RU2813964C2 - Device and method of analyzing substance - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to a device and a method for analysing a substance and can be used to measure glucose or blood sugar content. Device comprises a measuring element, which has a measuring surface and is configured to communicate at least partially with a substance in the region of the measuring surface to perform measurement or is configured to be brought into contact with it directly or also by means of a medium, also includes a detector device, which is at least partially integrated into the measuring element or connected to it. Using the exciting beam (beams), energy is emitted into the substance, and depending on the wavelength of the emitted light and substances present in the analysed substance, as well as their resonance oscillations or absorption frequencies, the exciting beams are absorbed in the substance to a greater or lesser extent.

EFFECT: simplified determination of analyzed liquid composition.

19 cl, 25 dwg

Description

The present invention relates to a device and method for analyzing a substance. They can be used, for example, to analyze tissues, animal or human fluids, in particular body fluids, and in one embodiment, to measure glucose or blood sugar.

Known methods for analyzing a substance, in particular measuring blood sugar levels, are described, for example, in the following publications:

1. Guo. et al.: “Noninvasive glucose detection in human skin using wavelength modulated differential laser photothermal radiometry”, Biomedical Optics Express, Vol, 3, 2012, no. eleven.

2. 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.

3. Farahi et al.: "Pump probe photothermal spectroscopy using quantum cascade lasers", J. Phys. D. Appl. Phys. 45 (2012) and

4. 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).

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

The object is to provide a device and a method by which a substance, in particular animal or human tissue, or a component or constituent of a tissue or liquid, can be analyzed in a particularly simple, accurate and cost-effective manner. One aspect of the invention is also to achieve a small overall size of the device.

In addition, reference is made to German patent DE 102014108424 B3.

This problem is solved, among other things, using a device with the features of paragraph 1 of the claims. Improvements to the device are given in dependent clauses. In addition, the invention relates to a method according to an independent method claim with corresponding improvements according to the dependent claim(s).

This application, in addition to those directly and explicitly indicated upon filing in the claims and in the examples of implementation of the objects, also refers to additional aspects that are listed at the end of this description. These aspects may be combined individually or in groups with features of the claims provided at the time of filing. These aspects also constitute independent inventions, considered individually or in combination with each other or with the subject matter of the claims of this application. The applicant reserves the right to later make these inventions the subject of the claims. This may be done as part of this application or as part of subsequent divisional applications, “continuation applications” in the United States, “continuation-in-part applications” in the United States, or subsequent applications claiming the priority of this application.

In the context of the following embodiments, the term “light” or “laser light” refers to electromagnetic waves or electromagnetic radiation in the visible, near, mid and far infrared and UV ranges.

In what follows, the objects of the claims listed when filing the application will be disclosed first.

The problem is solved using the features of the invention according to paragraph 1 of the formula using a device for analyzing a substance containing:

- a measuring element which has a measuring surface and can communicate at least partially with a substance in the region of the measuring surface to carry out the measurement, in particular can be communicated directly or through a medium, in particular a liquid, or directly or also through a medium can be brought into contact,

- an excitation beam source, which is configured to generate light or an excitation beam with different wavelengths, in particular a laser device, in particular with a quantum cascade laser (QCL), a tunable QCL and/or a laser array, preferably a QCL array , for generating one or more excitation beams of different wavelengths, preferably in the infrared or mid-infrared region of the spectrum, which is directed towards the substance when the measuring element in the region of the measuring surface is connected and/or in contact with the substance, and

- a detector device that is at least partially integrated into or associated with the measuring element, and includes the following:

a source of detector light, preferably coherent detector light, and

connected or configured to be connected to said detector light source, a first light guide structure, which directs the detector light and the refractive index of which at least in sections depends on temperature and/or pressure, wherein the first light guide structure contains at least one section, in wherein the light intensity is dependent on a phase shift of the detector light in at least a portion of the first light guide structure due to a change in temperature or pressure.

In this context, the phase shift of the detector light should be understood as a phase shift relative to the phase position of the detector light with or without a change in temperature or pressure. Thus, from the change in light intensity, the phase shift of the detector light and, from this, the change in refractive index can be determined. From the change in refractive index, for example, the intensity of the heat wave and/or the pressure wave can be determined, from which in turn, in preferred embodiments, the absorption value can be determined, and from which the concentration of the substance to be detected can be determined. In addition to visible light, the term "detector light" can also refer to infrared or ultraviolet light or another type of electromagnetic wave that can be directed through a light guide structure.

With the help of the exciting beam/rays, energy is emitted into the substance, and depending on the wavelength of the emitted light and the substances present in the substance being analyzed, as well as their resonant vibrations or absorption frequencies, the exciting beams are absorbed in the substance to a greater or lesser extent, the thermal energy released in the form of molecular vibrations. For a wavelength-tunable light source, in addition to being a tunable laser or laser array, it may be another type of light source, such as a broadband light source, from which individual wavelengths can optionally be isolated using filters. It is also possible, for example, to use one or more LEDs emitting in the infrared range, the emission of which can be selected to a narrow range in the desired wavelength ranges. Modulation may also occur in the light source or along the light path.

The heating process follows, in relation to its intensity, the modulation of the excitation beam and generates a heat and/or pressure wave, which propagates in the analyte, among other things, to the measuring surface and further propagates in the measuring element and in the detector device affects the first light guide structure. The measuring element is connected to the substance in the region of the measuring surface, so that a heat and/or pressure wave can be transmitted from the substance to the measuring element. The binding can take place directly through physical contact between the substance and the measuring element, but, for example, also with the intermediate introduction of a suitable solid or fluid, gaseous or liquid medium. Thus, coupling can also take place, for example, when an acoustic pressure wave is emitted from the substance to the measuring element, optionally also at some distance through a gaseous medium. By suitable selection of the medium between the substance and the measuring element, impedance matching can be ensured for the best input into the measuring element.

The excitation beam is preferably emitted into the substance in a region that is either adjacent to or otherwise connected to the measurement surface. The excitation beam can also be directed into a substance directly adjacent to an area of the measurement surface that is associated with or in contact with the substance under test. The excitation beam can furthermore be directed through the volume, through a recess or opening in the measuring element or, in particular, also at least in sections through the material of the measuring element, or also through the outer boundary of the measuring element in the immediate vicinity of the measuring element element. If the measuring element is provided with a recess/hole for the excitation beam, it may extend entirely through the measuring element or be designed as a blind hole, in which case the material of the measuring element or the coating of another material, for example with a thickness of from 0.05 mm to 0 .5 mm, in particular with a thickness of 0.1 mm to 0.3 mm, can be used in the area of the measuring surface.

By exposing the first light guide structure to a heat and/or pressure wave, the refractive index changes at least in portions of the first light guide structure, causing a phase shift in the detector light and resulting in a measurable change in light intensity in at least a portion of the first light guide structure. structures.

To detect such phase shifts, interferometric methods and devices are available, for example.

Accordingly, the invention also relates to the use of an interferometric measuring method or an interferometric measuring device for quantitatively measuring the temperature rise in a material upon passage of a heat and/or pressure wave.

The measuring element may be formed by a support body on which a detector light source and a first light guide structure may be mounted or placed. The detector light source may either be located immediately in front of the entry point of the first light guide structure or may be connected thereto by a light guide. The detector light source may also be integrated directly into the light guide structure in the form of an integrated semiconductor element, for example, on the same substrate as the light guide structure. The light guide can be made in the form of a fiber-optic light guide or an integrated light guide. The measuring element can, for example, also constitute or comprise a substrate on which integrated light guides can be arranged. The material of the measuring element can be made transparent or opaque to the exciting light. A sensing surface may be defined as the outer boundary surface of a sensing element that can be coupled or brought into contact with the substance under test, whereby a heat and/or pressure wave can be transmitted from the substance through the sensing surface to the sensing element.

When arranging the measuring element, it can be provided that the first light guide structure is positioned with respect to the measuring surface in such a way that it is affected by pressure or heat waves, which can be attributed to the absorption of exciting light when the measuring element in the region of the measuring surface is connected to the substance/is located in contact with him.

For example, it can be provided that at least the projection portion of the first light guide structure in the direction of normals to the measuring surface overlaps this measuring surface.

More generally, it can also be provided that at least a portion of the first light guide structure from the measuring surface, in particular from the region of the measuring surface in which the exciting beam passes it, is accessible to the wave in the forward direction.

Preferably, at least one section of the light guide structure, in particular the interferometric element, and also, in particular, at least one interferometer arm of the light guide structure, lies inside an imaginary cone, the axis of which is perpendicular to the measuring surface, and the apex of which lies at a point at which the exciting beam passes through the measuring surface, and which has an opening angle of not more than 90°, preferably not more than 60° and especially preferably not more than 20°. The opening angle means twice the angle between the axis of the cone and the generatrix of the imaginary cone.

In addition, it can be provided that at least a portion of the first light guide structure is spaced at a distance of less than 2 mm, preferably less than 1 mm, more preferably less than 0.5 mm from the measuring surface.

It should be ensured that the first light guide structure is positioned in relation to the measuring surface in such a way that thermal and/or temperature waves, which are caused by the absorption of exciting light in the substance when the measuring element is in contact with the substance in the region of the measuring surface, lead to the measured phase shifting the detector light in at least a portion of the first light guide structure.

The measuring surface may be implemented as a flat surface, but may also have a concave surface or a portion of the surface on which a placed body or object can be well centered or positioned. The measuring surface can then have, for example, the shape of a partially cylindrical channel or the shape of a cup, in particular the shape of a spherical segment, the radius of curvature of which is, for example, from 0.5 cm to 3 cm, in particular from 0.5 cm to 1.5. cm. If the measuring surface is not completely flat, then the surface normal for the measuring surface is the surface normal at the center of a concave recess on the measuring surface or the normal to the flat surface of a body placed on the measuring surface. The normal to the surface can also be the normal to a flat surface, which, overlapping the concave recess of the measuring surface, forms its continuation.

The measuring element can also be coated in the region of the measuring surface with a material that conducts the heat wave and/or pressure wave as losslessly as possible. This material may be, for example, gel-like or solid, and may also be transparent to the exciting beam or have a depression in the area where the exciting beam penetrates the measuring surface. The coating can be, for example, quite thin with a thickness that is less than 1 mm or less than 0.5 mm, or it can be quite thick, with a thickness that is greater than 0.5 mm, in particular greater than 1 mm, in particular more than 2 mm.

The above-mentioned curved outer surface shapes may be formed by a measuring element substrate with a uniformly thick coating applied, or the substrate may have a flat surface, the curved surface being realized by a coating thickness profile.

The first light guide structure may be located on a side of the sensing element opposite the sensing surface or on a surface of the sensing element facing the sensing surface. In this case, the measuring element may form a substrate on the side opposite the measuring surface, or directly below the measuring surface, light guides are deposited, for example by means of epitaxial vapor deposition technology.

The first light guide structure may also be located within the sensing element or substrate and surrounded on all sides by the sensing element/substrate material to provide, for example, good supply and good dissipation of heat or pressure waves. In this case, the first light guide structure can be “enclosed” within a substrate by a known production method, that is, it is coated on all sides with a different material, which in particular has a different refractive index than the light guide of the first light guide structure. If the light guide itself is made of silicon, it can, for example, be coated with silicon oxide. The substrate/measuring element may also consist entirely or partially of silicon. It is also possible to make integrated light guides from plastic, for example from polyethylene or from an optically transparent crystalline material. The first light guide structure may, for example, be located parallel to the measuring surface and/or located in a plane parallel to the measuring surface. In principle, integrated light guides can be designed as so-called strip or slot light guides, that is, as strips of material along which light waves are directed, or as suitablely shaped passage spaces (slots) between fully reflective boundaries formed from a specific boundary material .

In the case of a device of the type described, a modulation device may be provided for modulating the intensity of the excitation beam.

The modulation device may control the intensity of the excitation beam by mechanical interlocking (mechanical chopper) or by an adjustable diaphragm or deflecting mirror device or adjustable transmittance body/layer. In addition, modulation can also be achieved directly by controlling the excitation light source/laser light source, or by using a diaphragm or electronic intensity control that completely or partially blocks or deflects the excitation beam on its path from the excitation light source/laser device to the test substance. This can also be accomplished using an interferometric device or an electronically controlled piezocrystal or liquid crystal or other electronically controlled device that changes the transparency or reflectivity with respect to the excitation light beam. Such a device may be implemented as an integral part of the laser device or as a functional element that is functionally integrated into the measuring element/substrate. This is possible because, when the substrate is formed, three-dimensional functional structures of integrated optics and electronics can be formed using one or more layers. MEMS structures (microelectromechanical structures) can thus also be integrated into a substrate, for example to create a controllable deflection mirror for light modulation.

One possible aspect of the method presented here is to focus the measurement of the response signal at selected depth locations below (distance intervals from) the surface of the material. The variable d has the greatest influence on the range of depths measured by this method. It is defined as d = √ (D / (π * f)), where D is the coefficient of thermal diffusivity of the sample (here, for example, skin), f is the modulation frequency of the exciting beam. For more information on skin thermal diffusivity, see the following publications:

- 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.

It should be noted that the same term “response signal” is used in this disclosure in several senses. On the one hand, it can denote a physical response to excitation by an exciting beam, such as a sound wave, heat, and the like. On the other hand, it can also refer to an optical or electrical signal that reflects this physical response, such as the intensity of a detector light (as an example of an optical signal), or a measured intensity value that refers to electrical signals. For simplicity and consistency, the same term “response signal” is always used, and it is clear from the context without further explanation whether it is a physical response (for example, a pressure wave or a temperature wave), a physical consequence of this physical response (for example, a phase shift detector light) or an associated measured signal (for example, the intensity of the detector light measured by a photosensor).

To eliminate response signals from the uppermost layers of matter to improve the quality of the measurement, in one embodiment, changes in measured values compared to previous measurements can be used if the measured values in the uppermost layers change less or more slowly compared to other, deeper layers. This may apply, in one embodiment, to measurements on human skin, where the uppermost layers of the skin are substantially not exchanged with the lower layers, and therefore the physiological parameters are substantially unchanged. The time derivative of the measured response signal values can be used to exclude signals from the uppermost layers of the skin. Thus, measurement, or at least assessment, may be limited to or focused on the interstitial fluid in the skin.

For this purpose, the measurement may involve recording response signals for spectra that are determined several times at different modulation frequencies of the excitation light source, the results for different modulation frequencies being related to each other, for example by forming a difference or quotient of the measured response signal values for identical wavelengths and different modulation frequencies. To carry out such a measurement, a device must also be provided with a corresponding control device for the excitation beam and an evaluation device for the response signal spectra.

A measuring device may also be provided for directly or indirectly determining the light intensity in the first light guide structure, in particular in a region in which the light intensity is dependent on a phase shift of the detector light in at least a portion of the first light guide structure due to a change in temperature or pressure. The measuring device may directly measure the intensity of light in the first light guide structure or the intensity of a detector light component emitted at the connection point. The measuring device may comprise a photosensitive semiconductor element, such as, for example, a photodiode, embedded in the substrate. In this way, the light intensity can be directly measured. Indirect measurement methods can be provided, for example, by measuring other parameters, such as temperature or field strength, on the first light guide structure.

In addition, it can be provided that the detector device has an interferometric device, in particular an interferometer and/or a resonant light guide element, in particular a resonant ring or a resonant plate.

An interferometer can be used as an interferometric device, in particular a Mach-Zehnder interferometer, in which the detector light is divided by a beam splitter into two partial beams that pass through two separate arms of the interferometer. Both arms of the interferometer are exposed to varying degrees by the temperature and/or pressure wave, with the measuring arm being more susceptible to the influence of the temperature and/or pressure wave than the reference arm, or the influence of the temperature and/or pressure wave in relation to the change in the refractive index of the measuring arm. shoulder is stronger than that of the supporting shoulder. In the optimal case, the reference arm is not at all affected by the temperature and/or pressure wave, while the measuring arm is fully affected.

In addition to directly measuring the light intensity in the embodiments described above, the intensity of the detector light can also be measured indirectly by another parameter such as temperature or field strength, provided that the measured parameter depends on the light intensity.

To ensure that the measuring arm is more susceptible to the influence of temperature and/or pressure waves, it can be provided, for example, that at least a portion of the projection of the measuring arm of the first light guide structure in the direction normal to the measuring surface overlaps with this measuring surface.

In addition, for high measuring efficiency, it can be provided that at least a portion of the measuring arm of the first light guide structure is spaced from the measuring surface by less than 2 mm, preferably less than 1 mm, more preferably less than 0.5 mm. The support arm may be further from the measuring surface than the measuring arm, as described in more detail elsewhere herein.

It should also be ensured that the measuring arm of the first light guide structure is positioned with respect to the measuring surface in such a way that heat and/or temperature waves, which are caused by the absorption of exciting light in the substance when the measuring element in the region of the measuring surface is in contact with the substance, cause to a measurable phase shift of the detector light in at least a portion of the measurement arm of the first light guide structure. The measuring arm and/or the reference arm of the interferometer may preferably be oriented parallel to the measuring surface and/or extend in a plane parallel to the measuring surface.

The light from both arms is recombined after passing through said arms, and depending on the phase shift of the detector light in the arm that is more affected, the two mutually phase-shifted partial beams of the detector light are at least partially canceled out. The measured light intensity in this case is minimal unless the phase shift exceeds 180 degrees and, in extreme cases, goes through several complete cycles of 360 degrees each (2 Pi). In this case, as the temperature and/or pressure rise develops, the zero crossings in the phase cancellation of the two partial beams can also be counted to determine the absolute phase shift. However, in many cases the phase shift does not exceed 180 degrees due to the low detectable effects of temperature and/or pressure. The operating point of the interferometer can then be adjusted so that the resulting changes in light intensity monotonically reproduce the changes in pressure/temperature.

The following measures can ensure that the measuring arm is more susceptible to the temperature and/or pressure wave than the reference arm, or that the effect of the temperature and/or pressure wave on the change in refractive index is stronger for the measuring arm than for the reference arm:

The measuring arm, with or without a resonant ring built into it or associated with it, is in mechanical contact with the substrate. The light guide of the measuring arm can be connected to the substrate with a positive connection and/or in a permanent manner and/or with a force connection. It can also be pressed against the substrate or connected to it by clamping means.

If the interferometric device contains only one or more resonant rings or other resonant light guide elements, these may also be in mechanical contact with the substrate. The light guide(s) of the resonant ring(s) or resonant elements may also be connected to the substrate in a form-fitted and/or permanently and/or force-fitted manner. They can also be pressed against the substrate or connected to it by clamping means.

The interferometer or one or both of its measurement arms, as well as one or more resonant rings or other resonant elements, can be integrated into the substrate through a manufacturing process and, for example, manufactured integrally with it in a single manufacturing process.

The reduced influence of the temperature wave and/or the pressure wave on the reference arm or the reduced influence on the refractive index of the light guide(s) or the optical path of light in the support arm can be realized, among other things, due to the fact that at least part of the light guide or all of the light guide of the reference The arm consists of a fiber-optic light guide, in which case the fiber-optic light guide is formed in sections either for the majority of its length or completely outside the substrate, in particular at a distance from it. The optical fiber may also extend outside the substrate material, for example, in a recess in the substrate, without connecting to the substrate material.

Also, at least a portion of the support arm may extend separately from the sensing arm through the second substrate, on the second substrate, or in or on a portion of the substrate that is at least portions separated or shielded or spaced away from the substrate.

In this case, the support arm or second substrate or partial substrate may be separated from the substrate at least in portions by an air gap or barrier. The barrier is considered to be a substance that is softer or less rigid than the substrate material and consists of, for example, plastic, elastomer, organic material, fabric, paper or foam.

In any case, for example, at least 10%, in particular at least 20%, more preferably at least 30% of the optical length of the reference arm can be located in the area of the same substrate as the measuring arm, or an additional substrate, which is at a distance of at least 2 mm from the measuring arm, in particular at least 5 mm, further in particular at least 8 mm. In this case, this region of the support arm can preferably be further removed from the measuring surface than the measuring arm. Said portion of the reference arm may preferably lie in a region that is not reached by the heat and/or pressure wave, or is at least less influenced than the region in which the measuring arm is located.

If the measurement arm and the reference arm are at least partially composed of different materials, a beam splitter may be provided to separate the detection light into the measurement arm and the reference arm. This beam splitter may be built into the substrate or provided separately from it. The beam splitter may be configured such that it distributes the detector light to an integrated light guide and a fiber optic light guide, or to two integrated light guides, or to two fiber optic light guides.

Regardless of the location and distance between the measuring arm and the reference arm, the measuring arm and the reference arm can at least partially or completely consist of different materials, the material of the support arm being selected so that its refractive index when exposed to a heat and/or pressure wave will be less influence than the refractive index of the measuring arm material. This can be achieved, for example, by selecting different base materials for the measuring arm and the reference arm, or by doping the same base material differently in the measuring and reference arms. It can also be provided that the detection light passes through at least part of the length of the support arm through a liquid, in particular a gas, for example air or nitrogen, or a transparent liquid.

If a resonant ring or other resonant element of a light guide is used as a detector device, then they can be located in a plane parallel to the measuring surface. Thus, all areas of the resonant ring are exposed as uniformly as possible to the temperature and/or pressure wave incident from the measuring surface onto the resonant ring. If a resonant ring or other resonant element is used as the detector device, either solely or in combination with an interferometer, instead of a single resonant ring or resonant element, a plurality of resonant rings or resonant elements can be used, optically connected in series or in parallel, to shape the frequency response as desired. . One or more operating points can be set by temperature control or by applying mechanical pressure to the resonant rings/resonant elements. The operating point can be set to provide maximum temperature or pressure sensitivity or maximum measurement range with a monotonic relationship between temperature or pressure and light intensity in the resonant ring/resonant element.

The substance analysis device may include an evaluation device that evaluates the change in the intensity of the detection light detected by the detector device and based on this determines the amount of absorption as a function of the wavelengths of the excitation beam, furthermore, due to modulation of the excitation beam, the intensity of the detection light can be detected taking into account and without the influence of the measured heat wave and/or pressure, and its difference or behavior or other dependent characteristic between these values can be estimated.

The evaluation device, in particular if a resonant light guide element or an interferometer with two measuring arms with measuring sections that are located and oriented relative to the measuring surface in such a way that the heat and/or pressure wave reaches them one after the other is provided as an interferometric element, can be configured in such a way that a change in the intensity of the detector light is detected, i.e. changing the mismatch of the resonant element by changing the refractive index, or changing the phase shift in two measuring sections/measuring arms of the interferometer during the passage of a heat and/or pressure wave, or one or more wave fronts.

In particular, when using an interferometer with multiple measurement sections, if both are exposed to a heat wave and/or wave, the phase shifts can cancel each other out so that no change in the intensity of the detector light can be observed. However, if the measuring arms/measuring sections are positioned/orientated in such a way that they are reached by the wave one behind the other, the result is a detector light intensity profile which reflects the different and time-shifted effect of the wave on the different measuring sections and thus ensures possibility of evaluation, since time intervals are provided when the wave acts differently on different measuring sections.

In the case of resonant elements of the light guide, a time profile of changes in the intensity of the detector light arises, which reflects the amplitude of the transmitted wave.

In the case of a modulated excitation beam and its corresponding passing heat and/or pressure waves, a suitable parameter, for example the amplitude of the periodic change in intensity of the detector light, can be used for evaluation.

In addition, it can be provided that the light guide structure, in particular the interferometric device of the first light guide structure, has at least one glass fiber light guide, which is rigidly connected to the measuring element at least in sections.

Fiberglass light guide is available at low cost and, thanks to its flexibility, can be easily adapted to existing needs. However, it must be in contact with the measuring element to be affected by the pressure and/or heat wave. For this purpose, the light guide can be glued to the substrate/measuring element or connected to it with a geometric or force-lock. For example, the glass fiber light guide may be secured in a substrate clamping device.

It can also be provided that the light guide of the first light guide structure, in particular the interferometric device of the first light guide structure, is integrated into the substrate of the measuring element or is connected to the substrate, wherein the first light guide structure in particular has at least one silicon light guide, which is connected with an insulating substrate or integrated into an insulating substrate, in particular the silicon light guide is at least partially coated with a dielectric, in particular silicon oxide, for example SiO ₂ .

In this case, the first light guide structure can be built on the substrate using known means of integrated optics, and regions with different refractive indices can be obtained, for example, by selectively doping the substrate material or by forming oxide layers or other layers from reaction products. Such integrated light guide structures may be provided within or on a silicon wafer. The light guide structure can also be formed in a polymer body. In addition, integrated light guides can be used, for example those obtained using combinations of GeO ₂ -SiO ₂ /SiO ₂ , GaAsInP/InP materials. Ti: _LiNbO3 .

In addition, it can be provided that the exciting beam passes into the material of the measuring element, in particular in the region of the measuring surface of the measuring element or in the region adjacent to the measuring surface, or in the region directly adjacent to the measuring surface, wherein the measuring element or region, through which the exciting beam passes through is transparent to the exciting beam.

Transparency of the measuring element and, in particular, also of the coating of the measuring element must be ensured in the wavelength range of the exciting beam or exciting light. Transparency also cannot be set to full, so some absorption of the exciting beam is allowed. The layer of the measuring element through which the exciting beam passes can be made as thin as possible, for example less than 1 mm, for example only as a thin layer in the region of the measuring surface.

It can also be provided that the excitation beam is directed inside the measuring element or onto the measuring element via a second light guide structure. The second light guide structure is configured in such a way that it can guide light or radiation in the wavelength range of the exciting beam with the minimum possible losses. The exciting beam is introduced into the light guide of the second light guide structure, removed from it in the area of the measuring surface and directed to the substance under study. In this case, a beam-forming optical element, in particular a focusing or collimating element, which is separate from or integrated into the light guide structure, can be provided at the input and/or output position. The first and second light guide structures may be provided separately and at some distance from each other. However, due to the linearity of the wave equation, they can also overlap without interaction, so that there are regions in the light guide structure(s) through which both the excitation beam and the detection light pass. In an extreme case, the first and second light guide structures may be identical and have the necessary entry and exit points for the excitation light and the detection light. It is also assumed that the effect of changes in pressure and/or temperature in the light guide structure on the excitation light is detected and taken into account in the evaluation. The laser device for generating the excitation beam may be integrated into the measuring element, and at least one or more or all of the electronic elements of the laser device may be placed on a substrate of the measuring element, in particular on the same substrate that also carries the integrated optical elements. The laser device's electrical elements and integrated optical elements may be fabricated or placed on one or more interconnected substrates in a common manufacturing process and/or in multiple sequential manufacturing processes. This results in an extremely compact design. Such an integrated arrangement can be provided both in the case where there is a second light guide structure for guiding the excitation beam and in the case where the excitation beam is directed through a recess in the measuring element onto the test substance.

It can also be provided that the excitation beam passes through a continuous recess of the measuring element between the laser device and the analyte, the recess ending in particular at a certain distance in front of the measuring surface or passing through the measuring surface or located in a region which is immediately adjacent to the measuring surface and/or borders it.

In this case, the excitation beam propagates in the recess and in some cases exits the recess on the analyte side of the measuring element without passing through the material of the measuring element. A thin layer of the measuring element can also remain in the area of the measuring surface, so that the recess does not go through and ends at some distance in front of the measuring surface. It is important that the volume of the substance into which the exciting beam is emitted adjoins the measuring surface and is in contact with it or is connected to it in some other suitable way, so that the generated temperature and/or heat wave at least partially affects the measuring surface. surface and was directed through it into the measuring element or to the detector device.

A continuous or substantially continuous recess in the measuring element may form a straight channel, but it may also form a channel with bends or kinks, in which case the excitation beam may be directed through the channel by means of deflecting or reflecting elements. The notch may extend through the coating on the measuring element, but it may also terminate in the coating so that the excitation beam passes through the coating.

If the exciting beam passes at least through a certain layer of the measuring element, then if the material of the measuring element at least partially absorbs the exciting beam, the exciting beam can already cause an increase in the temperature of the measuring element, which, however, can be accurately calculated. Periodic operation of the excitation light source generates thermal waves in the measuring element, which in some cases reach the detector device and can be detected by it. This influence can be calculated and subtracted from the desired signal.

It can also be provided that the exciting beam is directed directly along the outer boundary of the measuring element to the substance to be analyzed and penetrates into the substance at an extension of the measuring surface next to the measuring element. A first light guide structure of the detector device, for example an interferometer, may then be provided in the measuring element immediately adjacent to the region in which the exciting beam penetrates an imaginary extension of the measuring surface, so that at that location the heat and/or pressure wave emerging from the substance is at least at least partially enters the measuring element and reaches the first light guide structure.

Another embodiment may provide that the measuring element is made in the form of a flat body, in particular, in the form of a plane-parallel body in the form of a plate, in particular, the thickness of the measuring element in the direction perpendicular to the measuring surface is less than 50% of the shortest extent of the measuring element in the direction passing in the measuring surface, in particular less than 25%, further, in particular less than 10%.

This design may result from the use of a flat substrate, such as a wafer, for integrated optics. The required thickness of the measuring element is then limited by the space required for the detector device.

In another embodiment, it can be provided that the measuring element has or carries a mirror device for reflecting the excitation beam emitted by the laser device onto the measuring surface.

It is particularly important that the laser device is oriented in such a way that the excitation beam in the laser device is not generated perpendicular to the measuring surface, for example if the laser device is to be mounted next to the measuring element or at an angle to save space.

It can also be provided that the exciting beam is directed in the measuring element parallel to the measuring surface or at an angle to it of less than 30 degrees, in particular less than 20 degrees, and also in particular less than 10 degrees or less than 5 degrees, and that the exciting beam deflected or directed in the direction of the measuring surface, the exciting beam passing in particular through the measuring surface or through an imaginary extension of the measuring surface in the region of a continuous recess in the measuring element.

In this case, the laser device for generating the excitation beam can be arranged particularly compactly and oriented so that it generates or emits the excitation beam parallel to the measuring surface or at one of the above-mentioned planar angles relative to the measuring surface.

In addition, it can be provided that in the measuring element, when viewed from the side of the measuring surface, behind and/or next to the detector device, in particular adjacent to it or in thermal contact with it, at least one coolant in the form of a solid body or material, wherein the specific heat capacity and/or specific thermal conductivity of said body or coolant material is greater than the specific heat capacity and/or specific thermal conductivity of the material of the detector device and/or the light guide structure and/or the substrate of the light guide structure and/or other materials of which consists of a measuring element.

In principle, it may be advantageous to provide a cooler inside or on the measuring element in order to remove as quickly as possible the heat that is introduced into the detector device by the thermal wave, so that even at high modulation frequencies of the excitation beam, a thermal energy equilibrium or temperature equilibrium occurs, which allows measurements to be made periodically and briefly emitted amounts of heat or resulting temperature changes, without the measurements being distorted by previous temperature changes.

In some applications, particularly interferometric applications, particularly the Mach-Zehnder interferometer, it is also advantageous to expose one measurement arm to changes in temperature or pressure waves and protect the other arm, the reference arm, from changes in temperature or pressure waves. For this purpose, it may also be useful to distance the reference arm from the measurement arm and/or provide a barrier that at least partially prevents the heat and/or pressure wave from affecting a portion of the detector device, in particular the interferometer reference arm. Such a barrier may, for example, consist of a material that has a lower thermal conductivity than the material of the measuring element or the substrate of the measuring element. For mechanical decoupling from the pressure wave, the material may also be more flexible or elastic, or more easily deformable, than the material of the measuring element or the measuring element substrate. The barrier can also be formed, for example, by a gas gap that can be introduced into the substrate, for example by etching or material removal processing, or by an additive manufacturing process.

To distance the reference arm of the Mach-Zehnder interferometer from the measuring arm, it can also be provided that the measuring arm and the reference arm are located in different planes of the substrate, and the plane in which the reference arm is located is located at a greater distance from the measuring surface than the plane in which the measuring arm is located.

Changes in temperature and/or pressure can also be detected by a resonant light guide ring in which detector light propagates in resonance under suitable conditions. If temperature and/or pressure conditions change, the resonance is detuned by a change in refractive index and partial damping or cancellation occurs. Such a resonant ring has a sensitivity that is ideally much higher than that of a Mach-Zehnder interferometer. Such a resonant ring can also be built into an arm, preferably the measuring arm of a Mach-Zehnder interferometer.

In one embodiment of the invention, it can also be provided that the light guide structure of the detector device has at least two measuring sections, which are located in particular in different arms of the interferometer and in which the refractive index changes depending on the pressure and/or temperature change, in in particular, pressure and/or heat waves, such that there is a phase shift of the detector light passing through the measuring sections and, as a consequence, a change in the intensity of the detector light occurs in the next section depending on changes in pressure and/or temperature, both measuring sections being located in the measuring element in such a way that a pressure wave and/or a heat wave passes through them one after the other in time, in particular in time-shifted periods or with a time interval, which from the measuring surface, in particular from the area of the measuring surface, in which an exciting beam passes through it and propagates in the measuring element.

A pressure and/or heat wave that propagates through the measuring element, starting from the area of the measuring surface into which the exciting beam penetrates, then first reaches the first of the measuring areas and temporarily changes the refractive index there during its passage. In the time interval during which this changed refractive index operates, a first phase shift is generated with respect to the detection light that passes through the second measurement section (the detection light passes through both measurement sections in parallel). This phase shift can be detected by measuring the intensity of the detector light as described above. Then the wave reaches the second measuring section and exerts its effect there, changing the refractive index in it over a certain period of time. If two time intervals overlap, the phase shifts for the overlapping time interval are at least partially canceled out. Then, if the phase shift occurs only in the second measurement section, the effect of changing the intensity of the detector light occurs again. This time course can be recorded by the evaluation device, and from it the change in the refractive index in the first measuring section and in the second measuring section can be determined. A certain change in the refractive index can be associated with a change in temperature and/or pressure, which is a measure of the strength of absorption of the exciting beam in the analyte. The aforementioned measuring sections with their longitudinal axes of the light guide preferably extend transversely, in particular perpendicular to the direction of propagation of the pressure and/or temperature wave in the measuring element, and then, in particular, one after the other when viewed from the side of the measuring surface into which the exciting beam penetrates .

Also preferably, an evaluation device is provided which, based on a change in the intensity of the detector light in the light guide structure, determines the amount of change in the phase shift of the detector light in the measurement section and, based on this, the change in the refractive index. From this change in the refractive index, the change in pressure and/or temperature in the measuring sections, as well as the amount of absorption of the exciting beam in the analyzed substance, can be determined.

The invention also relates to a sensor which can be used, for example, in a device of the type described above, with a measuring element which has a measuring surface and, in the region of the measuring surface for measuring a temperature wave and/or a pressure wave, is at least partially connected to a substance, in particular, brought into contact,

and with a detector device which is at least partially integrated into or connected to the measuring element and which includes the following:

a source of coherent detector light, and

a first light guide structure that can be coupled or coupled to a detector light source and that directs the detector light, wherein the refractive index of said first light guide structure is, at least in portions, dependent on temperature and/or pressure,

at least one region in which the light intensity depends on the phase shift of the detector light in at least a portion of the first light guide structure due to a change in temperature or pressure, wherein the first light guide structure comprises an interferometric device, in particular an interferometer and/or a light guide resonant ring or another resonant element of the light guide, as well as

a measuring device for determining the intensity of light in or on an interferometric device.

All features of the temperature sensor of the claimed analysis device mentioned in this application can also be used to implement a sensor, separate from the analysis device, for other purposes, in particular, for all described arrangements, configurations, choice of materials, embodiments and shaping of the aligned optical resonance ring or measuring arm and reference arm of the interferometer.

With this sensor it is possible to measure changes in temperature or also pressure waves, which can be recorded using changes in the refractive index. In addition to the purposes explained above, the sensor can thus also be used, for example, for vibration measurements, for example seismic measurements or mechanical impulse measurements. Due to its short response time, the sensor is suitable for measurements where other sensors, such as MEMS sensors, cannot be used due to their inertia.

In addition to a device of the type described above, the present invention also relates to a method for controlling such a device, in which a modulated excitation beam, in particular through a measuring element, is directed at the substance to be analyzed, whereby a light intensity profile or periodic a change in light intensity, which is detected for a plurality of wavelengths of the excitation beam by measuring the change in light intensity in the first light guide structure or by measuring the light intensity from the first light guide structure, and an absorption spectrum of the analyte is obtained from the recorded data.

The method can also provide that the measurement is carried out for different modulation frequencies of the excitation beam, and a corrected absorption spectrum is determined from a combination of the obtained absorption spectra. In this way, it is possible to determine the depth profile of the analyte concentration in the test substance or reduce or eliminate the negative effects from certain depth ranges using mathematical referencing.

In principle, the invention also includes a method for analyzing a substance, in particular using a device of the type described above, wherein the method

- at least one intensity-modulated electromagnetic excitation beam with at least one excitation wavelength is generated by a transmitting excitation device, the transmitting excitation device emitting at least one electromagnetic excitation beam into a volume of the substance that is located below the surface of the substance,

- a response signal in the form of light intensity in the first light guide structure is detected by the detector device, and

- the substance is analyzed on the basis of the detected response signal, wherein the response signals, in particular the time curves of the response signals, are determined for different wavelengths of the exciting beam, and information about the depth profile below the surface of the substance to be analyzed is determined by the nature of the attenuation of the responses after the end of the modulation phase, in which the exciting beam has a high intensity, and the exciting beam is absorbed and a heat and/or pressure wave is generated.

It may also be provided that

- a plurality of response signal curves are determined one after another using different modulation frequencies of the transmitting drive device, and

- multiple response signal curves with different modulation frequencies are connected to each other, and at the same time

- in particular, they provide information relating to the deep region below the surface of the material.

Using a detector device, especially in the case of detecting a change in pressure, a response signal in the form of a sound wave can be detected, which is generated when the exciting beam is absorbed in the analyte and propagates at a known speed (in human tissue approx. 1500 m/s) to the measuring surface and detector area. Using an evaluation device that is connected to a modulation device for the excitation beam, thanks to the good time resolution of the measurement, it is possible to measure the phase shift between the modulation of the excitation beam and the response signal, and thus the depth of the tissue in which the absorption has taken place. Since signals are often a superposition of different response signals from different layers of tissue, interpretation of the signals can occur by creating a model with many absorption points distributed at different depths of the substance, and assigning values to them the value of absorption, as well as the time to reach the surface of the material, with the value of absorption are correlated with the time curve of the response signal, and the response signal curve can be reconstructed. From this, it is possible to determine the magnitude of absorption and thus the local concentrations of components that should be found in the substance.

Alternatively or additionally, different measurements can be performed at different modulation frequencies, and the response signals can be associated with different modulation frequencies, in particular to extract and eliminate signals from the upper layers of tissue, since they are particularly prone to errors due to contamination and dead skin cells .

The above-mentioned device can also be advantageously combined

- with at least one additional detector device, which is located next to the measuring surface and/or directly adjacent to it, wherein the additional detector device has a contact device with at least 2 electrodes for detecting piezoelectric signals, which are located opposite each other on different sides of the detector area. In this case, a material is placed in the detector area that changes its electrical resistance or generates an electrical signal depending on changes in temperature and/or pressure, in particular due to the piezoelectric effect.

With this additional detector device, for example, it is alternatively possible to measure temperature or pressure, this measurement being used as a reference measurement for ambient temperature or ambient pressure, as well as for measuring a heat wave and/or a temperature wave emitted by a substance, subject to analysis in order to relate the measured values obtained using the detector device with the measured values of the additional detector device.

The invention will now be explained based on the figures in the drawings and the following detailed description.

Shown:

FIG. 1 is a schematic side view of a measuring element with a laser device and a detector device.

Figure 2 is a side view of the measuring element,

Figure 3 is a side view of another measuring element.

FIG. 4 is a top view of the first light guide structure on the measuring element.

FIG. 5 is a top view of another embodiment of a first light guide structure on a measuring element.

Figure 6 is a cross-section of a substrate with integrated light guides.

FIGS. 6a-6i illustrate various embodiments of one or more interferometric device substrates, with sensing element shading shown in some views and omitted in other views for clarity.

FIG. 6k illustrates an embodiment with an interferometric device in which the time profile of the phase shift/refractive index change can be recorded as a function of the passage of various measurement sections by a pressure and/or heat wave.

FIG. 6l shows the time profile of the phase shift of the detector light in the measurement sections during the passage of a pressure and/or heat wave.

FIG. 6m shows the path of the excitation beam past the outer boundary surface of the measuring element into the substance and the position of the interferometric device.

FIG. 6n shows a measuring element with an acoustic coupling element for communication with the analyte.

Fig. 7 is a cross-section of an additional substrate with integrated light guides.

Fig. 8 is a cross-section of the substrate with glued light guides.

Fig. 9 is a cross-sectional view of a substrate with a through hole for the exciting beam.

Fig. 10 is a cross-sectional view of the substrate with an additional through hole for the exciting beam.

FIG. 11 is a sectional view of a substrate with a second light guide structure for the excitation beam.

FIG. 12 is a cross-sectional view of a substrate with an additional implementation of a second light guide structure for the excitation beam.

Fig. 13 is a schematic view of a device for analyzing a substance with a device for processing measurement results and signal output devices.

FIGS. 14-16 show a structure with a substrate to which an excitation light source and a detection light source are connected, as well as a detector, and into which an additional substrate with built-in optical elements can be inserted;

Fig. 17 is a cross-section of a measuring element with a first integrated lens and finger located on the measuring surface.

FIG. 18 is a cross-section of a measuring element with a second integrated lens.

FIG. 19 is a cross-section of a measuring element with a third integrated lens.

FIG. 20 is a cross-section of a measuring element with a first integrated lens and an exciting beam.

FIG. 21 is a cross-section of a measuring element with a second integrated lens and an exciting beam.

FIG. 22 is a cross-section of the measuring element with the third integrated lens and excitation beam, and

FIGS. 23, 24, 25 show several devices with a measuring element and an excitation light source in the form of a laser light source or an excitation beam source, in particular a laser device, wherein the excitation light is directed through the measuring element to the measuring surface by means of a light guide which is integrated into the substrate of the measuring element.

Figure 1 shows a sectional view of the measuring element 1, the internal structure of which is not shown in detail in this drawing. The first light guide structure 6, into which coherent detection light is emitted by the detection light source 5, is schematically shown inside the measuring element 1. The measuring device 7 is used to determine the light intensity in the first light guide structure 6, which depends on the pressure or temperature acting on the light guide structure 6.

The detection light source 5 may be in the form of a laser or a laser diode and may be placed or mounted on the measuring element 1. The detection light source 5 may also be connected to the first light guide structure 6 in a flexible manner using a glass fiber light guide. In addition, the detector light source 5 can be integrated as a semiconductor element into a substrate (not shown here) inside the measuring element 1 and connected there to the first light guide structure.

The measuring device 7 may also be connected to the first light guide structure 6 directly by a connector, or connected thereto by an integrated light guide or a flexible glass fiber light guide (not shown here). However, the measuring device 7 can also be integrated into the measuring element and implemented on the substrate of the measuring element 1 as a semiconductor element. The measuring device 7 can be made, for example, in the form of a photosensitive semiconductor element, for example, in the form of a photodiode.

In addition to the mentioned components, a temperature measuring device can also be provided for measuring the absolute temperature of the measuring element 1, in order to take into account when evaluating the measurements the average temperature measured over longer time intervals, for example one tenth of a second, half a second, one or more seconds, depending on the time constant of other sensors. In this way, for example, the temperature dependence of a photodiode or other semiconductor photosensitive element can be corrected. This can be useful, for example, in assessing the light intensity measured by the measuring device 7, which can be improved by temperature correction. As an alternative to this, a temperature stabilization device 29 can also be provided, which contains a heating or cooling element and which maintains a constant temperature of the measuring element 1. This temperature can, for example, correspond to the average ambient temperature, which can be set, for example, at 20 °C, but it may also correspond to the average body temperature of the patient whose bodily tissue or bodily fluid is to be measured, and which therefore, for example, may correspond to a temperature of about 37°C or 30° (exposed skin surface).

Figure 1 shows a laser device 4, which can be implemented as a quantum cascade laser or as a laser array. The quantum cascade laser can be designed in such a way that it can be at least partially tunable in wavelength, in particular in the infrared range, and also, in particular, in the mid-infrared range. If the laser device 4 is made in the form of a laser array, then the individual laser elements of the array can be tuned, adjusted or fixed to specific wavelengths. The wavelengths of the individual laser elements can be set, for example, so that they correspond to the wavelengths of the absorption maxima of the substance that is to be detected in the analyte, that is, for example, to the absorption maxima of glucose. For measuring the blood sugar level mentioned as an example, the wavelength of the excitation rays can be preferably selected so that the excitation rays are largely absorbed by glucose or blood sugar. For the measurement of glucose or blood sugar, the following glucose-relevant infrared wavelengths (vacuum wavelengths) are particularly suitable and can be set individually or in groups simultaneously or alternately as fixed wavelengths for measuring response signals: 8.1 µm , 8.3 µm, 8.5 µm, 8.8 µm, 9.2 µm, 9.4 µm and 9.7 µm. Additionally, glucose-tolerant wavelengths, which are not absorbed by glucose, can be used to identify other substances present and eliminate their influence on the measurement.

Since other substances, for example biological or chemical substances, can also be detected and analyzed using the device, it is also possible in this case to take into account the absorption maxima of the substances to be detected. The number of transmission elements in a laser array can be, for example, from 10 to 20 or from 10 to 30 elements, as well as more than 30 transmission elements.

The laser device 4, which can also be called an excitation beam generation device or an excitation beam transmission device, has a modulation device 8 that generates a modulated laser beam. In this case, the modulation device 8 can be placed, for example, in the control system of the laser device 4. The modulation frequency can, for example, be from 100 Hz to several megahertz or even several hundred megahertz. It is important here that the first light guide structure 6 has a suitable response time and can respond to intensity modulated pressure waves or thermal waves that arrive in accordance with the modulation frequency. This is the case when interferometric detector devices are used, described in more detail below.

Light from the laser device 4 exits in the form of an excitation beam 10 through the measuring surface 2, which is shown as the lower outer surface of the measuring element 1, into the region designated D, and in which the analyte 3 comes into contact with the measuring surface 2. After absorption of the beam 10 exciting light by the substance 3, the temperature and/or pressure wave 21 passes from the substance to the measuring element 1 and reaches the first light guide structure 6. The change in temperature and/or pressure causes a change in the intensity of the detector light in it, which is detected by the measuring device 7 and transmitted to the device 23 processing. The processing device 23 may have a lock-in amplifier that amplifies the signals synchronously with the modulation of the excitation beam 10.

Optionally, the measuring element 1 in the region of the measuring surface 2 can be provided with a coating 22, onto which the analyte 3 can be directly applied. This can be useful for protecting the substrate material provided in the measuring element 1, or for providing mechanical and/or thermal coupling substance 3 with the first light guide structure 6. The coating material 22 must be made in such a way that it conducts pressure and heat waves well. In addition, it can be chosen to be transparent to the excitation beam 10. A coating layer 22, in principle, can also be provided between the first light guide structure 6 and the analyte, for example provided on the surface of the first light guide structure 6, can also serve to provide direct interaction radiation in the first light guide structure 6 or at least prevent the attenuated portion of this radiation outside the actual light guide structure 6 from interacting with a substance deposited on the measuring surface 2, since such contact may have a reverse effect on the radiation in the first light guide structure 6.

An acoustic coupling between the measuring element and the substance being analyzed can also be provided, in which the measuring element perceives waves generated in the substance by means of a medium placed between it and the substance. The medium can be implemented as a fluid, that is, gaseous or liquid, so that a distance can be provided between the measuring element and the substance, for example in the form of a cavity or recess in the measuring element. The opening of the cavity can then be pressed against the substance so that the wave can pass through said cavity into the measuring element. The wall of the cavity, that is, the outer surface of the measuring element, can be coated with a material that provides good acoustic coupling, that is, impedance matching. Such acoustic coupling is shown and explained in more detail below with reference to FIG. 6n.

Figure 2 shows in a side view that the measuring element 1 may have a groove 24, which is covered with a coating 22. The groove 24 is designed to contact the measuring surface 2 in this area with the analyte 3. This allows the user to orient himself. In addition, when a body part, such as a fingertip, is applied to the measuring surface 2, this groove provides mechanical stabilization.

As an alternative embodiment shown in FIG. 3, the groove 24 is formed solely by an area in which the coating 22 has been reduced in thickness. Thus, for example, the substrate 1a provided inside the measuring element 1 can be used as a flat, plane-parallel body without machining.

Figure 4 shows a top view of a substrate 1a, which may be part of the measuring element 1. The substrate 1a is made in the form of a smooth, plane-parallel body, for example made of silicon, in particular in the form of a plate, which can be thinner than 1 mm. However, a multilayer structure (sandwich structure) can also be provided as the substrate, which has a plurality of wafer layers or a thicker wafer with one or more recesses, in particular etched areas. The light guide structure 6 in the form of an interferometer is deposited on or inside the substrate 1a. This can be achieved, for example, by first coating a silicon wafer with a layer of silicon oxide and applying a silicon light guide to it. They, in turn, can be coated with a layer of silicon oxide.

The substrate 1a can then be completely coated on one or both sides with a protective or functional layer, which, for example, can also consist of silicon, or also of a polymer or glass.

The shown interferometer 12 is designed as a Mach-Zehnder interferometer and has a measuring arm 12a and a reference arm 12b. The detection light generated by the detection light source 5 is directed through the input light guide 6a of the first light guide structure 6 to the beam splitter 6c, where the light is split into two partial light beams through the measurement and reference arms 12a, 12b. The reference arm 12b may have a minimum distance of at least 1 mm or at least 2 mm or at least 5 mm or at least 8 mm from the measuring arm 12a in order to eliminate or reduce the influence on the reference arm 12b of the incoming temperature wave and/or pressure wave. The measuring element 1 is then positioned relative to the excitation light beam 10 such that the temperature and/or pressure wave emitted by the analyte preferentially reaches the measuring arm 12a of the interferometer and there influences the refractive index of the light guide.

Both arms of the interferometer can, for example, lie in a plane parallel to the measurement surface, but also in a plane oriented perpendicular to the measurement surface.

The result is a phase shift of the light beams passing in different arms of the interferometer, which, when the light beams are coupled in the second connector 6d, depending on the phase position, leads to quenching or partial quenching of the detector light. Then, the intensity of the detector light is detected by the measuring device 7 at the output light guide 6b of the first light guide structure 6 or at its end or exit point. The detector light may include, for example, wavelengths in the visible range or also in the infrared range.

Alternatively, instead of an interferometer, a light guide resonant element, such as a resonant ring or plate resonator, may be used, with an input element for detector light and an output element as a sensor for changes in pressure and/or temperature.

Figure 5, as a variant of the interferometric block, shows an interferometer combined with a resonant ring 13 of the light guide. This is realized due to the fact that the measuring arm of the interferometer is connected to the resonant ring 13 at two connection points 13a, 13b. By integrating the resonant ring 13 into the interferometer arm, a significantly higher temperature sensitivity of the device can be achieved.

Figure 6 shows a cross section of the measuring element 1 with the substrate 1a. The first light guide 15 of the first light guide structure is located on the substrate 1a. The first light guide 15 may be integrated into the substrate 1a. Behind the light guide 15, when viewed from the side of the measuring surface 2, there is a cooler 20 in the form of a body, which passes over the light guide 15 parallel to the latter and is embedded, for example embedded, in the material of the measuring element. The cooler 20 may also be located directly on the light guide 15. The material of the cooler 20 has a higher thermal conductivity and/or a higher specific heat capacity than the material of the light guide 15 and/or than the material of the substrate 1a and/or than the material with which the substrate 1a is coated.

The first light guide 15 represents, for example, the measuring arm of an interferometer. The corresponding support arm is made in the form of a second light guide 16 and is integrated in another substrate 1b, which can either be manufactured together with the substrate 1a or connected and embedded with it in a common measuring element 1. Between the measuring surface 2, in particular between the substrate 1a, and The second light guide 16 provides a thermal barrier 30, which extends at least in sections parallel to the second light guide 16, between it and the measuring surface, and which protects against the influence of a pressure and/or temperature wave that passes through the measuring surface 2. Alternatively, or In addition to the thermal barrier 30, the light guide 16 can be shielded from the region of the measuring surface 2 by a gas gap. Such a gas gap may be introduced into the substrate 1a, for example, by etching or some other material removal process, or it may be provided in the potting material with which the substrate 1a is embedded to form the measuring element 1. The thermal barrier 30 may also be provided in the form of a body as a barrier against the pressure wave and for this purpose have a higher ductility or elasticity than the material of the measuring element 1, which directly surrounds the light guide 16. In many cases and due to the small size of the interferometric elements, it is advisable to implement a thermal barrier using etched grooves in the substrate, for example, in substrate 1a or substrate 1b. The thermal barrier has, for example, a conductivity for pressure waves or thermal waves that is significantly lower than that of the sealing material of the measuring element or the substrate 1a, 1b.

Figures 6a-6g show various embodiments of an interferometric device in which the measuring arm and the reference arm are configured such that the influence of the temperature and/or pressure wave on the reference arm with respect to the change in refractive index is less than the influence on the measuring arm. In some cases, this is achieved due to the fact that the support arm is located at a greater distance from the measuring surface 2 than the measuring arm. In some cases, there is an obstacle or barrier between the support arm and the measuring surface 2. In other cases, the support arm is distant from or spaced from the substrate, while the sensing arm is connected to the substrate by thermal conductivity and/or a rigid mechanical connection.

In fig. 6a shows a measuring arm in the form of a light guide 15a and a reference arm in the form of a light guide 16a. The beam splitter or splitter is designated as 35, while the connector in which the beams of the measuring arm and the reference arm are brought together again is designated as 36. The reference arm extends in the central region of the measuring element 1 from the measuring arm along a length L at a distance D. The reference arm extends in the central region of the measuring element 1 from the measuring arm along a length L at a distance D. located on the side of the measuring arm facing away from the measuring surface 2, and thus further from the measuring surface 2 by an amount D than the measuring arm.

In fig. 6b shows a measuring arm in the form of a light guide 15b and a reference arm in the form of a light guide 16b. Here also, as in the following figures, the beam splitter, which distributes the detector light to the measurement arm 15b and the reference arm 16b, is designated 35, and the connector is designated 36. Each splitter and connector can be configured as a separate optical element or as an integrated element into the substrate of the measuring element 1.

The support arm 16b extends in the central region of the measuring element 1 from the measuring arm 15b at a distance of at least the amount D.

A barrier, not shown here, can also be provided between the measuring arm and the reference arm, which protects the reference arm from heat waves and or pressure waves.

The measuring arm can also have a length that is greater than the length of the reference arm, due to the fact that the measuring arm extends at least in sections in loops and/or in the shape of a spiral or meander. However, it can also be provided that the support arm, at least in sections, extends in loops and/or in the shape of a spiral or meander. The loop, spiral or meander-shaped sections of the measuring arm and/or support arm can extend mainly in a plane parallel to the measuring surface 2, but also in a plane which runs perpendicular to the measuring surface 2.

In fig. 6c shows a measuring arm in the form of a light guide 15c and a reference arm in the form of a light guide 16c. The measuring arm extends as a light guide, which is cast or bonded into a recess in the substrate of the measuring element 1 using a solid material 37. The material 37 is suitable for conducting heat and/or pressure waves with the minimum possible delay. The material 37 may be, for example, a resin and/or a polymer. The light guide 15c may be, for example, a fiber optic light guide. The light guide 16c forming the support arm can run along the measuring element 1 without a rigid connection and can be made in the form of a fiber-optic light guide.

Fig. 6d shows a measuring arm in the form of a light guide 15d and a reference arm in the form of a light guide 16d. The light guide 15d can be integrated into the substrate of the measuring element 1 as an integrated light guide. The light guide 16d may extend over or in the sensing element 1, within an embedment in the material 38, the material 38 being configured to be less conductive of heat and/or pressure waves than the material of the sensing element 1 or the substrate of the sensing element 1. The material 38 may be made, for example, of silicone, usually in the form of an elastomer and/or foam.

Fig. 6e shows a measurement arm in the form of a light guide 15e and a reference arm in the form of a light guide 16e. Both light guides 15e, 16e pass inside the measuring element 1, in particular as light guides integrated into the substrate, but separated by a barrier layer 39. This consists of a material that conducts thermal waves and/or pressure waves less well than the material of the measuring element 1 or the substrate measuring element. The material of the barrier layer 39 can be made, for example, silicone, typically an elastomer and/or foam, or soft, such as thermoplastic plastic. The barrier layer 39 may also be designed as a gas gap, at least in portions.

In fig. 6f shows a measuring arm in the form of a light guide 15f and a reference arm in the form of a light guide 16f. The measuring arm is located between, for example, the slot-shaped recess 40 of the measuring element or the substrate of the measuring element 1 and the measuring surface 2. The support arm is located on the side of the recess 40 facing away from the measuring surface 2. The recess can be U-shaped, for example also in the form of a hole or many holes. The measuring arm may also have a length that is greater than the length of the support arm by having the measuring arm extend at least in sections in a loop and/or in a spiral or meander shape above the recess 40. However, as shown in the figure, it can also be provided that the support arm extends at least in sections in the form of loops and/or in the form of a spiral or meander shape.

Fig. 6g shows a measurement arm in the form of a light guide 15g and a reference arm in the form of a light guide 16g. The support arm is located on the side opposite to the measuring surface 2 of the slot-like recess 41, which penetrates into the measuring element 1 perpendicular to the plane of the drawing. The recess 41 may also be made in the form of one or more holes, but may also be realized using techniques conventional in the formation of substrates, such as etching techniques, laser cutting or other material removal processing. Such a substrate can also be formed using an additive method (3D printing). The measuring arm can have a length that is greater than the length of the reference arm, due to the fact that the measuring arm extends at least in sections in loops and/or in a spiral or meander shape. However, as shown in the figure, it can also be provided that the support arm extends at least in sections in loops and/or in a spiral or meander shape. Loops, spirals or meanders can extend in a plane parallel to measuring surface 2, but also in a plane perpendicular to measuring surface 2.

6h shows two light guides 15h, 16h, between which light waves can be transmitted using a resonant element 17h in the form of a light guide resonant ring.

The intensity of the light wave supplied to the light guide 15h and transferred/transmitted from the light guide 15h to the light guide 16h or through the additional resonance ring 19h of the light guide to the light guide 18h, for example, measured as the ratio of the light wave intensity at the output of the light guide 16h or 18h to the intensity at the input of the light guide 15h, depends on how far the wavelength of the light wave is removed from the resonant wavelength of the resonant element or set of resonant elements. By means of a pressure and/or temperature wave, the resonant element(s) can be detuned by changing the refractive index, so that the resonant element(s) represent/represent an effective temperature and/or pressure sensor. As shown in the figure, several, for example at least two, at least three, or at least five such elements can be connected in series to increase sensitivity.

A parallel connection of several, for example at least two, more than two, more than three or more than five, such elements 17i, 19i, as shown in Fig. 6i, between the input light guide 15i and the output light guide 16i is also implied. This also allows you to set the sensitivity of temperature and/or pressure measurement.

When using optical waveguide resonance elements, the time profile of the intensity of the detector light can be recorded by the evaluation device, and from this the time profile of temperature or pressure during the passage of pressure and/or heat waves can be measured. The amount of absorption of the excitation beam in the analyte can be determined from the time profile, which can be periodic when modulation is used, and from this the spectrum can be determined. Using the measured time profile of detector light intensity, for example, the amplitude or average intensity deviation when the modulated excitation beam is on and the intensity when the excitation beam is off can be estimated.

Similar to FIG. 6a, FIG. 6k shows a measuring arm in the form of a light guide 15a and a reference arm in the form of a light guide 16a. The beam splitter or splitter is designated as 35, while the connector in which the beams from the measuring arm and the reference arm are brought together again is designated as 36. The reference arm extends in the central region of the measuring element 1 from the measuring arm for a length L at a distance of magnitude D. The support arm 16a is located on the side of the measuring arm 15a facing away from the measuring surface 2, and thus further from the measuring surface 2 by an amount D than the measuring arm. Numeral numeral 23 denotes an evaluation device that detects and evaluates the light intensity behind the connector 36 and matches the phase shift of the detector light and thus the absorption intensity of the excitation beam in the analyte.

One or more coolers and/or one or more thermal barriers may or may not be located within the measuring element; Therefore, the measuring element 1 can also be homogeneous and have no coolers or thermal barriers.

The heat and/or pressure wave, which propagates from the substance through the measuring surface 2 into the measuring element 1, first enters the first measuring section (measuring arm 15a) of the interferometer and generates a phase shift of the detector light there. After a time t, determined by the speed of wave propagation in the measuring element and the distance D, a phase shift is generated in the second measuring section/reference arm 16 of the interferometer. If both phase shifts exist simultaneously for some time, the phase shifts cancel each other out and cause no change in the intensity of the detector light. During the time intervals during which the wave is active in only one arm/sensing section 15a, 16a, the detection light is advanced or delayed in the first arm and then in the other arm. The time profile of this development is predictable due to the known speed of wave propagation in the measuring element. The degree of change in the intensity of the detector light that is detected by the evaluation device 23 allows the amplitude of the heat and/or pressure wave and thus the amount of absorption of the excitation light in the analyte to be determined.

FIG. 6l shows the intensity profile I of the detector light after passing through the interferometric device on the vertical axis, plotted against time on the horizontal axis.

At time t1, the wave in the measuring element reaches the measuring arm 15a, where it causes a phase shift of the detector light relative to the light that passes through the reference arm 16a. As a result, the intensity drops from I1 to I2. At time t2, the wave reaches the reference arm 16a and also causes a phase shift to the same extent and in the same direction. As the influence of the wave on the measuring arm continues, the phase shifts cancel each other out so that there is no (partial) quenching of the light components from the different arms of the interferometric device. The detector light intensity reaches value I1 again after t2. The intensity then decreases after t3, since at this time there is only a phase shift in the reference arm 16a and after t4, that is, after the wave has completely passed through the interferometric device, the intensity I1 is established again. The amplitude of the wave and, consequently, the amount of absorption of the exciting beam in the substance can be determined by the difference between I1 and I2.

6m shows a device in which an excitation beam 10 from an excitation beam source 4 penetrates past the boundary surface of the measuring element 1 into a substance 3 for absorption there, as indicated by a stylized circle. From there, a heat and/or pressure wave emanates, which propagates, among other things, to the measuring element 1 and to the interferometric device 12.

In addition, another position of the excitation beam source 4 is shown, from which the excitation beam 10' is emitted at an angle past the measuring element 1 into the substance 3 and is absorbed there under the measuring element 1. In this case, an even larger part of the wave reaches the measuring element 1 and the interferometric device . It is also possible to direct the exciting beam using a light guide. A housing (shown in dotted lines) of a different material may be attached to the measuring element 1, which is, for example, transparent to the exciting beam 10, in particular more transparent than the material of the measuring element 1.

6n shows that the measuring element 1 can be connected to the analyte in the region of the measuring surface not only by direct physical contact, but also by using a medium such as an intermediate layer made of a solid material, or a liquid layer or even a gas layer .

In FIG. 6n, a recess 200 is specifically shown on the measuring surface 2, which can optionally also be surrounded by a raised edge 201 on the measuring surface 2. To create a cavity, it is also possible to provide only one surrounding raised edge on the measuring surface. If the measuring surface 2 is placed on the substance to be analyzed, for example on a part of the body of a living being, a cavity is formed between the substance and the measuring element, which forms an acoustic connecting element. The pressure and/or heat wave can penetrate into the cavity of the substance and enter the measuring element through the gaseous medium, where the wave can be detected by the interferometric element 6. Due to the high sensitivity of the interferometric measurement method, the wave can also be effectively detected acoustically and measured in relation to its intensity .

The excitation beam may be directed from the excitation beam source 4 directly through the cavity 200 to the test substance. For this purpose, the measuring element can at least partially have a recess for the exciting beam, or the beam can pass through the measuring element using a light guide. The excitation beam can also at least partially pass through the material of the measuring element 1.

Figure 7 shows a variant of the measuring element 1, in which the light guides 15, 16 of the interferometric device are located on the side of the substrate 1a, which faces the measuring surface 2. On this side, the substrate 1a is covered with a coating 42, which covers and protects the light guides 15, 16. When In this arrangement, at least one of the light guides 15, which represents the measuring arm of the interferometric device, can be reached by a temperature and/or pressure wave directly from the substance 3. The support arm 16 must be shielded from the influence of the pressure and/or temperature wave by means not shown. The reference arm 16 can, for example, be located far enough from the measuring arm 15 that it is significantly less affected by the pressure and/or temperature wave than the measuring arm.

In fig. 8 shows an embodiment in which an interferometric system is implemented with fiber-optic light guides 15', 16' firmly connected to the substrate 1a. In the example shown, the connection is provided by the adhesive 14. The light guides can be routed in grooves on the measuring element/substrate.

9 shows a cross-section of the measuring element 1, which has a continuous recess 18 in the form of an opening through which the excitation light beam 10 can pass in a straight line into the test substance 3. If the measuring element 1 is provided with a coating 22 on its underside, as shown in FIG. 1, recess 18 may end in a coating if the coating is transparent to the excitation beam 10. However, recess 18 may also extend through the coating 22.

For example, a beamforming element in the form of a lens or collimator 31 may be provided in the recess 18. The excitation beam direction shown in FIG. 9 can be combined with any type of interferometric device shown in the figures and further explained above (not shown in FIG. 9 ).

Figure 10 shows a device in which a beam 10 of excitation light is emitted into the measuring element 1 by a laser device 4 parallel to the measuring surface 2. The measuring element 1 has a continuous recess 18' having a bend at right angles in the direction of the measuring surface 2. Reflective element 32 , for example in the form of a mirror, is provided in the direction change area. In the device shown, the excitation light beam 10 can penetrate the analyte 3 perpendicularly through the measuring surface 2. The direction of the excitation beam shown in FIG. 10 can be combined with any type of interferometric devices shown in the figures and further explained above (not shown in FIG. 10).

FIG. 11 shows a cross-section of the measuring element 1, in which a second light guide structure 17 is provided for guiding the excitation light beam 10. It may be designed as an integrated light guide built into the substrate of the measuring element 1. The second light guide structure 17 is oriented such that the excitation light beam 10 is directed perpendicularly through the measuring surface 2. However, it is also possible for the light guide of the second light guide structure 17 to be directed towards measuring surface 1 at an angle of less than 90°, for example less than 70° or less than 50°. The laser device 4 may be coupled to the second light guide structure 17 directly or via a beamforming element such as a lens (not shown in FIG. 11), but a flexible fiber optic light guide may also be used to conduct the excitation light beam 10 between the laser device 4 and the second light guide structure 17. The excitation beam direction shown in FIG. 11 can be combined with any type of interferometric device shown in the figures and further explained above (not shown in FIG. 11).

The end of the integrated light guide of the second light guide structure 17 facing the measurement surface 2 may also be provided with a beamforming element, such as a lens (not shown in FIG. 11).

With respect to the second light guide structure 17, FIG. 12 shows a complex-shaped built-in light guide 17a that guides the excitation light beam 10. The excitation light beam 10 is introduced into the integrated light guide 17a of the second light guide structure 17, for example parallel to the measuring surface 2, and is deflected by this integrated light guide 17a in a direction that passes through the measuring surface 2, in particular perpendicularly or at an angle of less than 90°, for example less than 70 ° or less than 50°. In the region of the second light guide structure 17, a modulation device 8 is integrated into the substrate 1a, which is used to modulate the intensity of the excitation light beam through the processing device 23. The modulation device 8 may be implemented, for example, by using a piezoelectric element placed in or on the second light guide structure 17, or a heating element that modulates the transparency of the second light guide structure 17, or by using a MEMS mirror element to deflect the excitation light beam 10.

The integrated light guide 17a of the second light guide structure 17, which directs the excitation beam 10, has portions in which it extends parallel to the measurement surface and portions in which it extends in some direction toward the measurement surface 2, in particular perpendicular to the measurement surface 2. Such a light guide design can be implemented in a proven manner using integrated optics in the substrate 1a.

FIG. 13 schematically shows the processing of measurement data obtained by a substance analysis device. The left side of FIG. 13 shows a measuring element 1 and a laser device 4 for generating the excitation beam, as well as a measuring device 7. The measuring device 7 and in particular also the laser device 4 are connected to a processing device 23, which can be implemented as a microcontroller or microcomputer and has at least one processor. In the processing device, the variable light intensity measurement data obtained by the measuring device 7 is combined with the data of the modulated excitation beam, i.e. matched to the emitted wavelengths and modulation time profile. Three diagrams are shown symbolically, the top one shows the modulated laser pulses as a function of time, and the middle diagram shows the change in the measurement data over time. When a heat and/or pressure wave reaches the interferometric element, for example by turning on/off the excitation beam or modulating the excitation beam, it is detuned by changing the refractive index or canceling or partially canceling the wave components from the various measuring arms of the interferometer. As a result, the intensity of the detector light changes after passing through the interferometric element. In addition to the amount of absorption of the excitation beam in the analyte, this time curve also reflects the mixing properties of the signals that, for each modulation period of the excitation beam, are sent to the device as a superposition of signals from different depths below the surface of the substance, and which, due to different travel times, generate a certain signal attenuation behavior measurements after each laser pulse. Signals from different depths should not be separated from each other, but this can be achieved using various estimation techniques, which are explained elsewhere in this description.

The third and bottom diagram shows a spectral representation in which the measured light intensities are plotted against irradiation wavelengths or excitation light beam wavenumbers, respectively, in several spectra.

From these data, for example, physiological parameters of the patient can be obtained, which are obtained by measuring the concentration of certain substances in body tissues or body fluids. An example of this is blood sugar testing, which measures the concentration of glucose in a specific part of the body. According to FIG. 13, measured values or pre-processed values can be coordinated with a remote computer or distributed computer system (cloud) using the communication device 25. For example, reference values for interpreting measured values can be imported from the cloud or from a remote computer. The reference values may depend on the identity of the patient and on the data that is individually stored and can be retrieved for him. For this purpose, either the patient's identity must be entered into the processing device 23, or it must be determined through separate measurements, for example using a fingerprint sensor, which can be integrated into the measuring device.

In the cloud, a comparison with measured values of other patients or a comparison with previous measured values of the same patient can also be made, and environmental conditions such as temperature, air pressure or humidity at the patient's location can also be taken into account. Sensors for determining these values can be integrated into the equipment/device for analyzing the substance according to the invention.

As a result of the processing, the processing device 23, through the first output device 26, can output trend information, for example, in three or five steps, in the form of information such as optimal, good, reasonable, still good, alarm, or in the form of colors or symbols. In the optional output device 27, which allows a specific value to be displayed, the measured values can be displayed on a screen or on a digital display. In addition, the measured values or measured value trends can be output to a software module 28, which, for example, can also run in a separate mobile data processing device such as a mobile phone. In this device, the evaluated measurement results can then be used, for example, to create a recipe for the food to be taken or to select the available food and the amount of food. Recommendations may also be given for the consumption of certain foods, indicating quantities. This can be associated, for example, with a preparatory cooking recommendation, which can be called up from the database and, in particular, also transmitted electronically. These cooking recommendations can also be transferred to the cooking machine.

In one embodiment, the output/display device 27, or a signal device parallel thereto, may provide an insulin dose suggestion based on additional patient parameters (eg, an insulin correction factor) or automatically transmit a signal to a dosing device in the form of an insulin pump.

The processing device 23 may also be integrated into the device body 33, but it may also be implemented separately, for example, in a mobile computer or a mobile radio device. In this case, a communication interface must be provided between the components located in the housing 33, in particular the measuring device 7 and the data processing device 23, for example via a radio standard. The housing 33 may be designed as a portable housing, for example, also as a housing that can be worn on a person's wrist as a wristwatch (wearable). In another embodiment, the laser device can also be located outside the housing and can be connected for measurement. The communication can be realized, for example, using a fiber optic light guide and/or such that the excitation beam of the laser measuring device is suitably oriented by applying the laser device to the supporting surface of the housing relative to the measuring element.

FIG. 14 shows a top view of a substrate 100 which carries an excitation light source 4, for example in the form of a laser device, in particular a laser array. In addition, the substrate 100 carries a detector light source 5 and a measurement device 7, for example, in the form of a radiation-sensitive semiconductor component for measuring the intensity of the detector light. Each of the elements 4, 5 or 7 may also be fully or partially integrated into the semiconductor structure of the substrate 100 or may be produced therefrom by micromechanical manufacturing techniques and, for example, doping. The substrate has light guides 101, 102, 103, which are either fully or partially integrated into the substrate, or attached to it as fiber optic light guides, for example, in V-shaped grooves that position the light guides with reasonable accuracy. The light guide 101 directs the excitation beam/excitation radiation, while the light guides 102, 103 guide the detection light/detector radiation.

As can be seen in particular in FIG. 15, the substrate 100 has a micromechanically fine-tuned recess 105 into which an additional substrate 1a can be inserted so that one or more light guides 101, 102, 103 are immediately in front. corresponding connecting light guides (not shown) of the additional substrate, so that the guided radiation can be introduced directly into the light guide of the additional substrate 1a and can be transferred from them again to the light guide of the measuring device/detector 7. Connecting elements can also be provided for this purpose, which increase the efficiency connections. The substrate 1a then has, for example, as shown in FIG. 16 and the comparable FIG. 12, an integrated light guide which directs the excitation light to the measurement surface. In addition, the substrate 1a has a built-in interferometric element with integrated connecting light guides. The measuring surface may lie on one of two sides of the substrates 100, 1a. If the sensing surface is on the underside in FIG. 15, a window 106 may be formed in the substrate 100 as a continuous recess within the recess 105.

17, like FIGS. 18 to 22, shows a cross-section of a substrate 1a into which a first light guide structure 6 is embedded as part of a detector device. For clarity, the shading of the cut sections has been omitted. The measuring surface 2 is located on the figures in the upper part of the substrate 1a. By way of illustration, a human finger 107 is shown in FIG. 17, as well as in FIG. 20, as an exemplary measurement object whose substance is to be analyzed. The finger is placed on measuring surface 2 for analysis.

FIGS. 17-22 show substrates whose material is permeable or at least partially permeable to the excitation beam 10 in the infrared range or in the normal wavelength range of the excitation beam. This applies, for example, to a silicon substrate for the infrared range. In this way, the excitation beam can be directed through the substrate material, or at least through a layer of limited thickness on the measuring surface, and through it into the substance to be measured. In such a case, there is no need to provide a through hole in the substrate for the excitation beam 10. The excitation beam can be directed past or through the first light guide structure 6. Part of the path along which the exciting beam passes through the measuring element may also lie in a recess/cavity. For this purpose, a recess can be provided in the measuring element, at least in sections. For example, a thin layer of substrate may remain in the area of the measuring surface. However, a material insert in the form of a light guide made of a material that is more permeable to the excitation beam than the substrate material may also be provided in the portions of the measuring element.

FIGS. 17-22 and 23-25 show various designs for guiding the excitation beam. The detector device has been omitted for clarity. Of course, all of the described detector device structures can be implemented in combination with the excitation beam guiding structures shown in FIGS. 17-25.

On the side of the measuring element or substrate 1a opposite the measuring surface 2, a lens 108, 108', 108'' is integrated into the substrate, in particular formed by the material of the substrate and, for example, using a material removal method, in particular by etching, made from the substrate material.

Three examples of possible lens shapes are shown in FIGS. 17-22, with the first lens shown in FIGS. 17 and 20, the second lens in FIGS. 18 and 21, and the third lens in FIGS. 19 and 22.

The first lens 108 corresponds to a normally refractive convex refractive converging lens, the second lens 108' corresponds to a converging Fresnel (refractive) lens (cineform lens), and the third lens corresponds to a diffractive lens that focuses the excitation beam 10 by diffraction onto a concentric grating structure.

The optical axes of the lenses may be suitably perpendicular to the measuring surface 2, so that the excitation light source can be emitted directly through the substrate 1a. However, the optical axes can also be inclined with respect to the normal to the measuring surface 2 to allow compact placement of the excitation light source at an angle to the substrate.

FIGS. 20, 21, 22 show the shapes of lenses 108, 108', 108'' on a substrate 1a with excitation beams 10 and ray beams 10a focused on the analyte.

In FIGS. 17-22, interferometric elements are provided adjacent to the sensing surface in the substrate, but these figures generally show the direction of the excitation beam 10.

In FIG. 23, the measuring element 1 with the sensor layer 1' is shown in cross section, in which the excitation beam 10 is directed from the laser device 3 into a light guide 126, which passes through the measuring element 1 to the layer 1'. The light guide 126 can also pass through the layer 1' to the measuring surface 2, but it can also be provided that either a recess is provided in the layer 1' for the excitation beam 10, or the excitation beam passes through the material of the layer 1'. A certain thickness of the substrate layer, which in the exemplary embodiment shown forms the measuring element 1, can also remain in front of the measuring surface or in front of the layer 1', and the exciting beam 10 can pass through it. In the area of the measuring surface 2, for example, directly next to the measuring surface 2 and/or within the layer 1', a lens 140 may be provided to focus the excitation beam 10 onto a point in the test substance. The light guide 126 extends directly from the laser device 4 to the measuring surface 2 and passes through a detector device in the form of an interferometric element (not shown in detail) in the layer 1' or substrate 1. The light guide can also, for example, if the laser device 4' is located laterally next to measuring element, partially or completely pass over the surface and along the surface of the measuring element 1 (see Fig. 25). In FIG. 23, the light guide 127 extends from the laser device 4' first along a first part of its length at or on the surface of the measuring element and then extends over a second part of its length, like the light guide 126, through the measuring element. The excitation beam may be reflected in a region where the direction of the light guide changes, for example from a mirror, or the light guide may be curved. Such light guide 126, 127 can be integrated into the material of the measuring element 1 in a manufacturing process (for example, using SOI silicon on insulator technology) or as a fiber optic light guide connected thereto, for example by gluing, or the light guide can be integrated in part its length and on one other part of its length in the form of a fiber-optic light guide.

As can be seen in the two different light guide designs in FIG. 24, a curved light guide 133, 134 may also be provided which conducts the excitation beam 10 from a position on the measuring element 1 in which the laser device is located to the measuring surface 2. Since the direction of the light guide 133, 134 can be implemented relatively freely, it is possible to maintain a minimum distance between the region through which the excitation beam passes and the detector region. The excitation beam 10 may also strike the measuring surface 2 at an angle to the measuring surface 2, for example at an angle from 0 to 60 degrees, in particular from 0 to 45 degrees to the normal to the surface of the measuring surface 2, and pass through it.

Due to the small depth of penetration into the analyzed substance, the region of the substance in which the exciting beam 10 interacts with it is located, despite the inclined direction of irradiation, directly under the detector device, which can be implemented, for example, in the form of an interferometric element. The curved light guides 133, 134 can, for example, be routed at least in portions as fiber optic light guides in a hole or similar recess in the measuring element 1 and glued or embedded there.

As shown in FIG. 25, the light guide 135, 136, 137, 138 may also be provided for guiding the excitation beam 10, which, for example, extends in multiple directions and/or in two or three mutually perpendicular directions on one or two or three adjacent to each other on different surfaces of the measuring body 1. Such a light guide 135, 136, 137, 138 can be integrated into the corresponding measuring element, for example like the light guides shown in FIGS. 23 and 24. This is particularly easy to implement on the surface of the measuring element using SOI technology or, depending on the material of the measuring element 1, in the corresponding solid-state manufacturing technology. To do this, a light guide, which is coated with layers of silicon oxide or other layers, can be inserted into the silicon substrate and separated from the substrate. To do this, a suitable recess can be etched or sprayed into the substrate first, and then the coating and light guide material can be applied accordingly. In this case, the cover of the light guide may, for example, end flush with the surface of the measuring element, so that the light guide does not protrude beyond the measuring element 1. Running the light guide 135, 136, 137, 138 along the surfaces of the measuring element prevents interaction of the excitation beam with the detector device. The last light guide 138 then ends in the region in which the excitation beam 10 is to enter the analyte 3. There, an element may be provided at the end of the light guide 138 that directs the excitation beam into the substance 3, such as a mirror.

With reference to the portion of FIG. 25, shown by circle 142 in the lower right corner of FIG. 25, it is shown that the light guide 138 can also be located in the dotted groove of the measuring element 1, which extends at an angle to the measuring surface 2, such that the longitudinal the axis of the light guide is oriented parallel to the bottom 141 of the groove through the measuring surface 2 to the substance 3 that is to be analyzed.

The present patent application relates (as already mentioned), in addition to the above-described subject matter of the claims and exemplary embodiments, also to the following aspects. These aspects or some of their features may be combined individually or in groups with the features of the claims. Aspects also constitute independent inventions, considered individually or in combination with each other or with the subject matter of the claims. The applicant reserves the right to make these inventions the subject of claims at a later date. This may be done in the context of the present application, as well as subsequent divisional applications or subsequent applications claiming priority of the present application.

Aspects of the present invention:

1) A method for analyzing a substance in the body, including:

- emitting excitation light (excitation beam) with one or more specific excitation wavelengths through a first region of the body surface,

- modulating the intensity of the excitation light beam with one or more frequencies, in particular one after the other, by means of a mechanical, electrical or optical chopper, in particular by electronically controlling the excitation light source, an adjustment device for the excitation laser resonator serving as the excitation light source, or a movable mirror device, an adjustable diffraction device, a shutter device, or a mirror device that is coupled to a motor, such as a stepper motor, or to a MEMS or layer in the beam path that can be controlled for transmission or reflection, as well as detecting a response signal with time resolution,

- using a detector device located outside the body, wherein the response signal arises due to the effect of wavelength-dependent absorption of the exciting light beam in the body and the emission of a temperature wave and/or a thermal wave onto the detector device.

The detector device may, for example, comprise an optical medium/measuring element with a detector region which, in particular, is adjacent or directly adjacent to the measuring surface (which corresponds to the boundary surface of the measuring element in contact with the substance to be measured), and which, if changes in pressure or temperature due to changes in its refractive index affect the beam of detector light that passes through the measuring element. In particular, the intensity of the detector light may be affected by changes in pressure and/or temperature.

The detector/detector device may, for example, have a light guide integrated on the substrate, in particular using silicon-on-insulator technology. Silicon, for example, is used as a light guide. It is also possible to use SiN, wherein the light guide is at least partially coated with silicon oxide, the refractive index of which is different from that of Si or SiN.

In one embodiment, modulation may occur by interference with or influencing the phase or polarization of radiation from the transmitting drive device, particularly if it contains a laser light device. Modulation can also be achieved by controlling an actively operating piezo element which is part or component of the measuring element and whose transmittance or reflection properties or reflectivity can be controlled by a voltage regulator on the piezo element. The response signals can be, for example, intensities or angles of deflection of the reflected measuring beam or voltage signals from a detector operating with a piezoelectric effect.

2) The method according to aspect 1, characterized in that the excitation light/excitation beam is generated by several emitters or several joint emitters, in particular in the form of a laser array, which emit light of different wavelengths simultaneously or one after the other, or in pulsed combinations, also alternately.

3) A method according to any one of aspects 1 or 2, comprising the steps of:

- establishing contact between the optical medium/measuring element and the surface of the body, such that at least one surface region of the measuring element (for example, the measuring surface) is in contact with the first region of the body surface;

- emission of an exciting light beam with an excitation wavelength into a volume lying in the substance below the first surface area, in particular, through a surface area of the optical medium that is in contact with the first surface area of the substance,

- measuring temperature or temperature change and/or pressure change in the first zone of the surface of the measuring element by optical means,

- analysis of a substance based on the detected temperature increase depending on the wavelength of the exciting light beam. This process can be performed in one dimension for different modulation frequencies, and the results for different modulation frequencies can be combined with each other.

4) The method according to any one of aspects 1 to 3, characterized in that the detector light beam is generated by the same light source that generates the excitation light beam.

5) The method according to aspect 1 or any of the previous or subsequent ones, characterized in that the light excitation beam is an intensity modulated, in particular a pulsed light excitation beam, in particular in the infrared spectral range, in particular the modulation frequency is between 1 Hz and 10 kHz, preferably between 10 Hz and 3000 Hz.

6) The method according to aspect 1 or one of the preceding or subsequent ones, characterized in that the light of the light excitation beam(s) is generated by an integrated device with several individual lasers, in particular a laser array, simultaneously or one after the other, or partially simultaneously and partly one after the other.

7) The method according to aspect 1 or any of the previous or subsequent ones, characterized in that the intensity distribution of the response signals is determined from the response signals obtained at different modulation frequencies of the excitation light beam, depending on the depth below the surface at which the response signals occur.

8) The method according to aspect 1 or any of the preceding or subsequent ones, characterized in that by the phase position of the response signals, that is, a certain temperature and/or pressure curve in the analyte measured from the detector light intensity curve with respect to the phase of the modulated excitation light beam at at the same or different modulation frequencies of the excitation light beam, determine the intensity distribution of the response signals as a function of the depth below the surface at which the response signals occur.

9) The method according to aspect 7 or 8, characterized in that to determine the intensity distribution of the response signals depending on the depth below the surface, the measurement results with different modulation frequencies are weighed and related to each other.

10) The method according to aspect 7, 8 or 9, characterized in that from the determined intensity distribution along the depth below the surface of the body, the substance density is determined for the substance absorbing the light excitation beam in certain wavelength ranges at a certain depth or depth range.

11) The method according to aspect 1 or any of the previous or subsequent ones, characterized in that immediately before or after or during detection of the response signal(s), at least one biometric measurement is taken on the body in the first area of the surface in which the substance is analyzed, or in close proximity to it, in particular, the fingerprint measurement, and the body, in particular the person, are identified and, in particular, reference values (calibration values) associated with the identification of the person are assigned to the detection of response signals.

Biometric measurement may also include measuring the spectrum of response signals as the exciting light beam passes through the spectrum. By assessing the spectrum, it is possible to determine the profile of substances present in the body and their quantity or density ratio, which can allow identification of a person.

12) Device for analyzing a substance,

with a device for emitting one or more light excitation beams, each with its own excitation wavelength, into a volume lying in the substance below a first region of its surface, with a device for modulating the light excitation beam, which is formed by means of a radiation source modulation device, in particular, its control, an interference device, a phase or polarization modulating device and/or at least one controllable mirror located in the path of the beam, and/or a layer located in the path of the beam, which is adjustable in terms of its transparency, as well as with a detector a device for detecting a time-dependent response signal depending on the wavelength of the excitation light and modulation of the intensity of the excitation light, and a device for analyzing a substance based on the detected response signals.

13) Device according to aspect 16 with a device for determining response signals separately for different intensity modulation frequencies and/or with a device for determining response signals depending on the phase position of the corresponding response signal relative to the modulation phase of the excitation light beam, in particular depending on the modulation frequency light exciting beam.

14) A device for analyzing a substance according to aspect 12 or 13, with a measuring element for contacting a surface (for example, a so-called measuring surface) with a first portion of the surface of the substance, and with

a device for emitting a light excitation beam with one or more excitation wavelengths into a volume lying in a substance below a first surface portion, in particular through a surface portion of a measuring element (measuring surface) that is in contact with the surface of the substance, and

with a device for measuring response signals in the form of changes in temperature and/or pressure in a region inside the measuring element in the immediate vicinity of the measuring surface (using a detector device) that is in contact with a first region of the surface of the material, using an optical method that is based on a detector beam, and

with a device for analyzing a substance based on detected response signals in the form of temperature changes/pressure changes depending on the wavelength of the exciting light beam and the modulation intensities of the exciting light beam, in particular the modulation frequency of the exciting light beam.

15) The device according to aspect 18, characterized in that the excitation light source and/or the detection light source is mechanically rigidly connected directly to the measuring element.

The excitation light source and/or the detection light source may accordingly be directly coupled to and integrated into a light guide of the first or second light guide structure that is provided in, at, or on the measuring element. The excitation light source and/or the detection light source may also be connected to the first or second light guide structure of the above type through a corresponding optical fiber light guide.

16) The device according to aspect 18, 19 or 20, characterized in that the measuring element directly contains beamforming optics and/or that the beamforming optics are integrated into the measuring element.

17) The device according to any one of aspects 12 to 16, characterized in that the device has a wearable body that can be attached to the human body, and a device for emitting one or more light excitation beams and a detector device for detecting a time-dependent response signal are located and configured in such a way that the substance to be analyzed, during operation when the device is worn on the body, is on the side of the housing facing away from the body, in particular that the measuring surface of the measuring element is on the side opposite the body.

18) The device according to any one of aspects 12 to 16, characterized in that the device has a wearable body that can be attached to the human body, and that the device body has a window transparent to the light excitation beam on its side, which, when intended wearing position, facing away from the body.

The window can be positioned directly in front of the measuring housing. The window may simply be an opening in the housing, the surface of the window being formed by a measuring surface or a measuring surface lying in the opening. The measuring surface may also be located behind a layer covering the window opening, which is connected to the measuring surface in such a way that temperature and/or pressure waves are transmitted externally to the measuring surface.

19) A device for analyzing a substance with a transmitting excitation device for generating at least one electromagnetic excitation beam, in particular a light excitation beam, with at least one excitation wavelength, with a detector device for detecting the response signal and an analysis device substances based on the detected response signal.

20) An apparatus according to any one of the preceding aspects 12 to 19, characterized in that the transmitting drive device comprises an interrogating laser (laser on a chip) or an LED, for example a NIR (near infrared) LED.

21) The device according to any of the preceding aspects 12 to 20, characterized in that the transmitting excitation device includes a laser probe that has a smaller beam diameter than the additional pump laser that forms the laser for generating the excitation beam.

22) A device in accordance with one of the previous aspects 12 to 21, characterized in that the device is designed to be worn on the body by a person for an extended period of time, in one embodiment, using a holding device connected to the housing, such as a belt, tape or chain, or fasteners and/or the detector device has a detector area, which can also be used as an area for displaying information, for example, measured values, time and/or text information.

The detector area can be identical to the measuring surface or form its continuation/extension.

23) The device in accordance with the previous aspect 22, characterized in that the device has a peelable film in the area of the detection area/measuring surface, preferably adjacent to the detection area/measuring surface, for pre-treating the surface of the substance and providing a clean surface and/or in one of embodiments in the case of measuring glucose specifically for skin cleansing.

24) A device according to any of the preceding aspects 12 to 23, characterized in that the detection device is configured to read and recognize fingerprints, to request certain values/calibrations of a person and/or that it has a device to recognize the position of a finger, preferably to detect and detecting unwanted movement during measurement.

25) The device according to any of the preceding aspects 12 to 24, wherein the detector device has a results display, which is preferably color-coded as an analog display, in one embodiment, includes an error display (for example: "100 mg/dL plus/ minus 5 mg/dl") acoustically and/or by displaying the results of the measured values in larger increments than the measurement accuracy of the device allows (for example, using a multi-colored traffic light display). As a result, for example, small fluctuations that could confuse the user are not reported.

26) The device according to any one of the preceding aspects 12 to 25, characterized in that the device

has data interfaces for exchanging measured data and for receiving calibration or identification data or other data from other devices or cloud systems, for example wired or wireless interfaces (infrared, light or radio interfaces),

wherein the device is preferably configured such that data transmission can be encrypted, in particular encrypted using the user's fingerprint or other biometric data.

27) A device in accordance with one of the preceding aspects 12 to 26, characterized in that the device is configured in such a way that it generates a recommendation for administering a dose of insulin to a person or consuming a substance/food, along with the amount to be consumed, (eg, insulin correction factor), and/or that body weight, body fat can also be measured and/or entered manually or transmitted from other devices to said device.

28) A device according to any of the preceding aspects 12 to 27, characterized in that the device, to improve measurement accuracy, is configured to determine additional parameters, in one embodiment, through sensors for determining skin temperature, diffusivity/conductivity/humidity of the skin, or for measuring polarization light (excluding water/sweat on the surface of the finger).

Water and sweat on the surface of human skin, which can interfere with glucose measurements, can be detected using test excitation with excitation radiation from an excitation transfer device with water-specific bands at 1640 cm ^-1 (6.1 μm) and 690 cm ^-1 (15 µm) and can be taken into account in subsequent evaluation of the measurement. Alternatively, the electrical conductivity of a substance can be measured nearby or directly at the measurement point using multiple electrodes to determine the humidity. An error message and drying instructions can then be displayed, or the presence of moisture can be taken into account in a subsequent measurement evaluation.

29) A device according to any of the preceding aspects 12 to 28, characterized in that the device has a cover or blocking device in the path of the pump laser beam and/or the measurement beam. This can ensure mandatory eye safety for living beings.

30) A device according to any of the preceding aspects 12 to 29, characterized in that the device has a replaceable detector area/sensing surface.

31) A device according to any of the preceding aspects 12 to 30, characterized in that the device has a partially corrugated or with parallel grooves or distributed depressions or raised or rough crystal as a measuring element, which for a sample (for example, a finger) provides better alignment. The measuring point on which the analyzed material surface is placed should preferably be non-corrugated and smooth.

32) A device according to any of the preceding aspects 12 to 31, characterized in that the device measures not only at one point, but along a grid. This can be achieved either by moving the pump laser, laser probe, or detector unit relative to the surface of the subject's skin, or by varying the deflection of the excitation beam between two measurements.

In addition, the following aspects of the invention should also be stated:

33) Device for analyzing a substance, in particular also according to any one of claims 12 to 32, with

a transmitting excitation device/laser device for generating at least one electromagnetic excitation beam, in particular a light excitation beam, with at least one excitation wavelength,

a detection device for detecting a response signal, and

a device for analyzing a substance based on a detected response signal.

The time-dependent response signal may consist of an increase in temperature or pressure in the measuring element, as well as any measured quantity that detects this, for example, a change in the intensity of detector light passing through a material with a refractive index dependent on temperature or pressure.

34) A method of analyzing a substance in which

by means of a transmitting excitation device/laser device, at least one electromagnetic excitation beam with one or more excitation wavelengths is generated at least in part by simultaneous or sequential operation of several laser emitters of the laser light source and emitted into the substance,

the response signal is detected by the detector device, and

the substance is analyzed based on the detected response signal.

35) The method according to aspect 34, characterized in that by sequentially using different modulation frequencies of the transmitting drive device, response signals, in particular time curves of the response signal, are determined, and several response signal curves that are associated with different modulation frequencies are combined with each other, and from this information specific to the depth region below the surface of the substance is obtained.

36) The method according to aspect 35,

characterized by the fact that

The response signal curves at different modulation frequencies are determined respectively for different wavelengths of the excitation beam, and in particular, information specific to the depth region below the surface of the material is correspondingly obtained from them.

37) The method according to aspect 36,

characterized by the fact that

by using multiple excitation beam modulation frequencies simultaneously, the detected response signal is separated according to its frequencies using an analysis method, preferably Fourier transform, and

Only one partial signal that corresponds to the frequency being processed is filtered, measured and analyzed.

In this way, multiple signals at different modulation frequencies can be analyzed one by one, and the results for different modulation frequencies can be related to each other to obtain depth information for the signals or to exclude signals coming from the tissue surface.

38) The method according to any one of the preceding aspects 34 to 37, in which

Depending on the concentration of the substance determined in the substance, the dosing device is activated to dose the substance into the substance, in particular into the patient's body, and/or an acoustic and/or optical signal is output, and/or the signal is output to the processing device using a radio channel and/or that one or more foods or combinations of foods are assigned a measurable concentration of a substance using a database and are output as nutritional information, in particular dietary recommendations.

In addition to or in combination with such advice, an indication of the quantity of product or combinations of products may also be provided. Food combinations also refer to prepared portions of food.

All characteristics and measures of the excitation beam, its optical guidance and modulation, which are listed in the aspects associated with any measurement method, in particular in connection with the measuring light beam and the detection of its deviation, as well as characteristics for mechanical design and control, housing features and communications with external devices, databases and connected devices are also used in the detection method as specified in the claims of the present application, i.e. using the interferometric effect to detect a pressure wave and/or a thermal wave emanating from a substance as a response signal.

In principle, values determined for the phase shift of the response signal relative to the periodic modulation of the excitation beam can be used for depth profiling. (The heating/cooling phases of the surface of a substance should be assessed more accurately taking into account their occurrence).

Connected to the device described may be a supply of adhesive strips for removing dead skin layers to ensure that the human body is as free from interference as possible, as well as patches or other forms of introducing a bonding medium, particularly a gel or thermal paste, which can be regularly applied to the optical medium. The optical medium can be replaced by suitable mounting and adjustment of other parts.

Data acquisition (DAQ) and evaluation lock-in amplifier can be combined in one device, and evaluation can be digitized as a single unit. A lock-in amplifier is connected to the detector device and selects signals that have a phase relationship with the modulation of the excitation beam. For this purpose, the synchronous amplifier is connected, for example, to a control device for a laser device that generates the excitation beam and/or to a modulation device for the excitation beam.

The measurement can also be carried out by means of a device on the surface of the substance that moves relative to it, so that during the grid measurement process, the excitation light source and/or the measurement light source moves or moves along the grid across the skin during the measurement, which can lead to compensation or elimination of skin unevenness .

A further embodiment and explanation of the invention according to the claims is shown in the following disclosure. The details of this disclosure may also be combined with embodiments of the filed claims. This disclosure also constitutes at least one independent invention in combination with the above aspects or subject matter of the claims. The applicant reserves the right to make this invention or inventions the subject of claims at a later date. This may be done in the context of the present application, as well as in the context of subsequent divisional applications or subsequent applications claiming priority of the present application.

The following concept of non-invasive blood sugar measurement by sensing glucose in the skin via quantum cascade laser excitation and thermal wave measurement using radiant heat would also be covered by the invention and could be combined with the subject matter of the claims or dealt with independently in a divisional application:

A method is described that can determine the concentration of glucose or other substance in the interstitial fluid (ISF) of the skin. The glucose in the ISF is representative of blood glucose and quickly follows it as it changes. The method consists of at least individual or groups of the following stages or general sequence:

1. An area of the skin (in this case the first area of the surface of the substance) is irradiated with a focused beam of a quantum cascade laser, which, if necessary, is reflected from a mirror or concave mirror, which is gradually or continuously tuned to a certain infrared range in which glucose specifically absorbs radiation. Instead of a quantum cascade laser, it is also possible to use a laser array with multiple lasers emitting at separate wavelengths. The spectral range (or individual wavelengths, typically 5 or more wavelengths) may lie in particular between about 900 and about 1300 cm ^-1 where glucose has an absorption fingerprint, that is, typical and characteristic absorption lines.

2. The excitation beam is used continuously (CW laser) or in a pulsed mode with a high pulse repetition rate or modulated. In addition, the excitation beam is modulated at a low frequency, especially in the frequency range from 10 to 1000 Hz. Low frequency modulation may take place with various periodic functions, in various embodiments sine, square, sawtooth, or the like. The rectangular shape is the most preferred according to the emission characteristics of QCLs.

3. When irradiating the skin, IR radiation penetrates the skin to a depth of approximately 50-100 microns and, depending on the wavelength, stimulates certain vibrations in the glucose molecule. These excitations from the vibration level v0 to v1 return to the ground state in a very short time; During this stage, heat is generated.

4. As a result of the release of heat according to (3), a thermal wave is formed, which emanates isotropically from the absorption point. Depending on the thermal diffusion length, which is determined by the low-frequency modulation described in (2), the thermal wave periodically reaches the skin surface at the modulation frequency.

5. The periodic appearance of a thermal wave on the surface corresponds to the periodic modulation of the thermal radiation property of the skin (the surface of the sample substance). The skin can be roughly described as a black body whose total radiation is proportional to the fourth power of the surface temperature according to the Stefan-Boltzmann law. The measurement technique described here focuses on the measurement of thermal conductivity.

6. Using a detector device according to the claims of the present application, the effect of a heat wave and/or pressure applied to the detector device on the refractive index of a light guide device, in particular an interferometric device, is detected.

7. When processing response signals, the modulation frequency can be specifically taken into account, for which the response signal can be processed by a synchronous amplifier. By analyzing the phase position between the excitation signal and the thermal radiation signal (response signal) using a control and processing device, it is possible to obtain information about the depth below the surface of the material from which the response signals are predominantly obtained.

8. Depth information can also be obtained by selecting and analyzing different low frequency modulation frequencies as described in section (2) for the excitation beam, and linking the results for different modulation frequencies (whereby results for different modulation frequencies can also be weighted by differently). If necessary, difference methods, ratio generation of at least two response signals (eg, each for one wavelength and that wavelength in the measured spectrum), or other determination methods can be used to compensate for the absorption of the uppermost layers of the skin.

9. From the thermal signal measured in accordance with (6-8) and depending on the excitation wavelength, in one embodiment, if glucose is to be detected, first for non-glucose excitation beam wavelengths (or excluding them) is determined background, then for (or including) glucose-related wavelengths the difference with the background signal is determined. From this, the glucose concentration in the skin layer or skin layers is obtained, which is determined by the selected phase position according to (7) or the different modulation frequencies according to (8) or a combination thereof.

Although the invention has been illustrated and described in more detail by means of preferred exemplary embodiments, the invention is not limited to the disclosed examples, and other variations may be derived therefrom by one skilled in the art without departing from the scope of the present invention.

Claims (27)

1. A device for analyzing a substance, containing: - a measuring element (1, 1a), which has a measuring surface (2) and is configured to contact, at least partially, a substance (3) in the region of the measuring surface to carry out the measurement or is configured to be brought into contact with it directly or also by means of a medium, wherein said measuring surface (2) is implemented as a flat surface or contains a concave surface or part of a surface, - an exciting beam source, which is configured to generate light or an exciting beam with different wavelengths, wherein the exciting beam (10) is directed towards the substance (3) when the measuring element (1, 1a) in the area of the measuring surface (2) is connected and/ or is in contact with a substance (3), - modulation device (8) for modulating the intensity of the exciting beam (10) with a modulation frequency from 1 Hz to 10 kHz, - a detector device (5, 6, 7), which is at least partially integrated into or associated with the measuring element (1, 1a), and includes the following: a source (5) of detector light, preferably coherent detector light (11), and connected or configured to be connected to said detector light source, a first light guide structure (6), which directs the detector light, and whose refractive index at least in portions depends on temperature and/or pressure, wherein the first light guide structure comprises at least one portion (9) in which the light intensity depends on the phase shift of the detector light in at least one part of the first light guide structure (6) due to changes in temperature or pressure due to pressure waves or thermal waves caused by absorption of the excitation beam when the measuring element ( 1, 1a) is connected to the substance (3) in the area of the measuring surface, and measuring device (7) for directly or indirectly determining the light intensity in the specified area (9) of the first light guide structure (6), in which the light intensity depends on the phase shift of the detector light in the specified at least one part of the first light guide structure due to a change in temperature or pressure , wherein said measuring element (1, 1a) represents or contains a substrate (1a), and wherein at least one light guide (15, 16) of said first light guide structure (6) is integrated into said substrate (1a). 2. The device according to claim 1, in which at least the projection portion of the first light guide structure (6) in the direction of normals to the measuring surface (2) overlaps with this measuring surface (2). 3. The device according to claim 1 or 2, comprising a housing (33) made in the form of a portable housing that can be worn on a person’s wrist like a wristwatch. 4. The device according to claim 3, in which the source of the excitation beam is located outside the housing and is configured to be connected for measurement using a fiber-optic light guide. 5. Device according to any one of paragraphs. 1-4, characterized in that the detector device contains an interferometric device, in particular an interferometer (12) and/or a resonant light guide element, in particular a resonant ring (13) or a resonant plate. 6. Device according to any one of paragraphs. 1-5, characterized in that the first light guide structure (6), in particular the interferometric device of the first light guide structure, includes at least one glass fiber light guide (14), which is firmly connected at least in sections to the measuring element (1). 7. Device according to any one of paragraphs. 1-6, characterized in that the first light guide structure (6) contains at least one silicon optical light guide, which is connected to the insulating substrate or integrated into the insulating substrate, and, in particular, the silicon optical light guide is at least partially covered insulator, in particular SiO ₂ . 8. Device according to any one of paragraphs. 1-7, characterized in that the exciting beam (10) passes through the material of the measuring element (1, 1a), in particular, in the area of the measuring surface of the measuring element or in the area adjacent to the measuring surface (2) or in the area directly adjacent with a measuring surface, wherein the measuring element or area traversed by the exciting beam (10) is transparent to the exciting beam. 9. Device according to any one of paragraphs. 1-8, characterized in that the exciting beam (10) is directed inside the measuring element (1, 1a) or onto the measuring element through the second light guide structure (17). 10. Device according to any one of paragraphs. 1-9, characterized in that the exciting beam (10) passes in a continuous recess (18) of the measuring element between the laser device (4) and the substance (3) to be measured, and the recess ends, in particular, at a distance from the measuring surface or passes through the measuring surface (2), or is located in an area that is directly adjacent to and/or borders the measuring surface. 11. Device according to any one of paragraphs. 1-10, characterized in that the measuring element (1, 1a) is made in the form of a flat body, in particular, in the form of a plane-parallel body in the form of a plate, and, in particular, the thickness of the measuring element in the direction perpendicular to the measuring surface (2) , is less than 50% of the shortest extent of the measuring element in the direction passing in the measuring surface, in particular less than 25%, in particular less than 10%. 12. Device according to any one of paragraphs. 1-11, characterized in that the measuring element (1, 1a) has or carries a mirror device (19) for reflecting the exciting beam (10) emitted by the laser device (4) onto the measuring surface (2). 13. Device according to any one of paragraphs. 1-12, characterized in that the exciting beam (10) is directed parallel to the measuring surface (2) or at an angle of less than 30 degrees, in particular less than 20 degrees, more specifically less than 10 degrees or less than 5 degrees to the measuring surface in the measuring element (1, 1a), wherein the exciting beam is deflected or retracted in the direction of the measuring surface, the exciting beam passing in particular through the measuring surface or through an imaginary extension of the measuring surface in the region of a continuous recess (18) in the measuring element. 14. Device according to any one of paragraphs. 1-13, characterized in that in the measuring element (1, 1a), when viewed from the measuring surface (2) behind and/or next to the detector device (5, 6, 7), in particular the first light guide structure (6), in particular, adjacent to it and in thermal contact there is at least one cooler (20) in the form of a solid body or material, and, in particular, the specific heat capacity and/or specific thermal conductivity of said solid body or material of the cooler exceeds the specific heat capacity and/or specific heat thermal conductivity of the material of the detector device (5, 6, 7) and/or the first light guide structure and/or the substrate (1a) of the first light guide structure (6) and/or other materials that make up the measuring element (1, 1a), and/or a barrier (30, 40, 41) is provided in the measuring element (1, 1a), which at least partially prevents the thermal wave and/or pressure wave from affecting a part of the detector device, in particular a part of the first light guide structure (6), further, in particular on the reference arm of the interferometer, and/or the first light guide structure (6) of the detector device contains at least two measuring sections (15a, 16a), which are located, in particular, in different arms of the interferometer, and in which the refractive index changes depending on changes in pressure and/or temperature, in particular on a thermal wave and/or pressure wave, so that a phase shift of the detector light passing through the measuring sections and, as a consequence, a change in the intensity of the detector light, occurs in the next section depending on the changes pressure and/or temperature, wherein two measuring sections are arranged in the measuring element in such a way that a pressure wave and/or a heat wave passes through them one after the other in time, in particular in time-shifted time intervals or with a time interval, which propagates in the measuring element from the measuring surface (2), in particular from the region of the measuring surface in which the exciting beam passes through it. 15. Device according to any one of paragraphs. 1-14, characterized in that said measuring surface (2) is configured to communicate at least partially with a substance (3) in the region of the measuring surface to carry out the measurement. 16. Device according to any one of paragraphs. 1-15, characterized in that said measuring surface (2) is configured to communicate at least partially with a substance (3) in the region of the measuring surface to carry out measurement through a medium, in particular a liquid. 17. Device according to any one of paragraphs. 1-16, characterized in that said source of the exciting beam is a laser device (4), in particular a laser device with a quantum cascade laser (QCL), a tunable QCL and/or a laser array, preferably a QCL array, for generating one or more exciting beams (10) with different wavelengths, preferably in the infrared or mid-infrared region of the spectrum. 18. A method for controlling a device according to any one of claims. 1-17, characterized in that a modulated excitation beam (10), in particular through a measuring element, is directed to the substance (3) to be analyzed, whereby a light intensity profile or a periodic change in light intensity is determined by means of a detector device, wherein recording a plurality of wavelengths of the excitation beam by measuring a change in light intensity in the first light guide structure or by measuring the light intensity from the first light guide structure, and an absorption spectrum of the analyte is obtained from the recorded data. 19. Method according to claim 18, characterized in that the measurement is carried out for different modulation frequencies of the exciting beam (10), and the corrected absorption spectrum is determined from the combination of the obtained absorption spectra.