD 30. This means that any deflection angle obtained by the detection beam 20 will result in a significant shift in the position where the detection beam 22 strikes the PSD 30, thereby increasing the signal-to-noise ratio of the response signal. For example, the distance between the reflective portion at the front surface 82 of the protrusion 80 and the PSD 30 can be 4 cm or more, and in some embodiments even 9 cm or more.

[0179] exist Figure 7 In the illustrated embodiment, both the focusing lens 76 and the collimating lens 78 are shown as spherical lenses with focusing and collimating effects in both principal directions. However, in other embodiments, particularly the collimating lens 78, it may be a cylindrical lens, which only... Figure 7 It has a collimation effect in the y-direction, and with Figure 7 The difference shown is that the detection beam 20 can be in the xz plane, i.e. Figure 7 The light spot is unfolded on the paper. This means that the spot of the detection beam 22 on the PSD 30 will be elliptical, with the longer diameter parallel to the sensing direction of the PSD 30, which is also the direction in which the light spot moves after the detection beam 20 is deflected. This elongated shape of the light spot has also been found to result in a better signal-to-noise ratio and better linearity of the response signal.

[0180] As understood herein, the “deflection” of the detection beam 20 relates to the total deviation of the detection beam 20 from its “undisturbed” optical path, i.e., the absence of localized changes in refractive index due to heat or pressure waves received by the measuring body 16, as measured by a detection device such as PSD 30. Therefore, this “deflection” is the cumulative effect of localized changes in refractive index along its optical path on the detection beam 20. In practice, deflection tends to be very small, and improving the signal-to-noise ratio of the response signal is important to obtain more accurate and reliable measurement results. (See above for reference...) Figure 7 One possible method is explained, namely, increasing the distance between the exit surface 74 and PSD 30. (See below for reference.) Figure 9-11 Other methods to improve the signal-to-noise ratio are discussed.

[0181] Do not want to be bound by theory Figure 9 The deflection mechanism as currently understood by the inventors is shown, and this mechanism is completely consistent with actual measurements. Figure 9 In the image, the undisturbed detection beam is shown as a solid line, having an incident portion 22 and an exit portion 22b. When the excitation radiation pulse 18 is... Figure 12 When absorbed by the skin, as explained above, a thermal pulse is generated. This thermal pulse travels through the skin and into the measuring body 16, where it causes a localized change in refractive index, referred to herein as a "thermal lens," and is schematically shown. Figure 9 Reference symbol 20 is used in this embodiment. In this embodiment, the thermal lens 20 is found to be a region of increased refractive index, which results in refraction as shown by the dashed line and the reflection detection beam 20a. The deviation between the reflection detection beam 22a and the undisturbed reflection detection beam 22b is referred to herein as "deflection".

[0182] Note that in Figure 9 In this configuration, the incident surface 72 and the exit surface 74 of the measuring body 16 are at an angle to form right angles with the incident and exit detection beams 22. This orthogonal arrangement of the optical boundaries is a natural choice in this field because it allows for reduced reflection and avoids diffraction, which would complicate the optical setup. However, in… Figure 10 In one embodiment, at least the exit surface 74 is arranged such that the detection beam 22b is not perpendicular to the reflected beam. Instead, the detection beam 22b forms an angle α1 with respect to the normal of the exit surface 74, such that the undisturbed detection beam 22b is refracted when it leaves the measuring body 16 at an angle β1 greater than α1, because the refractive index of the measuring body 16 is higher than the refractive index of the surroundings, which in this embodiment is air.

[0183] The deflected beam 22a is also refracted at the exit surface 74. However, due to the interaction with the thermal lens 20, the incident angle α... 2The refracted beam 22b is larger than the undisturbed detection beam, and according to Snell's law, the refraction angle β2 is significantly larger than β1. In other words, the difference between the refraction angles β2-β1 is greater than the difference between the incident angles α2-α1, i.e., β2-β1>α2-α1, thus increasing the refraction angle through PSD 30 ( Figure 10 The deflection of the reflected detection beam 22a (not shown in the image) was measured. This allows for a further increase in the signal-to-noise ratio.

[0184] Finally, refer to Figure 11 The image shows an embodiment in which the contact surface 14 of the measuring body 16 is curved in the region where the detection beam 22 is reflected. In other words, the measuring body in this region has a concave, curved recess. Figure 11 As schematically illustrated, due to local variations in refractive index, partial deflection of the detection beam 22 occurs before it is reflected at the surface of the measuring body in thermal or pressure-transmitting contact with the finger 12. This means that local variations in refractive index also cause a shift in the precise position at which the detection beam 22 is reflected on the surface.

[0185] Given this understanding, in Figure 11 In the illustrated embodiment, the contact surface 14 has a curved portion 88. Due to this curvature, the change in the precise position of the detection beam 22 reflected on the curved portion 88 is accompanied by a change in the angle of incidence, and thus also results in a corresponding change in the reflection angle, such as... Figure 11 This is visible in the image. Therefore, using a curved reflective surface can increase the total deflection assessed by the detection device, such as the positional offset of the impact detection beam 22 detected by the position-sensitive detector 30, thereby further allowing for an increase in the signal-to-noise ratio. Note that in Figure 11 In the diagram, the curved portion 88 is shown as being formed in the otherwise flat contact surface 14, but the curved portion can also be formed in... Figure 7 and Figure 8 In the front surface 82 of the protrusion 80 shown. Furthermore, although in Figure 11 In the embodiment shown, the curved portion 88 is concave, but a similar effect can also be achieved using a convex curved portion (not shown), because in this case, the local change in refractive index will also be accompanied by a change in the position where the detection beam strikes the curved portion, and thus also by a change in the incident angle.

[0186] In addition, Figure 11In the present embodiment, the curved portion 88 is shown to have a spherical shape, i.e., it has the same or similar curvature in two principal directions. However, in other embodiments, the curved portion 88 may be curved primarily or even exclusively in only one direction, for example, having a cylindrical cross-sectional shape (the cross-sectional plane is parallel to the axis of the cylinder). This is particularly advantageous in the case of a concave curved portion 88, in which case the finger 12 can be placed parallel to the longitudinal axis of the concave curved portion, thereby allowing particularly good contact on the curved surface of the curved portion. As described above, in a preferred embodiment, the radius of the curved portion 88 in at least one principal direction ranges from 5 to 30 mm, more preferably 10 to 20 mm. In a preferred embodiment, the width of the curved region 88 in the principal direction is at least 300 μm and at most twice the radius of curvature.

[0187] As described above, in many embodiments, it is advantageous if the spot of the detection beam 22 on the PSD 30 has an elongated shape, such as an ellipse, with its major axis parallel to the detection direction. For example, this elongated shape can be obtained by collimating the detection beam 22 only in a direction perpendicular to the detection direction, as referenced above. Figure 7 As explained. However, alternatively or otherwise, the elongated shape of the light spot can be obtained by tilting the PSD 30 relative to the detection beam 22 in the detection light plane, as... Figure 12 As shown, it impacts the PSD 30 at an angle deviating from 90°. For example, the angle at which it is incident on the detection surface of the PSD 30 can be less than 80°, preferably less than 70°, and most preferably less than 50°.

[0188] Figure 13 and 14 The top view and perspective view show the relationship with Figure 7 Another similar device 10. With Figure 7 The device is similar to that of the device. Figure 13 and Figure 14 The apparatus includes a detection beam 22 reflected on the contact surface 14 of the measuring body 16 and a detection device, such as a PSD 30, that allows detection of the deflection of the detection beam 22 due to interaction with a thermal lens indicated at reference mark 20. Figure 13 and 14In this embodiment, the detection beam 22 is led out from the light source beam 88 via a beam splitter 90. The beam splitter 92 transmits a portion of the light source beam 88 that forms the detection beam 22 and reflects another portion that forms the reference beam 92. Using a mirror 94, the reference beam 92 is similarly guided to be wholly or partially reflected at the surface 14 of the measuring body 16 at a location close to the reflection position of the detection beam 22, and particularly in the area where the finger 12 (not shown) will contact the contact surface 14 during operation. However, the reflection point of the reference beam 92 on the contact surface (or more precisely, at the interface between the contact surface 14 and the material, i.e., the finger 12) is sufficiently far from the area where the excitation beam 18 is absorbed, such that any effect of thermal or pressure waves received from the finger 12 after the excitation radiation 18 is absorbed is negligible. This is as follows: Figure 13 and 14 As shown, the thermal lens 20 does not extend to the area where the reference beam 92 is reflected on the contact surface 14 of the measuring body 16.

[0189] exist Figure 14 In the diagram, reference marker 93 indicates the points where the detection beam 22 and the reference beam 92 enter and exit the measurement body 16, and is primarily shown to aid in imaging the three-dimensional structure. Note that in Figure 14 In the schematic diagram, for simplicity, refraction is not shown at the incident and exit surfaces for the detection beam 22 and the reference beam 92. Another detection device 96 is provided for detecting the degree of deflection of the reference beam 92, and in the illustrated embodiment, it is formed of a PSD of the same type as PSD 30.

[0190] As can be seen, the reference beam 92 will be exposed to all or almost all types of noise, vibration, disturbance, or external influences, the same as those of the detection beam 22, except for the effects of the thermal lens 20, or in other words, the thermal or pressure waves received due to absorption by the excitation beam 18. Therefore, all or at least most types of external influences that could cause deflection of the detection beam 22, except those attributable to absorption in the material, will also affect the reference beam 92 and can be measured by the additional detector 96. The measurement results of the additional detector 92 relative to the reference beam 92 can then be used to correct for these effects in the measurement results of the PSD 30 relative to the detection beam 22, thereby improving the quality of the measurement signal.

[0191] refer to Figure 15 and Figure 16Another embodiment of the device is shown, comprising an optical fiber 98 embedded in a measuring body 16. A detection light source 28 is provided at one end of the fiber 98 for coupling detection light into the fiber 98. A pattern detector 100 is provided at the other end of the fiber 98. The pattern detector 100 is adapted to detect the optical pattern of the detection light in response to changes in thermal and pressure waves received by the measuring body 16 from the material. For example, the pattern detector 100 may include a camera suitable for visualizing the pattern, and more precisely, the interference pattern of the optical pattern. Figure 15 On the right, an image generated by this mode camera is schematically shown, in which optical mode 104 can be seen in a specific rotational direction, and more precisely, the interference mode of the optical mode can be seen.

[0192] Figure 16 Showing with Figure 15 The same device, however, due to the difference from such as finger 12 ( Figure 15 and 16 The material (not shown in the image) receives heat or pressure waves, creating a thermal gradient 20. This will cause instantaneous deformation of the optical fiber 98, such as... Figure 16 The magnified portion is shown, where the distortion is highly magnified for illustrative purposes. This instantaneous distortion of fiber 98 will result in a change in the optical pattern detected by the pattern camera 100. Figure 16 In the exemplary embodiment shown, the change in mode is equivalent to the rotation of the interference mode, such as by... Figure 15 and Figure 16 The comparison of the pattern images is shown schematically. In other embodiments, the change in pattern may correspond, for example, to an offset of the interfering pattern.

[0193] In the illustrated embodiment, the pattern detector 100 includes a processor (not shown separately) configured to detect changes in the pattern based on image analysis of the camera images. As described above, detectable changes in the optical pattern can include a shift or rotation of the interference pattern of the optical pattern within the fiber and on the pattern camera 100. Therefore, the shift distance or rotation angle is a quantitative parameter related to the intensity of heat or pressure waves received from the material, and thus ultimately indicates the amount of excitation light absorbed by the material. Figure 15 and Figure 16 The advantage of this device is that it is very simple, robust, and requires almost no adjustments to the optical components. It is particularly suitable for portable devices.

[0194] Figure 17 A side view and perspective view of a device 10 according to another embodiment are shown. Device 10 is a portable glucose measuring device with a size similar to a small smartphone. Figure 17The top view shows a measuring body 16 with a contact surface 14, in which the measuring body has a contact surface 14 with the contact surface 14. Figure 11 Similar curved sections. On contact surface 14, it is possible to... Figure 17 The finger 12 is positioned as shown, where the finger 12 is schematically represented only by a cylindrical structure. Although Figure 16 and 17 Other details of the device are not shown, but the measurement principle of the device is similar to... Figure 11 Similarly, a detection beam reflected on a curved surface (not shown) is used. See reference... Figure 11 This explains why the measurement beam is deflected particularly large, and therefore the signal-to-noise ratio is particularly high.

[0195] Figure 17 The clamping device 106 is further shown, including a clamping member 108. The clamping member 108 is pivotally mounted at a first end (left end in the figure) and biased by a torsion spring 114. Figure 17 In the closed position shown in the top view, the clamping member 108 is close to the contact surface 14. At the second end of the clamping member 108, a handle member 110 is provided, which allows the clamping member 108 to be gripped and rotated against the biasing force of the torsion spring 114 to the open position, wherein the clamping member 108 moves away from the contact surface 14 of the measuring body 16. When the clamping member 108 is in the open position, the finger 12 can be placed on the contact surface 14, and the clamping member 108 is adapted to press the finger 12 against the contact surface 14 due to the biasing force toward the closed position. This ensures a predetermined contact pressure. A pad 112 is formed near the second end of the clamping member 108 when the finger 12 is clamped by the clamping member 108. Figure 17 When held in the manner shown, the pad 112 rests against the finger 12. In the illustrated embodiment, a pressure sensor (not shown) is provided in the pad 112 to interact with... Figure 7 The pressure sensor 86 shown monitors contact pressure in a similar manner. Note that the clamping mechanism is not limited to use in handheld devices, but can also be installed, for example, in desktop devices or any other variant. Furthermore, the biasing force of the clamping member 108 does not need to be generated by a torsion spring such as torsion spring 114, but can also be provided by the clamping member 108 acting as a leaf spring. Instead of torsion spring 114, there can be an adjustable support that allows adjustment of the rest position of the clamping member 108 (leaf spring), and thus the resulting biasing force.

[0196] Figure 18 and Figure 19 Another device 10 is shown, which in some respects is similar to... Figure 13 and Figure 14 The devices have similar structures. For example... Figure 13 and 14 As shown in the implementation plan, for organizations such as human organizations ( Figure 18 and 19 The physical response to the absorption of excited radiation 18 in materials such as (without showing tissue and excited radiation 18) is a localized change in refractive index, where the region of localized refractive index change is again denoted by reference symbol 20. However, in this case, the response signal is an interference signal, similar to... Figure 6 The implementation scheme, rather than measuring the deflection of the beam, such as Figure 13 and 14 The implementation plan is as follows.

[0197] Figure 18 and Figure 19 The apparatus includes a detection beam 98, which is split in a transmission section 100 and a reflection section 102 by a beam splitter 90. The reflection section 102 is redirected by a mirror 104, such as being guided parallel to the transmission section 100, and both sections are located in a plane parallel to the contact surface 14 of the measuring body 16. Therefore, with Figure 13 and 14 The implementation schemes differ, with the transmission portion 100 and the reflection portion 102 not reflecting at the contact surface 14 of the measuring body 16.

[0198] The transmission portion 100 of the detection beam 98 passes through the region 20 where the refractive index locally changes, while the reflection portion 102 avoids this region. Using an additional mirror 104 and a combiner 106, the two portions 100 and 102 of the detection beam 98 are recombined, and the interference signal of the recombined portions 100 and 104 is recorded by an optical detector 108. Any change in the refractive index in region 20 will cause a phase change in the transmission portion 100, and thus a change in the interference signal at the detector 108. For larger local changes in refractive index, the phase change is larger, thus indicating the degree of absorption of the excitation radiation beam 18.

[0199] Notice, Figure 18 and Figure 19 The implementation is merely exemplary, and any variations in which two beams interfere, wherein only one beam passes through region 20 in the measuring body 16, which is exposed to thermal or pressure waves received from the material placed on the contact surface 14 after absorbing excitation radiation.

[0200] Although Figure 7 In one embodiment, the protrusion 80 is formed on the contact surface 14 of the measuring body 16, but this is not the only way to provide a protrusion. Conversely, the measuring body itself may also form a protrusion, or form part of a protrusion. An example of this is... Figure 20As shown, with Figure 7 Very similar, except that the measuring body 16 is much smaller in this case and forms a protrusion 80 itself. Furthermore, although in Figure 7 In the implementation scheme, the focusing lens 76 and the collimating lens 78 are integrated with the measuring body 16, but... Figure 20 In the implementation scheme, they are replaced by separate focusing lenses 112 and collimating lenses 114, respectively.

[0201] like Figure 20 As shown, the contact surface of the measuring body 16 forms a front surface 82 of a protrusion 80. Furthermore, the front surface 82 of the protrusion 80 is raised relative to the surrounding structure, in this case, the structure is formed by the outer shell wall portion 110.

[0202] In the illustrated embodiment, the size of the protrusion 80 formed by the measuring body 16 is... Figure 7 In the embodiments, the protrusions 84 on the contact surface 14 are of the same or similar size. Note that all descriptions and explanations provided above regarding "protrusions" formed on the contact surface of the measuring body also apply to protrusions formed by or at least partially formed by the measuring body 16.

[0203] Figures 21-23 Another embodiment is shown, in which the measuring body 16 forms part of the protrusion 80. More precisely, Figure 21 A mounting block 112 is shown, on which a measuring body 16 is mounted. The mounting block 112 has an upper surface 114, on which a protrusion 80 is again formed. In this case, the protrusion 80 is partially formed by a container 116, in which a recess 118 is formed. The measuring body 16 is mounted in a frame 120, which is received within the recess 118 of the container 116. In this case, the container 116, the frame 120, and the measuring body 16 combine to form the protrusion 80, which protrudes onto the top surface 114 of the mounting structure 112. Hereinafter, the contact surface of the measuring body 16 (…) Figure 21 The upper surface of the protrusion 80 forms part of the front surface of the protrusion 80, which is raised relative to the top surface 114. In this case, the top surface 114 forms the aforementioned "surrounding structure".

[0204] Figure 22 The top view shows the protrusion 80 and top surface 114 of the mounting structure 112. Figure 23 Showing along Figure 23 Cross-sectional view of line AA. Especially from... Figure 22 As can be seen, the frame 120 can rotate a few degrees around the vertical axis and can be fixed in the desired position by screws 122. Scales 124 are provided on the top surfaces of both the frame 120 and the container 116 to facilitate adjustment of the desired rotational position.

[0205] like Figure 23 As shown, in this embodiment, the excitation beam 18 is vertically upward. The axis of rotation of the skeleton 120 is aligned with the beam propagation axis of the excitation beam 18. When the contact surface 14 of the measuring body 16 is placed on the top surface 114 and the protrusion 80, it can be seen that the excitation beam 18 is irradiated into the material, wherein the contact surface 14 simultaneously forms part of the front surface of the protrusion, and particularly the portion through which the excitation beam 18 irradiates into the material. Furthermore, as Figure 23 As further shown, the front surface is raised relative to the surrounding structure, namely any top surface 114 of the mounting structure 112.

[0206] exist Figures 21-23 In the implementation scheme shown, the protrusions are 80%... Figure 7 or Figure 20 The protrusion shown is much larger. Figure 21-23 In one implementation, the protrusion 80 is designed for measurement on the underside of a person's wrist. Compared to a flat surface on which the arm is placed, the protrusion 80 was found to improve contact, and in particular, to improve the coupling of the excitation light 18 into the tissue.

[0207] Note that in Figures 1-23 In the embodiment shown, the contact surface 14 of the measuring body 16 forms only a portion of the top surface of the protrusion 80, but it forms the portion through which the excitation radiation 18 irradiates into the material.

[0208] By rotating the frame 120 within the recess 118 of the container 116, the angle of incidence of the detection beam 22 onto the incident surface 72 of the measuring body can be adjusted. As explained above, the detection beam 22 should be incident on the incident surface at an angle different from 90°, such as 89° or less, 88° or less, and for example 87.5° or less. This avoids back reflection of the detection beam 22 on itself, which could lead to undesirable interference effects and damage to the detection light source. Meanwhile, the deviation from 90° should not be greater than the deviation required for this purpose. Therefore, this angle is preferably 80° or greater, more preferably 80% or greater, such as 84° or 85° or greater.

[0209] This document further discloses the following embodiments:

[0210] Example 1:

[0211] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0212] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows heat or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0213] An excitation radiation source, configured to irradiate the material with excitation radiation for absorption therein, and

[0214] A detection device for detecting the physical response of a measuring body or a component thereof to a thermal or pressure wave received from the material after absorption of the excitation radiation, and for generating a response signal based on the detected physical response, the response signal indicating the degree of absorption of the excitation radiation, wherein a pressure sensor is provided for measuring the contact pressure between the material and the measuring body.

[0215] In a preferred embodiment of Example 1, the apparatus further includes a control system configured to receive a signal from the pressure sensor indicating the contact pressure between the material and the measuring body, wherein the control system is configured to check whether the contact pressure is lower than a predetermined threshold, and, if the contact pressure is found to be lower than the threshold, perform one or more of the following:

[0216] Inform the user of the lack of contact pressure.

[0217] To prevent the analyte measurement process from starting, and

[0218] Interrupt the current analyte measurement process.

[0219] Example 2:

[0220] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0221] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows heat or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0222] An excitation radiation source, configured to irradiate the material with excitation radiation for absorption therein, and

[0223] A detection device for detecting the physical response of a measuring body or a component therein to a thermal or pressure wave received from the material after absorption of said excitation radiation, and for generating a response signal based on said detected physical response, the response signal indicating the degree of absorption of the excitation radiation.

[0224] The measuring body is permeable to the excitation radiation.

[0225] The excitation radiation source is configured to provide the excitation radiation as an excitation beam, and

[0226] The excitation radiation source is arranged such that the excitation beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the contact surface.

[0227] The excitation beam strikes the incident surface at an angle of 89.0° or less, preferably 88.0° or less, and most preferably 87.5° or less, and 82.0° or greater, preferably 84.0° or greater, and most preferably 85.0° or greater.

[0228] In a preferred embodiment of Example 2, the excitation beam strikes the surface of the measuring body at an angle of 90°±1.5°.

[0229] In a preferred embodiment of Example 2, the incident surface and the contact surface are tilted relative to each other at an angle of 1.0° or greater, preferably 2.0° or greater, and most preferably 2.5° or greater, and 8.0° or less, preferably 6.0° or less, and most preferably 5.0° or less, at their respective points where the excitation beam enters and exits the measuring body.

[0230] Example 3:

[0231] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0232] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows heat or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0233] An excitation radiation source, configured to irradiate the material with excitation radiation for absorption therein, and

[0234] A detection light source is used to generate a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, wherein the detection beam is directed to be fully or partially reflected at the contact surface, and wherein thermal or pressure waves generated by excitation radiation absorbed in the material are deflected after being transmitted to the measuring body.

[0235] A detector is used to detect the degree of deflection of the detection beam, particularly the deflection angle, after it is reflected at the contact surface.

[0236] The contact surface of the measuring body is bent in at least one main direction in the region where the detection beam is reflected.

[0237] In a preferred embodiment of Example 3, the bend in the at least one main direction corresponds to a radius bend in the range of 5-30 mm, preferably 10-20 mm.

[0238] In a preferred embodiment of Example 3, the bend in the main direction is either concave or convex.

[0239] In a preferred embodiment of Example 3, the detection beams before and after reflection at the front surface form a detection light plane, wherein the main direction is located within the detection light plane or forms an angle of less than 30°, preferably less than 20° with the detection light plane.

[0240] Example 4:

[0241] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0242] A measuring body having a contact surface suitable for thermal or pressure-transferring contact with the material, wherein the thermal or pressure-transferring contact allows thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0243] Configuration of an excitation radiation source for irradiating the material with excitation radiation for absorption therein, and

[0244] A detection light source is configured to generate a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, wherein the detection beam is oriented to be fully or partially reflected at the contact surface, and wherein the detection beam is deflected in response to thermal or pressure waves generated by excitation radiation absorbed in the material being transmitted to the measuring body.

[0245] A detector is used to detect the degree of deflection of the detection beam, particularly the deflection angle, after it is reflected at the contact surface.

[0246] The detection light source is arranged such that the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface.

[0247] The detection beam strikes the exit surface at an angle of 5° or greater, preferably 10° or greater, and most preferably 15° or greater, relative to the normal of the exit surface, such that the detection beam is refracted after leaving an unexpected surface of the measuring body, wherein the direction of the exit surface relative to the detection beam causes the deflection of the detection beam to increase the angle between the detection beam and the normal of the exit surface in response to the thermal or pressure wave transmitted to the measuring body.

[0248] Example 5:

[0249] An apparatus for analyzing a material containing at least one analyte, the apparatus comprising a measuring body having a contact surface adapted for thermal or pressure-transmitting contact with the material, the thermal or pressure-transmitting contact allowing thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0250] An excitation radiation source, configured to irradiate the material with excitation radiation for absorption therein, and

[0251] A detection light source is configured to generate a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, wherein the detection beam is oriented to be fully or partially reflected at the contact surface, and wherein the detection beam is deflected in response to thermal or pressure waves generated by excitation radiation absorbed in the material being transmitted to the measuring body.

[0252] A detector is used to detect the degree of deflection of the detection beam after it is reflected from the contact surface, particularly the deflection angle.

[0253] The detection light source is arranged such that the detection beam is irradiated into the measuring body at the incident surface, propagates through a portion of the measuring body, and exits the measuring body at the exit surface, wherein a focusing lens is attached to or integrally formed with the incident surface to focus the detection beam, and / or a collimating lens is attached to or integrally formed with the exit surface.

[0254] Example 6:

[0255] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0256] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0257] Configuration of an excitation radiation source for irradiating the material with excitation radiation for absorption therein, and

[0258] A detection light source is configured to generate a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, wherein the detection beam is directed to be fully or partially reflected at the contact surface, and wherein the detection beam is deflected in response to thermal or pressure waves generated by excitation radiation absorbed in the material being transmitted to the measuring body.

[0259] A detector is used to detect the degree of deflection of the detection beam, particularly the deflection angle, after it is reflected at the contact surface.

[0260] The detector includes a position-sensitive detector for the impact of the detection beam, wherein the position-sensitive detector is sensitive to detecting positional changes of the detection beam impacting it in at least one sensing direction, wherein the position-sensitive detector is arranged such that the deflection of the detection beam causes a positional change of the detection beam impacting it in the at least one sensing direction, and wherein a cylindrical lens is provided in the optical path of the detection beam to shape the profile of the detection beam, and / or the position-sensitive detector is arranged at an angle 90° away from the detection beam such that the diameter of the detection beam impacting the position-sensitive detector in the sensing direction is at least 1.5 times larger, preferably at least 2.0 times larger, than the diameter of the detection beam in the direction perpendicular to the sensing direction.

[0261] In a preferred embodiment of Example 6, the cylindrical lens is a collimating lens in the optical path of the detection beam disposed between its reflection at the contact surface and the position-sensitive detector, wherein the cylindrical lens is arranged to collimate the detection beam primarily in a dimension perpendicular to the sensing direction of the position-sensitive detector, wherein the cylindrical collimating lens is preferably integrally formed with the exit surface of the measuring body, at which the detection beam exits from the measuring body.

[0262] Example 7:

[0263] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0264] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0265] Configuration of an excitation radiation source for irradiating the material with excitation radiation for absorption therein, and

[0266] A detection light source is configured to generate a detection beam that travels through at least a portion of the measuring body or a component included in the measuring body, wherein the detection beam is directed for complete or partial reflection at the contact surface, and wherein the detection beam is tilted in response to thermal or pressure waves generated by excitation radiation absorbed in the material being transmitted to the measuring body.

[0267] The detector, used to detect the degree of deflection, particularly the deflection angle, of the detection beam after reflection at the contact surface, further includes a beam splitter for splitting the light source beam into the detection beam and a reference beam, wherein the reference beam is also oriented at the surface of the measuring body in thermal or pressure-transmitting contact with the material, but is completely or partially reflected in a region where any effect of the heat or pressure waves received from the material during absorption of excitation radiation is negligible, and wherein the detection device includes additional detection equipment for detecting the degree of deflection, particularly the deflection angle, of the reference beam after reflection at the contact surface, wherein the additional detection equipment preferably includes a photodetector, particularly a position-sensitive photodetector.

[0268] Example 8:

[0269] An apparatus for analyzing a material comprising at least one analyte, the apparatus comprising:

[0270] A measuring body having a contact surface suitable for thermal or pressure-transmitting contact with the material, wherein the thermal or pressure-transmitting contact allows thermal or pressure waves generated by excitation radiation absorbed in the material to be transmitted to the measuring body.

[0271] Configuration of an excitation radiation source for irradiating the material with excitation radiation for absorption therein, and

[0272] A detection device for detecting the physical response of a measuring body or a component therein to a thermal or pressure wave received from the material after absorption of the excitation radiation, and for generating a response signal based on the detected physical response, the response signal indicating the degree of absorption of the excitation radiation, wherein the device includes a fiber embedded in the measuring body, a detection light source disposed at one end of the fiber for coupling detection light into the fiber, and a mode detector disposed at the other end of the fiber, the mode detector being adapted to detect changes in the optical mode of the detection light in response to changes in the thermal or pressure wave received by the measuring body from the material, wherein the changes in the optical mode preferably include a shift or rotation of the optical mode within the fiber.

[0273] Although this application has been described with reference to specific embodiments, it should be understood that variations and modifications will occur to those skilled in the art, all of which are intended as aspects of this application. Therefore, only the limitations that appear in the claims should be applied to this application.

Claims

1. An apparatus (10) for analyzing a material (12) comprising at least one analyte, the apparatus comprising: - A measuring body (16) having a contact surface (14) suitable for thermal or pressure transmission contact with the material (12), the thermal or pressure transmission contact allowing heat or pressure waves generated by excitation radiation (18) absorbed in the material to be transmitted to the measuring body. - An excitation radiation source (26) configured to irradiate the material (12) with excitation radiation (18) for absorption therein, and - A detection device for detecting the physical response of the measuring body or a component therein to a thermal or pressure wave received from the material (12) after absorption of the excitation radiation (18), and for generating a response signal based on the detected physical response, the response signal indicating the degree of absorption of the excitation radiation. The measuring body (16) is characterized in that it is transparent to the excitation radiation (18). The excitation radiation source (26) is configured to provide the excitation radiation (18) as an excitation beam, and The excitation radiation source (26) is arranged such that the excitation beam is irradiated into the measuring body (16) at its incident surface (70), propagates through a portion of the measuring body (16), and exits from the measuring body (16) at the contact surface (14). The excitation beam strikes the incident surface (70) at an angle of 89.0° or less and 82.0° or greater. The incident surface (70) and the contact surface (14) are inclined relative to each other at an angle of 1.0° or greater and 8.0° or less at the respective portions where the excitation beam enters and exits the measuring body.

2. The device (10) as claimed in claim 1, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80), The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure.

3. The device (10) of claim 2, wherein the front surface (82) is flat.

4. The device (10) of claim 2, wherein the protrusion (80) has a footprint area of ​​less than 0.3 cm².

5. The device (10) of claim 2, wherein the protrusion (80) has a tapered shape, wherein one or more sidewalls (84) gradually narrow toward the front surface (82).

6. The device (10) of claim 2, wherein the protrusion (80) has a circular, elliptical or square footprint.

7. The device (10) of claim 2, wherein the protrusion (80) is ridge-shaped, having a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, wherein the longer extension is at least 1.5 times greater than the shorter extension.

8. The apparatus of claim 2, wherein the measuring body (16) forming the protrusion (80) or a portion thereof is received in a frame or container, wherein the contact surface (14) of the measuring body (16) protrudes from the frame or container, or wherein the frame or container protrudes from a surrounding structure.

9. The apparatus (10) of claim 1 or 2, wherein a pressure sensor (86) is provided for measuring the contact pressure between the material (12) and the measuring body.

10. The apparatus (10) of claim 9, wherein the apparatus (10) further comprises a control system configured to receive from the pressure sensor (86) a signal indicating a contact pressure between the material (12) and the measuring body (16), wherein the control system is configured to check whether the contact pressure is lower than a predetermined threshold, and, if the contact pressure is found to be lower than the threshold, to perform one or more of the following: Inform the user of the lack of contact pressure. To prevent the analyte measurement process from starting, and Interrupt the current analyte measurement process.

11. The apparatus (10) of claim 1 or 2, wherein the apparatus further comprises a clamping device (106) comprising a clamping member (108) movable between an open position and a closed position, wherein in the open position the clamping member (108) moves away from the contact surface (14) of the measuring body (16), and in the closed position it moves closer to the contact surface (14), the clamping member (108) being biased toward the closed position, wherein when the clamping member is in the open position the material (12) is able to be placed on the contact surface (14), and wherein the clamping member (108) is adapted to press the material (12) onto the contact surface (14) due to the biasing force toward the closed position.

12. The apparatus (10) of claim 11, wherein the pressure sensor (86) is arranged on the clamping device (106).

13. The apparatus of claim 1 or 2, further comprising a strap for securing the material (12) to the contact surface (14) of the measuring body (16).

14. The apparatus (10) of claim 1 or 2, wherein the excitation beam strikes the incident surface (70) at an angle of 88.0° or less and 84.0° or greater.

15. The apparatus (10) of claim 14, wherein the excitation beam strikes the contact surface (14) of the measuring body at an angle of 90° ± 1.5°.

16. The apparatus (10) of claim 14, wherein the incident surface (70) and the contact surface (14) are inclined relative to each other at an angle of 2.0° or greater and 6.0° or less at the respective portions where the excitation beam enters and exits the measuring body.

17. The apparatus (10) of claim 1, wherein the detection device includes a light source (28) for generating a detection beam (22) that travels through at least a portion of the measuring body (16) or a component included in the measuring body (16). The physical response of the measuring body (16) to the thermal or pressure waves received from the material (12) after absorbing the excitation radiation (18) is a local change in the refractive index of the measuring body (16) or the component, and The detection device is configured to detect either the optical path change or the phase change of the detection beam caused by the change in refractive index.

18. The apparatus of claim 17, wherein the detection device is configured such that the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72), wherein the detection beam (22) strikes the incident surface (72) at an incident angle of 89° or less and 80° or greater relative to the incident surface.

19. The apparatus of claim 18, wherein the measuring body (16) is received in a frame or container to allow rotation of the measuring body (16) and adjustment of the incident angle of the detection beam when impacted on the incident surface (72) of the measuring body (16).

20. The apparatus (10) of claim 17, wherein the measuring body (16) is transmissible to the detection beam (22), the detection beam (22) being oriented to be fully or partially reflected at a surface (14) of the measuring body (16) in thermal or pressure transmission contact with the material (12), and wherein the detection device includes a detector (30) for detecting the degree of deflection of the detection beam (22) after reflection at the contact surface (14) due to the local variation in refractive index.

21. The apparatus (10) of claim 20, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80). The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure. The detection beam (22) is oriented to be fully or partially reflected at the front surface (82) of the protrusion (80) in thermal or pressure contact with the material (12).

22. The device (10) of claim 21, wherein the front surface (82) of the protrusion (80) is curved in at least one main direction.

23. The device (10) of claim 22, wherein the bending in the at least one main direction corresponds to a radius bending of 5-30 mm.

24. The device (10) of claim 22, wherein the bending in the at least one main direction is one of concave or convex.

25. The apparatus (10) of claim 22, wherein the detection beam (22) before and after reflection at the front surface (82) defines a detection light plane, and wherein at least one principal direction lies within the detection light plane or forms an angle of less than 30° with the detection light plane.

26. The apparatus (10) of claim 20, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80). The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure. The detection beam (22) before and after reflection at the front surface (82) defines a detection light plane, and a first direction is parallel to the detection light plane or forms an angle of less than 30° with the detection light plane.

27. The apparatus (10) of claim 20, wherein the detection light source (28) is arranged such that the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72), propagates through a portion of the measuring body, and exits the measuring body at the exit surface (74). The detection beam (22) strikes the exit surface (74) at an angle of 5° or greater relative to the normal of the exit surface (74) without any deflection due to the local variation in refractive index, such that the detection beam (22) is refracted after leaving the exit surface (74) of the measuring body (16), wherein the direction of the exit surface (74) relative to the detection beam (22) is such that the detection beam (22) increases the angle between the detection beam and the normal of the exit surface in response to the deflection of the thermal or pressure wave transmitted to the measuring body (16).

28. The apparatus (10) of any one of claims 20 to 27, wherein the detection light source (28) is arranged such that the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72), propagates through a portion of the measuring body (16), and exits from the measuring body (16) at the exit surface (74), wherein a focusing lens (76) is integrally formed with the incident surface (72) for focusing the detection beam (22) entering the measuring body (16) in at least one dimension, and / or a collimating lens (78) is integrally formed with the exit surface (74) for collimating the detection beam (22) in at least one dimension.

29. The apparatus (10) of claim 28, wherein at least one of the focusing lens (76) and the collimating lens (78) is a cylindrical lens that focuses and collimates the detection beam (22) at least primarily in one dimension.

30. The apparatus (10) of claim 20, wherein the detector (30) comprises a position-sensitive detector of the impact of the detection beam (22), wherein the position-sensitive detector is sensitive to changes in the position of the detection beam (22) impacting it in at least one sensing direction. The position-sensitive detectors are arranged such that, in the at least one sensing direction, the deflection of the detection beam (22) causes a change in the position of the detection beam striking it, and A cylindrical lens is disposed in the optical path of the detection beam (22) to shape the profile of the detection beam (22), and / or the position-sensitive detector is arranged at an angle offset from the detection beam (22) by 90°, such that the diameter of the detection beam (22) striking the position-sensitive detector in the sensing direction is at least 1.5 times larger than the diameter of the detection beam (22) in the direction perpendicular to the sensing direction.

31. The apparatus (10) of claim 30, wherein the cylindrical lens is a collimating lens (78) disposed at the contact surface (14) in the optical path of the detection beam (22) reflected between the position-sensitive detector (62), wherein the cylindrical lens is arranged to collimate the detection beam (22) at least primarily in a dimension perpendicular to the sensing direction of the position-sensitive detector.

32. The apparatus (10) of claim 20 further includes a beam splitter (90) for splitting the light source beam into the detection beam (22) and the reference beam (92), wherein the reference beam (92) is also oriented at a surface (14) of the measuring body (16) in thermal or pressure-transmitting contact with the material (12), but is completely or partially reflected in a region where any effect of the heat or pressure wave received from the material upon absorption of excitation radiation (18) is negligible, and wherein the detection device includes an additional detection device (96) for detecting the degree of deflection of the reference beam (92) after its reflection at the contact surface (14).

33. The apparatus (10) of claim 17, wherein the detection device includes an interferometric measuring device (60) to allow evaluation of the phase change of the detection beam and to generate a response signal indicating the phase change.

34. The apparatus (10) of claim 1 or 2, wherein the measuring body (16) or the components in the measuring body (16) have electrical properties that change in response to local temperature changes or pressure changes associated therewith, and wherein the detection device includes electrodes (6a-6d) for capturing electrical signals representing the electrical properties.

35. The apparatus (10) of claim 1 or 2, wherein the apparatus (10) comprises an optical fiber embedded in the measuring body, a detection light source disposed at one end of the optical fiber (98) for coupling detection light into the optical fiber (98), and a pattern detector (100) disposed at the other end of the optical fiber (98), the pattern detector (100) being adapted to detect an optical mode of the detection light in response to a change in the thermal or pressure wave received by the measuring body (16) from the material (12).

36. The apparatus (10) of claim 1 or 2, wherein the material (12) is human skin and the analyte is glucose present in the interstitial fluid of the human skin.

37. The apparatus (10) of claim 1 or 2, wherein the excitation radiation (18) is generated using an array of lasers, each laser having a dedicated wavelength.

38. The apparatus (10) of claim 1 or 2, wherein the excitation radiation (18) is generated using at least one tunable laser.

39. The apparatus (10) of claim 1 or 2, wherein some or all of the excitation wavelengths are in the range of 5 µm to 13 µm.

40. A method for analyzing a material (12) comprising at least one analyte, the method comprising: - The measuring body (16) having a contact surface (14) is brought into thermal or pressure-transmitting contact with the material (12), the thermal or pressure-transmitting contact allowing thermal or pressure waves generated by excitation radiation (18) absorbed in the material to be transmitted to the measuring body. - Irradiate the material (12) with excitation radiation (18) so that it is absorbed therein, and - Detect the physical response of the measuring body or its components to thermal or pressure waves received from the material (12) after absorption of the excitation radiation (18), and generate a response signal based on the detected physical response, the response signal indicating the degree of absorption of the excitation radiation. The measuring body (16) is characterized in that it is transparent to the excitation radiation (18). The excitation radiation source (26) provides the excitation radiation (18) as an excitation beam, and The excitation beam is irradiated into the measuring body (16) at its incident surface (70), propagates through a portion of the measuring body (16), and exits from the measuring body (16) at the contact surface (14). The excitation beam strikes the incident surface (70) at an angle of 89.0° or less and 82.0° or greater. The incident surface (70) and the contact surface (14) are inclined relative to each other at an angle of 1.0° or greater and 8.0° or less at the respective portions where the excitation beam enters and exits the measuring body.

41. The method of claim 40, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80). The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure.

42. The method of claim 41, wherein the front surface (82) is flat.

43. The method of claim 41 or 42, wherein the protrusion (80) has a footprint area of ​​less than 0.3 cm².

44. The method of claim 41 or 42, wherein the protrusion (80) has a tapered shape, wherein one or more sidewalls (84) gradually narrow toward the front surface (82).

45. The method of claim 41 or 42, wherein the protrusion (80) has a circular, elliptical or square footprint.

46. ​​The method of claim 41 or 42, wherein the protrusion (80) is ridge-shaped, having a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, wherein the longer extension is at least 1.5 times greater than the shorter extension.

47. The method of claim 40 or 41, wherein the contact pressure between the material (12) and the measuring body is measured.

48. The method of claim 47, further comprising the step of checking whether the contact pressure is lower than a predetermined threshold, and, if the contact pressure is found to be lower than the threshold, performing one or more of the following steps: Inform the user of the lack of contact pressure. To prevent the analyte measurement process from starting, and Interrupt the current analyte measurement process.

49. The method of claim 40 or 41, further comprising the step of securing the material (12) to the contact surface (14) using a clamping device (106), the clamping device (106) including a clamping member (108) movable between an open position and a closed position, the clamping member (108) being moved away from the contact surface (14) of the measuring body (16) in the open position and being close to the contact surface (14) in the closed position, the clamping member (108) being biased toward the closed position, wherein when the clamping member is in the open position, the material (12) is placed on the contact surface (14), and wherein the clamping member (108) presses the material (12) onto the contact surface (14) due to the biasing force toward the closed position.

50. The method of claim 49, wherein the pressure sensor (86) is arranged on the clamping device (106).

51. The method of claim 40 or 41, further comprising the step of securing the material (12) to the contact surface (14) using a strap.

52. The method of claim 40 or 41, wherein the excitation beam strikes the incident surface (70) at an angle of 88.0° or less and 84.0° or greater.

53. The method of claim 52, wherein the excitation beam strikes the contact surface (14) of the measuring body at an angle of 90° ± 1.5°.

54. The method of claim 52, wherein the incident surface (70) and the contact surface (14) are inclined relative to each other at an angle of 2.0° or greater and 6.0° or less at the respective portions of the measuring body where the excitation beam enters and exits.

55. The method of claim 40, wherein the detection comprises generating a detection beam (22) that travels through at least a portion of the measuring body (16) or a component included in the measuring body (16). The physical response of the measuring body (16) to the thermal or pressure waves received from the material (12) after absorbing the excitation radiation (18) is a local change in the refractive index of the measuring body (16) or the component, and The detection includes detecting either the optical path change or the phase change of the detection beam caused by the change in refractive index.

56. The method of claim 55, wherein the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72) such that the detection beam (22) strikes the incident surface (72) at an incident angle of 89° or less and 80° or greater relative to the incident surface.

57. The method of claim 56, wherein the measuring body (16) is received in a frame or container to allow rotation of the measuring body (16) and adjustment of the incident angle of the detection beam when impacted on the incident surface (72) of the measuring body (16).

58. The method of claim 55, wherein the measuring body (16) is transmissible to the detection beam (22), the detection beam (22) being oriented to be fully or partially reflected at a surface (14) of the measuring body (16) in thermal or pressure transmission contact with the material (12), and wherein the detection includes detecting the degree of deflection of the detection beam (22) after reflection at the contact surface (14) due to local changes in refractive index, wherein the detection is performed using a detector (30).

59. The method of claim 58, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80). The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure. The detection beam (22) is oriented to be fully or partially reflected at the front surface (82) of the protrusion (80) in thermal or pressure contact with the material (12).

60. The method of claim 59, wherein the front surface (82) of the protrusion (80) is curved in at least one main direction.

61. The method of claim 60, wherein the bending in the at least one main direction corresponds to a radius bending of 5-30 mm.

62. The method of claim 60 or 61, wherein the bend in the at least one main direction is one of concave or convex.

63. The method of claim 60, wherein the detection beam (22) before and after reflection at the front surface (82) defines a detection light plane, and wherein at least one principal direction lies within the detection light plane or forms an angle of less than 30° with the detection light plane.

64. The method of claim 58, wherein a protrusion (80) is provided, the protrusion having a front surface (82) facing the material (12) and in contact with the material when the material contacts the contact surface, and the excitation radiation (18) is irradiated into the material (12) through the front surface (82) of the protrusion (80). The protrusion (80) is formed on the contact surface (14) of the measuring body (16), or The measuring body (16) forms the protrusion or a portion of the protrusion, wherein the contact surface (14) of the measuring body (16) forms at least a portion of the front surface of the protrusion and is raised relative to the surrounding structure. The detection beam (22) before and after reflection at the front surface (82) defines a detection light plane, and a first direction is parallel to the detection light plane or forms an angle of less than 30° with the detection light plane.

65. The method of claim 55, wherein the detection light source (28) is arranged such that the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72), propagates through a portion of the measuring body, and exits the measuring body at the exit surface (74). The detection beam (22) strikes the exit surface (74) at an angle of 5° or greater relative to the normal of the exit surface (74) without any deflection due to local changes in refractive index, such that after leaving the exit surface (74) of the measuring body (16), the detection beam (22) is refracted, wherein the orientation of the exit surface (74) relative to the detection beam (22) causes the detection beam (22) to increase the angle between the detection beam and the normal of the exit surface in response to the deflection of the thermal or pressure wave transmitted to the measuring body (16).

66. The method of claim 55, wherein the detection beam (22) is irradiated into the measuring body (16) at the incident surface (72), propagates through a portion of the measuring body (16), and exits from the measuring body (16) at the exit surface (74), wherein a focusing lens (76) is integrally formed with the incident surface (72) for focusing the detection beam (22) entering the measuring body (16) in at least one dimension, and / or a collimating lens (78) is integrally formed with the exit surface (74) for collimating the detection beam (22) in at least one dimension.

67. The method of claim 66, wherein at least one of the focusing lens (76) and the collimating lens (78) is a cylindrical lens that focuses and collimates the detection beam (22) at least primarily in one dimension.

68. The method of claim 58, wherein the detector (30) comprises a position-sensitive detector of the impact of the detection beam (22), wherein the position-sensitive detector detects positional changes of the impacting detection beam (22) in at least one sensing direction. The arrangement of the position-sensitive detectors such that the deflection of the detection beam (22) causes a change in the position of the detection beam striking it in the at least one sensing direction, and A cylindrical lens is provided in the optical path of the detection beam (22) to shape the contour of the detection beam (22), and / or the position sensitive detector is arranged at an angle deviating from the detection beam (22) by 90°, such that the diameter of the detection beam (22) striking the position sensitive detector in the sensing direction is at least 1.5 times larger than the diameter of the detection beam (22) in the direction perpendicular to the sensing direction.

69. The method of claim 68, wherein the cylindrical lens is a collimating lens (78) in the optical path of the detection beam (22) disposed between its reflection at the contact surface (14) and the position-sensitive detector (62), wherein the cylindrical lens collimates the detection beam (22) at least primarily in a dimension perpendicular to the sensing direction of the position-sensitive detector.

70. The method of claim 55, wherein the light source beam is split into a detection beam (22) and a reference beam (92), wherein the reference beam (92) is also oriented at a surface (14) of the measuring body (16) in thermal or pressure-transmitting contact with the material (12), but is completely or partially reflected in a region where any effect of the heat or pressure wave received from the material upon absorption of excitation radiation (18) is negligible, and wherein the degree of deflection of the reference beam (92) after its reflection at the contact surface (14).

71. The method of claim 55, wherein the detection includes using an interferometric measuring device (60) that allows for the evaluation of phase changes of the detection beam and the generation of a response signal indicating the phase changes.

72. The method of claim 40 or 41, wherein the measuring body (16) or a component therein has electrical properties that change in response to local variations in temperature or pressure associated therewith, and wherein the detection device includes electrodes (6a-6d) for capturing electrical signals representing the electrical properties.

73. The method of claim 40 or 41, wherein an optical fiber is embedded in the measuring body, a detection light source is disposed at one end of the optical fiber (98) for coupling detection light into the optical fiber (98), and a pattern detector (100) is disposed at the other end of the optical fiber (98), wherein the pattern detector (100) is used to detect changes in the optical pattern of the detection light in response to thermal or pressure waves received by the measuring body (16) from the material (12).

74. The method of claim 40 or 41, wherein the material (12) is human skin and the analyte is glucose present in the interstitial fluid of the human skin.

75. The method of claim 41 or 42, further comprising the step of generating the excitation radiation (18) using an array of lasers, each laser having a dedicated wavelength.

76. The method of claim 40 or 41, further comprising the step of generating the excitation radiation (18) using at least one tunable laser.

77. The method of claim 40 or 41, wherein some or all of the excitation wavelengths are in the range of 5 µm to 13 µm.

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