DEVICE AND METHOD FOR ANALYZING A SUBSTANCE

Description

[0001] The present patent relates to a device and a method for analyzing a substance, with particular, though not exclusive, consideration of detection methods that utilize a piezoelectric effect. The device and method described here can be used, for example, for analyzing animal or human tissue, body fluids, and, in one embodiment, for measuring glucose or blood sugar.

[0002] Known methods for analyzing a substance, in particular for measuring blood sugar, are described, for example, in the following publications: Guo et al.: "Noninvasive glucose detection in human skin using wavelength modulated differential laser photothermal radiometry", Biomedical Optics Express, Vol, 3, 2012, No. 11, Uemura et al.: "Non-invasive blood glucose measurement by Fourier transform infrared spectroscopic analysis through the mucous membrane of the lip: application of a chalcogenide optical fiber system", Front Med Biol Eng. 1999; 9(2): 137-153, Farahi et al.: "Pump probe photothermal spectroscopy using quantum cascade lasers", J. Phys. D. Appl. Phys. 45 (2012) und M. Fujinami et al.: "Highly sensitive detection of molecules at the liquid / liquid interface using total internal reflection-optical beam deflection based on photothermal spectroscopy", Rev. Sci. Instrum., Vol. 74, Number 1 (2003). (1) von Lilienfeld-Toal, H. Weidenmüller, M. Xhelaj, A. Mäntele, W.A Novel Approach to Non- Invasive Glucose Measurement by Mid-Infrared Spectroscopy: The Combination of Quantum Cascade Lasers (QCL) and Photoacoustic Detection Vibrational Spectroscopy, 38:209-215, 2005. (2) Pleitez, M. von Lilienfeld-Toal, H. Mäntele W. Infrared spectroscopic analysis of human interstitial fluid in vitro and in vivo using FT-IR spectroscopy and pulsed quantum cascade lasers (QCL): Establishing a new approach to non invasive glucose measurement Spectrochimica Acta. Part A, Molecular and biomolecular spectroscopy, 85:61-65, 2012 (3) Pleitez, M. et al. In Vivo Noninvasive Monitoring of Glucose Concentration in Human Epidermis by Mid-Infrared Pulsed Photoacoustic Spectroscopy Analytical Chemistry, 85:1013-1020, 2013. (4) Pleitez, M. Lieblein, T. Bauer, A. Hertzberg, O. von Lilienfeld-Toal, H. Mäntele, W.Windowless ultrasound photoacoustic cell for in vivo mid-IR spectroscopy of human epidermis: Low interference by changes of air pressure, temperature, and humidity caused by skin contact opens the possibility for a non-invasive monitoring of glucose in the interstitial fluid Review of Scientific Instruments 84, 2013 (5) M. A. Pleitez Rafael, O. Hertzberg, A. Bauer, M. Seeger, T. Lieblein, H. von Lilienfeld-Toal, and W. Mäntele. Photothermal deflectometry enhanced by total internal reflection enables non- invasive glucose monitoring in human epidermis. The Analyst, November 2014. .

[0003] US 2007 / 0015978 A1 discloses a method and apparatus for noninvasively measuring information relating to a living body using a light source configured to generate light containing a specific wavelength component. The apparatus comprises an irradiation unit configured to irradiate a subject with the light, and at least one acoustic signal detection unit comprising piezoelectric devices formed from a piezoelectric unit crystal containing lead titanate and configured to detect an acoustic signal generated as a result of the absorption of said light by a specific substance in or on the body.

[0004] JONAS KOTTMANN ET AL: "Mid-Infrared Fiber-Coupled Photoacoustic Sensor for Biomedical Applications," SENSORS, Vol. 13, No. 1, January 2, 2013 (2013-01-02), pages 535-549, describes the implementation of an MIR fiber-coupled photoacoustic (PA) sensor for the investigation of condensed samples in the MIR fingerprint range. Light from an external cavity quantum cascade laser (1010-1095 cm-1) is delivered via a silver halide attached to a PA cell. A PA chamber is conically shaped to adjust the beam emerging from the fiber and minimize the cell volume. This results in a compact and portable sensor for the investigation of biological samples and the monitoring of constituents both in vitro and in vivo. The performance of the fiber-coupled PA sensor is demonstrated by measuring glucose in aqueous solutions. These measurements result in a detection limit of 57 mg / dL (SNR = 1).In addition, the fiber-coupled sensor was used to record human skin spectra at different body sites to demonstrate its flexibility.

[0005] WO 2017 / 097824 A1 discloses a device for analyzing a substance, comprising an excitation transmission device for generating at least one electromagnetic excitation beam with at least one excitation wavelength, a detection device for detecting a reaction signal, and a device for analyzing the substance based on the detected reaction signal.

[0006] US 2017 / 0146455A1 discloses a device for analyzing a substance. An optical medium is arranged on a surface of the substance, wherein at least a region of the surface of the optical medium is in contact with the surface of the substance. An excitation light beam is irradiated through the contact region between the substance surface and the surface of the medium. A measuring light beam is irradiated through the optical medium to the contact region of the surface of the medium such that the measuring light beam and the excitation light beam overlap at the interface between the optical medium and the substance. The measuring light beam is reflected at this interface. A deflection of the reflected measuring light beam is detected as a function of the wavelength of the excitation light beam. The substance is analyzed based on the detected deflection of the measuring light beam as a function of the wavelength of the excitation light beam.

[0007] EP1048265A1 discloses a device for detecting a substance in a sample, in particular for detecting glucose in a body fluid or blood. The device comprises a semiconductor laser for emitting laser light in the mid-infrared range at at least two discrete wavelengths, each located at a corresponding peak or valley in the absorption spectrum of the substance in the sample. A photoacoustic detector detects acoustic signals resulting from the absorption of the laser light. A display unit evaluates the acoustic signals separately for each wavelength and calculates a detection result based on all acoustic signals of the different wavelengths.

[0008] The object is to provide a device and a method with which a substance, in particular animal or human tissue or a component or ingredient of the tissue, can be analyzed particularly simply and cost-effectively. One aspect of the invention also lies in achieving a compact device size.

[0009] This object is achieved, among other things, by a device having the features of claim 1. Further embodiments of the device are specified in the subclaims. Furthermore, the invention relates to a method according to the independent method claim with corresponding embodiments according to the subclaim(s) dependent thereon.

[0010] Reference is made to German patent DE 10 2014 108 424 B3, to whose content specific reference is made here and upon which this application is based; the complete content of German patent DE 10 2014 108 424 B3 is therefore to be regarded as part of the disclosure of this application through this explicit reference ("incorporation by reference" for all details of the disclosure therein). In particular, this reference refers to all features mentioned in the granted patent claims. Furthermore, the reference also refers in particular to details of the excitation light beam mentioned therein, for example, to the numerical values ​​of the pulse frequencies and wavelength ranges mentioned therein, as well as to the details for measuring glucose content in the interstitial fluid.

[0011] In addition to the subject matter of the claims and embodiments expressly cited upon filing, this patent application also relates to further aspects listed at the end of this description. These aspects can be combined individually or in groups with features of the claims cited upon filing. These aspects also represent independent inventions, either individually or when combined with one another or with subject matter of this application. The applicant reserves the right to make these inventions the subject matter of claims at a later date. This may be done within the scope of this application or within the scope of subsequent divisional applications, continuation applications ("continuation applications" in the USA), continuation-in-part applications ("continuation-in-part applications" in the USA), or subsequent applications claiming the priority of this application.

[0012] In the context of the following explanations, the term "light" or "laser light" refers to electromagnetic waves or electromagnetic radiation in the visible range, in the near, mid and far infrared range, as well as in the UV range.

[0013] One possible aspect of the method presented here is the focus of the response signal measurement on selected depth ranges below the (distance intervals from) the material surface. The quantity d has the greatest influence on the depth range measured with the method. It is defined as d = √(D / (π*f)), where D is the thermal diffusivity of the sample (here, for example, skin) and f is the modulation frequency of the excitation beam. Literature on the thermal diffusivity of skin: U. Werner, K. Giese, B. Sennhenn, K. Plamann, and K. Kölmel, "Measurement of the thermal diffusivity of human epidermis by studying thermal wave propagation," Phys. Med. Biol. 37(1), 21-35 (1992). A. M. Stoll, Heat Transfer in Biotechnology, Vol 4 of Advances in Heat Transfer, J. P. Hartnett and T. Irvin, eds. (New York, Academic, 1967), p 117.

[0014] To eliminate reaction signals from the uppermost layers of the material in order to improve the quality of the measurement, one embodiment can use changes in the measured values ​​compared to previous measurements if the measured values ​​in the uppermost layers change less or more slowly than in other, deeper layers. This can be the case in one embodiment with measurements on human skin, where the uppermost layers of the skin are subject to virtually no exchange with the lower layers and therefore physiological parameters are hardly variable. The time derivative of measured values ​​to reaction signals can also be used to exclude signals from the uppermost layers of the skin. In this way, the measurement or at least the evaluation can be limited or focused on the interstitial fluid in the skin.

[0015] For this purpose, a measurement may include the recording of response signals for spectra that are acquired multiple times at different modulation frequencies of the excitation light source, with the results for different modulation frequencies being linked, for example, by calculating the difference or quotient of the measured values ​​of response signals for the same wavelengths and different modulation frequencies. To carry out such a measurement, a device with a corresponding control device for the excitation beam and an evaluation device for the spectra of response signals should also be provided.

[0016] In the following, we will first address the subject matter of the claim listed at the time of filing.

[0017] The object is achieved with the features of the invention according to claim 1 by a device for analyzing a substance with: a measuring body having a measuring surface that is to be brought into contact with the substance at least partially for measurement, an excitation beam source, in particular a laser device, further in particular with a quantum cascade laser (QCL), a tunable QCL, and / or with a laser array, preferably an array of QCLs, for generating one or more excitation beams with different wavelengths in the infrared spectral range between 3 µm and 20 µm, which is directed through the measuring surface onto the substance, and a detection device comprising the following: a detection region, which is part of the measuring body and in particular adjacent or immediately adjacent to the measuring surface, and whose material has electrical properties that change depending on a change in pressure or temperature, and electrodes with which electrical signals representing said electrical properties can be detected,wherein at least two electrodes (60, 6d) are arranged spaced apart from one another on different sides of the detection area (4) in a direction perpendicular to a surface normal (7) of the measuring surface (2).

[0018] The mentioned properties of the area can in particular be properties of the material of the area.

[0019] Such a device for analyzing a substance is preferred in which the electrical property, which changes depending on the pressure or temperature, leads to piezoelectric signals at the electrodes as a function of pressure change and / or temperature change, or is formed by a specific electrical resistance that changes depending on temperature, wherein the device further comprises an electrical contact device having said electrodes which are electrically conductively connected to the detection region of the measuring body for detecting the electrical resistance and / or the piezoelectric signals.

[0020] In the case of detecting piezoelectric signals, the electrical property that changes depending on pressure or temperature can be referred to as "polarization." Other electrical properties that change depending on pressure and / or temperature and can be exploited for the purposes of the invention are also possible, for example, the dielectric constant.

[0021] In this context, the excitation beam is understood to mean a light beam, a laser beam, or a plurality of essentially parallel laser beams that are emitted sequentially or simultaneously from the excitation beam source, in particular a laser device or individual laser elements of an excitation beam source, in particular a laser device, to the substance to be analyzed. The coherence of the excitation beam is not required, so that non-coherent or only partially coherent radiation can be used. Therefore, other light sources, such as light-emitting diodes / semiconductor diodes or others that allow the selection of wavelengths or wavelength ranges, can also be used as beam sources.When using a broadband light source for the excitation beam, wavelength filters, such as tunable filters, can also be used to selectively generate excitation beams for different wavelengths or wavelength ranges.

[0022] For various applications, it may be appropriate to select an excitation beam in the mid-infrared range. For example, a laser operating according to the OPA (optical parametric amplification) or NOPA (non-collinear optical parametric amplification) or OPG (optical parametric generation) method can be chosen as the light source, allowing the generation of different wavelengths.

[0023] It is also possible to use a so-called optical parametric oscillator (OPO) in an optical resonator, which comprises an optically nonlinear crystal, for example, beta-barium borate. Due to the nonlinear three-wave interaction, the crystal generates, among other things, radiation of a transformed wavelength from the radiated pump wave. In this way, as with the aforementioned OPA / NOPA methods or arrangements, for example, radiation in the near-infrared wavelength range can be obtained to produce radiation in the mid-infrared range, which can be used for the spectroscopic methods described in this application.

[0024] The detection zone of the measuring body refers to a spatial area or section of the measuring body that exhibits the aforementioned properties by exhibiting a pressure- or temperature-dependent specific electrical resistance and / or generating electrical, particularly piezoelectric, voltage signals upon pressure or temperature changes. This is achieved by the choice of material and, optionally, further design, such as processing, of the material from which the detection zone is made.

[0025] It may be the case that the regions of the measuring body adjacent to the detection region differ from the material of the detection region in this regard, in particular due to the material they are made of. However, it can also be provided that the regions of the measuring body adjacent to the detection region, like the detection region, have a pressure- or temperature-dependent specific electrical resistance and / or generate electrical, in particular piezoelectric, voltage signals in the event of pressure or temperature changes. The detection region can be separated from other regions of the measuring body by electrodes and / or separating regions, wherein the separating regions can be made of a material that is significantly softer, more elastic, or more compliant than the material of the detection region, so that the material of the separating regions transmits an increase in pressure or temperature less effectively than the material of the detection region.

[0026] The measuring body can in particular also be formed from a first part and a second part of the measuring body designed as a sensor layer, wherein the sensor layer can have a different composition than the first part of the measuring body and in particular can consist at least partially of a piezoelectric material. The sensor layer can be applied, in particular glued, to the first part of the measuring body in the region of the measuring surface. The sensor layer can also consist of a material whose refractive index is more strongly dependent on pressure or temperature than the first part of the measuring body. The first part of the measuring body can be transparent to the excitation beam(s) and can consist of silicon, for example.If the sensor layer is not transparent to the excitation beam(s) or is less transparent than the first part of the measuring body, the sensor layer can have a recess for the passage of the excitation beam(s). For example, a lens can be provided in the recess to focus the excitation beam(s) on a point in the substance to be analyzed.

[0027] To guide the excitation beam(s), an optical waveguide can also be provided within the measuring body, which ends in, on, or in front of the measuring surface. The optical waveguide can be integrated into a substrate of the measuring body and manufactured using SOI technology. The optical waveguide can pass through the detection area or bypass it. The optical waveguide can be made of a material whose refractive index is minimally dependent on mechanical pressure, or no, in order to minimize the influence of piezoelectric pressure generation on the excitation beam. The material of the optical waveguide can also be mechanically spaced from the piezoelectric material provided in the detection area, or can be mechanically decoupled from it by a flexible, in particular elastic, material layer or a gas layer.

[0028] The object is alternatively achieved with the features of the invention according to claim 2 by a device for analyzing a substance with: a measuring body which has a measuring surface which is to be brought at least partially into contact with the substance for the measurement, an excitation beam source, in particular a laser device, further in particular with a quantum cascade laser (QCL), a tunable QCL, and / or with a laser array, preferably an array of QCLs, preferably in the infrared spectral range, for generating an excitation beam with various selectable wavelengths which is directed onto the substance while passing through the measuring surface, and with at least one detection device which is arranged adjacent to the measuring surface and / or directly adjoins it, wherein the detection device has a contact device with at least two electrodes for detecting piezoelectric signals which are located opposite one another on different sides of a detection area.In the detection area, a material is arranged which changes its electrical resistance or generates an electrical signal depending on temperature and / or pressure changes, in particular due to a piezoelectric effect.

[0029] In both the subject matter of patent claim 1 and the subject matter of patent claim 2, the excitation beam source, in particular a laser device, emits an excitation beam into the substance to be analyzed, which, for example, passes through specific wavenumbers / wavelengths or emits a plurality of excitation beams with specific fixed wavenumbers consecutively or simultaneously. Wavelength selection can also be performed by filters in the light path downstream of the excitation beam source.

[0030] When using an array, the laser array can comprise simple lasers with a fixed wavelength. At certain wavelengths, the beam is absorbed depending on the material of the substance to be analyzed, releasing energy that is transported at least partially in the form of a heat wave to the surface of the substance and further into the measuring body and from there to the detection zone. The excitation beam is advantageously intensity-modulated, whereby the use of various, even multiple, modulation frequencies is possible. It is also possible to form laser pulses that contain a plurality of modulation frequencies in the Fourier-transformed range. The pulsed heating of the material in the detection zone causes a change in resistance and / or the generation of an electrical voltage signal and / or other parameter changes, such as a change in the refractive index.The first two electrical phenomena can be transmitted via the contact device's electrodes and their leads to a measuring device that measures voltages and / or electrical resistances. This device evaluates these changes and assigns them to a temperature increase and / or an absorption intensity of the excitation beam in the material. The absorption intensity can thus be measured as an absorption spectrum depending on the wavenumbers / frequencies of the excitation beam.

[0031] The detection region is advantageously adjacent to the measuring surface, meaning it is either directly adjacent to it or at a distance from the measuring surface. This distance should be small (e.g., less than 10 micrometers or less than 100 micrometers, each measured at the smallest distance between the detection region and the measuring surface). The detection device can, for example, also comprise a plate or a body that, as part of the measuring body, is joined to another part of the measuring body, or a coating of a part of the measuring body in the region of the measuring surface.

[0032] The detection device can also detect a reaction signal in the form of a sound wave, particularly when a pressure change is detected, for example, when using a piezo-sensitive material / piezo sensor. This sound wave is generated by the absorption of the excitation beam in the substance to be analyzed and travels to the measurement surface and detection zone at a known speed (approximately 1500 m / s in human tissue). Using an evaluation device connected to a modulation device for the excitation beam, the good temporal resolution of the reaction signal measurement allows a phase shift between the modulation of the excitation beam and the reaction signal to be measured, thereby determining the depth in the tissue at which the absorption occurred.Since the signals are often a superposition of different reaction signals from different tissue layers, different measurements can be carried out with different modulation frequencies and the reaction signals can be linked to different modulation frequencies in order to calculate and eliminate signals from upper tissue layers in particular, as these are particularly susceptible to errors due to contamination and dead skin cells.

[0033] Note that in the present disclosure, the same term "response signal" is used in multiple senses. On the one hand, it can refer to the physical response to the excitation by the excitation beam, for example, a sound wave, heating, or the like. On the other hand, it can also refer to a (typically electrical) signal representing this physical response, for example, a voltage or current flow measured using the electrodes.For simplicity and coherence of the presentation, the same term "response signal" is used throughout, whereby it is clear from the context without further explanation whether this refers to the physical response (e.g. a pressure wave), a physical consequence of this physical response (e.g. a compression of a piezoelectric material) or the associated measurement signal (e.g. the voltage generated by the piezoelectric material).

[0034] Instead of different modulation frequencies, signals with a steep rise (ideally so-called Dirac pulses) can also be formed, which represent a mixture of many modulation frequencies and enable an analysis of different modulation frequencies by means of a Fourier analysis.

[0035] An implementation of the device can provide that at least two electrodes, in particular along a surface normal of the measuring surface, are arranged one behind the other at different distances from the measuring surface.

[0036] The measuring surface can be flat or curved. In the case of curvature, the surface normal is defined as a normal to the measuring surface at a point, particularly at a location where the excitation beam passes through the measuring surface.

[0037] At least two electrodes should be arranged so that they completely or partially surround the detection area, or so that the detection area lies completely or partially between the two electrodes. The electrodes can be distributed in various geometric arrangements on different sides of the detection area, particularly around the detection area.

[0038] A further implementation of the device can provide that the excitation beam passes through the measuring body, in particular the detection area, wherein in particular for guiding the excitation beam an optical waveguide is arranged in or on the measuring body and further in particular the optical waveguide is integrated into the measuring body.

[0039] The excitation beam thus passes through the measuring body, for example directly through the material of the measuring body or through an optical fiber arranged in it, and through the detection area or past the detection area to the point on the substance to be analyzed, which absorbs the excitation radiation and emits the thermal radiation.

[0040] An optical waveguide integrated into the material of the measuring body and / or the material of the detection area can be used as the optical waveguide for guiding the excitation beam. Such optical waveguides can be applied, for example, using an epitaxial process or by selectively doping wafer material into or onto a wafer. However, a fiber optic waveguide can be incorporated into the measuring body or even at least partially applied to its exterior.

[0041] It can also be provided that the excitation beam passes through the measuring surface in an area that is immediately adjacent to and / or borders on the detection area.

[0042] A further implementation of the device can provide a modulation device for modulating the intensity of the excitation beam. Various types of modulation are possible, including a mechanical chopper, a controllable aperture or deflection mirror device, or a body / layer whose transmission is controllable. Modulation can also be achieved directly by controlling the excitation light source / laser light source. A measurement can involve recording spectra at one or more modulation frequencies, with measurements at different modulation frequencies being linked to obtain depth information and / or to eliminate measurement data from specific depth ranges of the sample / substance to be analyzed. In particular, measurement data originating from the surface of the substance can thus be eliminated.These are measurement data and heat waves resulting from absorption of the excitation light beam on the surface of the material, and which can be caused by contamination or anomalies on the surface of the substance being analyzed. An example of this is the analysis of a patient's skin, the uppermost layers of skin, which are partially composed of dead cells, which have an inconclusive composition and / or provide false information. This is particularly the case when biologically active substances, active metabolism, metabolic products, or similar substances are to be detected in the skin.

[0043] Below, various geometric electrode configurations are listed and their advantages are discussed.

[0044] For this purpose, it can be provided, for example, that at least two, in particular at least three or four, further in particular at least 6, further in particular at least 8 electrodes are arranged one behind the other at different distances from the measuring surface or spaced apart from one another in the direction perpendicular to a surface normal of the measuring surface.

[0045] At least one or more of the electrodes are arranged on each side of the detection area. Thus, various electrode pairs are available with which electrical resistance or electrical voltage can be measured.

[0046] For this purpose, an electronic device is provided, which is connected to several or all of the electrodes via the supply lines. The electronic device has a control device and, in particular, also an evaluation device that detects and evaluates electrical resistances or voltages between various selectable electrodes, either sequentially or simultaneously.

[0047] For this purpose, various or all pairs of electrodes can be selected experimentally. The electrodes selected within an electrode pair for a test measurement should each have at least part of the detection range between them. Measured values ​​from individual electrode pairs can be compared and evaluated. Evaluation parameters can be, for example, the signal strength or the magnitude of the signal changes, a signal-to-noise ratio, or another parameter. In addition to the integration of the electrodes into the measuring body, the case in which several electrodes are staggered and glued, embedded, or vapor-deposited onto the surface of the measuring body / measuring surface should also be covered here.

[0048] It can also be provided that at least two, in particular at least three or four, further in particular at least 6, further in particular at least 8 electrodes are arranged one behind the other in the direction of a surface normal of the measuring surface or perpendicular thereto or in a direction between 0 and 90 degrees to the surface normal at different distances from the detection area, in particular at different distances from the center of the detection area. The detection area can be defined, for example, by a spatial region of the measuring body consisting of a special material. The detection area can also be defined by the overall arrangement as a region of the measuring body lying above the point of entry of the excitation beam into the substance to be analyzed.

[0049] In addition, the detection area can also be defined by the sum of the spatial points at which an electrical signal is potentially detectable by the available electrodes.

[0050] A further implementation may provide that at least two, in particular at least three or four, further in particular at least 6, further in particular at least 8 electrodes are arranged in a circular ring-shaped region or a spherical shell-shaped region around the detection region and at least partially opposite one another on different sides of the detection region, with different electrodes each having substantially the same distance from the center of the detection region or different distances from the center of the detection region. This should also include the case of electrodes distributed over the surface of the measuring body.

[0051] Due to the electrode distribution mentioned, the most suitable electrode pair(s) can be selected and used for the measurement, for example by measuring several electrode pairs.

[0052] As a measure of the quality of the measurement, the selection of the electrode pairs can be based, for example, on either a signal strength, a signal dynamic, a noise level, or a signal-to-noise ratio.

[0053] It can also be provided that one or more or all of the electrodes of the contact device are disc-shaped or plate-shaped, ring-shaped, ring-disk-shaped, in the form of a square or polygonal frame with an opening, dome-shaped or strand-shaped.

[0054] An implementation of the device can provide for one or more or all of the electrodes of the contact device to be arranged on a surface of the measuring body or the detection device and to be applied, in particular, by means of a joining process, further in particular by gluing or welding. Application by vapor deposition or painting is also conceivable. The measuring body can consist homogeneously of a single material or, in the detection area, of a special material that differs from the material of the other areas of the measuring body.

[0055] The electrodes for all designs are usually made of a metal, or at least of a material with good electrical conductivity. They can also be made of an electrically conductive plastic or a conductively filled material.

[0056] A further implementation of the device may provide for one or more or all of the electrodes of the contact device to be arranged inside or on the outside of the measuring body in one or more recesses, such as bores, depressions, or grooves, of the measuring body, wherein they are in particular inserted, cast, introduced by injection molding, or by an additive manufacturing process (3D printing). These variants enable the introduction of electrodes into a measuring body in a technically simple manner.

[0057] Electrodes can also be created in the measuring body by making areas of the measuring body's material electrically conductive through irradiation or particle bombardment. This is possible, for example, with plastics, where high-energy radiation partially destroys carbon molecules and forms conductive carbon deposits.

[0058] Furthermore, it can be provided that the measuring body is designed as a flat body, in particular as a plane-parallel body in the form of a plate, wherein in particular the thickness perpendicular to the measuring surface is less than 50% of the smallest extension of the measuring body in a direction running in the measuring surface, in particular less than 25%, further in particular less than 10%.

[0059] This design variant of the measuring body can be used for various detection methods for thermal response signals and is fundamentally not limited to the detection method using a piezoelectric effect. It can also be used for the measurement method with a measuring beam reflected from the measuring surface and a detector for its deflection, allowing a significant reduction in the dimensions of the measuring body in the direction perpendicular to the measuring surface.Regardless of the measuring method, for example using the piezoelectric effect or by measuring the deflection of a reflected beam, the measuring body designed as a flat body can have a layer in the area of ​​the measuring surface, which in the case of the piezoelectric measuring method can consist of a piezoelectric material and in the case of detection by measuring the deflection of a reflected measuring beam of a material in which the refractive index changes more strongly as a function of temperature than in the material of the other areas of the measuring body.

[0060] A further implementation of the device can provide that the measuring body has a mirror device for reflecting the excitation beam radiated by the excitation beam source, in particular laser device, onto the measuring surface or carries such a mirror device.

[0061] With a very flat measuring body, the excitation beam can be irradiated from the flat side of the measuring body. The excitation beam then initially propagates from the excitation beam source essentially parallel to the measuring surface within the measuring body or parallel to the boundary surfaces of the measuring body and is then redirected toward the measuring surface.

[0062] Instead of reflecting the excitation beam, it can also be diffracted toward the measuring surface by appropriately designing the material of the measuring body. The flat body can also incorporate optical focusing elements for the excitation beam or be connected to such elements, for example, one or more lenses.

[0063] It can also be provided that the excitation beam is radiated into the measuring body parallel to the measuring surface or at an angle of less than 30 degrees, in particular less than 20 degrees, further in particular less than 10 degrees or less than 5 degrees to the measuring surface and that the excitation beam is deflected or redirected in the direction of the measuring surface and passes through it.

[0064] A focusing device, for example in the form of a diffraction element / lens, can be provided, integrated into the measuring body or directly connected to it, particularly when using a flat body, which focuses the excitation beam onto the measuring surface and the material surface of the substance to be analyzed.

[0065] It can also be provided that the excitation beam passes through the material of the measuring body.

[0066] It can also be provided that the measuring body has at least one recess, in particular a bore through which the excitation beam passes, wherein the recess and / or bore extends in particular from the measuring surface into the measuring body or wherein the recess or cutout and / or bore extends through the entire measuring body from a boundary surface of the measuring body opposite the measuring surface to the measuring surface. The recess can also extend as a channel or bore with its longitudinal axis at least partially in the direction of the excitation beam parallel to the measuring surface. If a sensor layer is provided, the recess, cutout and / or bore can extend from the boundary surface of the sensor layer opposite the measuring surface into the measuring body, so that the sensor layer itself is not penetrated by the recess.

[0067] In this case, the measuring body can have a hollow channel / bore / recess for the excitation beam, so that the excitation beam does not penetrate the material of the measuring body, although the excitation beam passes through the measuring body and the measuring surface to the substance to be analyzed.

[0068] It can also be provided that the measuring body has a first part that has a continuous channel for the excitation beam, and that the measuring body has a sensor layer on its underside on the first part, which is either continuous without a recess or is provided with a continuation of the recess of the first part. If the sensor layer is thinner than 200 micrometers, in particular thinner than 100 micrometers, the excitation beam can pass through it - even if it is an infrared beam - without excessive absorption, and a recess, bore, or channel in the sensor layer is not necessary. The sensor layer of the measuring body can be made of a material that has piezoelectric properties and forms a detection region according to the invention.The sensor layer can also be made of a material in which a change in temperature and / or pressure causes a change in the refractive index, so that this change can also be detected as a response signal, for example, by detecting the angle of reflection of a detection beam reflected in the sensor layer. The first part of the measuring body can then be made of a material such as quartz or sapphire, which is transparent in the visible range and for a detection beam, but less transparent or opaque in the infrared spectral range.

[0069] A further implementation of the device can provide that in or on the measuring body, in particular in the detection device, or directly adjacent to it and in thermal contact with it, at least one heat sink in the form of a body is arranged, the specific heat capacity and / or specific thermal conductivity of which is greater than the specific heat capacity and / or specific thermal conductivity of the material from which the measuring body is made or which is designed as a Peltier element.

[0070] Instead of a heat sink in the form of a body whose specific heat capacity and / or specific thermal conductivity is greater than the specific heat capacity and / or specific thermal conductivity of the material from which the measuring body is made, an active or passive cooling element, in particular a Peltier cooling element, can also be provided to adjust a temperature gradient. The temperature gradient or the absolute temperature can also be controlled by means of the Peltier element with a control device.

[0071] Such heat sinks, for example in the form of metal or crystal bodies or actively operated Peltier elements, can be used to achieve the appropriate thermal properties of the measuring body with regard to thermal diffusivity, which are required so that, on the one hand, the temperature change builds up sufficiently with the modulation frequency in the detection area and, on the other hand, the heat is dissipated sufficiently quickly. This naturally depends primarily on the material of the measuring body / detection device, but can be influenced by the suitable addition of one or more heat sinks. These can, for example, be arranged at least partially around the detection area or provided on one side of the detection area.

[0072] A further implementation of the device can provide that in or on the measuring body, in particular in the detection device, or directly adjacent to it and in thermal contact with it, at least one heat barrier in the form of a body is arranged, the specific heat capacity and / or specific thermal conductivity of which is lower than the specific heat capacity and / or specific thermal conductivity of the material from which the measuring body is made.

[0073] Such thermal barriers, alone or in combination with heat sinks, can be used to achieve the appropriate thermal properties of the measuring body with regard to thermal diffusivity, which are required for the temperature change to build up sufficiently with the modulation frequency in the detection range and for the heat to be dissipated sufficiently quickly in accordance with the modulation frequency. This can be influenced by the appropriate addition of one or more thermal barriers. These can, for example, be arranged at least partially around the detection range or provided on one side of the detection range. Thermal barriers can be implemented, for example, using thermally insulating plastic elements.For example, one or more heat sinks may be provided on a first side of the detection area and one or more heat barriers may be provided on a second side of the detection area opposite the first in order to generate a temperature gradient and influence the direction of heat transport.

[0074] It can be provided that the detection device and / or the measuring body consists at least partially of a piezoelectric material, in particular a piezoelectric ceramic, in particular a PZT ceramic, further in particular a sintered ceramic, or a single-crystalline piezoelectric material, in particular quartz, tourmaline, lithium niobate, gallium orthophosphate, berlinite, Seignette salt, ferroelectrics such as barium titanate (BTO) or lead zirconate titanate, gallium phosphate or a lead magnesium niobate, or zinc oxide (ZnO) or aluminum nitride as a thin-film deposit or polarized polyvinylidene fluoride.

[0075] The respective material should be as transparent as possible in the infrared frequency range, preferably in the mid-infrared frequency range.

[0076] The aforementioned piezoelectric materials can be provided as a thin layer on a measuring body and form the measuring surface. The layer thickness should then be less than 0.5 mm, in particular less than 300 micrometers, and / or have a recess or cutout, for example, a bore or channel for the excitation beam. The remaining part of the measuring body can then be non-piezoelectric and transparent to the excitation beam and / or have a recess for the excitation beam. This remaining part of the measuring body can act as a heat sink for the coating with a piezoelectric material, i.e., have a higher specific heat capacity and / or thermal conductivity than the piezoelectric layer.

[0077] A further implementation of the device can provide that a piezoelectric element or a piezoelectric region of the measuring body can be connected as an actuator to a voltage source and represents a blockade for an excitation beam depending on a controllable input voltage.

[0078] In this way, the material of the measuring body can also be used as an optical chopper for the excitation beam by changing the dielectric constant.

[0079] A method for operating a device according to the invention can provide that a modulated excitation beam is directed, in particular through the measuring body, onto the substance to be analyzed and that signals from different electrode pairs of the contact device are detected and evaluated simultaneously or successively, that it is first determined on the basis of predetermined criteria which of the electrode pairs delivers / delivers signals suitable for further processing and that the signals from one or more selected electrode pairs are then used and evaluated for the measurement and that in particular a subsequent measurement is carried out in which the signals from the selected electrode pair(s) are detected and evaluated.

[0080] Suitable signals can be selected based on factors such as signal strength, signal-to-noise ratio, or the slope with which the signals follow the modulation of the excitation beam. By selecting the appropriate electrodes, it is also possible to detect and correct any misalignment of the substance being analyzed with respect to the measuring device, for example, if the heat wave does not reach the center of the measuring range. In this case, differently distributed electrodes may be selected for the current measurement.

[0081] During the measurement, the excitation beam's wavenumber / wavelength / frequency is varied continuously or in steps, or characteristic wavelength ranges are scanned. When using an array, an excitation beam can be emitted simultaneously or sequentially by different elements of an array at different wavelengths or wavelength ranges.

[0082] In an implementation of the method, it may also be provided that after a first measurement attempt, depending on the detected signals, a misalignment of the device relative to the substance to be analyzed is determined and signaled and, in particular, the user is prompted to realign.

[0083] This method can even be used in parallel with another detection method, for example with a reflected detection beam, just to detect and signal misalignments of a finger on which a measurement is to be taken.

[0084] Misalignments can be detected, for example, by determining the signal strengths of different pairs of electrodes during an initial measurement in the form of a profile / vector and comparing this profile / vector with corresponding values ​​from previous measurements or defined reference values. The profile can be normalized to a specific signal strength. If the difference from a reference profile exceeds certain thresholds for certain elements of the profile or with regard to asymmetry, misalignment can be concluded.

[0085] In a further implementation of a method it may also be provided that at least one intensity-modulated electromagnetic excitation beam having at least one excitation wavelength is generated by an excitation transmitting device, the excitation transmitting device radiates the at least one electromagnetic excitation beam into a volume of material which lies below the surface of the material, a reaction signal is detected by a detection device, and the material is analyzed on the basis of the detected reaction signal, wherein in particular reaction signals, in particular temporal reaction signal curves for different wavelengths of the excitation beam, are determined one after the other using different modulation frequencies of the excitation transmitting device and a plurality of reaction signal curves are linked to one another at different modulation frequencies, and wherein in particular information specific for a depth range below the material surface is obtained therefrom.

[0086] The Figures 1 to 17show schematically various elements of the device and its elements partly in different embodiments., further show Figure 18 : a cross-section of a measuring body with a first integrated lens and with a finger placed on the measuring surface, Figure 19 a cross-section of a measuring body with a second integrated lens, Figure 20 a cross-section of a measuring body with a third integrated lens, Figure 21 a cross-section of a measuring body with a first integrated lens and an excitation beam, Figure 22 a cross-section of a measuring body with a second integrated lens and an excitation beam, Figure 23 a cross-section of a measuring body with a third integrated lens and an excitation beam, as well as Figures 24, 25, 26several arrangements with a measuring body and an excitation light source in the form of a laser light source or excitation beam source, in particular a laser device, wherein the excitation light beam is guided through the measuring body to the measuring surface by means of an optical waveguide integrated into a substrate of the measuring body.

[0087] The Figure 1shows an embodiment of a device for analyzing a substance. The substance 5 preferably lies directly on a measuring body 1 or vice versa; in any case, the substance and a measuring surface 2 of the measuring body 1, which is also referred to as an "optical medium" in the present disclosure, are in direct physical contact for a measuring process. The measuring body 1 can be designed as a solid body that is transparent to light or at least in the infrared range, in particular a crystal or glass body or a plastic body, in particular a polymer body, which is transparent in particular in the infrared range, for example, when the device is intended for measuring the glucose or blood sugar content in a liquid, such as in one embodiment, for example, in blood. The device can then be used to generate a glucose or blood sugar level indication.

[0088] The device comprises an excitation transmission device 3 in the form of an excitation beam source, in particular a laser device for emitting one or more electromagnetic excitation beams, preferably in the form of excitation light beams with one or more excitation wavelengths, into a volume 5a located in the material 5 below a first region of the surface of the material. The excitation transmission device 3 is also referred to below as the laser device.The laser device can be a wavelength-tunable laser, in particular a tunable quantum cascade laser; preferably, as explained further below, a light source bar or a light source array with at least two individual emitters in the form of lasers, in particular semiconductor lasers with fixed wavelengths, or light-emitting semiconductor diodes is used, each of which emits a predetermined individual wavelength or light in a defined narrow wavelength range, wherein it is also possible to use light sources that are combined simultaneously or sequentially with suitable filters and connected in series in order to separate out specific wavelengths or wavelength ranges.If several individual emitters are combined, the individual excitation light beams can be coupled together into a single light path by a multiplexer, for example, into an optical fiber, a recessed channel, or another light path in the optical medium. A collimator can also be provided to align the light beams emitted by different emitters as parallel to each other as possible and, if possible, combine them into a single beam, whether multiple light beams are emitted simultaneously or consecutively.

[0089] An optical element for focusing the excitation light can also be provided along the path of the excitation light. This can be provided, for example, between the laser device and the measuring body, or on the measuring body itself where the excitation beam enters it, or on the measuring body in the area where the excitation beam exits the measuring body, for example, in the area of ​​the measuring surface, on the measuring surface, flush with the measuring surface, or between the measuring surface and the detection device.

[0090] The optical element can, for example, be made as a convex lens from the material of the measuring body or can consist of a material that is different from the material of the measuring body.

[0091] In addition, a device 9 for intensity modulation of the excitation beam(s) / excitation light beam(s) is provided, which is preferably formed by a modulation device for the excitation beam source, in particular a laser device, in particular its control, and / or at least one controlled mirror arranged in the beam path and / or a layer controllable with respect to its transparency and arranged in the beam path.

[0092] A heat wave emitted after absorption of the excitation beam in region 5a of the material enters the measuring body and can be detected there in a detection region 4 by a detection device. This occurs by detecting a local temperature increase or change that follows the absorption very quickly. The reversal of the temperature change (decrease in temperature) after the end of an absorption phase (when the intensity of the excitation beam decreases as part of the modulation of the excitation beam) also follows the intensity profile of the absorption intensity very quickly with a certain phase shift that depends on the depth at which the excitation beam is absorbed in the material.

[0093] The amplitude of the response signal depends on the wavelength of the excitation beam, the absorption properties of the sample, and the thermal properties, particularly the thermal diffusivity and thermal conductivity of the sample and the measuring body / optical medium 1. Furthermore, the coupling of the thermal signal from the sample into the measuring body also plays a role.

[0094] In the illustrated embodiment, the detection device 4, 6 is formed as a region 4 of the measuring body 1, which consists at least partially or in sections of a piezoelectric material. The detection device 4, 6 also has electrodes 6a, 6b, 6c, and 6d, which are arranged on opposite sides of the detection region 4. The electrodes 6a to 6d establish electrical contact with the material of the detection region 4 and are collectively referred to below as the "contact device" 6. In this way, a temperature or temperature change can be detected, depending on the material selection of the piezoelectric material, by a piezoelectric voltage generated between the electrodes or by an electrical resistance or a change in resistance.

[0095] In the example of the Figure 1The two rectangular, planar or plate-shaped, flat electrodes 6c and 6d are arranged parallel to each other along the surface normal 7 of the measuring surface 2 at different distances from the measuring surface 2. The two likewise planar, plate-shaped electrodes 6a and 6b are spaced apart from each other in the direction of arrow B perpendicular to the direction of the surface normal 7 and parallel to the measuring surface 2 and are arranged parallel to each other. The coordinate system formed by the arrows A, B and C, in which the arrow A is parallel to the surface normal 7 of the measuring surface 2 and the arrows B and C are oriented perpendicularly thereto, is the same as in Fig. 1 in the Figures 2 to 15 marked for orientation.

[0096] An evaluation device 16 for analyzing the substance, which is designed as an electronic device, in particular a digital processing device, for example as a microcontroller or processor or as a computer, is in electrical contact with the electrodes 6a, 6b, 6c and 6d of the contact device 6 via electrical lines 17, 18, evaluates the detected reaction signals and, in one embodiment, generates a glucose or blood sugar level indication (BZA).

[0097] The evaluation device 16 is also electrically connected to the modulation device 9, so that the information about the frequency / wavelength of the excitation beam and in particular also the frequency and / or phase of the modulation is available in the evaluation device 16 and can be taken into account in the evaluation. In this way, for example, the phase offset of the reaction signals relative to the modulation function of the excitation beam can also be evaluated in order to obtain information about the depth in the substance, i.e. also the distance from the measuring surface 2 or the detection area 4, at which the reaction signal was generated. This makes it possible to obtain information about a depth profiling of the distribution of a detected substance, for example glucose, in the substance 5.

[0098] The information about the modulation of the excitation beam can be sent from the modulation device 9 to the evaluation device 16; however, it can also be provided that the evaluation device 16 controls the modulation directly. The evaluation device 16 can also have a lock-in amplifier for evaluation, which evaluates the signals specifically at the modulation frequency.

[0099] The arrangement of electrode pairs 6a / 6b, 6c / 6d shown is only an example. A single electrode pair may also be sufficient, although it is important that at least part of the detection area 4 lies between the two electrodes. Furthermore, for optimal function, the substance to be analyzed, for example, a subject's finger, must be in contact with the measuring surface 2 at the designated location. A lateral offset of the finger / substance can result in the heat pulse not exerting its effect precisely between the electrodes, resulting in suboptimal or incorrect measured values.

[0100] The electrodes 6a, 6b, 6c, 6d can be inserted into or attached to the measuring body 1 by an additive process (3D printing), by casting, vapor deposition, doping, targeted modification of the original material of the measuring body (for example, conversion of hydrocarbons into electrically conductive carbon by corpuscular radiation or gamma radiation or laser radiation), gluing or insertion into previously introduced recesses or cutouts.

[0101] The operation of the facility should be in accordance with Figure 1 and in this context, a method for analyzing a substance 5 will be described in more detail by way of example for the case that the substance 5 to be analyzed is human or animal tissue and a glucose or blood sugar level is to be determined as part of the analysis of the substance.

[0102] One or more excitation beams 8, which are preferably infrared rays, are generated successively or simultaneously using the laser light source 3. The wavelength of the infrared beam(s) is preferably in a range between 3 µm and 20 µm, particularly preferably in a range between 8 µm and 11 µm.

[0103] The excitation beams 8 are intensity- or amplitude-modulated by the intensity-modulation device 9. In one embodiment, the intensity-modulation device 9 generates short light pulses, preferably with a pulse frequency between 1 kHz and 1 MHz, or pulse packets (double or multiple modulation), preferably with an envelope frequency between 1 kHz and 10 kHz.

[0104] The modulated excitation beams 8 are coupled into the optical medium / measuring body 1, in particular directly into the material of the measuring body, and after passing the measuring surface 2 reach the volume 5a within the tissue 5.

[0105] Passing through the measuring body 1 or entering the material from which the measuring body is made is possible for the functioning of the invention, but not necessary, as long as it is ensured that the excitation beam 8 reaches the substance 5 to be analyzed on the underside of the measuring surface 2. This is illustrated by the fact that a recess / cutout 13 in the Figure 1is depicted as a potential recess forming a narrow channel, for example, a bore, that opens into the measuring surface 2 on the underside of the measuring body 1 and through which the excitation beam 8 can reach the underside of the measuring surface 2 and into the material 5. In this broad sense, the above-mentioned feature is to be understood as meaning that the output beam is directed toward the material 5 "passing through the measuring surface 2." Normally, a structure without such a recess 13 can be provided, provided that the excitation beam 8 can easily pass through the material of the measuring body 1. Such a recess 13 can also only partially penetrate the measuring body. Instead of a recess 13, an integrated optical fiber can also be provided in the same area, into which the excitation beam can be coupled. This can end in or on the measuring surface or a sensor layer.The optical waveguide can be integrated into a substrate of the measuring body using conventional manufacturing processes. For example, if the measuring body is made entirely or partially of silicon, the optical waveguide can be integrated as an SOI (silicon on insulator) optical waveguide. Such an optical waveguide can be straight or curved. This allows the position of the excitation beam source, in particular a laser device that generates the excitation beam, relative to the measuring body to be freely configured.

[0106] The wavelength of the excitation beams 8 is preferably selected such that the excitation beams 8 are significantly absorbed by glucose or blood sugar, respectively, with regard to the blood glucose measurement explained here as an example. The following glucose-relevant infrared wavelengths are particularly well suited for measuring glucose or blood sugar (vacuum wavelengths) and can be set individually or in groups, simultaneously or sequentially, as fixed wavelengths for measuring the reaction signals: 8.1 µm, 8.3 µm, 8.5 µm, 8.8 µm, 9.2 µm, 9.4 µm, and 9.7 µm. In addition, glucose-tolerant wavelengths, which are not absorbed by glucose, can be used to detect other substances present and exclude their influence on the measurement.

[0107] For a measurement, a spectral range can be traversed continuously by scanning the excitation beam source, in particular a laser device 3, or the spectrum can be covered discontinuously at support points by certain suitable fixed wavelengths.

[0108] If substances other than glucose are to be detected, appropriate wavelengths for the excitation rays must be selected which are characteristic absorption wavelengths for these substances.

[0109] The absorption of the excitation beams 8 in the tissue 5 causes a local temperature increase in the region of the volume 5a, which triggers heat transport and, with it, pressure waves and heat pulses towards the surface of the tissue 5 and the measuring surface 2 in contact with it. The resulting temperature and pressure fluctuations at the measuring surface 2 and adjacent to it in the measuring body 1 modulate the density, refractive index or deformation, microstructure, and reflection behavior in the detection area 4 near the measuring surface 2. As a result, an electrical resistance is influenced as a reaction signal in the case of a piezo material, or a piezo voltage is generated or changed / modulated.

[0110] The degree / amplitude of the intensity modulation of the measured values / response signal depends on the wavelength of the excitation rays (due to the necessary absorption in the tissue) and on the pulse frequency / modulation frequency of the excitation rays (due to the heat transport and pressure waves from the tissue interior towards the measuring surface 2) and the thermal properties of the sample and the measuring body 1.

[0111] The measurement can be performed for several different modulation frequencies, and the measurement results, for example in the form of spectra, can be linked together. The individual spectra represent the response signal, for example, a piezoelectric voltage or the amplitude of a variable piezoelectric voltage as a function of the wavelength of the excitation beam. Different spectra can be linked together in such a way that measured values ​​from the surface of the sample (substance 5) can be subtracted / eliminated or that specific information can be obtained from a specific depth range.

[0112] Each of the spectra at a specific modulation frequency results from the superposition of response signals from the substance 5 to be analyzed from different depths, since the excitation beam 8 is partially absorbed in different depth layers on its way into the sample.

[0113] The reaction signal therefore represents a mixture of signals from different depths.

[0114] The mixing ratio of the signals from different depths depends on the frequency of the modulation of the excitation beam 8.

[0115] By linking different spectra to different modulation frequencies, for example by forming a difference between spectra at higher modulation frequencies and spectra at lower modulation frequencies or by forming a quotient between spectra at higher modulation frequencies and spectra at lower modulation frequencies, each with different weighting of the individual spectra, influences from upper material layers can at least be reduced or eliminated.

[0116] Based on comparisons with previously performed calibration or comparison measurements or reference data sets, which in one embodiment are stored in the form of comparison tables or comparison curves in a memory of the evaluation device 16, the device can determine the current concentration of glucose or blood sugar within the tissue or within the volume 5a and generate a corresponding glucose or blood sugar level reading. The comparison tables or comparison curves can, for example, have been created based on glucose or blood sugar values ​​determined from blood samples analyzed outside the patient's body.

[0117] The excitation beam source, which in the illustrated embodiment is formed by a laser device 3 for emitting the excitation light beam(s) 8, can be designed as an array. The array has at least 5, advantageously at least 10, more advantageously at least 15, or at least 50 or 100 individually controllable emitters 100a, each for monochromatic light of different, fixed wavelengths in the absorption spectrum of a substance to be analyzed. The individual emitters can be laser emitters, but they can also be other types of emitters, for example, suitable light-emitting diodes or other semiconductor components that specifically emit radiation in a specific wavelength range.

[0118] The array preferably generates beams of monochromatic light having one or more, particularly preferably all, of the following wavelengths (vacuum wavelengths): 8.1 µm, 8.3 µm, 8.5 µm, 8.8 µm, 9.2 µm, 9.4 µm and 9.7 µm and, if desired, additional glucose-tolerant wavelengths.

[0119] It can be provided that the excitation transmitter / excitation light source 3 is mechanically firmly connected to the optical medium / measuring body 1, either directly or by means of an adjustment device. The adjustment device preferably enables adjustment of the distance of the excitation light source 3 from the measuring body 1, or adjustment in the longitudinal direction of the beam and / or adjustment in the plane perpendicular thereto.

[0120] It can also be provided that the excitation transmitter 3 and the measuring body 1 with the detection device 4, 6 are attached directly to each other or to a common support (not shown). The support can be formed by a plastic part, a circuit board, or a metal sheet mounted in a housing.

[0121] The carrier can also be formed by the housing itself or a housing part.

[0122] It can also be provided that the device for analyzing a substance can be fastened to the body, for example to the torso of a person, with a housing (not shown) in which it is arranged, wherein the excitation transmitter device 3 for emitting one or more excitation light beams 8 and the detection device 4, 6 for detecting the time-dependent reaction signal are arranged and configured such that the side suitable for measurement and the measuring surface 2 of the device are located on the side of the device facing away from the body / torso, so that the substance to be analyzed can be measured on the side of the housing facing away from the body / torso, for example by the patient placing a finger on the measuring surface 2. For this purpose, it is provided, for example, that the housing is fastened to the body of a person by means of a strap belonging to the housing, in one embodiment in the form of a bracelet on a wrist.On the side facing away from the wrist, the housing then has a window that is permeable to the excitation light beam 8, or the measuring body 1 is fitted with its outwardly facing measuring surface 2 directly into the side of the housing facing outwards away from the body and, for example, forms the surface of the housing in sections with the measuring surface 2.

[0123] With this concept, a fingertip can then be placed on the measuring body 1 and measured.

[0124] The measuring body 1 can be mounted inside the housing, just like the carrier, or directly to the housing. The measuring body 1 can also be directly connected to the carrier, in which case an adjustment device should be provided for positioning the carrier relative to the optical medium / measuring body 1.

[0125] It is also conceivable to attach the excitation light source 3 directly to the measuring body.

[0126] Other parameters of the material surface or the fingertip placed against it can also be measured through the optical window in the housing and / or through the measuring body 1, such as a fingerprint in one embodiment. For this purpose, an optical detector in the form of a camera, for example, can be attached to the carrier in the housing, which digitally records an image of the surface of the material 5 through the measuring body or past it, next to the measuring body. This image is processed within a processing device, which can be directly connected to the detection device 4, 6 and also to the excitation transmission device 3, in the same way as the measurement information from the detection device 4, 6. The processing device can also perform control tasks for the measurement. It can also be at least partially separated and removed from the other parts of the device and communicate with them via a radio link.

[0127] The image data from the camera can thus be further processed within the housing or via a radio connection outside the housing and compared with a person identity database in order to retrieve calibration data of the identified person and use this as the basis for the measurement.

[0128] Such calibration data can also be stored remotely in a database, in one embodiment, a cloud, for retrieval. The measurement data from the detection device can also be further processed both inside and outside the housing.

[0129] If data is processed outside the housing, the resulting data should preferably be radioed back to the device inside the housing so that it can be displayed there.

[0130] In any case, a display (not shown) can be provided on the housing, which can advantageously be read through the optical window, in one embodiment also partially through the measuring body or on the measuring body 1. The display can also project an illuminated display onto a display surface through the optical window and can have a projection device for this purpose. In one embodiment, the display can show a measurement or analysis result, in particular a glucose concentration. In one embodiment, the output can be via a character or color code. In one embodiment, the display or a signal device parallel to it can suggest an insulin dose depending on other patient parameters (e.g. insulin correction factor) or automatically transmit a signal to a dosing device in the form of an insulin pump.

[0131] Alternatively, a recommendation for the consumption of certain foods can be provided, including a specific amount. This can, for example, be combined with a preparation suggestion that can be retrieved from a database and transmitted electronically. These preparation instructions can also be transmitted to an automatic food preparation device.

[0132] The connection of the device to and from an external data processing device can be realized using all common standards, such as fiber optics, cables, radio (e.g. Bluetooth, WiFi), or even ultrasound or infrared signals.

[0133] The Figures 2 to 16 show, among other things, special designs of the contact device 6 with electrodes distributed in a variety of ways.

[0134] The Figure 17 shows an embodiment of the invention with a detection device that detects the reflection of a measuring light beam.

[0135] In the Figure 2 is again shown schematically a measuring body 1 with a measuring surface 2 and a detection area 4 as well as a contact device 6. From the Figure 2It can be seen that the contact device 6 can also have a plurality of electrodes on each side of the detection area 4. In the example shown, the electrodes 6e, 6f are shown on a first side of the detection area 4 and the electrodes 6g, 6h are shown on the opposite side of the detection area 4. The individual electrodes in the example shown are rectangular, plate-shaped. For a measurement, the evaluation device 16 can evaluate a piezo signal (in the form of a piezo voltage or a changed resistance) between two electrodes 6e, 6f, 6g, 6h and the results can be compared. An electrode pair can then be selected for further evaluation of the measurement or for a subsequent measurement. In this case, it can be taken into account which electrode pair delivers the largest signals or the signals least susceptible to interference.Preferably, a pair of adjacent electrodes can be selected for the measurement, for example, electrodes 6f and 6g, or electrodes 6e and 6f, or 6g and 6h. However, it is also possible to use the electrode pair 6e, 6h for a measurement and evaluate the signals between these electrodes. It should be noted that the electrodes not currently being used for a measurement may dielectrically shield other electrodes. The unused electrodes can, for example, be left at a floating potential or, in certain cases, connected to ground potential.

[0136] From the Figure 31 shows an arrangement of a contact device 6, which has three circular electrodes 6i, 6j, 6k on each side of the detection area 4. These electrodes can also be used in pairs for measurement. In the illustrated case, the diameter of the circular electrodes increases from the detection area 4 outwards, so that the electrode 6i has a larger diameter than the electrode 6j, and the latter has a larger diameter than the electrode 6k.

[0137] In addition, a pair of flat, plate-shaped electrodes 6l, 6m can be provided outside behind the electrodes 6i, 6j, 6k, for example.

[0138] The ring-shaped design of the electrodes, together with the outwardly increasing size, can result in the outer electrodes being less shielded by the inner electrodes and different electrode pairs being able to be used independently of each other.

[0139] The Figure 4 shows an embodiment with a contact device 6 with three annular electrodes 6n, 6o, 6p arranged one behind the other on each side of the detection area in the horizontal direction - i.e. the direction B - parallel to the measuring surface 2, wherein the diameter of the annular electrodes decreases with increasing distance from the detection area 4.

[0140] A heat sink 14, 14a is shown laterally outside the electrodes on each side of the detection area. This heat sink can be embedded in the measuring body or applied to its exterior. These heat sinks can be made, for example, of a metal or another material whose heat capacity and / or thermal conductivity is greater than that of the material(s) from which the measuring body 1 is made.

[0141] A single, for example, ring-shaped body can also be provided as a heat sink, surrounding the detection area 4 or the entire measuring body 1. A heat sink can also be implemented as a Peltier element. The heat sink ensures that the temperature increase caused by the arrival of a heat wave / heat pulse in the detection area can be compensated for as quickly as possible by cooling, so that the material of the measuring body 1 in the detection area 4 can react as quickly as possible to a subsequent heat pulse.

[0142] The heat pulses follow one another at the modulation frequency of the excitation beam.

[0143] Above the detection area, a plate-shaped heat barrier 15 is provided, which has an opening for the passage of an excitation beam 8. This ensures that the heat pulse, when it arrives in the detection area, is not dissipated too quickly if the thermal conductivity of the material of the measuring body 1 is too high, so that a temperature increase can build up briefly in the detection area 4 before the heat is dissipated, for example via heat sinks.

[0144] One or more heat sinks and / or one or more heat barriers can be integrated into a measuring body or attached to its exterior to appropriately direct heat transfer. This can be particularly useful for flat measuring bodies or for measuring bodies that have a thin coating of a piezoelectric material and are otherwise made of a material that does not exhibit a piezoelectric effect.

[0145] The Figure 5shows a contact device 6 with two frame-shaped electrodes 6q, 6r on each side of the detection area 4, wherein the frame-shaped electrodes are designed as rectangular frames and can be arranged at the same distance from the detection area 4 or at different distances from the detection area 4. The electrodes 6q, 6r can thus be arranged on each side of the detection area 4, for example, coplanar and concentric with each other or staggered with respect to the distance from the detection area 4.

[0146] The Figure 6 shows a contact device 6 with three ring-shaped electrodes each above and below the detection area 4, ie the electrodes are arranged one behind the other at different distances from the measuring surface 2 with respect to the surface normal in direction A on both sides of the detection area 4.

[0147] The Figure 7shows an example of the use of electrodes of a contact device 6. On each side of the detection area 4, two frame-shaped electrodes 6q, 6r are provided at different distances from the detection area 4. Normally, when the substance to be analyzed is arranged in the middle under the measuring surface 2, as indicated in Figure 7 by the area 5 of the substance, the selection of two electrodes on either side of the detection area 4 can be optimal for a measurement. However, if a sample is placed on the measuring surface 2 at the wrong location, for example if a test subject's finger is displaced laterally relative to the optimal position, the substance to be analyzed will move towards the illustrated position 5' and an optimal detection area will be in the area of ​​the measuring body 1, which is designated 4'.In this case, it may be useful to select two other electrodes—in the illustrated case, electrodes 6q, 6r—for a measurement and evaluate the electrical signals generated between them. In this case, different pairs of electrodes can also be used on a trial basis, the corresponding signals evaluated, and compared to determine the exact location of the substance 5 to be analyzed on the measuring surface 2 and which electrode pair produces the best measurement results.

[0148] In the Figure 8Six ring-shaped electrodes are shown arranged one behind the other in the direction of the surface normal A on both sides of the detection area 4. On each side of the detection area, there are three circular electrodes arranged coaxially to one another, with the diameter of the individual electrodes increasing with increasing distance from the detection area 4. Here, too, different pairs of electrodes, which are arranged symmetrically or asymmetrically to one another in relation to the detection area 4, can be selected for a measurement. The evaluation device has been omitted in this illustration, as well as in some other figures, for the sake of clarity; as has an illustration of the excitation beam and the laser device.

[0149] In the Figure 91 shows a measuring body 1 with a detection area 4, wherein the contact device 6 has a plurality of electrodes 6s, 6t, 6u distributed in a circular region 10 around the detection area 4. With this distribution of the electrodes 6s, 6t, 6u, it is expedient to select signals between two diametrically opposed electrodes 6s, 6u for a measurement, wherein different electrode pairs can be operated experimentally for selection.

[0150] In this context, it should be noted that the detection area 4 is identified in the figures as a region of the measuring body 1 that corresponds to the required material selection, so that it exhibits a piezoelectric effect, and which, at the same time, lies in a region of the measuring body 1 in which a reaction signal from the substance 5 to be analyzed arrives in the form of a heat pulse. A possible detection area 4 also depends on the electrodes 6 selected for the measurement and is typically located between the electrodes 6 selected for the measurement, as long as the measuring body 1 in this area 4 is made of the required material or exhibits a piezoelectric effect.The detection area 4 is therefore not necessarily predetermined in the measuring body, but results as the area in which the reaction signals from the substance to be analyzed can be detected by means of the physical effect used by the selected contact electrodes 6 with suitable positioning of the substance 5 under the measuring surface 2.

[0151] The Figure 9 The electrodes 6s, 6t, 6u shown can be rectangular, round, or oval and can be flat or partially cylindrical, ie curved in one axis.

[0152] The Figure 10 shows in an example that the circular ring-shaped region 10, in which the electrodes are arranged around a detection region, does not have to be arranged in the form of a circular ring parallel to the measuring surface, but can be provided as a circular ring in the space of the measuring body 1 in different angular positions.

[0153] In the Figure 11An arrangement is shown in which the contact device 6 is provided directly in the region of the measuring surface 2 in the measuring body 1 or on the measuring body 1. Individual electrodes 6v, 6w are arranged directly on the measuring surface 2 in a circular region 10 distributed around the detection region 4.

[0154] The Figure 12 shows a special embodiment of the structure, which is used in the Figure 11 is indicated. In the Figure 12the measuring body 1 is shown from the underside, i.e. looking from the outside at the measuring surface 2, wherein recesses for receiving electrodes are provided around the annular region 10 in a lower layer 1' of the measuring body 1. The recesses are designated 17, 18, 19, 20, 21. Electrode bodies 6x, 6y can be inserted into the recesses and can be held there in a force-fitting or material-fitting manner. The electrodes 6x, 6y can, for example, be latched into the recesses 21, 20. The recesses 17, 18, 19, 20, 21 have, for example, contacts that are connected to conductor tracks 32 on the measuring surface 2. The conductor tracks 32 are electrically connected to an evaluation device (not shown). When the electrodes 6x, 6y are inserted into the recesses, they are electrically connected to the conductor tracks 32 and thus to an evaluation device.

[0155] The electrodes can be selected for a measurement in the same way as described above.

[0156] For example, it can be provided that the layer 1' of the measuring body 1 consists of a piezoelectric material, while the rest of the measuring body 1 consists of another material, either also piezoelectrically sensitive or non-piezoelectric.

[0157] In the Figure 13A variant is shown in which the layer 1' of the measuring body 1 carries electrodes 22, 23, which are applied externally to the layer 1' (sensor layer), for example glued or vapor-deposited. The layer thickness of the sensor layer 1', which consists of piezoelectric material, can be between 0 and 1 mm, in particular between 0 and 500 micrometers, in particular less than 100 micrometers. The layer can be glued to the first part / remaining region of the measuring body 1 or joined to it using another joining technique. The excitation beam can pass through this layer 1'. A channel-shaped recess for the excitation beam can be provided in the remaining region of the measuring body 1 (in the so-called first part of the measuring body 1). The material of this remaining region of the measuring body 1 can then consist of a material opaque to infrared radiation, for example quartz or sapphire.These electrodes allow the measurement of a piezoelectric effect in the detection area 4 within the layer 1'. Additional electrodes of the same type can be provided below the measuring surface 2 or in recesses in the measuring surface 2 in a circular region 10 around the detection area 4.

[0158] The Figure 14 shows an embodiment with a piezoelectric layer 1' of a measuring body 1, in which two electrodes 24, 25 are placed laterally on the layer 1'. These electrodes 24, 25 can also be glued or vapor-deposited, for example, or applied in another form to the surface of the layer 1' or inserted into recesses in the layer 1. The remaining side surfaces of the layer 1' can also have electrodes 26, 27, with all electrodes being connected to an evaluation device by optical fibers or conductor tracks.

[0159] The Figure 15shows a plurality of electrodes 28, 29 which are arranged on the underside of a piezoelectric layer 1' of a measuring body, i.e. on the measuring surface 2, in a circular region 10 around a detection region 4. Here, too, different pairs of electrodes can be used for a measurement, whereby the two electrodes of a pair should be located opposite each other on different sides of the detection region 4. These electrodes can also be glued or vapor-deposited or applied in another form to the surface of the layer 1' or introduced into recesses / gaps in the layer. Different pairs of electrodes can be combined and operated for a measurement on an experimental basis in order to select the optimal electrode pair depending on the positioning of the material 5 under the measuring surface 2, i.e. depending on the position of the optimal detection region 4.

[0160] The Figure 16shows a measuring body 11, which is designed as a flat body and can, for example, be constructed in a similar way and provided with electrodes as those shown in the Figures 14 , 15illustrated layers 1' of the measuring body 1. However, in this case, the entire measuring body 1 can be formed by the flat body 11. The measuring surface 2 is provided on the underside of the flat body 11, and the extension of the flat body 11 in the direction of the surface normal 7 of the measuring surface 2 is small compared to the extension in the directions parallel to the measuring surface 2. In order to require minimal space for the construction of the device in the direction of the surface normal 7, it can be provided to arrange the laser device 3 laterally next to the flat body above an imaginary extension of the measuring surface on one of its flat sides and to radiate the excitation beam 8 parallel to the measuring surface 2 or essentially parallel to it into the measuring body / flat body 11. A channel-shaped recess can then also be introduced into the flat body for the excitation beam 8, similar to that shown in Fig. 1is shown under reference numeral 13. For example, a mirror device 12 is then provided within the flat body, which reflects the measuring beam 8 toward the measuring surface 2 and further through the measuring surface 2 into the material 5. The flat body can also consist entirely of a piezoelectric material or have a piezoelectric layer in the region of the measuring surface.

[0161] Alternatively, it can also be provided that the laser device 3 is arranged slightly above the flat body 11, so that the excitation beam 8 is radiated parallel to the flat body to a mirror device 12 arranged on top of the flat body 11 and is reflected there into the flat body 11 perpendicular to the measuring surface 2. In both cases, the extension of the device in the direction of the surface normal 7 is smaller than in the embodiment shown in the Figure 1The measuring body 11 and the laser device 3 can thus be housed together in a flat housing, if necessary together with the evaluation device 16.

[0162] The electrodes 22, 23 used for measurements at the detection area 4 can be provided inside, below, or to the side of the flat body 11. In this embodiment, any of the arrangements of two or more electrodes already explained above can also be used.

[0163] Such a measuring body embodied as a flat body 11 can also be formed from a first part and a sensor layer, for example a piezoelectric layer, joined to or glued onto the first part. The piezoelectric layer then forms the measuring surface and is provided with electrodes. In this case, too, a recess for the excitation beam can be provided in the first part of the measuring body 11, and this can then optionally be made of a material that is opaque or slightly permeable to infrared radiation, such as quartz or sapphire.

[0164] In the lower part of the Figure 16 the arrangement shown in perspective above is shown in a side view in order to clearly illustrate the reflection path of the excitation beam 8.

[0165] In the case where a flat body as described above is used with a laser device arranged laterally next to it and aligned such that it emits an intensity-modulated and wavelength-varied excitation beam essentially parallel to the measuring surface into or across the flat body, wherein the excitation beam is deflected towards the measuring surface, a measuring beam generated separately by a beam source, irradiated into the measuring body, and reflected in the region of the measuring surface can be used for detection. The deflection (deflection angle) of this measuring beam in the measuring body in the region of the measuring surface is influenced by the reaction signals from the substance to be analyzed. The deflection angle can be measured, and from this, the intensity of the reaction signals can be determined, which corresponds to the absorption intensity of the excitation beam in the substance 5 and the density / concentration of an absorbing substance / substance to be detected in the substance.

[0166] For such an application, the flat body can also be constructed homogeneously from a material whose refractive index depends on the temperature, or it can have a layer in the area of ​​the measuring surface that consists of a material whose refractive index depends on the temperature.

[0167] The Figure 18 shows, as well as the Figures 19 to 23 , in a cross-sectional view, a substrate 120, in which a first electrode arrangement 119 with two schematically drawn, parallel plate electrodes 123, 124 is embedded as part of a piezoelectric detection device. Hatching of cut sections has been omitted for clarity. The measuring surface 118 is located in the upper part of the substrate 120 in the figures, which can consist entirely or partially of silicon. For illustration, Figure 18 as well as in the Figure 20A human finger 117 is shown as an example of a measurement object whose substance is to be analyzed. The finger is placed on the measurement surface 118 for analysis.

[0168] In the Figures 18 to 23 In the area of ​​the measuring body, substrates 120 are shown, the material of which is permeable to an excitation beam 121 in the infrared range, in the mid-infrared range, or generally in the wavelength range of the excitation beam 121. This applies, for example, to a substrate 120 made of silicon for the mid-infrared range. In addition to the substrate 120, the measuring body can comprise other bodies and layers, such as the piezoelectric regions / detection region and one or more cover layers for mechanical protection of the measuring surface 118 and / or for impedance matching, which are shown in the Figures 18-23adjacent to the measuring surface 118 are schematically shown. Provided the substrate 120 is transparent for its wavelength ranges, an excitation beam 121 can be directed through the substrate material onto the measuring surface 118 and through it into the material to be measured (for example, the finger 117). In such a case, it is not necessary to provide an opening in the substrate 120 for the excitation beam 121. The excitation beam 121 can be directed past the electrode device 119 or through it.

[0169] On the side of the measuring body or the substrate 120 opposite the measuring surface 118, a lens 116, 116', 116" is integrated into the substrate 120, in particular formed by the material of the substrate 120 and machined out of the material of the substrate, for example, by ablation processes, in particular by etching or sputtering.

[0170] There are in the Figures 18 to 23Three examples of possible lens shapes are shown, with the first lens in the Figures 18 and 21 shown, the second lens in the Figures 19 and 22 and the third lens in the Figures 20 and 23 .

[0171] The first lens 116 corresponds to a normally refracting, refractive convex converging lens, the second lens 116' corresponds to a converging lens (refractive) with a Fresnel cut (kinoform lens), and the third lens 116" corresponds to a diffractive lens that focuses the excitation beam 10 through diffraction at a concentric grating structure. The optical axes of the lenses 116-116" can each be perpendicular to the measurement surface 118, so that an excitation light source can shine directly through the substrate 120. However, the optical axes can also be inclined relative to the perpendicular to the measurement surface 118 in order to allow a potentially space-saving positioning of the excitation light source at an angle to the substrate.

[0172] In the Figures 21, 22 and 23 the lens shapes 116, 116', 116" on the substrate 120 with the excitation beams 121 and the beam bundles 122 focused on the substance to be analyzed are shown.

[0173] In the Figure 24A measuring body 1 with a sensor layer 1' is shown in cross-section, in which an excitation beam 8 is guided from the laser arrangement 3 into an optical waveguide 126, which penetrates the measuring body 1 up to the layer 1'. The optical waveguide 126 can also extend through the layer 1' to the measuring surface 2, however, it can also be provided that either the layer 1' has a recess for the excitation beam 8 or the excitation beam 8 passes through the material of the layer 1'. In the area of ​​the measuring surface 2, for example directly adjacent to the measuring surface 2 and / or within the layer 1', a lens 140 can be provided to focus the excitation beam 8 onto a point in the material to be examined. The optical waveguide 126 runs straight from the laser device 3 to the measuring surface 2 and penetrates the detection device and / or the area between the electrodes 123, 124.To prevent interference from the piezoelectric effect and the resulting force of the material of the detection zone on the optical fiber, the optical fiber can be made of a material with no or minimal dependence of the refractive index on external forces or pressure. An optical fiber can also run partially or completely along and on the surface of the measuring body, for example, if the laser device is arranged laterally next to the measuring body (see . Figure 26 ). In the Figure 24The optical waveguide 127 runs from the laser device 3' initially along a first part of its length on or on the surface of the measuring body, and then continues along a second part of its length through the measuring body like the optical waveguide 126. The excitation beam 8 can be reflected in the region of the change in direction of the optical waveguide, for example, by a mirror, or the optical waveguide can be curved there. Such an optical waveguide 126, 127 can be integrated into the material of the measuring body by manufacturing technology (for example, using SOI - Silicon on Insulator technology) or connected to it as a fiber optic optical waveguide, for example by gluing, or the optical waveguide can be integrated along part of its length and designed as a fiber optic optical waveguide along another part of its length.

[0174] In the Figure 24It is also shown that the electrodes 123, 124 are typically provided in recesses or slots of the measuring body. These recesses 128, 129, which in this case are sealed with a polymer by pouring, serve to separate a detection area and thus a piezoelectric body defining the detection area, which can expand and contract as a result of a heat and / or pressure wave, thereby exhibiting the piezoelectric, measurable effects. These can then be detected by the electrodes.

[0175] Corresponding recesses 128, 129 can be provided on all electrodes shown in the present text in the various measuring bodies and can optionally be cast with a non-piezoelectric material, for example with a polymer.

[0176] The material recesses 128, 129 can, for example, be provided during the manufacture of the measuring body 1 or can be introduced later by etching or sputtering or by sawing or laser cutting.

[0177] However, as can be seen from the Figure 25As can be seen in two different variants of the optical waveguide design, a curved optical waveguide 133, 134 can also be provided, which guides the excitation beam from a position on the measuring body 1, at which the laser device 3' is provided, to the measuring surface 2. Because the guidance of the optical waveguide 133, 134 can be designed relatively freely, a minimum distance can be maintained between the area traversed by the excitation beam 8 and the detection area. The excitation beam 8 can also strike the measuring surface 2 at an angle to the measuring surface 2, for example at an angle between 0 degrees and 60 degrees, in particular between 0 and 45 degrees to the surface normal of the measuring surface 2, and pass through it.

[0178] Due to the shallow penetration depth into the substance to be analyzed, the area of ​​the substance in which the excitation beam 8 interacts with it lies directly below the detection device and the electrodes 123, 124, despite an oblique beam direction. The curved optical waveguides 133, 134 can, for example, be laid at least in sections as fiber optic optical waveguides in a bore or similar recess of the measuring body 1 and glued or cast there.

[0179] It can also, as can be seen from the Figure 26 As can be seen, an optical waveguide 135, 136, 137, 138 can be provided for guiding the excitation beam 8, which is guided, for example, in several directions and / or in two or three mutually perpendicular directions along one or two or three different, adjacent surfaces of the measuring body 1. Such an optical waveguide 135, 136, 137, 138 can, for example, as in the Figures 24 and 25shown optical waveguide, can be integrated into the respective measuring body 1. On the surfaces of a measuring body, this is particularly easily achieved using SOI technology or, depending on the material of the measuring body, using a related solid-state manufacturing technology. For this purpose, an optical waveguide can be introduced into a silicon substrate, which is covered by silicon oxide layers or other layers and separated from the substrate. For this purpose, a suitable recess can first be etched or sputtered into the substrate in order to then suitably deposit the material of the cover and the optical waveguide. In this case, the cover of the optical waveguide can, for example, be flush with the surface of the measuring body so that the optical waveguide 135, 136, 137, 138 does not protrude beyond the measuring body 1.By routing the optical waveguides 135, 136, 137, 138 along the surfaces of the measuring body 1, any interaction of the excitation beam 8 with the detection device and the effects of the piezoelectric material is avoided. The last optical waveguide 138 then ends in the area where the excitation beam 8 is to enter the substance to be analyzed. An element can be provided at the end of the optical waveguide 138 to direct the excitation beam 8 into the substance, for example, a mirror.

[0180] In the section of the figure shown in a circle 142 at the bottom right of the Figure 26 It is shown that the optical waveguide 138 can also be arranged in a groove (shown in dashed lines) of the measuring body 1 which runs obliquely towards the measuring surface 2, so that the longitudinal axis of the optical waveguide is aligned parallel to the bottom 141 of the groove through the measuring surface 2 onto the substance to be analyzed.

[0181] This patent application relates (as already mentioned in the introduction) to the above-described subject matter of the claims and exemplary embodiments, as well as to the following aspects. These aspects or individual features thereof can be combined individually or in groups with features of the claims. Furthermore, the aspects also represent independent inventions, either individually or when combined with one another or with subject matter of the claims. The applicant reserves the right to make these inventions the subject matter of claims at a later date. This can be done within the scope of this application or within the scope of subsequent divisional or subsequent applications claiming the priority of this application. ASPECTS:

[0182] 1) A method for analyzing a substance in a body, comprising: emitting an excitation light beam (excitation beam) with one or more specific excitation wavelengths through a first region of the surface of the body, intensity modulation of the excitation light beam with one or more frequencies, in particular sequentially, by a mechanical, electrical, or optical chopper, in particular by electronic control of the excitation light source, an adjustment device for a resonator of an excitation laser serving as the excitation light source or a movable mirror device, a controllable diffraction device, a shutter or mirror device coupled to a motor, such as a stepper motor, or to a MEMS, or a layer in the beam path that is controllable with respect to transmission or reflection, time-resolved detection of a reaction signal by means of a detector arranged outside the body,which is due to the effect of the wavelength-dependent absorption of the excitation light beam in the body.

[0183] The detector can, for example, be formed by an optical medium / measuring body with a detection region which is in particular adjacent or immediately adjacent to the measuring surface (= interface of the measuring body in contact with the substance to be analyzed) and which has a pressure- or temperature-dependent specific electrical resistance and / or generates electrical, in particular piezoelectric, voltage signals in the event of pressure or temperature changes, and with an electrical contact device which has electrodes which are electrically conductively connected to the detection region of the optical medium / measuring body for detecting the electrical resistance and / or the electrical signals, wherein a detection device is formed with the contact device and the detection region.

[0184] The detector / detection device can, for example, comprise a piezoelectric material or a temperature-dependent resistor with a positive or negative temperature coefficient (thermistor) or a thermocouple.

[0185] In one embodiment, the modulation can be achieved by interference or influencing the phase or polarization of the radiation from the excitation transmitter, particularly if this comprises a laser light device. The modulation can also be achieved by controlling an actively operated piezoelectric element, which is a part / element of the measuring body and whose transmission or reflection properties / reflectivity can be controlled by a voltage control on the piezoelectric element. The response signals can be, for example, intensities or deflection angles of a reflected measuring beam or voltage signals from a detector operating with a piezoelectric effect.

[0186] 2) Method according to aspect 1, characterized in that the excitation light beam / excitation beam is generated by several emitters or multi-emitters, in particular in the form of a laser array, which emit light with different wavelengths simultaneously or successively or in pulse patterns, also alternately.

[0187] 3) Method according to aspect 1 or 2, characterized in that an acoustic reaction signal is detected by an acoustic sensor at the first region of the surface of the body.

[0188] 4) Method according to one of aspects 1 to 3, characterized in that a reaction signal is detected at the first region of the surface of the body by an infrared radiation sensor, in particular a thermocouple, a bolometer, or a semiconductor detector, for example a quantum cascade detector, or a piezoelectric detector. The piezoelectric detector can be formed, for example, in or on a measuring body / optical medium.

[0189] 5) Method according to one of aspects 1 to 4, comprising the steps: Establishing contact between an optical medium / measuring body and a material surface of the body such that at least one region of the surface of the optical medium / measuring body (for example a measuring surface) is in contact with the first region of the surface of the body; emitting an excitation light beam having an excitation wavelength into a volume in the material below the first region of the surface, in particular through the region of the surface of the optical medium that is in contact with the first region of the material surface; measuring the temperature or temperature change and / or a pressure change in the first region of the surface of the optical medium using an optical pyrometric or photothermal method; analyzing the material based on the detected temperature increase as a function of the wavelength of the excitation light beam.This process can be performed for different modulation frequencies in one measurement, and the results for different modulation frequencies can be combined.

[0190] 6) Method according to aspect 5, characterized by Emitting a measuring light beam through the optical medium / measuring body onto the area of ​​the surface of the optical medium that is in direct contact with the material surface, such that the measuring light beam and the excitation light beam are immediately adjacent or overlap at the interface between the optical medium / measuring body and the material surface at which the measuring light beam is reflected; directly or indirectly detecting a deflection of the reflected measuring light beam as a function of the wavelength of the excitation light beam, and analyzing the material based on the detected deflection of the measuring light beam as a function of the wavelength of the excitation light beam. This process can be performed for different modulation frequencies in one measurement, and the results for different modulation frequencies can be combined.

[0191] This method can also be used, for example, with a flat measuring body and lateral irradiation of the excitation beam (essentially parallel to the measuring surface) as well as with reflection of the excitation beam onto the measuring surface and onto the substance to be analyzed.

[0192] 7) Method according to one of aspects 5 or 6, characterized in that the measuring light beam is generated by the same light source that generates the excitation light beam.

[0193] 8) Method according to one of aspects 5, 6 or 7, characterized in that the measuring light beam is reflected once or several times after the deflection and before the detection within the optical medium, outside the optical medium or partly within and partly outside the optical medium.

[0194] 9) Method according to aspect 1 or one of the other preceding or following, characterized in that the excitation light beam is an intensity-modulated, in particular pulsed excitation light beam, in particular in the infrared spectral range, wherein in particular the modulation rate is between 1 Hz and 10 kHz, preferably between 10 Hz and 3000 Hz.

[0195] 10) Method according to aspect 1 or one of the other preceding or following, characterized in that the light of the excitation light beam(s) is / are generated by an integrated arrangement with several individual lasers, in particular a laser array, simultaneously or sequentially or partly simultaneously and partly sequentially.

[0196] 11) Method according to aspect 1 or one of the other preceding or following, characterized in that an intensity distribution of the reaction signals is determined from the reaction signals obtained at different modulation frequencies of the excitation light beam as a function of the depth below the surface at which the reaction signals arise.

[0197] 12) Method according to aspect 1 or one of the other preceding or following, characterized in that from the phase position of the reaction signals in relation to a modulated excitation light beam at one or different modulation frequencies of the excitation light beam, an intensity distribution of the reaction signals is determined as a function of the depth below the surface at which the reaction signals arise.

[0198] 13) Method according to aspect 11 or 12, characterized in that in order to determine the intensity distribution of the reaction signals as a function of the depth below the surface, the measurement results are weighted and linked to different modulation frequencies.

[0199] 14) Method according to aspect 11, 12 or 13, characterized in that from the obtained intensity distribution over the depth below the surface of the body, a material density of a material absorbing the excitation light beam in specific wavelength ranges at a certain depth or depth range is determined.

[0200] 15) Method according to aspect 1 or one of the other preceding or following, characterized in that immediately before or after or during the detection of the reaction signal(s), at least one biometric measurement is carried out on the body in the first region of the surface in which the substance analysis is carried out or immediately adjacent thereto, in particular a measurement of a fingerprint, and the body, in particular a person, is identified and that in particular reference values ​​(calibration values) associated with the detection of the reaction signals are assigned by the identification of the person.

[0201] Biometric measurement can also include measuring a spectrum of response signals as the excitation light beam passes through a spectrum. By evaluating the spectrum, a profile of substances present in the body and their quantitative or dense ratios can be determined, which can enable the identification of a person.

[0202] 16) Device for analyzing a substance, with a device for emitting one or more excitation light beams, each with an excitation wavelength, into a volume in the substance below a first region of its surface, with a device for modulating an excitation light beam, which is formed by a modulation device of the radiation source, in particular its control, an interference device, a phase or polarization modulation device and / or at least one controlled mirror arranged in the beam path, and / or a layer arranged in the beam path which is controllable with regard to its transparency, and with a detection device for detecting a time-dependent reaction signal as a function of the wavelength of the excitation light and the intensity modulation of the excitation light and with a device for analyzing the substance on the basis of the detected reaction signals.

[0203] 17) Device according to aspect 16 with a device for determining reaction signals separately according to different intensity modulation frequencies and / or with a device for determining reaction signals depending on the phase position of the respective reaction signal relative to the phase of the modulation of the excitation light beam, in particular depending on the modulation frequency of the excitation light beam.

[0204] 18) Device for analyzing a substance according to aspect 16 or 17, with an optical medium / a measuring body for establishing contact between the surface of the optical medium (for example a so-called measuring surface) and a first region of the substance surface, and with a device for emitting an excitation light beam with one or more excitation wavelengths into a volume in the material below the first area of ​​the surface, in particular through the area of ​​the surface of the optical medium (the measuring surface) that is in contact with the material surface, as well as a device for measuring reaction signals in the form of temperature and / or pressure changes in the area within the measuring body in the immediate vicinity of the measuring surface (a so-called detection area), which is in contact with the first area of ​​the material surface by an optical method that uses a measuring light beam or by the method described above using a piezo effect,and with a device for analyzing the substance based on the detected reaction signals in the form of temperature changes / pressure changes depending on the wavelength of the excitation light beam and the intensity modulation of the excitation light beam, in particular the modulation frequency of the excitation light beam.

[0205] In this aspect and the following aspects relating to it, it can also be provided that the measuring body has a first part that has a recess / cutout in the form of a continuous channel for the excitation beam, and that the measuring body has a sensor layer on its underside on the first part, which is either continuous without a recess / cutout for the excitation beam or is provided with a continuation of the recess of the first part. If the sensor layer is thin enough, for example thinner than 200 micrometers, in particular thinner than 100 micrometers, then the excitation beam can pass through it without excessive absorption, depending on the material selected for the layer, even if it is an infrared beam, and a recess / cutout in the sensor layer is not necessary.The sensor layer of the measuring body can be glued to the first part / remaining part of the measuring body or joined using another joining technique and can consist of a material that has piezoelectric properties and forms a detection region according to the invention. The sensor layer can also consist of a material in which a change in temperature and / or pressure causes a change in the refractive index, so that this change can also be detected as a reaction signal, for example by detecting the reflection angle of a detection beam reflected in or at the sensor layer. The first part / remaining part of the measuring body can then consist, for example, of a material that is transparent in the visible range and for a detection beam, but less transparent or opaque in the infrared spectral range, such as quartz or sapphire or a plastic, for example a polymer.

[0206] 19) Device according to aspect 18, characterized in that the excitation light source is mechanically firmly connected directly to the optical medium / measuring body.

[0207] 20) Device according to aspect 18, characterized in that a device is provided for emitting a measuring light beam into the region of the optical medium / measuring body which is in contact with the first region of the material surface and that this device / or the detection device for detecting the measuring light beam is mechanically firmly connected directly to the optical medium / measuring body, integrated into it or coupled to it by means of an optical waveguide.

[0208] 21) Device according to aspect 18, 19 or 20, characterized in that the optical medium / the measuring body directly carries an imaging optics and / or that an imaging optics is integrated into the optical medium / the measuring body.

[0209] 22) Device according to aspect 18 or one of the other preceding or following, characterized in that the surface of the optical medium / measuring body has several mutually inclined partial surfaces at which the measuring light beam is reflected several times.

[0210] 23) Device according to aspect 18 or one of the other preceding or following, characterized in that one or more mirror surfaces are provided in or on the optical medium / measuring body for reflecting the measuring light beam.

[0211] 24) Due to the multiple reflection of the measuring beam, the path of the beam is extended so that angular deviations can be detected more easily (see also Fig. 17 ).

[0212] 25) Device according to aspect 16 or 17, characterized in that the detection device for detecting a time-dependent reaction signal comprises an acoustic detector for detecting acoustic waves on the material surface, in particular with a resonator, further in particular with a Helmholtz resonator.

[0213] Independently, a quartz fork with preferably the same resonant frequency as a designated resonator can serve as a detector. The resonator can be open or closed. The quartz fork is preferably arranged in or on the neck of the resonator (off-beam) or inside / outside the resonator (in-beam).

[0214] 26) Device according to aspect 16, 17 or 18, characterized in that the detection device for detecting a time-dependent reaction signal has a thermal radiation detector for detecting the thermal radiation at the material surface, in particular an infrared detector, further in particular a thermocouple, a bolometer, or a semiconductor detector or a piezo element.

[0215] 27) Device according to one of aspects 16 to 25, characterized in that the excitation light source and the detection device are fastened directly to one another or to a common carrier, which is formed in particular by a housing or housing part of the device.

[0216] 28) Device according to one of aspects 16 to 26, characterized in that the device has a portable housing which can be fastened to the body of a person, wherein the device for emitting one or more excitation light beams and the detection device for detecting a time-dependent reaction signal are arranged and set up in such a way that the substance to be analyzed is measured on the side of the housing facing away from the body during operation when the device is worn on the body, in particular that the measuring surface of the measuring body is located on the side facing away from the body.

[0217] 29) Device according to one of aspects 16 to 26, characterized in that the device has a portable housing which can be fastened to the body of a person and in that the housing of the device has a window which is permeable to the excitation light beam on its side facing away from the body in the intended carrying position.

[0218] The window can be located directly in front of the measuring body or be formed by the measuring surface of the measuring body.

[0219] 29a) Device for analyzing a substance with an excitation transmitter for generating at least one electromagnetic excitation beam, in particular excitation light beam, with at least one excitation wavelength, a detection device for detecting a reaction signal and a device for analyzing the substance based on the detected reaction signal.

[0220] 30) Device according to one of the preceding aspects 16 to 29a, characterized in that the detection device is arranged to measure the deformation of a crystal or another material transparent in the visible range of the spectrum.

[0221] Analogous to the photothermal 'bouncing method', the deformation can be measured more effectively by choosing steeper (larger) angles of incidence of the measuring beam to the sample surface and minimizing the influence of the deflection of the measuring beam caused by the mirage effect. Literature:

[0222] M. Bertolotti, GL Liakhou, R. Li Voti, S. Paolino, and C. Sibilia. Analysis of the photothermal deflection technique in the surface refection topic: Theory and Experiment. Journal of Applied Physics 83, 966 (1998)

[0223] A cantilever can be placed either directly on the sample or on a sufficiently thin optical medium, with the sample on one side and the cantilever on the opposite side. The thermal expansion of the sample or optical element causes the cantilever to oscillate as a result of the absorption of the modulated pump beam / excitation beam. The measurement beam is reflected off a measurement surface of the cantilever and deflected by the oscillation, depending on the incident wavelength, the thermal properties of the sample, and the modulation frequency. This deflection is detected.

[0224] 31) Device according to one of the preceding aspects 16 to 30, characterized in that the excitation transmitting device contains an interrogation laser or an LED, for example an NIR (near-infrared) LED.

[0225] 32) Device according to one of the preceding aspects 16 to 31, characterized in that the excitation transmitting device has a probe laser which has a smaller diameter than an additional pump laser (= laser for generating the excitation beam).

[0226] 33) Device according to one of the preceding aspects 16 to 32, characterized in that, in order to achieve a more favorable signal-to-noise ratio, a special coating, in particular of the emitter, e.g. IRE, is provided so that heat is dissipated more effectively (e.g. "thermal paste").

[0227] The optical element can be coated on the contact surface to improve the conduction of the thermal signal into the optical medium. Furthermore, the coating can also serve as scratch protection and, with a clever choice of material, can also provide a reflective surface for the measurement beam. Transparency for the excitation light must be maintained.

[0228] 34) Device according to one of the preceding aspects 16 to 33, characterized in that the device comprises a device for i. Pulse trains / double modulation ii. Oscillating mirror iii. MEMS interferometers has.

[0229] 35) Device according to one of the preceding aspects 16 to 34, characterized in that the device is designed to be permanently wearable on the body by a person in one embodiment by means of a holding device connected to the housing, such as a belt, a band or a chain or a clasp, and / or the detection device has a detection surface which can also be used as a display surface for information such as measured values, times and / or text information.

[0230] The detection area can be identical to the measuring area or be its extension / extension.

[0231] 36) Device according to the preceding aspect 35, characterized in that the device has a peel-off film in the region of the detection surface / measurement surface, preferably next to the detection surface / measurement surface, for pretreating the material surface and ensuring a clean surface and / or in one embodiment in the case of glucose measurement specifically for skin cleansing.

[0232] 37) Device according to one of the preceding aspects 16 to 36, characterized in that the detection device is configured to read and recognize fingerprints in order to retrieve certain values / calibrations of a person and / or that it has a device for detecting the position of a finger, preferably for detecting and determining an unwanted movement during the measurement.

[0233] 38) Device according to one of the preceding aspects 16 to 37, characterized in that the detection device has a result display, which is preferably color-coded, as an analog display, in one embodiment including an error display (for example: "100 mg / dl plus / minus 5 mg / dl"), acoustically, and / or with result display of measured values ​​in larger increments than the measuring accuracy of the device allows (for example, by a multi-color traffic light display). This prevents small fluctuations that could unsettle a user, for example, from being communicated.

[0234] 39) Device according to one of the preceding aspects 16 to 38, characterized in that the device for exchanging measured data and for retrieving calibration or identification data or other data from other devices or cloud systems, it has data interfaces, for example wired or wireless interfaces (infrared, light or radio interfaces), wherein the device is preferably set up so that the data transmission can be encrypted, in particular encrypted by fingerprint or other biometric data of the operator.

[0235] 40) Device according to one of the preceding aspects 16 to 39, characterized in that the device is set up in such a way that a suggestion for an insulin dose to be given to the person or substances / foods to be consumed together with the quantity to be consumed can be determined by the device (e.g. insulin correction factor) and / or that the body weight, body fat can be measured and / or manually entered or transmitted to the device from other devices.

[0236] 41) Device according to one of the preceding aspects 16 to 40, characterized in that the device is designed to increase the measuring accuracy for determining further parameters, in one embodiment by means of sensors for determining the skin temperature, diffusivity / conductivity / moisture of the skin, for measuring the polarization of the light (exclusion of water / sweat on the finger surface).

[0237] Water and sweat on a person's skin surface, which can affect glucose measurements, can be detected by a test excitation with excitation radiation from the excitation transmitter with the water-specific bands at 1640 cm-1 (6.1 µm) and 690 cm-1 (15 µm). If the absorption exceeds a certain value, the measurement site / fabric surface / skin surface is too wet for a reliable measurement. Alternatively, the conductivity of the material can be measured near or directly at the measurement site to determine the moisture content. An error message and instructions to dry the device can then be issued.

[0238] 42) Device according to one of the preceding aspects 16 to 41, characterized in that the device has a cover in the beam path of the pump and / or measuring beam laser. This can ensure the mandatory eye safety of living beings.

[0239] 43) Device according to one of the preceding aspects 16 to 42, characterized in that the device has an exchangeable detection surface / measuring surface.

[0240] 44) Device according to one of the preceding aspects 16 to 43, characterized in that the device has a partially ridged or roughened crystal as the optical medium / measuring body, which allows for better alignment of the sample (e.g., the finger). The measuring point, onto which the material surface to be analyzed is placed, is preferably smooth and without ridges.

[0241] 45) Device according to one of the preceding aspects 16 to 44, characterized in that a cylindrical TEMpl TEMoo mode or, instead of the cylindrical TEMpl TEMoo mode, other modes TEMo1 (doughnut), TEMo2, or TEMo3 are used for the measuring beam. The latter, in particular, have the advantage that their intensity can be tuned to the sensitivity profile of the quadrant diode, which represents the detector for the deflected measuring beam. Furthermore, rectangular TEMmn modes such as TEM30 or TEMo3 or higher can be used. This allows the use of scanning / measuring beams that are less sensitive to interference in the horizontal or vertical direction.

[0242] 46) Device according to one of the preceding aspects 16 to 45, characterized in that the device measures not only at one point, but in a grid. This can be done either by shifting the pump or probe laser or the detection unit relative to the skin surface of a subject. Instead of a shift, one or more arrays of pump or probe lasers spatially distributed across the array are also conceivable.

[0243] In addition, the following aspects of the invention should also be mentioned: 47) Device (10) for analyzing a substance, in particular also according to one of claims 16 to 46, with an excitation transmitter / laser device for generating at least one electromagnetic excitation beam, in particular excitation light beam, with at least one excitation wavelength, a detection device for detecting a reaction signal, and a device for analyzing the substance based on the detected reaction signal. The time-dependent reaction signal can consist of the temperature or pressure increase in the measuring body as well as any measured variable detecting these, for example the deflection of a measuring beam or an electrical signal of a piezo element located in or on the measuring body. 48) Device according to aspect 47, (reference numerals refer to the Figure 17) characterized in that the excitation transmitting device is a radiation source 3, in one embodiment a monochromatic, in particular a polarized radiation source, further in particular a laser light source, the device has an optical medium / a measuring body 1, 1', which is in direct contact with the substance 5, in particular a first region 5a of the surface of the substance (The measuring body can be homogeneous overall and consist of a material whose refractive index changes with temperature or it can have a layer 1' of such a material at least in the region of the measuring surface or a layer in which the refractive index changes more strongly as a function of temperature than in the other regions of the measuring body), wherein preferably the excitation transmitting device is arranged such that the emitted excitation beam 8 the optical medium / the measuring body 1,1' (not necessarily the material of the measuring body) and leaves the contour of the measuring body again at the surface of the optical medium / at the measuring surface, and the device comprises a device 105 for emitting a measuring beam, in particular a measuring light beam 112, which is arranged such that the emitted measuring beam penetrates the optical medium and wherein, preferably during operation, the measuring beam and the excitation beam overlap at an interface / measuring surface 2 of the optical medium and the surface of the material at which the measuring beam (112) is reflected (this area can be identical or partially identical to the measuring surface), and the detection device is a device 106 for receiving the reflected measuring beam 112 forming the reaction signal and / or for directly or indirectly detecting a deflection of the reflected measuring beam. It can also be providedthat the excitation transmission device 3 comprises more than two transmitting elements in the form of lasers, in particular in the form of a one-, two- or multi-dimensional transmitting element array, and the fixed wavelengths of the electromagnetic excitation beams of the two or more transmitting elements differ, and a modulation device is provided for an intensity modulation of the excitation beam, and that a detection device is provided for detecting a reaction signal and a device 107, 109 for analyzing the substance on the basis of the detected reaction signal, wherein the measuring body consists of a material transparent to the measuring beam, in particular glass, crystal or a transparent plastic, wherein the detection device comprises a device 106 for receiving the reaction signal forming the reaction signal once or several times (according to, Fig. 17In addition to layer 1', the device for emitting a measuring beam and the detection device are aligned with one another in such a way that the detection device detects the measuring beam as the time-dependent reaction signal after it has been reflected at least once in the region of the measuring surface of the optical medium / measuring body. The detection device 106 can comprise a position-sensitive photoelectric detection element, for example a quadrant diode, which is arranged in the beam path of the measuring light beam behind the reflection point on the measuring surface and detects the position of the measuring beam.

[0244] The detection device is thus suitable for detecting a time-dependent reaction signal as a function of the wavelength of the excitation light and / or the intensity modulation of the excitation light. For this purpose, the evaluation device 109 is also connected to a modulation device 9 for the excitation beam. Furthermore, the device is suitable for analyzing the substance based on the detected reaction signal. Using different modulation frequencies of the excitation transmitter, reaction signals, in particular temporal reaction signal profiles, are determined successively for different wavelengths of the excitation beam. Several reaction signal profiles at different modulation frequencies are linked to one another by the evaluation device 109, and information specific to a depth range below the substance surface is obtained therefrom.

[0245] For the embodiments according to aspect 47 or 48, it is also conceivable to design the measuring body as a flat body, with a thickness / dimension perpendicular to the measuring surface that can be less than 50%, in particular less than 20%, further in particular less than 10% of the smallest of the dimensions of the measuring body parallel to the measuring surface. The excitation transmitter / laser device for generating the excitation beam can then be arranged and aligned laterally next to the measuring body in such a way that it radiates the excitation beam into the measuring body essentially parallel to the measuring surface (or with an angular deviation of less than 20 degrees from this direction). (This may require that the excitation beam be coupled from the excitation transmitter into an optical fiber and from there into the measuring body.)However, a mirror device can also be provided between the excitation transmitter / laser device and the measuring body, so that the excitation beam is first reflected from the excitation transmitter by a first mirror toward a lateral, imaginary extension of the measuring surface and then deflected in a direction parallel to the measuring surface. The excitation beam can then be deflected toward the measuring surface and from there penetrate the substance to be analyzed.

[0246] 49) Device according to one of aspects 47 or 48, characterized in that the device has an optical medium / a measuring body which is in direct contact with the substance, in particular a first region of the surface of the substance, and in that the detection device for detecting a reaction signal detects a parameter change of the optical medium / measuring body, in particular in a region adjacent to the first region, as a result of the reaction signal, in particular a deformation and / or density change or a change in the refractive index of the optical medium.

[0247] In the devices of the type mentioned above, in particular in the devices according to aspects 47, 48 or 49, it can also be provided in particular that the measuring body is coated in the region of the measuring surface with a material that changes its refractive index more significantly as a function of temperature or pressure than the remaining region of the measuring body, wherein the coating is advantageously thinner than 1 mm, further advantageously thinner than 0.5 mm, in particular thinner than 0.2 mm or thinner than 0.1 mm. The coating can also be designed as a sensor layer that is glued on or attached to a remaining / first part of the measuring body.

[0248] In the remaining part of the measuring body, which adjoins the coating or sensor layer, a recess 13 (cf. Fig. 17) must be introduced in such a way that the excitation beam in this area of ​​the measuring body does not touch or pass through the material of at least a first part of the measuring body. The remaining area of ​​the measuring body must be transparent to the measuring beam, i.e., in the visible range of the spectrum, so that this measuring beam can reach the coating / sensor layer and be reflected by or in it.

[0249] The material of the measuring body that adjoins the coating / sensor layer 1' (see also Figure 17) can have a specific heat capacity or thermal conductivity that is greater than that of the material of the coating 1', so that the remaining part of the measuring body that adjoins the coating can serve as a heat sink for the coating. Alternatively or additionally, an additional heat sink or a Peltier element 110 can be provided on the measuring body, by means of which the temperature of the measuring body can be regulated using a control device.

[0250] In this case, the reflection angle of the measuring beam represents the reaction signal to be recorded.

[0251] 50) Device according to one of aspects 47, 48 or 49, characterized in that the detection device has a piezo element connected to the optical medium or integrated therein as a detector for detecting the deformation and / or temperature or density change.

[0252] 51) Device according to aspect 47 or one of the following, characterized in that the detection device has temperature sensors as a detector for detecting the reaction signal.

[0253] 52) Device according to aspect 47 or one of the following, characterized in that the device comprises a device for intensity modulation of the excitation light beam and the detection device is suitable for detecting a time-dependent reaction signal as a function of the wavelength of the excitation light and / or the intensity modulation of the excitation light.

[0254] 53) Device according to aspect 47 or one of the following, characterized in that the excitation transmitting device / laser light source for generating the excitation beam radiates the at least one electromagnetic excitation beam into a volume of material which lies below a first region of the surface of the material.

[0255] 54) Device according to aspect 47 or one of the following, characterized in that the excitation transmission device / laser light source for generating the excitation beam comprises two or more transmission elements, in particular in the form of a one-, two- or multi-dimensional transmission element array.

[0256] The individual transmitting elements can be, for example, QC lasers or semiconductor lasers with a fixed wavelength.

[0257] 55) Device according to aspect 47 or one of the following, characterized in that the two or more transmitting elements each generate their own electromagnetic excitation beam and radiate this into the volume below the first region.

[0258] 56) Device according to aspect 47 or one of the following, characterized in that the wavelengths of the electromagnetic excitation beams of the two or more transmitting elements differ.

[0259] 57) Device according to aspect 47 or one of the following, characterized in that the excitation transmitting device / laser light source for generating the excitation beam comprises two or more lasers, in particular in the form of a one- or two-dimensional laser array, and / or two or more light-emitting diodes, in particular in the form of a one-, two- or multi-dimensional diode array.

[0260] 58) Device according to aspect 47 or one of the following, characterized in that the excitation transmitting device is directly - or indirectly by means of an adjusting device - mechanically firmly connected to an optical medium / measuring body which is mechanically firmly connected to the substance, in particular to the first region of the surface of the substance in which the measurement for substance analysis is carried out.

[0261] 59) Device according to aspect 47 or one of the following, characterized in that the device for intensity modulation comprises or is formed by an electrical modulation device which is electrically connected to the excitation transmission device / laser light source for generating the excitation beam and electrically controls it.

[0262] 60) Device according to aspect 47 or one of the following, characterized in that the device for intensity modulation comprises at least one controlled mirror arranged in the beam path.

[0263] 61) Device according to aspect 47 or one of the following, characterized in that the device for intensity modulation comprises or is formed by at least one layer which is controllable with regard to its transparency and is arranged in the beam path.

[0264] 62) Device according to aspect 47 or one of the following, characterized in that a device (105) is provided for emitting a measuring beam, in particular a measuring light beam, into that region of an optical medium / measuring body which is in contact with the first region of the surface of the substance on which the substance analysis is carried out. The corresponding surface of the measuring body is also called the measuring surface.

[0265] 63) Device according to aspect 47 or one of the following, characterized in that the device for emitting a measuring beam and the detection device are aligned with each other in such a way that the detection device detects the measuring beam as the time-dependent reaction signal after it has been reflected at least once at that interface of the optical medium (= the measuring surface) which is in contact with the substance, in particular the first region of the surface of the substance.

[0266] The measuring surface can be the outer surface of a sensor layer which forms part of the measuring body and is connected to the remaining part of the measuring body, in particular by gluing.

[0267] 64) Device according to aspect 47 or one of the following, characterized in that the device for emitting a measuring beam and / or the detection device and / or excitation transmission device is mechanically firmly connected directly to the optical medium / measuring body and / or is coupled to it by means of an optical waveguide.

[0268] 65) Device according to aspect 47 or one of the following, characterized in that the optical medium / measuring body directly carries an imaging optic and / or an imaging optic is integrated into the optical medium. The imaging optic can, for example, contain one or more lenses or reflective surfaces molded into the measuring body. The surface of the measuring body can, for example, be shaped in the form of a lens for this purpose.

[0269] 66) Device according to aspect 47 or one of the following, characterized in that the surface of the optical medium has a plurality of partial surfaces inclined towards one another, at which a measuring beam, in particular the measuring light beam, is reflected several times.

[0270] 67) Device according to aspect 47 or one of the following, characterized in that one or more mirror surfaces are provided in or on the optical medium / measuring body for reflecting the excitation beam or a measuring beam, in particular a measuring light beam.

[0271] 68) Device according to aspect 47 or one of the following, characterized in that the excitation transmission device (and / or the device for emitting the measuring beam and / or the detection device) are fastened directly to one another or to a common carrier. This carrier can be movable in a controlled manner relative to the measuring body as a whole and can be adjusted relative to the latter by means of an adjusting device.

[0272] 69) Device according to aspect 47 or one of the following, characterized in that the carrier is formed by a printed circuit board, a metal plate or plastic plate or a housing or housing part of the device.

[0273] 70) Device according to aspect 47 or one of the following, characterized in that the excitation transmission device comprises an integrated semiconductor component which has one or more laser elements and at least one micro-optical component and preferably additionally a modulation element.

[0274] 71) Device according to aspect 47 or one of the following, characterized in that the modulation element has at least one element, in particular a mirror, which is movable relative to the remaining semiconductor component and controllable with respect to a position.

[0275] 72) Device according to aspect 47 or one of the following, characterized in that the modulation element has a layer whose radiation permeability can be controlled.

[0276] 73) Device according to aspect 47 or one of the following, characterized in that the modulation element has an electronic control circuit for the modulation of the one or more laser elements.

[0277] 74) Device according to one of the preceding aspects, characterized in that the measuring body or the optical medium is designed as a flat body, in particular as a plane-parallel body in the form of a plate, wherein in particular the thickness perpendicular to the measuring surface (that is to say the interface of the optical medium to which the substance to be analyzed is applied) is less than 50% of the smallest extent of the measuring body in a direction parallel to the measuring surface, in particular less than 25%, further in particular less than 10% or less than 5% or less than 1%.

[0278] An imaging optic can be attached to a boundary surface adjacent to or opposite the measuring surface, or to the measuring surface itself, or an imaging optic can be integrated into this surface. The imaging optic can contain at least one lens.

[0279] 75) Device according to one of the preceding aspects, characterized in that the measuring body / the optical medium has or carries a mirror device for reflecting the excitation beam radiated by the laser device to the measuring surface (or to the interface of the optical medium to which the substance to be analyzed is applied).

[0280] 76) Device for analyzing a substance according to claim 1 or one of the following, characterized in that the excitation beam is radiated into the measuring body parallel to the measuring surface (or the interface of the optical medium to which the substance to be analyzed is applied) or at an angle of less than 30 degrees, in particular less than 20 degrees, more particularly less than 10 degrees or less than 5 degrees to the measuring surface (or the interface of the optical medium to which the substance to be analyzed is applied) and that the excitation beam is deflected or redirected in the direction of the measuring surface (or the interface of the optical medium to which the substance to be analyzed is applied) and passes through it.

[0281] The measuring body can have a channel-like recess for the excitation beam, the longitudinal direction of which runs parallel to the measuring surface, so that the distance the excitation beam travels in the material of the measuring body until it exits through the measuring surface is reduced, in particular reduced to zero. If a sensor layer is integrated into the measuring body, the recess / cutout in the measuring body can extend up to this layer.

[0282] 77) A method for analyzing a substance, wherein the method at least one electromagnetic excitation beam having one or more excitation wavelengths is generated by an excitation transmitting device through the at least partially simultaneous or successive operation of several laser emitters of a laser light source and is radiated into the substance, a reaction signal is detected by a detection device and the substance is analyzed on the basis of the detected reaction signal.

[0283] 78) Method according to aspect 77, characterized in that reaction signals, in particular temporal reaction signal curves, are determined one after the other using different modulation frequencies of the excitation transmission device and that a plurality of reaction signal curves are linked to one another at different modulation frequencies and that therefrom, in particular, information specific for a depth range below the material surface is obtained.

[0284] 79) Method according to aspect 78, characterized in that reaction signal curves are determined for different modulation frequencies for different wavelengths of the excitation beam and, in particular, information specific for a depth range below the material surface is obtained therefrom.

[0285] 80) Method according to aspect 79, characterized in that When using several modulation frequencies of the excitation beam at the same time, the detected reaction signal is separated according to its frequencies by means of an analysis method, preferably a Fourier transformation, and only one partial signal is filtered out, measured and analyzed which corresponds to a frequency to be processed.

[0286] In this way, a plurality of signals at different modulation frequencies can be analyzed sequentially and the results at different modulation frequencies can be combined to obtain depth information about the signals or to eliminate signals coming from the material surface.

[0287] 81) Method according to one of the preceding aspects 77 to 80, characterized in that an optical medium / a measuring body is brought into direct contact with the material, in particular a first region of the surface of the material, the emitted excitation beam is generated by the excitation transmission device and is particularly emitted in such a way that it penetrates the optical medium and leaves it again at a predetermined point on the surface of the optical medium, in particular at a measuring surface, a measuring beam, in particular a measuring light beam, is generated by a device for emitting a measuring beam in such a way that it penetrates the optical medium / the measuring body and that in particular the measuring beam and the excitation beam overlap during operation on an interface between the optical medium and the surface of the material at which the measuring beam is reflected, in particular at the measuring surface,and a reflected measuring beam forming the reaction signal is measured with the detection device and / or the deflection of the reflected measuring beam is detected directly or indirectly.

[0288] The reflected measuring beam can be measured, for example, by detecting its intensity with a spatially resolving light-sensitive semiconductor component, in particular a quadrant diode.

[0289] 82) Method according to one of the preceding aspects 77 to 81, characterized in that, depending on a substance concentration determined in the substance, a dosing device for dispensing a substance into the substance, in particular into a patient's body, is controlled and / or an acoustic and / or optical signal is output and / or a signal is output to a processing device by means of a radio connection and / or that one or more foods or food combinations are assigned to the measured substance concentration by means of a database and output as nutritional information, in particular nutritional recommendation.

[0290] In addition to or in combination with such a recommendation, a quantity indication for the food or food combinations may also be provided. Food combinations are also understood to include prepared food portions.

[0291] All features and measures of the excitation beam, its optical guidance and modulation, which are mentioned in the aspects in connection with any measuring method, in particular in connection with a measuring light beam and the detection of its deflection, as well as the features of the mechanical structure and adjustability, the features of the housing and the communication with external devices, databases and connected devices, can also be used in the detection method as claimed in the patent claims of the present application, i.e. using a piezo effect to detect the heat wave emitted from the material as a reaction signal in a measuring body.

[0292] Further detection methods for detecting a response signal after emitting an excitation beam may include: Photoacoustic detection - photoacoustic detection using a tuning fork or other vibrating element, or a slightly modified form of photoacoustics using an open QePAS cell (Quartz Enhanced PhotoAcoustic Spectroscopy). These methods can detect pressure fluctuations / vibrations on the material surface and evaluate them in the same way as described above for the measured beam deflection.

[0293] In principle, measured values ​​of a phase shift of the reaction signal compared to a periodic modulation of the excitation beam can be used for depth profiling. (The heating / cooling phases of the material surface should be evaluated more precisely with regard to their progression.)

[0294] The described device can be connected to a supply of adhesive strips for removing dead skin layers to allow for the most interference-free measurement possible on a human body, as well as patches containing thermal paste that can be regularly applied to the optical medium. The optical medium can be replaceable with appropriate attachment and adjustment of the other components.

[0295] The device may be designed and arranged to measure not only on a person's finger, but also on a lip or an earlobe.

[0296] The measurement can be improved in terms of accuracy and reliability by combining several of the described and explained measuring systems with similar susceptibility to errors.

[0297] DAQ and lock-in amplifiers in the evaluation can be combined in one device and the evaluation can be digitized as a whole.

[0298] The measurement can also be carried out with the device on a material surface that is moving relative to it, so that in the course of a raster measurement: the excitation light source and / or the measuring light source move over the skin in a grid during the measurement, and any skin irregularities can be compensated or averaged out.

[0299] The sensitivity of the detection device / deflection unit can be optimized by adjusting / varying the wavelength of the probe beam / measurement light source. For this purpose, the measurement light source can be variable in wavelength or contain several laser light sources of different wavelengths for selection or combination.

[0300] An optimal transverse mode (TEM) can be selected for the deflection of the pump / probe laser.

[0301] The excitation transmitter, measuring light source and detector can be constructed as a common array and the beams can be appropriately deflected in the optical medium in order to concentrate the emission and reception of all beams at one location.

[0302] A lens on or in the crystal of the optical medium can help to deflect the measuring light beam more strongly depending on the reaction signal.

[0303] In addition, the use of a gap-free photodiode for detection is conceivable; then a lens could bundle the measuring light beam after it exits, thus enabling a more precise measurement.

[0304] An additional embodiment of the invention according to the patent claims is presented in the following concept. Furthermore, this concept, taken on its own, combined with the above aspects or with subject matter of the claims, represents at least an independent invention. The applicant reserves the right to make this invention or inventions the subject matter of claims at a later date. This may be done within the scope of this application or within the scope of subsequent divisional or subsequent applications claiming the priority of this application.

[0305] The following concept for non-invasive blood glucose measurement by determining glucose in the skin using quantum cascade laser excitation and measuring the heat wave by radiant heat is also intended to be encompassed by the invention and can be combined with the subject matter of the claims or pursued independently in a divisional application: A method is described with which the concentration of glucose or another substance in the interstitial fluid (ISF) in the skin can be determined. Glucose in the ISF is representative of blood glucose and quickly follows changes. The method consists of at least individual or groups of the following steps or of the entire sequence: 1. The skin area (in this case, the first area of ​​the fabric surface) is irradiated with a focused beam from a quantum cascade laser, optionally reflected by a mirror or concave mirror, which is tuned stepwise or continuously across a specific infrared range in which glucose specifically absorbs radiation. Instead of the quantum cascade laser, a laser array with multiple lasers emitting individual wavelengths can also be used. The spectral range (or the individual wavelengths, typically 5 or more wavelengths) can be between approximately 900 and approximately 1300 cm -1 , in which glucose exhibits an absorption fingerprint, i.e., typical and representative absorption lines. 2. The excitation beam is used continuously (CW laser) or pulsed with a high pulse repetition rate, or modulated.In addition, the excitation beam is modulated at low frequency, particularly in the frequency range between 10 and 1000 Hz. The low-frequency modulation can be performed using various periodic functions, in various embodiments sine, square, sawtooth, or similar. 3. By irradiating the skin, the IR radiation penetrates to a depth of approximately 50–100 µm and, depending on the wavelength, excites certain vibrations in the glucose molecule. These excitations, from vibration level v0 to v1, return to the ground state within a very short time; heat is released during this step. 4. As a result of the heat development according to (3), a heat wave develops, emanating isotropically from the site of absorption. Depending on the thermal diffusion length, which is determined by the low-frequency modulation described in (2), the heat wave reaches the surface of the skin periodically at the modulation frequency. 5.The periodic appearance of the heat wave at the surface corresponds to a periodic modulation of the thermal radiation properties of the skin (material surface of the sample). The skin can be approximately described as a blackbody radiator, whose total emission is proportional to the fourth power of the surface temperature according to the Stefan-Boltzmann law. 6. Using a thermal radiation detector, i.e., an infrared detector, i.e., a thermocouple, bolometer, semiconductor detector, piezoelectric detector, or similar, directed at the skin site of irradiation, the periodic temperature increase described under (5) is recorded. It depends on the infrared irradiation described under (1) and (2) and on the absorption described under (3), and thus depends on the glucose concentration.

[0306] The thermal radiation (in this case, the reaction signal) is collected, for example, by means of an optical element, in one embodiment an infrared lens or a mirror, in particular a concave parabolic mirror, and directed to the detector via a convex mirror. For this purpose, a collecting mirror used can, in one embodiment, have an opening through which the collected beam is directed. Furthermore, a filter can be provided in the beam path that only transmits infrared radiation of a specific wavelength range.

[0307] In another embodiment, the thermal radiation is detected by means of a measuring body as claimed in the patent claims, through a piezo effect.

[0308] 7. When processing the reaction signals, the modulation frequency can be specifically considered. For this purpose, the reaction signal can be processed in a lock-in amplifier. By analyzing the phase relationship between the excitation signal and the thermal radiation signal (reaction signal) using a control and processing device, depth information about the depth below the material surface, from which the reaction signals are primarily obtained, can be obtained.

[0309] 8. By selecting and analyzing various low-frequency modulation frequencies for the excitation beam as described under (2) and combining the results for different modulation frequencies (whereby the results for different modulation frequencies can also be weighted differently), depth information can also be obtained. If necessary, differential methods, a quotient calculation of at least two response signals (e.g., each for a single wavelength and wavelength by wavelength throughout the measured spectrum), or other determination methods can be used to compensate for the absorption of the uppermost skin layers.

[0310] 9. In order to make the detection of thermal radiation according to (6) as sensitive as possible, it is used spectrally broadband for the entire infrared range in question.

[0311] The goal is to utilize as many regions of the Planck radiation curve as possible. To make the detection insensitive to the intense excitation radiation, the thermal radiation detection system is equipped with a notch filter for these excitation wavelengths.

[0312] 10. From the heat signal measured according to (6-9), which is dependent on the excitation wavelength, in one embodiment, if glucose is to be detected, the background is first determined at wavelengths of the excitation beam that are not (or with the exception of) glucose-relevant wavelengths, and then the difference to the background signal is determined at (or with the inclusion of) glucose-relevant wavelengths. This results in the glucose concentration in the skin layer or layers, which are determined by the selected phase position according to (7) or the various modulation frequencies according to (8), or their combination.

[0313] Although the invention has been illustrated and described in detail by means of preferred embodiments, the invention is not limited by the disclosed examples and other variations can be derived therefrom by those skilled in the art without departing from the scope of the invention. List of reference symbols

[0314] 1Measuring body 1'Layer 2Measuring surface 3Laser device 4Detection area 4'Detection area 5Area, material 5'Position 6Contact device 6e - 6yElectrodes 7Surface normal 8Excitation beam 9Modulation device 10Area 11Flat body 12Mirror device 13Recess 14, 14aHeat sink 15Heat barrier 16Evaluation device 17-21Recesses 22 - 29Electrodes 32Conductor tracks ADirection, surface normal BRedirection

Claims

1. A device for analysing a substance (5) having: - a measuring body (1, 1', 11) which has a measuring surface (2) that is to be brought at least partially into contact with the substance (5) for the measurement, - an excitation beam source, in particular a laser device (3), more particularly with a quantum cascade laser (QCL), a tuneable QCL, and / or with a laser array, preferably an array of QCLs, for generating one or more excitation beams (8) with different wavelengths in the infrared spectral range between 3 µm and 20 µm, which is directed at the substance while passing through the measuring surface, and - a detection device (4, 6), which comprises the following: • a detection region (4, 4') which is part of the measuring body (1, 1', 11) and arranged in particular adjacent or directly adjacent to the measuring surface (2), and has electrical properties that vary as a function of a change in pressure or temperature, and • electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131) that can be used to detect electrical signals representing the above-mentioned electrical properties, characterized in that at least two electrodes (6a, 6b) are spaced apart from one another in a direction perpendicular to the surface normal (7) on different sides of the detection region (4).

2. The device for analysing a substance according to Claim 1, in which the electrical property which varies according to the pressure or temperature • gives rise to piezoelectric signals on the electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 13i) as a function of the pressure change and / or temperature change, or • is formed by a specific electrical resistance, which varies according to the temperature, wherein the device also comprises an electrical contact device (6) which comprises the said electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131), which are electrically conductively connected to the detection region of the measuring body for detecting the electrical resistance and / or piezoelectric signals.

3. The device for analysing a substance according to any one of the preceding claims, characterized in that at least two electrodes (6c, 6d) are arranged along the surface normal (7) of the measuring surface (2), one behind the other at different distances from the measuring surface (2) .

4. The device for analysing a substance according to any one of the preceding claims, characterized in that the excitation beam (8) passes through the measuring body (1), in particular the detection region (4, 4') of the measuring body, wherein an optical waveguide (126, 133, 134, 135, 136, 137) is arranged in or on the measuring body (1) in particular to guide the excitation beam and, more particularly, the optical waveguide is integrated into the measuring body.

5. The device for analysing a substance according to one of the preceding claims, further comprising an optical element for focusing and excitation beam (8), wherein the optical element is provided • between the excitation radiation source and the measuring body (1), • at the measuring body (1) at a position, where the excitation beam (8) enters the measuring body (1), or • at the measuring body (1) is at a position, where the excitation beam leaves the measuring body (1).

6. The device for analysing a substance according to any one of Claims 1 to 5, characterized in that a modulation device (9) is provided for modulating the intensity of the excitation beam (8), and / or in that at least two, in particular at least three or four, more particularly at least 6, more particularly at least 8 electrodes are arranged one behind another at different distances from the measuring surface (3), or spaced apart from each other in a direction perpendicular to a surface normal (7) of the measuring surface.

7. The device for analysing a substance according to any one of Claims 1 to 6, characterized in that at least two, in particular at least three or four, more particularly at least 6, more particularly at least 8 electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131) are arranged one behind another in the direction of a surface normal (7) of the measuring surface (2) or perpendicular thereto or in a direction between 0 and 90 degrees to the surface normal (7) at different distances from the detection region (4, 4'), in particular at different distances from the centre of the detection region, and / orin that at least two, in particular at least three or four, more particularly at least 6, more particularly at least 8 electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29 123, 124, 130, 131) are arranged in an annular region (10) or a spherical shell-shaped region around the detection region (4, 4') and at least partially opposite one another on different sides of the detection region, different electrodes each being substantially the same distance from the centre of the detection region or different distances from the centre of the detection region.

8. The device for analysing a substance according to any one of the preceding claims, characterized in that one or more or all of the electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131) of the contact device (6) are disc- or plate-shaped, annular, annular disc-shaped, in the form of a rectangular or polygonal frame with an opening, cap-shaped or rod-shaped, and / orin that one or more or all of the electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131) of the contact device (6) are arranged on a surface of the measuring body (1, 1', 11) or the detection device (4, 4', 6) and in particular are attached by means of a joining method, more particularly by adhesive bonding or welding.

9. The device for analysing a substance according to any one of the preceding claims, characterized in that one or more or all of the electrodes (6a to 6y, 22, 23, 24, 25, 26, 27, 28, 29, 123, 124, 130, 131) of the contact device (6) are arranged on the inside of the measuring body (1, 1', 11) or on an outer side thereof in one or more recesses (17, 18, 19, 20, 21) of the measuring body, wherein they are, in particular, inserted, introduced by casting, by injection moulding or by an additive manufacturing method (3D printing), and / or in that the measuring body (1, 1', 11) is formed as a flat body (11), in particular as a plane-parallel body in the form of a plate, wherein in particular the thickness of the measuring body (1) in the direction perpendicular to the measuring surface (2) is less than 50 % of the smallest extension of the measuring body in a direction extending in the measuring surface, in particular, less than 25 %, more particularly less than 10 %, wherein the measuring body (1, 1', 11) preferably has or carries a mirror device (12) for reflecting the excitation beam (8) irradiated by the excitation beam source, in particular laser device (3), onto the measuring surface (2).

10. The device for analysing a substance according to any one of the preceding claims, characterized in that the excitation beam (8) is irradiated into the measuring body (1, 1', 11) parallel to the measuring surface (2) or at an angle of less than 30 degrees, in particular less than 20 degrees, more particularly less than 10 degrees or less than 5 degrees to the measuring surface, and that the excitation beam is diverted or deflected in the direction of the measuring surface (2) and passes through it, and / or the excitation beam (8) passes through the material of the measuring body (1).

11. The device according to any one of the preceding claims, characterized in that the measuring body (1, 1', 11) has at least one recess or slot (13), in particular a bored hole, through which the excitation beam (8) passes, wherein the recess or slot and / or bored hole extends into the measuring body, in particular from the measuring surface (2) or from a sensor layer of the measuring body bounded by the measuring surface, or wherein the recess or slot (13) and / or bored hole penetrates the entire measuring body from a boundary surface of the measuring body opposite the measuring surface (2) as far as the measuring surface (2), and / or in that in the measuring body (1, 1', 11), in particular in the detection device (4, 4', 6) or directly adjacent thereto and in thermal contact therewith, at least one heat sink (14) is arranged in the form of a body, the specific thermal capacity and / or specific thermal conductivity of which is greater than the specific thermal capacity and / or specific thermal conductivity of the material or the materials from which the measuring body is made, or which is designed as a Peltier element.

12. The device according to any one of the preceding claims, characterized in that in the measuring body (1, 1', 11), in particular in the detection device (4, 4', 6) or directly adjacent thereto and in thermal contact therewith, at least one thermal barrier (15) is arranged in the form of a body, the specific thermal capacity and / or specific thermal conductivity of which is greater than the specific thermal capacity and / or specific thermal conductivity of the material from which the measuring body (1) is made, and / or in that the detection device (4, 4', 6) and / or the measuring body (1, 1', 11) and / or a sensor layer (1') of the measuring body, is at least partially made of a piezoelectric material, in particular a piezoelectric ceramic, in particular a PZT ceramic, more particularly a sintered ceramic, or a mono-crystalline piezoelectric material, in particular quartz, tourmaline, lithium niobate, gallium orthophosphate, berlinite, Seignette salt, ferroelectrics such as barium titanate (BTO) or lead zirconate-titanate, gallium phosphate or a lead-magnesium niobate, or zinc oxide (ZnO) or aluminium nitride as a thin-layer deposit or polarized polyvinyl fluoride, and / or in that a piezoelectric element or piezoelectric region of the measuring body (1, 1', 11) can be connected as an actuator to a voltage source and depending on the input voltage, represents a blockage for an excitation beam.

13. A method for operating a device according to any one of the preceding claims, characterized in that a modulated excitation beam (8) is directed, in particular through the measuring body (1, 1', 11), at the substance to be analysed (5) and that signals from different electrode pairs of the contact device (6) are acquired and evaluated simultaneously or sequentially, that it is firstly determined based on criteria which one or more of the pairs of electrodes delivers / deliver signals suitable for further processing, and that the signals from one or more selected electrode pairs are then used for measurement and evaluated, and that in particular a subsequent measurement is performed in which the signals of the selected electrode pair or pairs are acquired and evaluated.

14. The method according to Claim 13, characterized in that after an initial measurement test, depending on the signals detected a misalignment of the device relative to the substance to be analysed (5) is determined and indicated and, in particular, the user is prompted to perform a realignment.

15. A method for analysing a substance (5) using a device according to any one of Claims 1 to 12, wherein in the method - with an excitation transmission device (3), at least one intensity-modulated electromagnetic excitation beam (8) with at least one excitation wavelength is generated, the excitation transmission device (3) irradiates the at least one electromagnetic excitation beam (8) into a volume of substance (5) which is located below the surface of the substance (5), - a response signal is detected using a detection device (16, 106, 107, 109), and - the substance is analysed on the basis of the detected response signal, wherein in particular - using different modulation frequencies of the excitation transmission device, response signals, in particular temporal response signal waveforms for different wavelengths of the excitation beam, are successively determined and - a plurality of response signal waveforms at different modulation frequencies are correlated with one another and wherein - information specific to a depth range under the surface of the substance is obtained from these.