Apparatus and method for analyte measurement with improved coupling of excitation radiation to analyte-containing materials - Patent Application 20070122999

Abstract

An apparatus (10) for analyzing a substance (12) containing at least one analyte, comprising: a measuring body (16) having a contact surface (14) suitable for being in thermal or pressure-transmitting contact with said substance (12); an excitation radiation source (26) configured to irradiate the substance (12) with excitation radiation (18) so that it is absorbed by the substance (12); and a detection device for detecting a physical response of the measuring body to heat or pressure waves received from said substance (12) upon absorption of said excitation radiation (18), and for generating a response signal indicative of the degree of absorption of the excitation radiation, wherein the measuring body has a protrusion (16a). The device (10) includes a protrusion (80) having a front surface (82) facing the substance (12) and contacting the substance when the substance is brought into contact with the contact surface, the excitation radiation (18) is irradiated onto the substance (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 part of the protrusion, and 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] The present invention relates generally to devices and methods for analyzing substances, for example fluids, containing at least one analyte, and in particular to devices and methods for the non-invasive measurement of analytes in body fluids, such as glucose concentration in human skin, especially in the interstitial fluid of human skin. [Background technology]

[0002] The present invention relates to an apparatus and method for analyzing a substance comprising at least one analyte, the apparatus comprising a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with said substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in said substance to be transferred to said measuring body.

[0003] The apparatus further comprises an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material, and a detection device for detecting a physical response of the measuring body or a component comprised in the measuring body to heat or pressure waves received from the material upon absorption of said excitation radiation, and for generating a response signal based on said detected physical response, wherein the response signal is indicative of the degree of absorption of the excitation radiation.

[0004] The present invention is not limited to any particular physical response to heat or pressure waves received from the material upon absorption of excitation radiation, nor is it limited to any particular method of detecting this physical response so as to enable generation of a response signal indicative of the degree of absorption of excitation radiation. Various physical responses and corresponding detection methods have previously been proposed by the applicant for these types of analyte measurement procedures, and are briefly summarized below, each of which may be applied to the present invention.

[0005] For example, the detection device may comprise a light source for generating a detection light beam which travels through at least a part of the measuring body or a component contained in the measuring body, and the physical response of the measuring body to heat or pressure waves received from the material upon absorption of the excitation radiation may be a local change in the refractive index of the measuring body or the component, in which case the detection device may be configured to detect one of a change in the optical path or a change in the phase of the detection light beam due to the change in the refractive index of the material of the measuring body or the component contained in the measuring body.

[0006] For example, in various methods and devices described in detail in the applicant's two previous applications published as WO 2015 / 193310 and WO 2017 / 097824, both of which are incorporated herein by reference, the measuring body is transparent to the detection light beam, which is directed to be totally or partially reflected at a surface of the measuring body that is in thermal contact with the substance. In this case, the detection device may comprise an optical detector, in particular a position-sensitive optical detector, capable of detecting the degree of deflection, in particular the angle of deflection, of the detection light beam due to the local change in refractive index. Thus, in this case, the physical response to the heat or pressure wave received by the measuring body is a local change in refractive index, and the response signal is the detected degree of deflection, which has been found to actually indicate the degree of absorption of the excitation radiation.

[0007] In an alternative variant proposed by the applicant, as disclosed, for example, in International Application No. PCT / EP2019 / 064356, which is incorporated herein by reference, the detection device may comprise an interferometer device making it possible to evaluate said phase change of the detection beam and to generate a response signal indicative of said phase change, in which case the physical response of the measuring body (or a component comprised in the measuring body) to heat or pressure waves received from the material upon absorption of said excitation radiation is again a local change in refractive index, and the response signal is in this case an interference signal reflecting the change in phase of the detection beam due to the local change in refractive index.

[0008] In a further alternative embodiment, the measuring body or a component of the measuring body may have electrical properties that change in response to local changes in temperature or associated changes in pressure, and the detection device may include electrodes for capturing electrical signals representative of the electrical properties. International Publication No. 2019 / 110597, incorporated herein by reference, discloses various possible setups. For example, the measuring body may include a section with piezoelectric properties, and pressure changes associated with the received heat result in electrical signals that can be recorded by the electrodes. In this case, the pressure changes resemble the physical response of the measuring body or components contained in the measuring body to heat received from a substance upon absorption of excitation radiation, and are detected using the piezoelectric properties of the measuring body and electrodes, resulting in an electrical signal representative of the aforementioned response signal indicative of the degree of absorption of the excitation radiation. In a further variant, a highly sensitive temperature sensor may be used to directly measure the temperature change due to the received heat.

[0009] It should be noted that in the following description, the physical response of the measuring body to heat received from the material is described in detail. However, it should be understood that in various embodiments of the method and device of the present invention, 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 specification, the expression "pressure-transmitting contact" is intended to include all relationships, in particular acoustically coupled relationships, that allow the transfer of pressure waves from the material to the measuring body, and the coupling may be established by gas, liquid, or solid. All detailed descriptions given in relation to thermal contact and the physical response to heat received by the measuring body from the material are to be understood, where applicable, in conjunction with a scenario that includes pressure-transmitting contact and a physical response to pressure waves, without explicit reference thereto.

[0010] The device may further be configured to perform an analysis step, the analysis being performed at least in part based on the response signal. To this end, the device may include a control system including one or more processors programmed to perform the analysis. For example, if it is of interest to determine the concentration of an analyte in a substance, the excitation radiation may be selected to have a wavelength characteristic of the absorption spectrum of the analyte, e.g., associated with an absorption peak of the analyte. 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 substance. Thus, the analysis step may be based at least in part on a measure of the concentration of the analyte in the substance, and in some non-limiting applications may actually result in determining this concentration.

[0011] For example, a device of the type outlined above has been employed by the present applicant for the noninvasive measurement of a user's glucose levels. In this particular application, the "analyte" is formed by glucose and the "substance" is the user's skin. This technique has previously been demonstrated to enable highly accurate measurement of glucose concentration in interstitial fluid within a person's skin, which has been found to be directly related to and therefore representative of the glucose content of the patient's blood. Figure 4 of this application shows the results of a Clarke Error Grid analysis taken from WO 2017 / 097824, demonstrating that the device and analytical method described above enable highly accurate prediction of a person's actual glucose concentration.

[0012] Nevertheless, it is desirable to further improve the accuracy and reliability of analytical results. Summary of the Invention [Problem to be solved by the invention]

[0013] The object underlying the present invention is to provide an apparatus and a method for analyzing the above-mentioned substances, which makes it possible to improve the accuracy or reliability of the analytical results. [Means for solving the problem]

[0014] According to one aspect of the present invention, this problem is solved by providing a protrusion having a front surface facing the substance and contacting the substance when the substance is brought into contact with the contact surface, and the excitation radiation is irradiated onto the substance through the front surface of the protrusion. Here, the protrusion may be formed on the contact surface of the measuring body.

[0015] In an alternative embodiment, the measuring body itself may form the protrusion or form part of said protrusion, in which case the contact surface of the measuring body simultaneously forms the front surface of said protrusion or at least part of the front surface of said protrusion and is elevated relative to the surrounding structure, which may for example be a wall part of the housing of the device.

[0016] The present inventors have realized that one important aspect of the measurement procedure performed by the device is the reliable and consistent transmission of excitation radiation to the substance. In some of the devices described by the applicant in the above-cited prior applications, the excitation radiation was guided through the measuring body so as to enter the substance at the interface between the contact surface of the measuring body and the substance, and it was found that at this interface, the excitation radiation can actually generally be coupled into the substance very well. This has proven particularly true in applications where the substance is formed by a user's fingertip and the device is used to measure the glucose content 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 substance through the contact surface of the measuring body.

[0017] However, extensive research has shown that imperfect, particularly unstable, optical coupling can cause measurement inaccuracies. In particular, the inventors have realized that optical coupling can change during the course of a single measurement, i.e., without intentionally moving or even removing the fingertip from the contact surface. If optical coupling changes during the course of a measurement, this results in a change in the intensity of the excitation radiation actually absorbed by the analyte, and therefore a change in the response signal, which is unrelated to the analyte's absorbance or analyte concentration at the excitation radiation wavelength. In other words, a loss of optical coupling during part of a measurement can be mistaken for a lower absorbance at a given excitation wavelength. Analyte spectrum evaluation typically involves measuring the absorption at multiple characteristic wavelengths, e.g., wavelengths corresponding to peaks or absorption minima in the analyte absorption spectrum, and further includes mathematical combination of the response signals associated with different wavelengths, e.g., subtracting the response signal obtained at the absorption spectrum minima from the response signal at the absorption peak. It is therefore understandable that the optical coupling, and therefore the effective intensity of the excitation radiation within the material, may vary between measurements at different wavelengths, or even during measurements at a particular wavelength, resulting in artifacts and inaccuracies in the measurement results.

[0018] It was not clear to the inventors that unstable optical coupling would be a significant source of error, and it was also not clear exactly why the optical coupling between the contact surface and the material would change significantly during measurement, since the fingertip was not intentionally moved during measurement. One possible cause could be that the contact pressure between the finger and the contact surface could become inconsistent without the user's intention. Another possible cause could be that the user unintentionally moves their fingertip slightly across the contact surface, and very small movements could have an unexpectedly large effect. This could be, for example, if the fingertip moves between a position where the excitation radiation enters the skin at a skin ridge on the fingertip and a position where the excitation radiation enters the skin between two skin ridges, causing a decrease in optical coupling.

[0019] Regardless of the exact underlying reason, the inventors have realized that optical contact and its consistency can be improved if a contact surface is formed with protrusions, the protrusions having a front surface that faces a material and contacts the material when the material is brought into contact with the contact surface, and if excitation radiation is irradiated onto the material through the front surface of the protrusions. That is, it has been found that on the front surface of the protrusions, when the same total force is applied to the contact surface by a finger, the local contact pressure is significantly higher than on a flat contact surface. This local increase in contact pressure allows for better optical coupling, and in particular, more consistent optical coupling during the course of a measurement.

[0020] It should be noted that the protrusions not only allow for improved optical coupling, but also for improved thermal or pressure transmission coupling. Therefore, the protrusions also facilitate improved transfer of heat or pressure waves, which are often generated by absorption of excitation radiation in the material and which are to be transferred to the measurement body. Although not an embodiment of the claimed invention, the use of such protrusions is also considered here, even when the excitation radiation is not irradiated onto the material through its front surface.

[0021] In a preferred embodiment, the front surface is flat, however the invention is not limited to this and a curved front surface may also be advantageous, particularly if detection relies on a reflected detection beam, as will be described below.

[0022] In a preferred embodiment, the protrusion is 0.3 cm 2 Less than 0.2 cm, preferably 2 Less than 0.1 cm, more preferably 2 less than, and even more preferably 0.05 cm 2 Less than 0.02 cm, most preferably 2 It has a footprint area of ​​less than

[0023] In a preferred embodiment, the protrusion has a tapered shape with one or more side walls tapering toward the front surface. This tapered shape implies that the front surface can be smaller than the footprint area, thus resulting in a higher local contact pressure. The tapered side walls also increase the stability of the protrusion. Furthermore, in some embodiments where detection relies on a reflected detection beam, as will be apparent from the detailed embodiment description below, the tapered side walls facilitate entry of the detection light beam into the protrusion while keeping the contact surface small.

[0024] In some embodiments, the protrusions have a circular, oval, or square footprint.

[0025] In a particularly preferred embodiment, the protrusion is ridge-shaped and has a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, the longer extension being 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 longer than the shorter extension, where "the longer extension is at least 1.5 times longer than the shorter extension" means that if the shorter extension is 2 mm, the longer extension is at least 3 mm.

[0026] In a preferred embodiment, the protrusion or the measuring body forming the part of the protrusion is received in a frame or receptacle, and the contact surface of the measuring body protrudes from the frame or receptacle, or the frame or receptacle protrudes from the surrounding structure.

[0027] In a preferred embodiment, a pressure sensor is provided to measure the contact pressure between the substance and the measuring body, wherein the device preferably further comprises a control system configured to receive a signal from said pressure sensor indicative of the contact pressure between the substance and the measuring body, said control system being configured to check whether said contact pressure is below a predetermined threshold. If the contact pressure is found to be below said threshold, the control system: indicating to the user a lack of contact pressure; preventing the analyte measurement process from being initiated; and Interrupting the current analyte measurement process The device is configured to perform one or more of the following:

[0028] In other words, the protrusions help to establish a high contact pressure exactly where it is needed, i.e., at the front surface where the excitation radiation is coupled into the material, but reliability can be further improved if the contact pressure is monitored and if insufficient contact pressure can be indicated to the user and corrected. Furthermore, inaccurate measurement results in the event of insufficient contact pressure may be avoided by preventing an analyte measurement process from being started or by interrupting an analyte measurement process already in progress.

[0029] In a preferred embodiment, the apparatus further comprises a clamping device, the clamping device comprising a clamping member movable between an open position in which the clamping member is moved away from the contact surface of the measuring body and a closed position in which the clamping member is close to the contact surface, the clamping member being biased toward the closed position. A substance may be placed on the contact surface when the clamping member is in the open position, and the clamping member is adapted to press the substance against the contact surface with a biasing force toward the closed position. In this way, a predetermined contact pressure can be ensured.

[0030] In a preferred embodiment, the pressure sensor is arranged in the clamping device, which in this embodiment is combined with a protrusion on the contact surface / formed at least in part by the measuring body, although embodiments without such a protrusion are also possible.

[0031] In a further embodiment, the device further comprises a strap for securing the substance against the contact surface of the measuring body.

[0032] In a preferred embodiment, the measurement body is transparent to the excitation radiation, and the excitation radiation source is configured to provide the excitation radiation as an excitation beam. Furthermore, the excitation radiation source is positioned so that the excitation beam is irradiated onto the measurement body at its incident surface, propagates through a portion of the measurement body, and exits the measurement body at the contact surface. In previous devices, the applicant ensured that the excitation radiation beam impinged on the incident surface at a 90° angle to avoid refraction and excessive reflection of the excitation radiation beam at the incident surface. However, extensive research has revealed that a further cause of unintended variations in the excitation radiation actually reaching the substance 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 measurement body. It has been found that this interference actually leads to variations in the intensity of the excitation radiation within the substance, thus immediately resulting in changes in the response signal that are unrelated to the analyte concentration. Furthermore, the inventors have found that this effect can be suppressed by slightly tilting the angle of incidence 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, unintended interference can be reliably prevented. A further advantageous effect is that the excitation radiation can be prevented from being reflected back to the excitation radiation source, which could potentially damage the excitation radiation source. On the other hand, to avoid losses due to excessive reflection, the angle of incidence should not deviate significantly from 90°. Therefore, in this embodiment, the angle of incidence should be 82.0° or more, preferably 84.0° or more, and most preferably 85.0° or more. This embodiment is advantageously used with or at least partially formed by a protrusion on the contact surface of the measuring body, but can also be employed in an embodiment without such a protrusion.

[0033] In a preferred embodiment, the excitation beam impinges on the contact surface of the measurement body at an angle of 90°±1.5°, thereby minimizing losses due to reflection at the contact surface.

[0034] In a preferred embodiment, the incidence surface and the contact surface at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined relative to each other by an angle of 1.0° or more, preferably 2.0° or more, most preferably 2.5° or more, and 8.0° or less, preferably 6.0° or less, most preferably 5.0° or less. Schematically, the measurement body according to this embodiment may have a slightly "wedge-shaped" shape, which makes it possible to establish both a slight tilt of the excitation beam at the incidence surface and an orthogonal orientation of the excitation beam at the contact surface.

[0035] In a preferred embodiment, the detection device comprises a light source for generating a detection light beam which travels through at least a part of the measuring body or a component contained in the measuring body, wherein the physical response of the measuring body to heat or pressure waves received from the substance upon absorption of the excitation radiation is a local change in the refractive index of the measuring body or component, and the detection device is configured to detect one of a change in the optical path or a change in the phase of the detection beam due to said change in refractive index.

[0036] In a preferred embodiment, the detection device is configured such that the detection light beam is irradiated onto the measurement body at an incident surface, and the detection light beam impinges on the incident surface at an incident angle of 89° or less, preferably 88° or less, most preferably 87.5° or less, and 80° or more, preferably 82° or more, more preferably 84° or more, most preferably 85° or more with respect to the incident surface. In this way, it is possible to prevent the detection light beam from being reflected back onto itself, which could result in interference and undesirable interference phenomena. A further advantageous effect of this is that it is possible to prevent the detection light beam from being reflected back onto the detection light source, which could potentially damage the detection light source.

[0037] In a preferred embodiment, the measurement body is received in a frame or receptacle that allows the measurement body to be rotated to adjust the angle of incidence of the detection light beam when it strikes the incident surface of the measurement body. In this way, adjusting the appropriate angle of incidence of the detection light beam on the measurement body is made much easier than adjusting any optical element, such as a detection light source or a mirror in the optical path of the detection light beam. Preferably, the frame or receptacle allows the measurement body to be rotated about an axis parallel to the excitation light beam or deviated from parallel by less than 10°, preferably less than 5°. In a most preferred embodiment, the rotation axis of the measurement body coincides with the excitation light beam.

[0038] In a related embodiment, the measuring body is transparent to the detection light beam, the detection light beam is directed to be totally or partially reflected at a surface of the measuring body in thermal or pressure-transmitting contact with the substance, and the detection device comprises a detector for detecting the degree of deflection, in particular the deflection angle, of the detection light beam after reflection at the contact surface due to the local change in refractive index, wherein the detection device preferably comprises a photodetector, in particular a position-sensitive photodetector.

[0039] In this embodiment, the detection light beam is preferably directed so as to be totally or partially reflected by the front surface of the protrusion, which is in thermal or pressure-transmitting contact with the substance. In other words, in this embodiment, the detection light beam is reflected by the same surface at which the excitation radiation leaves the measurement body and enters the substance. This implies that the detection light beam is reflected in an area where a relatively large local change in refractive index due to heat or pressure waves received from the substance upon absorption of the excitation radiation can be expected, which in turn implies that a relatively large deflection of the detection light beam due to the local change in refractive index can be expected.

[0040] It should be noted that the concept of a "deflected" detection light beam relates to the overall change in angle or change in impingement position at the detector, or in other words, how different the detection position of the detection light beam is from its position without excitation and absorption by the material. Therefore, this "deflection" is the cumulative effect of local changes in refractive index on the detection light beam along its optical path. More detailed studies reveal that in many cases, part of the deflection of the light beam due to the local change in refractive index occurs before the detection light beam is reflected from the surface of the measurement body that is in thermal or pressure-transmitting contact with the material, in this case formed by the front surface of the protrusion. Therefore, the local change in refractive index also typically results in a shift in the exact position on the surface where the detection light beam is reflected.

[0041] In light of this understanding, in a preferred embodiment, the front surface of the protrusion is curved in at least one principal direction. This curvature implies that the change in the position at which the detection light beam is reflected is also accompanied by a change in the angle of incidence, and therefore a corresponding change in the angle of reflection. Thus, the use of a curved reflective surface can increase the total deflection evaluated by the detection device, such as the shift in position detected by the position-sensing detector.

[0042] In a preferred embodiment, said curvature in said at least one main direction corresponds to a radius of curvature in the range of 5 to 30 mm, preferably 10 to 20 mm.

[0043] In a preferred embodiment, the curvature in the at least one main direction is one of concave or convex.

[0044] In a preferred embodiment, the detection light beam before and after reflection at said front surface defines a detection light plane, and said at least one main direction lies in said detection light plane or forms an angle with said detection light plane of less than 30°, preferably less than 20°, in this way ensuring that the main effect of curvature on the deflection lies in the detection light plane.

[0045] It should be noted that when the detection light beam is reflected from the front surface of the protrusion, the geometry of the protrusion generally limits the possible tilt angle of the detection light beam relative to the contact surface. For example, if the protrusion has a height h and a circular footprint of radius r, the tilt angle α of the detection light beam relative to the contact surface must obey the condition tan(α) > h / r to "fit" the protrusion. From another perspective, given the desired height h and desired angle α of the protrusion, a lower limit on the radius r, or in other words, the footprint size, must be considered. As explained above, by using one or more tapered sidewalls, the size of the front surface of the protrusion can be reduced compared to the size of the footprint, thereby allowing a smaller front surface and therefore a higher contact pressure, even for a larger footprint area.

[0046] In a preferred embodiment, the protrusion has a ridge-shaped configuration, a longer extension in a first direction, and a shorter extension in a second direction perpendicular to the first direction, the longer extension being 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 longer than the shorter extension, and the first direction is parallel to the detection light plane or forms an angle with the detection light plane of less than 30°, preferably less than 20°. In other words, according to this embodiment, the detection light plane corresponds at least approximately to the longitudinal direction of the ridge-shaped protrusion, which means that for a given height of the protrusion, the inclination angle of the detection light beam with respect to the front surface of the protrusion can be smaller. At the same time, with this orientation of the detection light plane, the extension of the ridge-shaped protrusion in the second, shorter direction is generally independent of the inclination angle and can therefore be selected relatively small, thereby reducing the size of the front surface and enabling a higher contact pressure at the front surface.

[0047] In a preferred embodiment, the detection light source is arranged so that the detection light beam is irradiated onto the measurement body at an incident surface, propagates through a portion of the measurement body and exits the measurement body at an exit surface, wherein the detection beam, in the absence of any deflection due to the local change in refractive index, would strike the exit surface at an angle of 5° or more, preferably 10° or more, most preferably 15° or more relative to the normal to the exit surface, the detection beam is refracted upon exiting the exit surface of the measurement body, and the orientation of the exit surface relative to the detection light beam is such that the deflection of the detection light beam in response to the heat or pressure waves transferred to the measurement body increases the angle of the detection light beam relative to the normal to the exit surface.

[0048] In the applicant's previous designs, the shape of the measurement body was generally selected so that the detection beam was perpendicular to the entrance and exit surfaces to avoid reflection losses and refraction, which can be easily understood to make the optical setup more complex. However, according to this embodiment, the detection light source is arranged so that the detection light beam is intentionally refracted at least at the exit surface in the manner defined above. Since the refractive index of the measurement body is usually higher than that of the surroundings, an increase in the angle of the detection light beam relative to the normal to the exit surface results in a greater increase in the angle of the refracted light beam, thus further increasing the deflection of the light beam detected by the detection device, thereby resulting in a larger response signal. In this way, the signal-to-noise ratio can be increased. Generally, the more the angle of incidence of the detection beam deviates from the normal to the exit surface, the greater the effect. However, it is natural to avoid reaching the "critical" angle of total internal reflection. Furthermore, for angles close to this critical angle, the proportion of light in the detection light beam that is reflected at the exit surface increases, thereby attenuating the intensity of the refracted detection light beam that actually reaches the detection device, such as a photodetector. Therefore, the best choice for the angle of incidence may be a compromise between a greater degree of refraction and a sufficient intensity of the refraction detection light beam. In any case, the deviation of the angle of incidence from the normal to the axial plane should be at least 5°, preferably at least 10°, and most preferably at least 15°. This embodiment is advantageously used with protrusions on the contact surface / formed at least in part by the measuring body, but can also be employed in embodiments without such protrusions.

[0049] In a preferred embodiment, the detection light source is arranged so that the detection light beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body, and exits the measurement body at an exit surface, and a focusing lens is attached to or integrally formed with the entrance surface to focus the detection light beam entering the measurement body in at least one dimension, and / or a collimating lens is attached to or integrally formed with the exit surface to collimate the detection light beam in at least one dimension.

[0050] The inventors have realized that the quality of the measurement is improved if the detection light beam is focused when reflected from the contact surface, which is also the region where the beam interacts with the thermal lens generated in the measurement body. Due to the clear characteristic deflection, it is advantageous if the diameter of the detection light beam in this region is relatively small, which can be achieved by the focusing lens described above. In other words, the purpose of the focusing lens is not necessarily to precisely focus the detection light beam to a focal point, but to reduce the diameter of the detection light beam, at least in the region where it interacts with the thermal lens. However, this focusing implies that the detection light beam widens on its way to the detection device. This is usually less of a problem when the detection device, such as a position-sensitive detector, is positioned directly adjacent to the exit surface of the detection beam, or at least close to the exit surface. However, the inventors have found that the signal-to-noise ratio of the measurement can be further increased if the distance between the exit surface and the detector is increased, since this results in a greater degree of deflection, represented, for example, by a greater shift in the position where the detection light beam impinges on the position-sensitive detector. It should be noted that, in this specification, a "larger degree of deflection" does not relate to a larger deflection angle, which is one possible meaning of "degree of deflection," but rather to the effect of a larger deflection detected by the detection device. For example, the distance between reflection at the contact surface of the measurement body and detection at the detection device may be at least 4 cm, and in some embodiments, 9 cm or more, thereby introducing a kind of leverage for 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 for the detection light beam to be collimated after exiting the measurement body in order to maintain a constant diameter of the detection beam. Nevertheless, it is emphasized that focusing and collimation do not necessarily need to occur in both dimensions, and that in many practical applications, some degree of divergence in one of the directions may still be desired, as explained below. Therefore, focusing lenses and / or other collimating lenses must be effective in at least one dimension only.Indeed, in a preferred embodiment, at least one of the focusing lens and the collimating lens is a cylindrical lens that respectively focuses and collimates the detection light beam at least primarily in one dimension.

[0051] Furthermore, by attaching the focusing and / or collimating lenses to the measuring body, or even more preferably by forming them integrally with the measuring body, no separate adjustment of these lenses is necessary during assembly of the device or even during use of the device. This embodiment is advantageously used with / at least partly formed by protrusions on the contact surface, although it is also possible to employ embodiments without such protrusions.

[0052] In a preferred embodiment, the detector comprises a position sensitive detector impinged by the detection light beam, the position sensitive detector being sensitive to detect a shift in the position of the detection light beam impinging on the position sensitive detector in at least one sensing direction. Furthermore, the position sensitive detector is positioned such that the deflection of the detection light beam results in a shift in the position of the detection light beam impinging on the position sensitive detector in the at least one sensing direction. Finally, a cylindrical lens is provided in the optical path of the detection light beam to shape the profile of the detection light beam, such that the diameter of the detection light beam impinging on the position sensitive detector in the sensing direction is at least 1.5 times, preferably at least 2.0 times, the diameter of the detection light beam in a direction perpendicular to the sensing direction. The inventors have realized that when using a position sensitive detector sensitive to detect a shift in the position of the detection light beam impinging on the position sensitive detector in at least one sensing direction, the signal-to-noise ratio and, in some embodiments, the linearity of the sensor output, can be increased if the light spot of the beam profile formed on the position sensitive detector is elongated in the sensing direction as defined above. This is particularly true for position sensitive detectors that measure the current difference at each end. The elongated shape of the light spot according to this aspect of the invention is established using such a cylindrical lens. This embodiment is advantageously used with / at least partly formed by a protrusion on the contact surface of the measuring body, but can also be employed in embodiments without such a protrusion.

[0053] In a preferred embodiment, the cylindrical lens is a collimating lens arranged in the optical path of the detection light beam between reflection at the contact surface and the position sensitive detector, the cylindrical lens being arranged to collimate the detection light beam at least primarily (but possibly exclusively) in a dimension perpendicular to the sensing direction of the position sensitive detector, the cylindrical collimating lens preferably being integrally formed with the exit surface of the measuring body from which the detection light beam emerges from the measuring body.

[0054] Additionally or alternatively, the position sensitive detector may be positioned at a 90° angle from the detection light beam, which angle creates an elongated light spot on the position sensitive detector that has a greater extension in the sensing direction.

[0055] In a preferred embodiment, the apparatus further comprises a beam splitter for splitting the source light beam into the detection light beam and a reference light beam, the reference light beam likewise being directed so as to be totally or partially reflected at a surface of the measuring body in thermal or pressure-transmitting contact with the substance, but within a region in which the influence of heat or pressure waves received from the substance upon absorption of the excitation radiation is negligible. Furthermore, the apparatus comprises a further detection device for detecting the degree of deflection, in particular the angle of deflection, of the reference light beam after reflection at the contact surface, the detection device preferably comprising a photodetector, in particular a position-sensitive photodetector.

[0056] This reference light beam is subjected to the same types of external influences as the detection light beam, with the exception of heat or pressure waves due to absorption of excitation radiation. Therefore, by measuring the possible deflection of the reference light beam, these external influences can be taken into account and removed from the measurement result obtained by the detection light beam. In a preferred embodiment, the additional reference beam is combined with a protrusion at the contact surface / formed at least in part by the measuring body, but it is also possible to employ an embodiment without such a protrusion.

[0057] In an alternative preferred embodiment, the detection device comprises an interferometer device making it possible to evaluate the phase change of the detection beam and to generate a response signal indicative of the phase change.

[0058] In a further alternative embodiment, the measuring body or a component of the measuring body has an electrical property that changes in response to a local change in temperature or a change in pressure associated therewith, and the detection device comprises electrodes for capturing an electrical signal representative of the electrical property.

[0059] In yet another embodiment, the device includes a fiber embedded in the measurement body, a detection light source provided at one end of the fiber for coupling detection light into the fiber, and a mode detector provided at the other end of the fiber. The mode detector is suitable for detecting a change in the optical mode of the detection light in response to heat or pressure waves received by the measurement body from the material. For example, the mode detector can include a camera suitable for visualizing the interference pattern of the modes, typically several modes, and a processor configured to detect the change in mode based on image analysis of the camera image. The processor may be a dedicated processor associated with the mode detector or may be provided by the control system of the above-described device. The detectable change in the optical mode may include a shift or rotation of the interference pattern of the optical mode at the mode detector. Therefore, the shift distance or rotation angle is a quantitative parameter related to the amount of heat or pressure wave intensity received from the material, and thus ultimately indicates the amount of excitation light absorbed by the material. Such changes in the mode interference pattern can be easily detected using a camera or image sensor, but other devices are also possible, such as sensors or detectors that allow for measuring certain spatially resolved intensity values, without necessarily providing a complete image. In this embodiment, the "physical response" is a temporary change in the optical properties of the fiber due to the received heat or pressure wave, and the "response signal" is a detectable change in the optical mode, such as a change in the interference pattern of some modes. In a preferred embodiment, this type of mode detection is combined with protrusions at the contact surface / formed at least in part by said measuring body, but it can also be employed in embodiments without such protrusions.

[0060] In a preferred embodiment, the substance is human tissue, particularly human skin, and the analyte is glucose present in the skin, particularly in the interstitial fluid of the skin.

[0061] In a preferred embodiment, the excitation radiation is generated using an array of lasers, particularly quantum cascade lasers, each with a dedicated wavelength.

[0062] In an alternative preferred embodiment, said excitation radiation is generated using at least one tunable laser, in particular at least one tunable quantum cascade laser.

[0063] In a preferred embodiment, some or all of the excitation wavelengths are in the range of 5 μm to 13 μm, preferably 8 μm to 11 μm. In an alternative embodiment, some or all of the excitation wavelengths are in the range of 3 μm to 5 μm. This wavelength range is useful, for example, for detecting absorption of CH2 and CH3 vibrations in fatty acids.

[0064] A further aspect of the present invention is a method for analyzing a substance comprising at least one analyte, comprising the steps of: - bringing a measuring body having a contact surface into thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to the measuring body; irradiating the material with excitation radiation so that it is absorbed by the material; detecting a physical response of the measuring body or a component contained in the measuring body to heat or pressure waves received from the material upon absorption of the excitation radiation, and generating a response signal based on the detected physical response, the response signal being indicative of the degree of absorption of the excitation radiation; a protrusion is provided, the protrusion having a front surface facing the substance and contacting the substance when the substance is brought into contact with the contact surface, the excitation radiation being irradiated onto the substance through the front surface of the protrusion, the protrusion being formed on the contact surface of the measuring body, or the measuring body forms the protrusion or a part of the protrusion, and the contact surface of the measuring body forms the front surface of the protrusion and is elevated relative to the surrounding structure; The present invention relates to a method characterized in that

[0065] In a preferred embodiment of the method, the front surface is flat.

[0066] In a preferred embodiment of the method, the protrusion is 0.3 cm 2 Less than 0.2 cm, preferably 2 Less than 0.1 cm, more preferably 2 less than, and even more preferably 0.05 cm 2 Less than 0.02 cm, most preferably 2 It has a footprint area of ​​less than

[0067] In a preferred embodiment of the method, the protrusion has a tapered shape with one or more side walls tapering towards the front surface.

[0068] In a preferred embodiment of the method, the protrusions have a circular, oval, or square footprint.

[0069] In a preferred embodiment of the method, the protrusion is ridge-shaped and has a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, the longer extension exceeding 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.

[0070] In a preferred embodiment of the method, the contact pressure between the substance and the measuring body is measured.

[0071] Preferably, the method further comprises the step of checking whether said contact pressure is below a predetermined threshold, and if it is found that the contact pressure is below said threshold: indicating the lack of contact pressure to the user; preventing the analyte measurement process from being initiated; and Interrupting the current analyte measurement process. Implement one or more of the following:

[0072] Preferably, the method further comprises the step of fixing the substance to the contact surface using a clamping device, the clamping device comprising a clamping member movable between an open position in which the clamping member is moved away from the contact surface of the measuring body and a closed position in which the clamping member is close to the contact surface, the clamping member being biased towards the closed position, the substance being placed on the contact surface when the clamping member is in the open position, and the clamping member pressing the substance against the contact surface with a biasing force towards the closed position.

[0073] In a preferred embodiment of the method, the pressure sensor is disposed in the clamping device.

[0074] In a preferred embodiment, the method includes the step of securing the substance to the contact surface using a strap.

[0075] In a preferred embodiment of the method, the measuring body is transparent to the excitation radiation, the excitation radiation source provides the excitation radiation as an excitation beam; an excitation beam is irradiated onto the measurement body at its incident surface, propagates through a portion of the measurement body, and exits the measurement body at the contact surface; The excitation beam impinges on the entrance surface at an angle of 89.0° or less, preferably 88.0° or less, most preferably 87.5° or less, and 82.0° or more, preferably 84.0° or more, most preferably 85.0° or more.

[0076] In a preferred embodiment of the method, the excitation beam impinges on the contact surface of the measuring body at an angle of 90°±1.5°.

[0077] In a preferred embodiment of the method, the incidence surface and the contact surface at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined with respect to each other by an angle of 1.0° or more, preferably 2.0° or more, most preferably 2.5° or more, and 8.0° or less, preferably 6.0° or less, most preferably 5.0° or less.

[0078] In a preferred embodiment of the method, said detecting comprises generating a detection light beam which travels through at least a part of said measuring body or a component contained in said measuring body, the physical response of the measuring body to heat or pressure waves received from the material upon absorption of the excitation radiation is a local change in the refractive index of the measuring body or of the component; The detecting includes detecting one of a change in the optical path or a change in the phase of the detection beam due to the change in refractive index.

[0079] In a preferred embodiment of the method, the detection light beam is irradiated onto the measurement body at an incident surface, and the detection light beam strikes the incident surface at an incident angle of 89° or less, preferably 88° or less, most preferably 87.5° or less, and 80° or more, preferably 82° or more, more preferably 84° or more, most preferably 85° or more, relative to the incident surface.

[0080] In a related embodiment of the method, the measuring body is received in a frame or receptacle that allows the measuring body to be rotated so as to adjust the angle of incidence of the detection light beam when it strikes the incident surface of the measuring body, in particular the frame or receptacle allows the measuring body to be rotated around an axis parallel to the excitation light beam or deviated from parallel by less than 10°, preferably less than 5°, and most preferably the rotation axis of the measuring body coincides with the excitation light beam.

[0081] In a preferred embodiment of the method, the measuring body is transparent to the detection light beam, the detection light beam is directed so as to be totally or partially reflected at a surface of the measuring body that is in thermal or pressure-transmitting contact with the substance, and the detection comprises detecting the degree of deflection, in particular the deflection angle, of the detection light beam after reflection at the contact surface due to the local change in refractive index, the detection being preferably performed using a photodetector, in particular a position-sensitive photodetector.

[0082] In a preferred embodiment of the method, the detection light beam is directed so as to be totally or partially reflected by the front surface of the protrusion, which is in thermal or pressure transmitting contact with the substance.

[0083] In a preferred embodiment of the method, the front surface of the protrusion is curved in at least one main direction, wherein said curvature in said at least one main direction corresponds to a radius of curvature in the range of 5 to 30 mm, preferably 10 to 20 mm, and said curvature in said at least one main direction is one of concave or convex.

[0084] In a preferred embodiment of the method, the detection light beam before and after reflection at the front surface defines a detection light plane, and the at least one main direction lies within the detection light plane or forms an angle with it of less than 30°, preferably less than 20°.

[0085] In a preferred embodiment of the method, the detection light beam before and after reflection from the front surface defines a detection light plane, and the first direction is parallel to the detection light plane or forms an angle with the detection light plane of less than 30°, preferably less than 20°.

[0086] In a preferred embodiment of the method, the detection light source is arranged so that the detection light beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body and exits the measurement body at an exit surface, the detection beam would, in the absence of any deflection due to the local change in refractive index, impinge on the exit surface at an angle of 5° or more, preferably 10° or more, most preferably 15° or more relative to the normal to the exit surface, the detection beam is refracted upon exiting the exit surface of the measurement body, and the orientation of the exit surface relative to the detection light beam is such that the deflection of the detection light beam in response to the heat or pressure waves transferred to the measurement body increases the angle of the detection light beam relative to the normal to the exit surface.

[0087] In a preferred embodiment of the invention, the detection light beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body, and exits the measurement body at an exit surface, and a focusing lens is integrally formed with the entrance surface to focus the detection light beam entering the measurement body in at least one dimension and / or a collimating lens is integrally formed with the exit surface to collimate the detection light beam in at least one dimension, wherein at least one of the focusing lens and the collimating lens is preferably a cylindrical lens that focuses and collimates the detection light beam at least primarily in one dimension, respectively.

[0088] In a preferred embodiment of the method, the detector comprises a position sensitive detector impinging on the detection light beam, the position sensitive detector detecting a shift in the position of the detection light beam impinging on the position sensitive detector in at least one sensitive direction; the position sensitive detector is arranged such that the deflection of the detection light beam results in a shift in a position of the detection light beam impinging on the position sensitive detector in the at least one sensitive direction; A cylindrical lens is provided in the path of the detection light beam to shape the profile of the detection light beam, and / or the position sensitive detector is positioned at an angle offset from 90° to the detection light beam, so that the diameter of the detection light beam impinging on said position sensitive detector in said sensing direction is at least 1.5 times, preferably at least 2.0 times, the diameter of the detection light beam in a direction perpendicular to said sensing direction.

[0089] In a preferred embodiment of the method, the cylindrical lens is a collimating lens arranged in the optical path of the detection light beam between reflection at the contact surface and the position sensitive detector, the cylindrical lens collimating the detection light beam at least primarily in a dimension perpendicular to the sensing direction of the position sensitive detector, and the cylindrical collimating lens is preferably formed integrally with the exit surface of the measuring body from which the detection light beam exits the measuring body.

[0090] In a preferred embodiment of the method, the light source light beam is split into the detection light beam and the reference light beam, and the reference light beam is likewise directed so as to be totally or partially reflected at the surface of the measuring body which is in thermal or pressure-transmitting contact with the substance, but within a region in which the influence of heat or pressure waves received from the substance upon absorption of the excitation radiation is negligible, and the degree of deflection of the reference light beam after reflection at the contact surface, in particular the deflection angle, is detected, preferably using a light detector, in particular a position-sensitive light detector.

[0091] In a preferred embodiment of the method, said detecting comprises using an interferometer device capable of evaluating said phase change of a detection beam and generating a response signal indicative of said phase change.

[0092] In a preferred embodiment of the method, the measuring body or a component of the measuring body has an electrical property that changes in response to a local change in temperature or a change in pressure associated therewith, and the detection device comprises electrodes for capturing an electrical signal representative of the electrical property.

[0093] In a preferred embodiment of the method, an optical fiber is embedded in the measurement body, a detection light source is provided at one end of the fiber for coupling detection light into the optical fiber, and a mode detector is provided at the other end of the fiber, and the mode detector is used to detect a change in the optical mode of the detection light in response to heat or pressure waves received by the measurement body from the substance, the change in optical mode preferably including a shift or rotation of an interference pattern of the optical mode at the mode detector.

[0094] In a preferred embodiment of the method, the substance is human tissue, particularly human skin, and the analyte is glucose present in the skin, particularly in the interstitial fluid of the skin.

[0095] Preferably, the method further comprises the step of generating said excitation radiation using an array of lasers, in particular quantum cascade lasers, each having a dedicated wavelength.

[0096] Preferably, the method further comprises the step of generating said excitation radiation using at least one tunable laser, in particular at least one tunable quantum cascade laser.

[0097] In a preferred embodiment of the method, some or all of the excitation wavelengths are in the range of 5 μm to 13 μm, preferably 8 μm to 11 μm. [Brief explanation of the drawings]

[0098] [Figure 1] 1 is a schematic illustration of the measurement principle underlying some embodiments of the present invention; [Figure 2] FIG. 1 shows the absorption spectrum of glucose in water with the water background subtracted. [Figure 3] 1 is a schematic cross-sectional view of an apparatus for analyzing materials that relies on a response signal based on the deflection of a detection light beam. [Figure 4] Figure 3 shows the results of a Clark-Error Grid analysis obtained with an apparatus of the type shown. [Figure 5] 1 is a schematic diagram of an apparatus for analyzing materials that relies on a response signal based on a piezoelectric response to heat or pressure waves received by the material being analyzed. [Figure 6] 1 is a schematic diagram of an apparatus for analyzing materials that relies on a response signal based on a phase change in an interferometrically detected detection light beam. [Figure 7] 1 is a schematic diagram of an apparatus according to one embodiment of the present invention in a side cross-sectional view. [Figure 8] 8 is a schematic diagram of the device of FIG. 7 in a front cross-sectional view. [Figure 9] 1 is a schematic diagram of the apparatus showing the deflection of the detection light beam; [Figure 10] 10 is a schematic diagram of an apparatus similar to that of FIG. 9, but with an additional refraction of the detection light beam at the exit surface of the measurement body. [Figure 11] FIG. 10 is a schematic diagram illustrating increased deflection of a detection light beam using a curved reflective surface. [Figure 12] FIG. 8 is a schematic diagram of an apparatus similar to that of FIG. 7 in which the position sensitive detector is positioned at an angle to the detection light beam. [Figure 13] FIG. 8 is a schematic top view of an apparatus similar to that of FIG. 7, in which a reference light beam is used in addition to the detection light beam. [Figure 14] FIG. 14 is a perspective view of the device of FIG. 13. [Figure 15] 10 is a schematic diagram of a further apparatus in which the response signal corresponds to a change in an optical mode generated in a fiber contained in the measuring body; [Figure 16] FIG. 16 shows the same device as in FIG. 15, but with a temperature gradient generated in the measurement body. [Figure 17] FIG. 1 shows an apparatus including a clamping device. [Figure 18] FIG. 10 is a top view of a further apparatus for measuring an analyte based on an interference signal of two portions of a detection light beam. [Figure 19] FIG. 19 is a perspective view of the device of FIG. 18. [Figure 20] 1 is a schematic illustration of an apparatus according to an embodiment of the invention in a side cross-sectional view, in which the protrusion is formed by the measuring body; [Figure 21] FIG. 1 is a perspective view of a support structure including a protrusion of which the measuring body is a part. [Figure 22] FIG. 22 is a top view of the support structure of FIG. 21. [Figure 23] FIG. 22 is a cross-sectional view of a portion of the support structure of FIG. 21. DETAILED DESCRIPTION OF THE INVENTION

[0099] It should be understood that the foregoing general description and the following description are exemplary and explanatory only and are not intended to limit the methods and devices described herein. In this application, the use of the singular may include the plural unless specifically stated otherwise. Also, the use of "or" means "and / or" where appropriate or unless stated otherwise. Those skilled in the art will appreciate that the following description is exemplary only and is not intended to be limiting in any way. Other embodiments will readily occur to those skilled in the art having the benefit of this disclosure. Reference will now be made in detail to various implementations of the exemplary embodiments that are illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings and the following description to refer to the same or similar elements.

[0100] 1 is a schematic diagram of the measurement principles underlying the analyte measurement procedure summarized above and described in more detail below. While the methods and apparatus of the present invention are suitable for analyzing a variety of substances, including at least one analyte, the following description focuses on a specific embodiment in which the substance is a patient's skin and the analyte is glucose in the interstitial fluid of the skin. It should be understood that all details and descriptions given below with specific reference to glucose measurement are equally applicable to other substances and analytes, where appropriate, even if not explicitly mentioned below.

[0101] In the example of FIG. 1, a user's fingertip 12 is in thermal contact with the contact surface 14 of the measuring body 16. In an alternative embodiment not shown, the fingertip may be acoustically coupled to the measuring body via an acoustic cell, which may include a hollow space filled with a liquid or gas, allowing the transfer of pressure waves to the measuring body. An excitation beam 18 is irradiated to the measuring body 16 through air or through a waveguide (not shown), and then through the measuring body 16 to the skin of the fingertip 12. To determine the concentration of glucose in the skin, particularly in the interstitial fluid of the skin, various wavelengths of excitation radiation 18 can be selected sequentially or at least partially simultaneously for absorption measurements, and the glucose concentration can be determined from the measured absorption values. FIG. 2 shows the absorption spectrum for various concentrations of glucose in water, where the contribution of water absorption has been subtracted. As can be seen in this figure, glucose molecules emit light at 993 cm and 993 cm , which correspond to wavelengths ranging from 10.07 μm to 8.32 μm, respectively. -1 ~1202cm -1 The mid-infrared region has several characteristic absorption peaks at wavenumbers ranging between 0 and 100. Absorption minima are found between adjacent absorption peaks, which are indicated in Figure 2 by vertical arrows without wavenumber designations. As is clear from Figure 2, the difference in absorption, particularly between the absorption peaks and the absorption minima, is characteristic of glucose concentration. Therefore, to be able to determine the glucose concentration, it is preferable to measure the absorption at some or all of the absorption peaks and some or all of the absorption minima, and possibly also at some point between the maximum and minimum. These wavelengths are referred to herein as "analyte (glucose) characteristic wavelengths." Wavelengths that are exactly at the absorption peaks or absorption minima are preferred choices for glucose characteristic wavelengths, although wavelengths close to the peaks / minima but at individually defined distances from them may also be used. Therefore, as understood herein, an "analyte characteristic wavelength" is also a wavelength whose difference in absorption relative to the wavelength at the nearest absorption peak or nearest absorption minimum is less than 30%, preferably less than 20%, of the difference in absorption between the nearest absorption peak and the nearest absorption minimum.

[0102] The intensity of the excitation beam 18 is temporally modulated at a particular frequency f so that the excitation radiation, in this case excitation light, has alternating intervals of high intensity and low or even extinct intensity. Without wishing to limit the modulation to any particular waveform, hereafter the high intensity intervals will be referred to as "excitation light pulses." During an excitation light pulse, excitation light having a wavelength characteristic of glucose is absorbed, and the radiant energy is converted to heat. Because glucose molecules relax from the excited state within approximately 10-12 seconds, the generation of the corresponding heat pulse and / or pressure wave may be considered instantaneous for all practical purposes.

[0103] Thus, together with the excitation light pulse, a localized heat pulse is generated at the absorption site, resulting in a temperature field, sometimes referred to as a thermal wave, that varies as a function of space and time. As explained above, the term thermal "wave" is somewhat misleading, since the progression of heat through matter is governed by a diffusion equation rather than a wave equation. However, the concept of a "thermal wave" is appropriate, at least insofar as the heat pulse propagates from within the skin to the surface 14 of the measurement body 16 and into the measurement body 16, similar to what we are familiar with from wave propagation. The thermal gradient 20 caused by such a heat pulse is shown schematically in FIG. 1.

[0104] The heat received by the measuring body 16 from the skin of the finger 12 causes a physical response that can be detected using one of a variety of possible detection devices devised to generate a response signal based on the physical response, the response signal indicating the degree of absorption of the excitation light. Various methods for detecting the physical response and generating an appropriate response signal are described below.

[0105] However, it is worth noting that, regardless of the exact method of detecting the physical response, the maximum depth below the surface of the skin at which absorption can be detected by a heat pulse traveling to the measurement body 16 has been found to be limited to a good approximation by the thermal diffusion length μ of the skin, μ t teeth,

number

[0106] Referring again to FIG. 1 , in the illustrated embodiment, the physical response to the absorbed heat received from the skin is a change in the refractive index in a region close to the surface 14 of the measurement body 16, where a thermal gradient 20 is temporarily generated. This local change in refractive index creates what can be considered a thermal lens that can be detected by a detection light 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 measurement body 16 and the skin of the finger 12. Whenever a heat pulse is received from the skin, a local change in refractive index occurs, which results in a deflection of the detection beam 22 due to interaction with the material of the measurement body in the region of the thermal lens. In FIG. 1 , reference numeral 22b corresponds to the undeflected detection beam 22, and reference numeral 22a corresponds to the detection beam when deflected by the thermal lens generated in the thermal gradient region 20. This deflection can be measured to generate an example of the aforementioned response signal. The degree of deflection indicates the amount of heat received and, therefore, the degree of absorption of the excitation light 18 in the skin of the finger 12. Here, the "degree of deflection" may refer to the angle of deflection, but more generally corresponds to any deviation between the detected light beams that is detectable by a corresponding detection device.

[0107] FIG. 3 shows a more detailed cross-sectional view of device 10 that relies on the measurement principle illustrated with reference to FIG. 1. Device 10 comprises a housing 24 that includes a measuring body 16 having an upper surface (contact surface) 14 on which finger 12 rests. An excitation light source 26 is provided within housing 24, generating excitation light beam 18. In the illustrated embodiment, excitation light source 26 comprises an array of quantum cascade lasers, each with a dedicated wavelength. For example, the quantum cascade laser array may include individual quantum cascade laser elements with wavelengths corresponding to the absorption peaks and minima shown in FIG. 2 (i.e., glucose characteristic wavelengths) and other wavelengths that may be used for reference measurements or to detect other components that may interfere with glucose measurement, such as lactate or albumin. The laser array may irradiate the excitation beam directly into and through the measurement volume 16, or into an optical waveguide (not shown) that couples the laser array to the measurement volume and directs the excitation beam, curved or uncurved, to the measurement volume 16. An optical waveguide may also be used in the case of generation of the excitation beam by a single tunable laser.

[0108] The device 10 further comprises a light source 28, e.g., a laser, for emitting the detection beam 22 and a position-sensing detector 30, which allows for detecting the deflection of the detection beam 22. As understood herein, the term "light beam" is not limited to light in the visible range, but it should be noted that in a preferred embodiment, the detection light beam 22 is actually in the visible range of the light spectrum. The measuring body 16 in this case is transparent to both the excitation light beam 18 and the detection light beam 22. Furthermore, a camera 32 or another imaging device is provided, which allows for taking an image of the contact surface 14 of the optical medium 16, thereby recording the fingerprint of the finger 12 resting on the contact surface 14. This fingerprint can be processed by a control unit 34 to identify the user by their fingerprint. The control unit 34 also functions to control the light sources 26 and 28 for the excitation and detection light, respectively, and the sensor 30. The control unit 34 also wirelessly connects to an external data processing device 36 for data exchange. For example, via the wireless connection, user-specific calibration data can be retrieved by the control unit 34 for a user identified by their fingerprint. Control unit 34 and external data processing device 36 together form one example of a "control system" as referred to herein. The control system may be comprised of one or more processors, microcontrollers, computers, ASICs, FPGAs, etc. The control system may be distributed across various components in data communication with each other, as shown in FIG. 3, or may be formed by a single control unit, such as control unit 34, designed for all of the control functions described herein. The control system may generally be embodied in hardware, software, or a combination of both.

[0109] 3, the excitation and detection light sources 26 and 28, and the position sensitive detector 30 are all mounted on a common carrier structure 38. This means that these components can be precisely pre-assembled on this structure 38, and therefore there is no need to individually adjust or calibrate these components when assembling the device 10. One or more of the excitation and / or detection light sources 26 and 28, and the position sensitive detector 30 may also be mounted directly on the measurement body 16 to avoid additional adjustment or calibration.

[0110] Furthermore, the apparatus 10 comprises a keratin measuring device 40 that allows the moisture content of the skin to be measured. Corneum measuring devices for measuring the moisture content in the upper layers of the skin are known per se in the art and need not be described in detail here. For example, known keratin measuring devices measure the impedance of the skin, in particular the capacitive impedance, using two interdigitated electrodes to which an AC voltage is applied. The keratin measuring device 40 of FIG. 3 comes into contact with the fingertip 12 when the fingertip 12 rests on the contact surface 14 of the measuring body 16.

[0111] The device also comprises a pH sensor 42 for measuring the pH value of the skin. pH sensors for measuring the pH value of surfaces, including the surface of the skin, are known per se from the prior art and do not need to be described in detail here. pH sensors for measuring the pH value of the skin are commercially available for medical as well as cosmetic purposes.

[0112] Figure 4 shows the results of a Clarke Error Grid analysis obtained with a device of the type shown in Figure 3, and demonstrates that, using the measurement procedure described with reference to Figures 1-3, blood glucose concentrations can indeed be measured very reliably in a purely non-invasive manner. The data shown in Figure 4 are taken from WO 2017 / 09782 and do not yet reflect the improvements of the present invention. As will be described below, the present invention makes it possible to further improve the reliability of the method.

[0113] FIG. 5 schematically illustrates an apparatus 10 that relies on the same general principle as those of FIGS. 1 and 3 , involving absorption of a heat pulse from a substance 12 by a measuring body 16, but differs in the physical response utilized and the manner in which a corresponding response signal is generated. Such an apparatus 10 and its numerous variations are described in detail in International Publication No. 2019 / 11059782, which is incorporated herein by reference, and therefore will not be described in detail herein. As before, the apparatus includes a measuring body 16 having a contact surface 14 that contacts or couples with the skin of a finger 12. Also provided is a light source 26 for an excitation light beam 18 having a modulated intensity, which is directed to a region 44 below the surface of the skin 12 and absorbed therein. In this embodiment, the excitation light beam 18 passes through a hole 46 in the measuring body 16, indicated by a dashed line through the measuring body 16; therefore, the material of the measuring body 16 itself does not need to be transparent to the excitation light beam 18.

[0114] A control unit 48 is provided for modulating the intensity of the excitation light beam 18. This can generally be done in a variety of ways, including a mechanical chopper or an element whose transmittance or reflectance can be electronically controlled. However, in a preferred embodiment, the intensity is modulated by modulating the on / off times of the excitation light source 26 and the operating current during the on times of the excitation light source 26.

[0115] Thermal waves caused by the time-varying absorption of the intensity-modulated excitation beam 18 in the region 44 of the skin 12, symbolized by arrows 50, enter the measuring body 16 and can be detected in a detection region 52 having piezoelectric properties. Pressure changes associated with the received heat 50 or pressure waves result in electrical signals in the form of voltage changes that can be recorded by the electrodes 6a-6d, which are connected via conductive leads 54 to an estimation device 56 for analyzing the material (the skin of the finger 12). The estimation device 56 can be a digital processing device, such as a microcontroller, processor, or computer. In this case, the pressure changes resemble the physical response of the measuring body 16 or other components contained in the measuring body 16 to the heat received from the material 12 upon absorption of the excitation radiation, and are detected using the piezoelectric properties of the measuring body 16 or parts thereof, or piezoelectric elements embedded in the measuring body, and the electrodes 6a-6d, resulting in an electrical signal representing a response signal indicative of the degree of absorption of the excitation radiation 18.

[0116] In an alternative variant proposed by the applicant, as disclosed, for example, in International Application PCT / EP2019 / 064356, which is incorporated herein by reference, the detection device may be embedded in the measurement body and may include an interferometer device that allows for evaluating the phase change of a first portion of the detection beam relative to a second portion of the detection beam, where only one of the portions of the detection beam passing through the measurement arm is affected by heat or pressure waves in the measurement body, and generates a response signal at the output side of the interferometer device indicative of the phase change in the measurement arm. In this case, the physical response of the measurement body 16 (or a component contained in the measurement body 16) to the heat received from the substance 12 upon absorption of the excitation radiation 18 is again a local change in refractive index, and the response signal is in this case an interference signal reflecting the change in phase of one portion of the detection beam due to the local change in refractive index. This is shown schematically in FIG. 6, which shows the measurement body 16 in contact with a substance (such as a finger, not shown in FIG. 6). In this case, the measurement body 16 may be a silicon substrate provided with a light-guiding structure 58 that forms an interferometer device 60. The interferometer device 60 forms a Mach-Zehnder interferometer having a measurement arm 60a and a reference arm 60b. The detection light 22 generated by the detection light source 28 is fed to the light-guiding structure 58 and split by a splitter 60c into a portion or portions of the detection beam traveling along the measurement arm 60a and a portion or portions traveling along the reference arm 60b, which are then combined by a coupler 60d. The measurement body 16 is used or positioned such that the reference arm 60a is exposed to heat received from the skin upon absorption of the excitation light, while the reference arm 60b is not, or at least only slightly, exposed to it. The received heat causes a change in the refractive index in the measurement arm 60a, which results in a phase shift of the detection light 22 traveling along the measurement arm 60a. Because the light traveling along the reference arm 60b is not affected by the received heat, there is a change in the relative phase of the two portions of light combined by the coupler 60d, and this change results in an interference pattern that can be detected using the detector 62.It should be noted that the camera shown in FIG. 3 for detecting and analyzing fingerprints may also be combined with the measuring body 16 and device shown in FIGS.

[0117] FIG. 7 shows a schematic diagram of a device 10 according to one embodiment of the present invention in a side cross-sectional view. FIG. 8 shows the same device 10 in a front cross-sectional view. In the embodiment shown in FIGS. 7 and 8, the substance is again the skin of a user's finger 12, and the analyte to be evaluated is the glucose content in the skin, in particular in the interstitial fluid of the skin. The embodiment of FIGS. 7 and 8 makes it possible to ensure a reliable and consistent transmission of excitation radiation 18 to the skin of the finger 12. The measuring body 16 shown in FIGS. 7 and 8 is transparent to the excitation radiation 18 and has, in addition to the contact surface 14, an entrance surface 70 for the excitation radiation 18, which is the bottom surface in the example shown in FIGS. 7 and 8.

[0118] 7, the measurement body 16 further has an entrance surface 72 for the detection light beam 22, which corresponds to the left wall, and an exit surface 74, which corresponds to the right wall. A focusing lens 76 and a collimating lens 78 are formed integrally with the entrance surface 72 and the exit surface 74, respectively. In the illustrated embodiment, the focusing and collimating lenses 76 and 78 are formed monolithically with the rest of the measurement body 16. In other embodiments, the focusing and collimating lenses 76 and 78 may be formed separately from the measurement body 16 but may be attached to the entrance and exit surfaces 70, 74, respectively, so that their individual adjustment is not necessary.

[0119] 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, through which the excitation radiation 18 formed by the excitation light beam 18 in the mid-infrared range in this embodiment is emitted to the skin. The protrusion 80 has four side walls 84, each tapering toward the front surface 82. In this way, the area of ​​the front surface 82 is smaller than the footprint area of ​​the protrusion 80 on the contact surface 14. As can be seen from a comparison of FIGS. 7 and 8 , the protrusion 80 has a ridge shape and has a longer extension in a first direction, which is the x-direction extending into the plane of the paper in FIG. 7 , and a shorter extension in a second direction, which is the y-direction extending into the plane of the paper in FIG. 8 , perpendicular to the first direction.

[0120] Finally, the contact surface 14 is provided with a pressure sensor 86 that measures the contact pressure between the finger 12 and the contact surface 14. The pressure sensor 86 is connected to a control system (not shown), such as the control unit 34 of FIG.

[0121] The function of the various features shown in Figures 7 and 8 will now be explained. As can be seen in Figure 7, the incidence surface 70 for the excitation radiation 18 is not parallel to the contact surface 14 or the front surface 82 of the protrusion 80. Instead, the measurement body is slightly wedge-shaped. Furthermore, the excitation light source 26 is positioned so that the excitation beam 18 impinges on the incidence surface at an angle that deviates from 90°.

[0122] This differs from the arrangement shown in FIG. 3 , for example, in which the excitation beam is intentionally made to impinge on the incident surface at a 90° angle to avoid refraction and excessive reflection of the excitation radiation beam at the incident surface. However, as explained above, in such a configuration, a portion of the excitation radiation 18 may be reflected from the incident surface 70 and interfere with the excitation radiation 18 emitted from the excitation radiation source 26. The inventors have discovered that this interference can result in fluctuations in the intensity of the excitation radiation 18 at the skin of the finger 12, thereby resulting in artificial fluctuations in the response signal that are completely unrelated to the analyte concentration. However, avoiding normal incidence of the excitation beam 18 on the incident surface 70 can suppress the interference between the incident radiation 18 and the reflected radiation 18′ shown in FIG. 7 , and can improve the accuracy and reliability of the overall measurement.

[0123] In preferred embodiments, the angle of incidence should deviate from 90° by only a few degrees. A preferred 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 also depends on the distance between the excitation radiation source 26 and the incidence surface 70. The deviation from 90° should not be selected greater than necessary to ensure that undesired interference effects are avoided. Thus, in preferred embodiments, the angle of incidence is 82.0° or greater, preferably 84.0° or greater, and most preferably 85.0° or greater.

[0124] The protrusion 80 has the particular technical effect that the local contact pressure between the finger 12 and the measuring body 16 is increased. More precisely, the higher contact pressure occurs at the front surface 82 of the protrusion 80, which is the location where the excitation light beam 18 is coupled from the measuring body 16 into the skin of the finger 12. This increased contact pressure makes it possible to ensure a good and reliable optical coupling between the measuring body 14 and the skin.

[0125] The significant improvement that could be achieved with this protrusion 80 came as a surprise to the inventors, as generally sufficient optical coupling was obtained with applicant's previous devices having completely flat contact surfaces 14, and therefore it was not clear that the additional manufacturing cost and increased complexity involved in providing the protrusion 80 was worth the effort.

[0126] However, the inventors have discovered that while optical coupling with a perfectly flat contact surface 14 appears generally satisfactory, particularly inconsistent or unstable optical coupling can cause measurement inaccuracies. As explained in the summary above, the inventors have realized that optical coupling can change during the course of a single measurement, i.e., without intentionally moving or even removing the fingertip from the contact surface. This has been found to, in some cases, cause a change in the intensity of excitation radiation actually absorbed by the analyte and therefore a change in response signal that is unrelated to the analyte's absorbance or analyte concentration at the excitation radiation wavelength. In other words, a loss of optical coupling during part of a measurement can be mistaken for a lower absorbance at a given excitation wavelength. As also explained above, evaluation of an analyte spectrum typically involves measuring the absorbance at multiple characteristic wavelengths, e.g., wavelengths corresponding to peaks or absorption minima in the analyte absorption spectrum, and further involves mathematical combination of the response signals associated with the different wavelengths. For example, the response signal obtained at the minimum of the absorption spectrum may be subtracted from the response signal at the absorption peak to give a value representing the concentration of glucose in the skin. Clearly, any changes in the optical coupling, and therefore the effective intensity of the excitation radiation within the material, between measurements at different wavelengths or even during a measurement at a particular wavelength can introduce artifacts or inaccuracies into the measurement results.

[0127] As explained in the Summary of the Invention, the exact reason why the optical coupling between the contact surface and the material changes during measurement is not entirely clear, for example, whether it is because the user is unable to maintain a constant contact pressure between the finger and the contact surface, or whether the user unintentionally moves their fingertip across the contact surface. Regardless of the exact underlying reason, the inventors have realized that optical contact can be significantly stabilized using a protrusion such as protrusion 80 shown in Figures 7 and 8, which has a front surface 82 that contacts the skin of finger 12 with an increased local contact pressure. The front surface is 5 mm 2 Less than 3mm 2 They may have a size of less than 1 / 4" and may be flat or curved concavely or convexly.

[0128] To further ensure a constant contact pressure during measurement, a pressure sensor 86 is provided. The pressure sensor 86 generates a signal indicative of the contact pressure between the finger 12 and the contact surface 14 of the measuring body 16. The signal is transmitted to a control system (not shown) configured to check whether the sensed contact pressure is below a predetermined threshold. If found to be below the threshold, this is indicated to the user by an appropriate output device, such as a display, an optical signal, or an acoustic signal, and the user may be prompted to increase the contact pressure. Furthermore, the control system is configured to prevent the analyte measurement process from beginning while the contact pressure is below the threshold, thereby avoiding measurements that are of questionable quality and may have to be repeated, resulting in user frustration or annoyance. Furthermore, if the contact pressure is found to fall below the threshold during measurement, the analyte measurement process is interrupted, and the user is given the opportunity to return to the original contact pressure so that the measurement can be completed. The pressure sensor may be implemented as a piezoelectric element (not shown) located under the protrusion 80 of the measuring body 16 and may be transparent to the excitation beam.

[0129] 7 are each associated with ensuring a consistent amount of coupling of excitation radiation to the skin of finger 12, and are therefore independent of the particular type of physical response of the measuring body (or components contained within the measuring body) to heat or pressure waves received from the skin of finger 12, or the detection device generating the corresponding response signal. Thus, these features may be used in combination with any of the variations shown in FIGS. 1, 3, 5, and 6.

[0130] In the embodiment of FIG. 7 , the physical response to the heat or pressure wave received by the measuring body 16 is a local change in refractive index, and this physical response is detected by a deflection of the detection light beam 22 reflected at the front surface 82 of the protrusion 84. As seen in FIG. 7 , the detection light beam 22 is generated by a detection light source 28, and the deflection of the detection light beam 22 is detected using a position sensitive detector (PSD) 30, which may also be referred to as a position sensing device. As understood herein, the "deflection of the detection light beam 22" refers to the total deviation of the detection light beam at the corresponding detection device; with particular reference to the embodiment of FIG. 7 , this refers to the shift in position of the detection light beam 22 at the PSD 30. This deviation is the combined effect of all changes to the propagation of the detection light beam 22 along the optical path caused by the local change in refractive index.

[0131] The particular raised geometry of the protrusion 80 shown in Figures 7 and 8 is adapted to this detection setup. The detection light beam 22 before and after reflection on the front surface 82 of the protrusion 80 defines a detection light plane, which in the embodiment of Figures 7 and 8 corresponds to the xz plane, i.e., the plane of the paper in Figure 7, and which coincides with the first, longer direction of the protrusion-shaped protrusion 80. Indeed, as is clear from Figure 7, this larger extension of the protrusion 80 in the detection light plane is necessary so that the incident and reflected detection light beam 22 can fit on the protrusion 80. Conversely, as is clear from Figure 8, in the direction perpendicular to this detection light plane, i.e., the "second direction" of the protrusion-shaped protrusion 80, the extension can be made smaller, thereby keeping the overall surface area of ​​the front surface 82 small and thus increasing the local contact pressure.

[0132] Furthermore, the focusing lens 76 at the entrance surface 72 of the detection light beam 22 allows the detection light beam diameter 22 to be kept narrow in the region where the detection light beam 22 is reflected by the front surface 82 of the protrusion 80, which is also the region where a thermal lens (not shown in FIG. 7) is created. The narrow beam diameter promotes a clear and characteristic deflection of the detection light beam 22 at the thermal lens, which itself is only relatively small in size.

[0133] The collimating lens 78 at the exit face 74 of the detection beam 22 allows the diameter of the detection beam 22 to remain at least approximately constant as it travels between the exit face 74 and the PSD 30. This allows the distance between the PSD 30 and the exit face 74 to be increased, which means that any deflection angle acquired by the detection beam 20 results in a larger shift in the position at which the detection beam 22 impinges on the PSD 30, thereby increasing the signal-to-noise ratio of the response signal. For example, the distance between the reflection site at the front face 82 of the protrusion 80 and the PSD 30 may be 4 cm or more, and in some embodiments, 9 cm or more.

[0134] In the embodiment shown in FIG. 7 , 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, the collimating lens 78 in particular may be a cylindrical lens with its collimating effect only in the y direction in FIG. 7 . However, unlike the embodiment shown in FIG. 7 , the detection light beam 20 may extend in the xz plane, i.e., the plane of the paper in FIG. 7 . This means that the light spot of the detection light beam 22 at the PSD 30 is elliptical, with its major axis parallel to the sensing direction of the PSD 30, which is also the direction in which the light spot moves when the detection light beam 20 is deflected. This elongated shape of the light spot has been found to result in a better signal-to-noise ratio and better linearity of the response signal.

[0135] As understood herein, the "deflection" of the detection light beam 20 refers to the total deviation of the detection light beam 20 from its "unperturbed" optical path, i.e., an optical path without local changes in refractive index due to thermal or pressure waves received by the measurement body 16, as measured by a detection device such as the PSD 30. Therefore, this "deflection" is the cumulative effect of local changes in refractive index on the detection light beam 20 along its optical path. In practice, the deflection always tends to be small, and to obtain more accurate and reliable measurement results, it is important to increase the signal-to-noise ratio of the response signal. One possible approach is described above with reference to FIG. 7, namely, by increasing the distance between the exit face 74 and the PSD 30. Further methods for improving the signal-to-noise ratio are discussed with reference to FIGS. 9-11 below.

[0136] While not wishing to be bound by theory, FIG. 9 illustrates the mechanism of deflection as currently understood by the inventors, which is entirely consistent with actual measurements. In FIG. 9, the unperturbed detection light beam is shown by a solid line and has an incident portion 22 and an exiting portion 22b. When the excitation radiation pulse 18 is absorbed in the skin of FIG. 12, a heat pulse is generated that travels through the skin into the measurement volume 16, as explained above. Within the measurement volume 16, the heat pulse causes a local change in refractive index, referred to herein as a “thermal lens” and shown schematically in FIG. 9 by reference numeral 20. The thermal lens 20, in this embodiment, is found to be a region of higher refractive index, resulting in refraction as shown by the dashed refraction and reflected detection light beam 20a. The deviation of the reflected detection light beam 22a from the unperturbed reflected detection light beam 22b is referred to herein as “deflection.”

[0137] Note that in FIG. 9 , the entrance surface 72 and exit surface 74 of the measurement body 16 are angled to form a right angle with the incoming and outgoing detection light beam 22. This orthogonal arrangement of optical boundaries is a natural choice in the art because it allows for reduced reflection and also allows for avoidance of diffraction, but it makes the optical setup more complex. However, in the embodiment of FIG. 10 , at least the exit surface 74 is positioned so that it is not perpendicular to the reflected detection light beam 22 b. Instead, the detection light beam 22 b forms an angle α1 with the normal to the exit surface 74, and because the refractive index of the measurement body 16 is higher than the refractive index of the surroundings, which in this embodiment is air, the undisturbed detection light beam 22 b is refracted at an angle β1 greater than α1 when it leaves the measurement body 16.

[0138] The deflected light beam 22a is similarly refracted at the exit surface 74. However, due to interaction with the thermal lens 20, the incident angle α2 is larger than that of the undisturbed detection beam 22b, and according to Snell's law, the refraction angle β2 is significantly larger than β1. In other words, the difference in refraction angles β2 - β1 is larger than the difference in incident angles α2 - α1, i.e., β2 - β1 > α2 - α1, and therefore the deflection of the reflected detection light beam 22a measured by the PSD 30 (not shown in FIG. 10) is increased. This allows for a further increase in the signal-to-noise ratio.

[0139] Finally, referring to Fig. 11, an embodiment is shown in which the contact surface 14 of the measuring body 16 is curved in the region where the detection light beam 22 is reflected. In other words, the measuring body in this region has a concavely curved recess. As shown schematically in Fig. 11, part of the deflection of the light beam 22 due to the local change in refractive index occurs before the detection light beam 22 is reflected from the surface of the measuring body in thermal or pressure-transmitting contact with the finger 12. This means that the local change in refractive index also leads to a shift in the exact position on the surface where the detection light beam 22 is reflected.

[0140] With this understanding in mind, in the embodiment shown in FIG. 11 , the contact surface 14 has a curved portion 88. This curvature causes a change in the exact location where the detection light beam 22 is reflected from the curved portion 88 to be accompanied by a change in the angle of incidence, and thus a corresponding change in the angle of reflection, as can be seen in FIG. 11 . Thus, using a curved reflective surface can increase the total deflection evaluated by the detection device, such as a shift in the position of the impinging detection light beam 22 detected by the position sensitive detector 30, thereby further enabling an increased signal-to-noise ratio. Note that while FIG. 11 shows the curved portion 88 formed on the otherwise flat contact surface 14, a curved portion may similarly be formed on the front surface 82 of the protrusion 80 shown in FIGS. 7 and 8 . Furthermore, in the embodiment shown in FIG. 11 , the curved portion 88 was concave, but a convex curved portion (not shown) may achieve a similar effect, since a local change in refractive index is also accompanied by a change in the location where the detection light beam impinges on the curved portion, and therefore a change in the angle of incidence.

[0141] Furthermore, in FIG. 11 , the curved portion 88 is shown as having a spherical shape, i.e., having the same or similar curvature in two main directions. However, in other embodiments, the curved portion 88 may be curved primarily or even exclusively in one direction, e.g., having the shape of a cylindrical cross section (the cross-sectional plane of which is parallel to the cylindrical axis). This is particularly advantageous in the case of a concavely curved portion 88, in which case the fingers 12 may be arranged parallel to the longitudinal axis of the concavely curved portion, allowing particularly good contact with the curved surface of the curved portion. As mentioned above, in preferred embodiments, the radius of curvature of the curved portion 88 in at least one main direction is in the range of 5 to 30 mm, more preferably 10 to 20 mm. In preferred embodiments, the width of the curved region 88 in a main direction is at least 300 μm and at most twice the radius of curvature.

[0142] As mentioned above, in many embodiments, it is advantageous for the light spot of the detection light beam 22 at the PSD 30 to have an elongated shape, e.g., an elliptical shape with its major axis parallel to the detection direction. This elongated shape may be obtained, for example, by collimating the detection light beam 22 only in a direction perpendicular to the detection direction, as described above with reference to FIG. 7. However, additionally or alternatively, the elongated shape of the light spot may be obtained by tilting the PSD 30 in the detection light plane relative to the detection light beam 22, as shown in FIG. 12, so that the detection light beam 22 impinges on the PSD at an angle that deviates from 90°. For example, the angle of incidence on the detection surface of the PSD 30 may be less than 80°, preferably less than 70°, and most preferably less than 50°.

[0143] 13 and 14 show a further apparatus 10 similar to that of FIG. 7 in a top view and a perspective view, respectively. Like the apparatus of FIG. 7, the apparatus of FIGS. 13 and 14 comprises a detection light beam 22 reflected from the contact surface 14 of the measuring body 16 and a detection device, such as a PSD 30, which allows for detecting a deflection of the detection light beam 22 due to interaction with a thermal lens, indicated by reference numeral 20. In the embodiment of FIGS. 13 and 14, the detection light beam 22 is derived from a source light beam 88 by a splitter 90. The splitter 90 transmits a portion of the source light beam 88, forming the detection light beam 22, and reflects another portion, forming a reference light beam 92. Using a mirror 94, the reference light beam 92 is likewise directed to be totally or partially reflected from the surface 14 of the measuring body 16 at a position close to the reflection position of the detection light beam 22, particularly in the area where a finger 12 (not shown) contacts the contact surface 14 during operation. However, the point of reflection of the reference light beam 92 at 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, so that the influence of heat or pressure waves received from the finger 12 upon absorption of the excitation radiation 18 is negligible. This is shown in Figures 13 and 14, where it can be seen that the thermal lens 20 does not extend to the area where the reference light beam 92 is reflected at the contact surface 14 of the measuring body 16.

[0144] In Figure 14, reference numeral 93 indicates the points at which the detection light 22 and reference light beam 92 enter and exit the measurement volume 16, and is shown mainly to assist in obtaining an image of the three-dimensional structure. It should be noted that in the schematic diagram of Figure 14, for simplicity, the refraction of the detection and reference light beams 22, 92 at the entrance and exit planes is not shown. A further detection device 96 is provided to detect the degree of deflection of the reference light beam 92, and in the embodiment shown, the detection device 96 is formed by a PSD of the same type as PSD 30.

[0145] It is seen that the reference light beam 92 is subjected to all or nearly all of the same types of noise, vibrations, perturbations, or external influences as the detection light beam 22, except for the effects of the thermal lens 20, in other words, heat or pressure waves received due to absorption of the excitation light beam 18. Therefore, all or at least most types of external effects that can result in a deflection of the detection light beam 22, other than deflection due to absorption in a material, also affect the reference light beam 92 and can be measured by the additional detector 96. The measurement results of the additional detector 92 on the reference light beam 92 can then be used to correct for these effects in the measurement results of the PSD 30 on the detection light beam 22, thereby improving the measurement signal quality.

[0146] 15 and 16, a further embodiment of the device is shown, which comprises an optical fiber 98 embedded in the measurement body 16. A detection light source 28 is provided at one end of the fiber 98 to couple detection light into the fiber 98. A mode detector 100 is provided at the other end of the fiber 98. The mode detector 100 is suitable for detecting changes in the optical mode of the detection light in response to heat or pressure waves received by the measurement body 16 from the material. For example, the mode detector 100 can comprise a camera suitable for visualizing modes, or more precisely, interference patterns of optical modes. On the right side of FIG. 15, an image produced by such a mode camera is schematically shown, in which optical modes 104, or more precisely, interference patterns of optical modes, can be seen at a specific rotational orientation.

[0147] FIG. 16 shows the same apparatus as FIG. 15 , except that the thermal gradient 20 is generated by heat or pressure waves received from a substance, such as a finger 12 (not shown in FIGS. 15 and 16 ). This results in a temporary deformation of the optical fiber 98, which is shown in the enlarged portion of FIG. 16 , where the deformation is greatly exaggerated for illustrative purposes. Such temporary deformation of the optical fiber 98 results in a change in the optical mode, which is detected by the mode camera 100. In the exemplary embodiment shown in FIG. 16 , the change in mode corresponds to a rotation of the mode's interference pattern, as can be seen by comparing the mode images shown schematically in FIGS. 15 and 16 . In other embodiments, the change in mode may correspond to, for example, a shift in the mode's interference pattern.

[0148] In the illustrated embodiment, the mode detector 100 includes a processor (not separately shown) configured to detect mode changes based on image analysis of the camera image. As described above, detectable changes in the optical mode can include a shift or rotation of the optical mode's interference pattern within the fiber and also at the mode camera 100. The shift distance or rotation angle is therefore a quantitative parameter related to the amount of heat received from the material or the intensity of the pressure wave, and thus ultimately indicates the amount of excitation light absorbed by the material. The device of Figures 15 and 16 is advantageous in that it is very simple and robust, requiring little adjustment of the optical components. This is particularly useful for portable devices.

[0149] FIG. 17 shows a side view and a perspective view of an apparatus 10 according to a further embodiment. The apparatus 10 is a portable glucose measurement device having a size similar to that of a small smartphone. The upper view of FIG. 17 shows a measuring body 16 having a contact surface 14, which in this case has a curved portion similar to that of FIG. 11. A finger 12 can be placed on the contact surface 14, as shown in FIG. 17, where the finger 12 is only schematically represented by a cylindrical structure. Further details of the apparatus are not shown in FIGS. 16 and 17, but the measurement principle of the device is similar to that of FIG. 11 and uses a detection light beam (not shown) reflected from a curved surface. As explained with reference to FIG. 11, this results in a particularly large deflection of the measurement beam and therefore a particularly high signal-to-noise ratio.

[0150] FIG. 17 further shows a clamping device 106 comprising a clamping member 108. The clamping member 108 is pivotally mounted at a first end (the left end of the figure) and biased by a torsion spring 114 to a closed position, shown in the upper view of FIG. 17, in which the clamping member 108 is close to the contact surface 14. A handle member 110 is provided at a second end of the clamping member 108, allowing the clamping member 108 to be grasped and rotated against the biasing force of the torsion spring 114 to an open position in which the clamping member 108 is moved away from the contact surface 14 of the measuring body 16. A finger 12 can be placed on the contact surface 14 when the clamping member 108 is in the open position, and the clamping member 108 is adapted to press the finger 12 against the contact surface 14 due to the biasing force towards the closed position. In this way, a predetermined contact pressure can be ensured. A cushion 112 is formed near the second end of the clamp member 108, and the cushion 112 rests on the finger 12 when the finger 12 is held by the clamp member 108, as shown in FIG. 17 . In the illustrated embodiment, the cushion 112 is provided with a pressure sensor (not shown) that monitors contact pressure, similar to the pressure sensor 86 shown in FIG. 7 . It should be noted that the clamp mechanism is not limited to use in handheld devices, but may also be provided in, for example, tabletop devices or any other variants. Furthermore, the biasing force of the clamp member 108 need not be generated by a torsion spring, such as the torsion spring 114, but may instead be provided by the clamp member 108 acting as a leaf spring. Instead of the torsion spring 114, there may be an adjustable mounting portion that allows the rest position of the clamp member 108 (leaf spring) and, therefore, the biasing force generated by the clamp member 108 to be adjusted.

[0151] Figures 18 and 19 show yet another apparatus 10 that is structurally similar in some respects to the apparatus of Figures 13 and 14. As with the embodiment of Figures 13 and 14, the physical response to absorption of excitation radiation 18 in a substance such as human tissue (neither the tissue nor the excitation radiation 18 is shown in Figures 18 and 19) is a local change in refractive index, and the region of local change in refractive index is again indicated by reference numeral 20. In this case, however, the response signal is not a deflection of the measurement beam as is the case for the embodiment of Figures 13 and 14, but an interference signal similar to that of the embodiment of Figure 6.

[0152] 18 and 19 comprises a detection light beam 98 that is split by a splitter 90 into a transmitted portion 100 and a reflected portion 102. The reflected portion 102 is redirected by a mirror 104 so that it is guided parallel to the transmitted portion 100, both portions lying in a plane parallel to the contact surface 14 of the measuring body 16. Thus, unlike the embodiments of Figures 13 and 14, the transmitted and reflected portions 100, 102 are not reflected by the contact surface 14 of the measuring body 16.

[0153] A transmitted portion 100 of the detection light beam 98 passes through the region 20 where a local change in refractive index occurs, while a reflected portion 102 avoids this region. Using an additional mirror 104 and a combiner 106, the two portions 100, 102 of the detection light beam 98 are recombined, and an interference signal of the recombined portions 100, 102 is recorded by a photodetector 108. The change in refractive index in the region 20 results in a shift in the phase of the transmitted portion 100 and therefore a change in the interference signal at the detector 108. The phase change is larger the greater the local change in refractive index, and therefore this phase change indicates the degree of absorption of the excitation radiation beam 18.

[0154] It should be noted that the embodiments of Figures 18 and 19 are merely exemplary and any variant in which two light beams are interfered is considered in this specification, one of which passes through an area 20 in the measuring body 16 that is exposed to heat or pressure waves received from a substance placed on the contact surface 14 upon absorption of excitation radiation.

[0155] In the embodiment of FIG. 7, 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. Instead, the measuring body itself can form the protrusion or form part of the protrusion. An example of this is shown in FIG. 20, which is very similar to FIG. 7, except that in this case the measuring body 16 is much smaller and forms the protrusion 80 itself. Furthermore, while in the embodiment of FIG. 7 the focusing lens 76 and the collimating lens 78 are integrated with the measuring body 16, in the embodiment of FIG. 20 these are replaced by separate focusing lens 112 and collimating lens 114, respectively.

[0156] 20, the contact surface of the measuring body 16 forms the front face 82 of the protrusion 80. Furthermore, the front face 82 of the protrusion 80 is elevated with respect to the surrounding structure, which in this case is formed by the housing wall portion 110.

[0157] In the illustrated embodiment, the protrusions 80 formed by the measuring body 16 are the same or similar in size as the protrusions 84 on the contact surface 14 in the embodiment of Figure 7. It should be noted that all descriptions and explanations provided above regarding "protrusions" formed on the contact surface of the measuring body apply equally to protrusions formed by or at least partially formed by the measuring body 16.

[0158] 21 to 23 show a further embodiment in which the measuring body 16 forms part of the protrusion 80. More precisely, FIG. 21 shows a mounting block 112 to which the measuring body 16 is attached. The mounting block 112 has an upper surface 114, on which the protrusion 80 is also formed. In this case, the protrusion 80 is partly formed by a receptacle 116 having a recess 118 formed therein. The measuring body 16 is attached to a frame 120 that is received in the recess 118 of the receptacle 116. In this case, the receptacle 116, the frame 120 and the measuring body 16 combine to form the protrusion 80, which protrudes beyond the upper surface 114 of the mounting structure 112. Here, the contact surface of the measuring body 16 (the upper surface in FIG. 21 ) forms part of the front surface of the protrusion 80, which is elevated relative to the upper surface 114, which in this case forms the aforementioned “surrounding structure”.

[0159] Figure 22 shows a top view of the protrusion 80 and the top surface 114 of the mounting structure 112. Figure 23 shows a cross-sectional view along line AA in Figure 23. As can be seen particularly from Figure 22, the frame 120 may be rotated a few degrees about a vertical axis and secured in a desired position by screws 122. To facilitate adjustment of the desired rotational position, scales 124 are provided on both the frame 120 and the top surface of the receptacle 116.

[0160] As can be seen from Fig. 23, in this embodiment, the excitation light beam 18 is directed vertically upward. The rotation axis about which the frame 120 can be rotated coincides with the light beam propagation axis of the excitation light beam 18. It can be seen that the excitation light beam 18 is irradiated onto the substance through the contact surface 14 of the measuring body 16 when the substance is placed on the upper surface 114 and the protrusion 80, whereby the contact surface 14 simultaneously forms part of the front surface of the protrusion, in particular the part through which the excitation light beam 18 is irradiated onto the substance. Furthermore, as can be further seen in Fig. 23, this front surface is elevated with respect to the surrounding structure, i.e. the upper surface 114 of the mounting structure 112.

[0161] In the embodiment shown in Figures 21-23, the protrusions 80 are significantly larger than those shown in Figures 7 or 20. In the embodiment of Figures 21-23, the protrusions 80 are designed for measurements on the underside of a person's wrist. This protrusion 80 has been found to improve contact, and particularly coupling, of the excitation light 18 into the tissue compared to a flat surface for resting the arm.

[0162] It should be noted that in the embodiment shown in Figures 1 to 23, the contact surface 14 of the measuring body 16 forms only a part of the upper surface of the protrusion 80, but forms the part where the excitation radiation 18 is irradiated onto the material.

[0163] By rotating the frame 120 in the recess 118 of the receptacle 116, the angle of incidence of the detection light beam 22 on the incident surface 72 of the measurement body can be adjusted. As explained above, the detection light beam 22 should impinge on the incident surface at an angle of incidence relative to the incident surface that is not 90°, such as 89° or less, 88° or less, and for example 87.5° or less. This avoids back-reflection of the detection light beam 22 on itself, which can result in negative interference effects and also damage to the detection light source. At the same time, the deviation from 90° should not be greater than necessary for this purpose. Therefore, this angle is preferably 80° or more, more preferably 80% or more, such as 84° or 85° or more.

[0164] The following examples are further disclosed herein. [Example]

[0165] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; An apparatus is provided in which a pressure sensor for measuring the contact pressure between the substance and the measuring body is provided, the pressure sensor comprising: a detection device for detecting a physical response of the measuring body or a component contained in the measuring body to heat or pressure waves received from the substance upon 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.

[0166] In a preferred embodiment of Example 1, the apparatus further comprises a control system configured to receive a signal from the pressure sensor indicative of a contact pressure between the substance and the measuring body, the control system being configured to check whether the contact pressure is less than a predetermined threshold, and if it is found that the contact pressure is less than the threshold: indicating to the user a lack of contact pressure; preventing the analyte measurement process from being initiated; and interrupting the current analyte measurement process; The device is configured to perform one or more of the following: [Example]

[0167] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection device for detecting a physical response of the measuring body or a component contained in the measuring body to heat or pressure waves received from the substance upon absorption of the excitation radiation, and for generating a response signal based on the detected physical response, the response signal being indicative of the degree of absorption of the excitation radiation; the measuring body is transparent to the excitation radiation, the excitation radiation source is configured to provide the excitation radiation as an excitation beam; an excitation radiation source arranged such that the excitation beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body, and exits the measurement body at the contact surface; An apparatus wherein the excitation beam impinges on the entrance surface at an angle of 89.0° or less, preferably 88.0° or less, most preferably 87.5° or less, and 82.0° or more, preferably 84.0° or more, most preferably 85.0° or more.

[0168] In a preferred embodiment of Example 2, the excitation beam impinges on the contact surface of the measurement body at an angle of 90°±1.5°.

[0169] In a preferred embodiment of Example 2, the incidence surface and the contact surface at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined with respect to each other by an angle of 1.0° or more, preferably 2.0° or more, most preferably 2.5° or more, and 8.0° or less, preferably 6.0° or less, most preferably 5.0° or less. [Example]

[0170] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection light source for generating a detection light beam which travels through the measuring body or at least a part of a component contained in the measuring body, the detection light beam being directed so as to be totally or partially reflected at the contact surface, the detection light beam being deflected when heat or pressure waves generated by absorption of excitation radiation in a substance are transferred to the measuring body; a detector for detecting the degree of deflection, in particular the angle of deflection, of the detection light beam after reflection at the contact surface, An apparatus, wherein the contact surface of the measuring body is curved in at least one main direction in the area where the detection light beam is reflected.

[0171] In a preferred embodiment of Example 3, said curvature in said at least one main direction corresponds to a radius of curvature in the range of 5 to 30 mm, preferably 10 to 20 mm.

[0172] In a preferred embodiment of Example 3, said curvature in said main direction is one of concave or convex.

[0173] In a preferred embodiment of Example 3, the detection light beam before and after reflection from the front surface forms a detection light plane, and the main direction is within the detection light plane or forms an angle with the detection light plane of less than 30°, preferably less than 20°. [Example]

[0174] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection light source for generating a detection light beam which travels through the measuring body or at least a part of a component contained in the measuring body, the detection light beam being directed so as to be totally or partially reflected at the contact surface, the detection light beam being deflected when heat or pressure waves generated by absorption of excitation radiation in a substance are transferred to the measuring body; a detector for detecting the degree of deflection, in particular the angle of deflection, of the detection light beam after reflection at the contact surface, a detection light source arranged such that the detection light beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body, and exits the measurement body at an exit surface; an apparatus wherein the detection beam impinges on the exit surface at an angle of 5° or more, preferably 10° or more, and most preferably 15° or more, relative to a normal to the exit surface, the detection beam is refracted upon exiting the exit surface of the measurement body, and the orientation of the exit surface relative to the detection light beam is such that the deflection of the detection light beam in response to the heat or pressure waves transferred to the measurement body increases the angle of the detection light beam relative to the normal to the exit surface. [Example]

[0175] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection light source for generating a detection light beam that travels through the measurement body or at least a part of a component contained in the measurement body, the detection light beam being directed so as to be totally or partially reflected at the contact surface, the detection light beam being deflected in response to heat or pressure waves generated by absorption of excitation radiation in a substance being transferred to the measurement body; a detector for detecting the degree of deflection, in particular the angle of deflection, of the detection light beam after reflection at the contact surface, The detection light source is arranged so that the detection light beam is irradiated onto the measurement body at an entrance surface, propagates through a portion of the measurement body, and exits the measurement body at an exit surface, and a focusing lens is attached to or integrally formed with the entrance surface to focus the detection beam, and / or a collimating lens is attached to or integrally formed with the exit surface. [Example]

[0176] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection light source for generating a detection light beam that travels through the measurement body or at least a part of a component contained in the measurement body, the detection light beam being directed so as to be totally or partially reflected at the contact surface, the detection light beam being deflected in response to heat or pressure waves generated by absorption of excitation radiation in a substance being transferred to the measurement body; a detector for detecting the degree of deflection, in particular the angle of deflection, of the detection light beam after reflection at the contact surface, the detector comprises a position sensitive detector impinged by the detection light beam, the position sensitive detector being sensitive to detect shifts in the position of the detection light beam impinging on the position sensitive detector in at least one sensitive direction; the position sensitive detector is positioned such that the deflection of the detection light beam results in a shift in the position of the detection light beam impinging on the position sensitive detector in the at least one sensing direction, a cylindrical lens is provided in the optical path of the detection light beam to shape the profile of the detection light beam, and / or the position sensitive detector is positioned at an angle deviated from 90° to the detection light beam, and the diameter of the detection light beam impinging on the position sensitive detector in the sensing direction is at least 1.5 times, preferably at least 2.0 times, the diameter of the detection light beam in a direction perpendicular to the sensing direction.

[0177] In a preferred embodiment of Example 6, a cylindrical lens is a collimating lens arranged in the optical path of the detection light beam between reflection at the contact surface and the position sensitive detector, and the cylindrical lens is arranged to collimate the detection light beam primarily in a dimension perpendicular to the sensing direction of the position sensitive detector, and the cylindrical collimating lens is preferably formed integrally with the exit surface of the measurement body from which the detection light beam exits the measurement body. [Example]

[0178] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; a detection light source for generating a detection light beam that travels through the measurement body or at least a part of a component contained in the measurement body, the detection light beam being directed so as to be totally or partially reflected at the contact surface, the detection light beam being deflected in response to heat or pressure waves generated by absorption of excitation radiation in a substance being transferred to the measurement body; a detector for detecting the degree of deflection, in particular the angle of deflection, of the detection light beam after reflection at the contact surface, the apparatus further comprising a beam splitter for splitting the light source light beam into the detection light beam and the reference light beam, the reference light beam likewise being directed so as to be totally or partially reflected at a surface of the measuring body that is in thermal or pressure-transmitting contact with the substance, but within a region where the influence of heat or pressure waves received from the substance upon absorption of the excitation radiation is negligible, the detection device comprising an additional detection device for detecting the degree of deflection, in particular the deflection angle, of the reference light beam after reflection at the contact surface, the additional detection device preferably comprising a photodetector, in particular a position-sensitive photodetector. [Example]

[0179] 1. An apparatus for analyzing a substance comprising at least one analyte, comprising: a measuring body having a contact surface suitable for being in thermal or pressure-transmitting contact with the substance, said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation in the substance to be transferred to said measuring body; an excitation radiation source configured to irradiate the material with excitation radiation to be absorbed by the material; and a detection device for detecting a physical response of a measuring body or a component contained in the measuring body to heat or pressure waves received from the substance upon 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, the apparatus comprising an optical fiber embedded in the measuring body, a detection light source provided at one end of the fiber for coupling detection light into the fiber, and a mode detector provided at the other end of the fiber, the mode detector being suitable for detecting a change in the optical mode of the detection light in response to heat or pressure waves received by the measuring body from the substance, the change in optical mode preferably including a shift or rotation of the optical mode within the fiber.

[0180] While the present invention has been described with respect to particular embodiments, it is to be understood that variations and modifications will occur to those skilled in the art, all of which are intended as aspects of the present invention. Accordingly, only such limitations as appear in the claims should be placed on the invention.

Claims

1. An apparatus (10) for analyzing a substance (12) containing at least one analyte, comprising: a measuring body (16) having a contact surface (14) suitable for being in thermal or pressure-transmitting contact with said substance (12), said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation (18) in said substance to be transferred to said measuring body; an excitation radiation source (26) configured to irradiate the material (12) with excitation radiation (18) so as to be absorbed by the material (12); a detection device for detecting a physical response of the measuring body or a component contained in the measuring body (16) to heat or pressure waves received from the substance (12) upon absorption of the excitation radiation (18) and for generating a response signal based on the detected physical response, the response signal being indicative of the degree of absorption of the excitation radiation; the measuring body (16) is transparent to the excitation radiation (18), the excitation radiation source (26) is configured to provide the excitation radiation (18) as an excitation beam; the excitation radiation source (26) is arranged such that the excitation beam is irradiated onto the measurement body (16) at its entrance surface (70), propagates through a portion of the measurement body (16), and exits the measurement body (16) at the contact surface (14); the excitation beam (18) impinges on the incidence surface (70) at an angle of less than or equal to 89.0° and greater than or equal to 82.0°; The incident surface (70) and the contact surface (14) at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined with respect to each other at an angle of 1.0° or more and 8.0° or less.

1. An apparatus (10) comprising:

2. a protrusion (80) is provided, the protrusion having a front surface (82) facing the substance (12) and contacting the substance when the substance is brought into contact with the contact surface, the excitation radiation (18) being irradiated onto the substance (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 2. The device (10) according to claim 1, wherein the measuring body (16) forms the protrusion or part of the protrusion, and 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.

3. 3. The device (10) of claim 1 or 2, wherein the protrusion (80) has a tapered shape with one or more side walls (84) tapering toward the front surface (82).

4. 4. The device (10) of claim 2 or 3, wherein the protrusion (80) is ridge-shaped and has a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, the longer extension being at least 1.5 times greater than the shorter extension.

5. 5. The device according to claim 1, wherein the protrusion (80) or the measuring body (16) forming the part of the protrusion (80) is received in a frame or receptacle, and the contact surface (14) of the measuring body (16) protrudes from the frame or receptacle, or the frame or receptacle protrudes from a surrounding structure.

6. a pressure sensor (86) is provided to measure the contact pressure between the substance (12) and the measuring body; The device (10) further comprises a control system configured to receive a signal from the pressure sensor (86) indicative of the contact pressure between the substance (12) and the measuring body (16), the control system being configured to check whether the contact pressure is below a predetermined threshold, and if it is found that the contact pressure is below the threshold: indicating to the user a lack of contact pressure; preventing the analyte measurement process from being initiated; and interrupting the current analyte measurement process; The apparatus (10) of any one of claims 1 to 5, configured to perform one or more of the following:

7. the excitation beam (18) impinges on the incidence surface (70) at an angle of 88.0° or less and / or 84.0° or more; the incidence surface (70) and the contact surface (14) at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined with respect to each other at an angle of 2.0° or more and / or 6.0° or less; An apparatus (10) according to any one of claims 1 to 6.

8. 8. The device (10) according to claim 7, wherein the excitation beam (18) impinges on the contact surface (14) of the measuring body at an angle of 90°±1.5°.

9. the detection device comprises a light source (28) for generating a detection light beam (22) which travels through the measuring body (16) or at least a part of a component contained in the measuring body (16), the physical response of the measuring body (16) to heat or pressure waves received from the substance (12) upon absorption of the excitation radiation (18) is a local change in the refractive index of the measuring body (16) or of the component; the detection device is configured to detect one of a change in the optical path or a change in the phase of a detection beam due to the change in refractive index; An apparatus (10) according to any one of claims 1 to 8.

10. 10. The apparatus according to claim 9, wherein the detection device is configured such that the detection light beam (22) is irradiated onto the measurement body (16) at an incident surface (72), and the detection light beam (22) impinges on the incident surface (72) at an incident angle with respect to the incident surface of less than 89° and greater than 80°.

11. 11. The apparatus of claim 10, wherein the measuring body (16) is received in a frame or receptacle that allows the measuring body (16) to be rotated so as to adjust the angle of incidence of the detection light beam when it impinges on the incident surface (72) of the measuring body (16), in particular the frame or receptacle that allows the measuring body (16) to be rotated about an axis parallel to the excitation light beam or deviated from parallel by less than 10°.

12. 12. The apparatus (10) according to claim 9, wherein the measuring body (16) is transparent to the detection light beam (22), the detection light beam (22) is directed so as to be totally or partially reflected at a surface (14) of the measuring body (16) that is in thermal or pressure-transmitting contact with the substance (12), and the detection device comprises a detector (30) for detecting the degree of deflection, in particular the deflection angle, of the detection light beam (22) after reflection at the contact surface (14) due to the local change in refractive index.

13. the detection light source (28) is arranged so that the detection light beam (22) is irradiated onto the measurement body (16) at an entrance surface (72), propagates through a portion of the measurement body, and exits the measurement body at an exit surface (74); the detection light beam (22) impinges on the exit surface (74) at an angle of 5° or more relative to the normal to the exit surface (74) in the absence of any deflection due to the local change in refractive index, the detection beam (22) is refracted upon exiting the exit surface (74) of the measurement body (16), and the orientation of the exit surface (74) relative to the detection light beam (22) is such that the deflection of the detection light beam (22) in response to the heat or pressure waves transferred to the measurement body (16) increases the angle between the detection light beam and the normal to the exit surface.

13. The device (10) according to claim 12.

14. the detection light source (28) is arranged so that the detection light beam (22) is irradiated onto the measurement body (16) at an entrance surface (72), propagates through a portion of the measurement body (16), and exits the measurement body (16) at an exit surface (74); a focusing lens (76) is integrally formed with the entrance surface (72) to focus the detection light beam (22) entering the measurement body (16) in at least one dimension, and / or a collimating lens (78) is integrally formed with the exit surface (74) to collimate the detection light beam (22) in at least one dimension.

14. Apparatus (10) according to claim 12 or 13.

15. A method for analyzing a substance (12) containing at least one analyte, comprising: - bringing a measuring body (16) having a contact surface (14) into thermal or pressure-transmitting contact with the substance (12), said thermal or pressure-transmitting contact allowing heat or pressure waves generated by absorption of excitation radiation (18) in the substance to be transferred to the measuring body; irradiating the material (12) with excitation radiation (18) so that the excitation radiation is absorbed by the material (12); detecting a physical response of the measuring body (16) or a component contained in the measuring body (16) to heat or pressure waves received from the material (12) upon absorption of the excitation radiation (18), and generating a response signal based on the detected physical response, the response signal indicating a degree of absorption of the excitation radiation; Including, the measuring body (16) is transparent to the excitation radiation (18), the excitation radiation source (26) provides the excitation radiation (18) as an excitation beam; the excitation beam is irradiated onto the measurement body (16) at its entrance surface (70), propagates through a portion of the measurement body (16), and exits the measurement body (16) at the contact surface (14); the excitation beam (18) impinges on the incidence surface (70) at an angle of less than or equal to 89.0° and greater than or equal to 82.0°; The incident surface (70) and the contact surface (14) at the portions where the excitation beam enters and exits the measurement body, respectively, are inclined with respect to each other at an angle of 1.0° or more and 8.0° or less. A method characterized by:

16. a protrusion (80) is provided, the protrusion having a front surface (82) facing the substance (12) and contacting the substance when the substance is brought into contact with the contact surface, the excitation radiation (18) being irradiated onto the substance (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 16. The method according to claim 15, wherein the measuring body (16) forms the protrusion or part of the protrusion, and 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.

17. 17. The method of claim 16, wherein the protrusion (80) has a tapered shape with one or more side walls (84) tapering toward the front surface (82).

18. 18. The method according to claim 16 or 17, wherein the protrusion (80) is ridge-shaped and has a longer extension in a first direction and a shorter extension in a second direction perpendicular to the first direction, the longer extension exceeding the shorter extension by at least 1.5 times.

19. the excitation beam (18) impinges on the incidence surface (70) at an angle of less than or equal to 88.0° and greater than or equal to 84.0°; 19. The method of any one of claims 15 to 18.

20. 20. The method according to any one of claims 15 to 19, wherein the excitation beam (18) impinges on the contact surface (14) of the measuring body at an angle of 90°±1.5°.

21. 21. The method according to claim 19 or 20, wherein the entrance surface (70) and the contact surface (14) at the respective portions where the excitation beam enters and exits the measurement body are inclined with respect to each other at an angle of 1.0° or more and 8.0° or less.

22. the detecting includes generating a detection light beam (22) that travels through at least a portion of the measuring body (16) or a component contained in the measuring body (16); the physical response of the measuring body (16) to heat or pressure waves received from the substance (12) upon absorption of the excitation radiation (18) is a local change in the refractive index of the measuring body (16) or of the component; the detecting includes detecting one of a change in the optical path or a change in the phase of a detection beam due to the change in refractive index.

22. The method of any one of claims 15 to 21.

23. 23. The method according to claim 22, wherein the detection light beam (22) is irradiated onto the measuring body (16) at an incident surface (72), and the detection light beam (22) impinges on the incident surface (72) at an incident angle with respect to the incident surface of less than 89° and greater than 80°.

24. 24. The method of claim 23, wherein the measuring body (16) is received in a frame or receptacle that allows the measuring body (16) to be rotated so as to adjust the angle of incidence of the detection light beam when it impinges on the incident surface (72) of the measuring body (16), in particular the frame or receptacle allows the measuring body (16) to be rotated about an axis parallel to the excitation light beam or deviated from parallel by less than 10°.

25. 25. The method according to claim 22, wherein the measuring body (16) is transparent to the detection light beam (22), the detection light beam (22) is directed to be totally or partially reflected at a surface (14) of the measuring body (16) that is in thermal or pressure-transmitting contact with the substance (12), and the detection comprises detecting the degree of deflection, in particular the deflection angle, of the detection light beam (20) after reflection at the contact surface (14) due to the local change in refractive index.

26. the detection light source (28) is arranged so that the detection light beam (22) is irradiated onto the measurement body (16) at an entrance surface (72), propagates through a portion of the measurement body, and exits the measurement body at an exit surface (74); the detection light beam (22) impinges on the exit surface (74) at an angle of 5° or more relative to the normal to the exit surface (74) in the absence of any deflection due to the local change in refractive index, the detection beam (22) is refracted upon exiting the exit surface (74) of the measurement body (16), and the orientation of the exit surface (74) relative to the detection light beam (22) is such that the deflection of the detection light beam (22) in response to the heat or pressure waves transferred to the measurement body (16) increases the angle between the detection light beam and the normal to the exit surface.

26. The method of any one of claims 22 to 25.

27. the detection light beam (22) is irradiated onto the measurement body (16) at an entrance surface (72), propagates through a portion of the measurement body (16), and exits the measurement body (16) at an exit surface (74), a focusing lens (76) being integrally formed with the entrance surface (72) to focus the detection light beam (22) entering the measurement body (16) in at least one dimension, and / or a collimating lens (78) being integrally formed with the exit surface (74) to collimate the detection light beam (22) in at least one dimension; 27. The method of any one of claims 22 to 26.

28. 28. The method of claim 27, wherein at least one of the focusing lens (76) and the collimating lens (78) is a cylindrical lens that focuses and collimates, respectively, the detection light beam (22) in at least primarily one dimension.

29. the detector (30) comprises a position sensitive detector impinging upon the detection light beam (22), the position sensitive detector (30) detecting a shift in the position of the impinging detection light beam (22) in at least one sensitive direction; the position sensitive detector (30) is arranged such that the deflection of the detection light beam (22) results in a shift in the position of the detection light beam impinging on the position sensitive detector (30) in the at least one sensitive direction; a cylindrical lens is provided in the optical path of the detection light beam (22) to shape the profile of the detection light beam (22), and / or the position sensitive detector (30) is arranged at an angle offset from 90° to the detection light beam (22), such that the diameter of the detection light beam (22) impinging on the position sensitive detector (30) in the sensing direction is at least 1.5 times the diameter of the detection light beam (22) in a direction perpendicular to the sensing direction.

29. The method of any one of claims 22 to 28.

30. 30. The method of claim 29, wherein the cylindrical lens is a collimating lens (78) disposed in the optical path of the detection light beam (22) between reflection at the contact surface (14) and the position sensitive detector (30, 62), the cylindrical lens collimating the detection light beam (22) at least primarily in a dimension orthogonal to the sensing direction of the position sensitive detector (30).

31. 31. The method according to any one of claims 15 to 30, wherein the substance (12) is human tissue, in particular human skin, and the analyte is glucose present in the skin, in particular in the interstitial fluid of the skin.

32. 32. The method of any one of claims 15 to 31, further comprising the step of generating the excitation radiation (18) using an array of lasers, in particular quantum cascade lasers, each having a dedicated wavelength.

33. 33. The method according to any one of claims 15 to 32, further comprising the step of generating said excitation radiation (18) using at least one tunable laser, in particular at least one tunable quantum cascade laser.

34. 34. The method of any one of claims 15 to 33, wherein some or all of the excitation wavelengths are in the range of 5 μm to 13 μm.

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