HK40009358A - Device and method for analysing a material - Google Patents

Description

This right of protection relates to a device and a method for the analysis of a substance. e device and the method described herein may be used, for example, for the analysis of animal or human tissue, in an embodiment for the measurement of glucose or blood sugar.

Err1:Expecting ',' delimiter: line 1 column 213 (char 212)The results of the study were published in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Physical Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal of the journal Chemistry in the journal Chemistry in the journal Chemistry in the journal of the journal of the journal Chemistry in the journal of the journal Chemistry in the journal of the journal of Chemistry in the journal of the journal of the journal of the journal of the journal of the journal of the scientific chemistry in the journal of the journal of the journal of the journal of the scientific chemistry in the journal of the journal85:1013-1020, 2013.(4) Pleitez, M. Lieblein, T. Bauer, A. Hertzberg, O. von Lilienfeld-Toal, H. Mäntele, W. Windowless ultrasound photoacoustic cell for in vivo mid-IR spectroscopy of human epidermis: Low interference by changes of air pressure, temperature, and humidity caused by skin contact opens the possibility for a non-invasive monitoring of glucose in the interstitial fluid review of Scientific Instruments 84, 2013(5) Rafael M. Pleitez, 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 monitoring of glucose in the human epidermis. The analyst, November 2014.

The objective is to specify a device which allows a substance, in particular animal or human tissue, or a component or constituent of tissue, to be analysed in a particularly simple and cost-effective manner.

This task is solved, inter alia, by a device having the characteristics of claim 1.

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The following will, however, firstly deal with the claims listed at the time of filing.

A device for analysing a substance shall be provided with an excitation transmitter to produce at least one electromagnetic excitation beam, in particular an excitation light beam, with at least one excitation wavelength, a detection device to detect a reaction signal and a device to analyse the substance on the basis of the detected reaction signal.

A major advantage of this device is that it is very simple and reliable to analyse a substance.

The measurement of concentrations of a particular substance in body fluid is also illustrated in this right by the example of glucose in the ISF (interstitial fluid).

Other substances (intrinsic and non-intrinsic) may also be measured, such as those described in DE 10 2014 108 424 B3 and in the priority of this challenging PCT application.

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Drug level determination can also be used to improve the dosage of medicines with a small therapeutic range. Drug monitoring is useful, in particular for medicines that can be easily over- or underdosed, whose concentrations are easily affected by other medicines or which have toxic effects at a certain concentration. An example of a guideline to be achieved is to achieve or maintain a set level of activity and to determine the necessary individual dose of the medicinal product.

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The device described in the claims may also be connected to a dosing device for the dosing of one or more of the substances in question in order to form a control circuit.

It is noteworthy, especially in the context of the measurement of glucose in the ISF, that the only really clinically useful results are obtained in the evaluation of characteristic extremes in the middle infrared range, and in particular when the detection of absorption maxima and minima is carried out with a variety of relatively close-contiguous wavelengths. This balances the inaccuracy (due to temperature sensitivity of the laser, noise of the measurements, etc.) so that a sufficiently accurate measurement result is always achieved.

The term light here refers to electromagnetic waves or electromagnetic radiation in the visible range, near and far infrared and UV.

The device shall be designed in such a way that: Other the stimulation device is a radiation source, in one embodiment a monochromatic source, in particular a polarized radiation source or a light source, in particular a laser light source, the device has an optical medium in direct contact with the substance, in particular a first area of the surface of the substance,preferably the excitation device is so arranged that the emitted excitation beam enters the optical medium and leaves it at a predetermined point on the surface of the optical medium, and the device includes a device for emitting a measuring beam, in particular a measuring beam, arranged so that the emitted beam is reflected into the optical medium and preferably in operation of the measuring beam and the upper excitation beam at an interface between the optical surface and the measuring beam, reflected at a predetermined point on the surface of the measuring medium, the device is a detection device for receiving and reflecting the image of the measuring medium, or a detection device for reflecting and reflecting the image of the measuring medium.

Preferably, the device has an optical medium in direct contact with the substance, in particular a first area of the surface of the substance, in an embodiment of human skin, where the detection device for detecting a reaction signal detects a parameter change of the optical medium, in particular in an area adjacent to the first area, as a result of the reaction signal, in particular a deformation and/or density change of the optical medium as a result of local time-dependent heating. The optical medium may be altered by an optical or infrared or ultraviolet heating reaction, generally for the purpose of heating and cooling the measuring beam, resulting in a change in the material, such as transparent glass, zinc (Zinc-Zinc-Zinc), silicon (SiO-SiO-Si), or a material that is transparent (SiO-Si-Si-Si) or transparent (SiO-Si-Si-Si-Si) or a material that is in a state of local heat transfer, such as a crystal, a material or a material in a material, or a material, or a material, which is in a state of heat transfer, or heat transfer, and conduction, or in a local thermal analytical medium, such as a material.

The substance may be the tissue of a living organism, in particular a human being, in one embodiment, the surface of the substance being the skin, and substances in the tissue may then be analysed or measured.

The detection device may also be provided with a piezoelectric element connected to or integrated into the optical medium as a detector to detect voltage, distortion and/or density change.

In addition, it may be provided that the detection device shall have at least one temperature sensor as detector for the detection of the reaction signal, which may be located directly on or around the optical medium, depending on the measurement principle.

Preferably, the device shall have a device for modulating the intensity of the excitation beam.

The detection device shall preferably be capable of detecting a time-dependent response signal depending on the wavelength of the excitation light and/or the intensity modulation of the excitation light.

It may also be provided that the excitation device emits at least one electromagnetic excitation beam into a volume of material below a first area of the surface of the material.

In particular, the stimulation device is preferably composed of two or more transmitters, in particular in the form of a one- or two-dimensional array of transmitters, which may be formed as a surface array of transmitters or as a band of transmitters (in one embodiment, semiconductor laser arrays or QCL arrays, where QCL stands for quantum cascade lasers).

In addition, it may be provided that the two or more transmitters each generate their own electromagnetic excitation beam and radiate it into the volume below the first range. The different excitation beams may be transmitted successively or at least partially simultaneously. The different transmitters may also operate simultaneously at different modulation frequencies.

The wavelengths of the electromagnetic excitation beams of the two or more transmitters are preferably different; the wavelengths are preferably chosen in such a way that a substance to be detected in the substance to be analyzed absorbs radiation of these wavelengths particularly well; additional or alternative wavelengths or wavelength ranges which do not absorb the substance to be detected but which are absorbed by other substances (so-called tolerant wavelengths) may also be chosen to distinguish the substance to be analyzed from other substances.

The excitation device consists of two or more lasers, in particular in the form of a one- or two-dimensional laser array, where several rows of laser elements may be stacked and arranged in succession to save space, in the form of a laser bar, and/or two or more light-emitting diodes, in particular in the form of a one- or two-dimensional diode array, also deeply stacked and arranged against each other, in the form of a flat array or a bar. The outputs of the arrays may have the same beam output for each beam individually, either close together or in parallel, or by means of integrated optics.

As regards the design of the device, provision may be made for the stimulation device to be mechanically fixed, directly or indirectly, preferably by means of an adjustment device, to an optical medium in direct contact with the fabric, in particular the first area of the surface of the fabric, so that the stimulation device can be adjusted and fixed to the optical medium at the time of manufacture or at least before use in operation.

The optical medium may have at least an integrated lift and/or hoist, such as a stand, shoulder, suspended sphere, suspended frame, cone or bore, nut, nozzle or other hoist, in which or to which the said elements (the stimulation device and/or elements of a detection device) are mounted, supported or adjusted or fixed, and may also be provided for working aligned pass surfaces by machining the optical medium or in a casting process.

As regards the intensity modulation device, it may be provided that it comprises or is formed by an electrical or electromechanical modulation device which is electrically connected to and in particular electrically controlled by the stimulation device; the modulation device may produce an intensity modulation of the stimulation beam, in one embodiment a periodic intensity modulation, furthermore, for example in the form of rectangular pulses, a sawtooth function or a sine function or another periodic function.

Alternatively or additionally, the intensity modulation device may include at least one controlled mirror in the beam path, the control of which allows the intensity of the excitation beam to be modulated by deflection.

Alternatively or additionally, the intensity modulation device may comprise or be formed by at least one layer, which is controllable in terms of its transparency, arranged in the beam path. Thus, the modulation element may be designed in the form of a transmission element controlled in terms of its transmission. The modulation element may produce several light rays from a beam of light, separated spatially. The modulation element may also be provided in one embodiment to roughen the surface of a sample. The modulation element may be controlled in one embodiment together with the array of light sources/laser sources.

A device for transmitting a measuring beam, in particular a measuring beam, shall be provided in an embodiment for transmitting the measuring beam to the area of an optical medium which is in contact with the first area of the surface of the material.

The device to emit a measuring beam and the detection device shall be so arranged in the embodiment that the detection device, as the time-dependent response signal, detects the measuring beam after it has been reflected at least once at the interface of the optical medium in contact with the substance, in particular the first area of the surface of the substance.

In view of the ease of installation, it is advantageous to have the device for transmitting a measuring beam and/or the detection device and/or the stimulation device mechanically fixed directly to the optical medium and/or coupled to it by means of one or more light-wave conductors.

Design in which the optical medium directly bears an image optic and/or an image optic is integrated into the optical medium is also conceivable.

In addition, designs are conceivable in which the surface of the optical medium has several inter-inclined sub-surfaces on which the measuring beam, in particular the measuring beam, is reflected several times.

The device may also be equipped with one or more mirror surfaces in or on the optical medium for reflecting the measuring beam, in particular the measuring beam.

In view of a compact design, it is conceivable that the stimulation device and/or the device for the emission of the measuring beam and/or the detection device are attached directly to each other or to a common support. These different devices may be attached to the support in one embodiment by welding or gluing or by screwing or by a restraint connection, with adjustment being possible either during assembly or later by a rectifier or other mechanical device. In particular, the device for the emission of the measuring beam and/or the detection device should be well aligned or aligned to each other. It may therefore be reasonable to use both devices on the same optical platform. The device may be integrated into a common direction of measurement/determination and may be used as a common optical controller or as a means of maintaining the optical beam in a more or less parallel position, even in relation to a particular conductor or media. The device may be integrated into a common direction of measurement/determination and may be used as a means of maintaining the optical controller or the optical controller in a more or less direct position relative to each other, and also in relation to a particular conductor or media.

The support shall preferably be made of a printed circuit board, metal or plastic plate or a housing or part of a housing of the device.

It may also be provided that the stimulation device comprises an integrated semiconductor module containing one or more laser elements and at least one micro-optical component and preferably a modulation element, which may be made together from a semiconductor core, etched in one embodiment or at least contained in a common housing.

It may also be provided that the modulation element shall have at least one moving and positionally controllable element relative to the other semiconductor unit, in particular a mirror, which may be controllable by a MEMS device.

It may also be provided that the modulation element has a layer that can be controlled in its radiation permeability.

The modulation element may also be provided with an electronic control circuit for modulating one or more laser elements, and may be designed in such an embodiment that it alters the excitation beam time-dependently by interference, phase shift/pass shift, or a pole filter device or other known modulation mechanisms.

The micro-optical component (s) may be mirrors or lenses integrated into or derived from the semiconductor component, in particular those derived from etching.

The device for analysing a substance described may have a measuring value for a substance concentration, in one embodiment a glucose concentration. The device may have an interface to a device for displaying and evaluating measuring values, for example by means of a colour code, for a user of the device and/or to a dosing device for a substance which may be released into the substance, in particular into the tissues or, more generally, into the body of a living organism. The device may also include such a dosing device directly. The device may also have a measuring or analysing device for the surface of the substance, in one embodiment, the surface of the skin or in one embodiment, the surface of the iris or iris of an organism,which allows the identification of a person or organism by reference to reference data and can thus be used to ensure that appropriate reference and/or calibration values are provided for the analysis of the substance and the control of the dosing device. Determined characteristics of the surface of the substance, in an embodiment, a fingerprint or the structure of an iris of an eye, can be used not only to identify and authenticate a person but also to encrypt the communication of state values and control of the dosing unit, which can, in principle, be derived from the database, whether encrypted or unencrypted. The dosing unit can be equipped with a sensor to detect the presence of a substance in a filling;be provided with a device such as an insulin and/or glucagon, heparin or anaesthetic and have a device to transmit the level of the fill to the device for analysis of substances and/or directly to the database.

The device may also have an interface, in one embodiment, a radio interface to the database to which the measured values can be sent and which can process the data. The database may be designed to process and store data from several patients, i.e. in one embodiment, data from several identical devices for analysing a substance and in one embodiment, control individual dosing devices for delivering substances. The database may also process the data obtained on the analyzed substance and derive analysis results such as a trend of values, temporal first and second derivations, minimum, maximum, standard deviations of substance amounts or concentrations,The database may also record and process the level of filling of the dosing device in order to determine in an embodiment a time range of filling or the need for refilling and to signal directly to the patient's device or a service facility. For this purpose, the database may be connected to a communication device in a service facility, in an embodiment to a hospital or a doctor's office. For the purpose of transmitting data to and/or from a database, the device may be connected in an embodiment by means of a radio transmission, in a Bluetooth or WLAN or other wireless or mobile transmission method or by a blood-transfer device.The device may also be directly equipped with a Wi-Fi interface and an Internet client.

The subject also refers to a method for analysing a substance whereby, in the process with an excitation device, at least one electromagnetic excitation beam, with at least one excitation wavelength, is generated by the operation of at least partly simultaneous or consecutive laser beams from a laser light source, a reaction signal is detected by a detection device and analysed from the detected reaction signal of the substance.

An embodiment may provide for the sequential detection of reaction signals, in particular time-scale reaction signal paths, using different modulation frequencies of the stimulation device and for the interconnection of several reaction signal paths at different modulation frequencies, in particular to obtain information specific to a deep region below the surface of the substance.

It may also be possible to determine reaction signal paths at different modulation frequencies for different wavelengths of the excitation beam, in particular to obtain information specific to a depth below the surface of the material. For example, if several modulation frequencies of the pump beam are used at the same time, it is possible to resolve the detected signal according to their frequencies by a corresponding analytical method, e.g. an integral transformation, e.g. a Fourier transformation; the FT would only filter out the signal corresponding to the desired frequency.

It may also be provided that an optical medium is brought into direct contact with the substance, in particular a first area of the surface of the substance, the radiation beam emitted is generated by the excitation device and, in particular, radiated in such a way that it enters the optical medium and leaves it at a predetermined point on the surface of the optical medium, a device for measuring a measuring beam is generated by a measuring beam, in particular a light beam, in such a way that it enters the optical medium and that, in particular, the measuring beam and the excitation beam are reflected in operation at an interface between the optical medium and the surface of the measuring beam at which the measuring beam is reflected, and are reflected indirectly or through a detection device and the direction of the measuring beam is measured and the reflected beam is reflected.

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To eliminate reaction signals from the top layers of the material, one embodiment may use changes in measurement values compared to previous measurements if the measurement values in the top layers change less or more slowly compared to other, lower layers. This may be the case in an embodiment for measurements on human skin where the top layers of the skin are practically not interchanged with the lower layers and therefore physiological parameters are not very variable.

It may also be provided that, depending on the concentration of the substance in the substance, a dosing device is controlled to deliver a substance, in particular into a patient's body, and/or an acoustic and/or optical signal is given and/or a signal is given via a radio connection to a processing device, depending on the measured substance concentration in the substance. This may include, in addition to a measured value, a time evolution of the measured value, a derivation of the measured value, averages of measured values, maximum, minimum, standard deviation and predetermined thresholds of measured values, and be linked to the current measured value. The processing device may be in an embodiment or connected to a database that collects and processes data from several patients. The device may be connected directly to a data bank or a communication interface from and to this control unit.

In order to ensure greater safety in the operation of a dosing device, in particular for insulin, provision may be made for the device to be operated locally or from a database by means of a standard preset procedure with preset doses at specified or determinable times and for the device described above to detect meaningful deviations from preset doses, which are used to correct and improve the control of the dosing device, thus ensuring at least one normal or emergency operation of the dosing device even in the event of a failure of the device.

The method of the invention may also provide that the measurement, which involves the detection of the response signal at one or more modulation frequencies or time resolution after a transmission pulse and at one or more wavelengths, is repeated successively at different input/input angles of the stimulus beam and that the results are linked, in particular subtracted, to eliminate or reduce the effects of the upper skin layers, at least at or near 90 degrees, i.e. at the lowest angle of the input of the stimulus beam into the skin/substance to be analysed.

This concept assumes that the stimulation signal travels a longer distance in the upper and upper layers of the skin at a flatter, smaller angle of incidence than at a steeper, larger angle of incidence, so that a greater proportion of the stimulation radiation is absorbed in the upper layers of the skin at a smaller angle of incidence than at a larger angle of incidence, so that the influence of the upper layers of the skin can be at least partially isolated and partially eliminated by linking the measurement results at different angles of incidence.

The advantage is that the area in which the excitation radiation is absorbed does not shift appreciably parallel to the surface of the material, in particular the skin, by changing the angle of incidence. Angle changes between the different entry/invasion angles of at least 5 degrees, in particular at least 10 degrees, and in particular at least 20 or at least 30 degrees can be achieved by refraction or reflection of the excitation beam outside or within the optical medium, within the medium, for example by a targeted change in the index of refraction, for example by applying an electrical voltage to the crystal of an electro-geological optical effect.

The above framework may also provide for a method whereby the measurement involves the detection of the response signal at at least one modulation frequency chosen so that the resulting thermal diffusion length, which is a function of the modulation frequency, allows a sufficiently deep reading of the sample.

In addition, when measuring the response signal at at least one or more modulation frequencies, the phase position of the response signal may be included in the evaluation, so that amplitudes and phase positions of one or more frequencies may be linked, for example by subtracting the amplitudes and/or calculating phase-dependent signal responses.

The procedures described above may also provide that the sample beam is operated at least temporarily during the measurement in the wavelength range between 15000/cm and 16000/cm, in particular temporarily between 15500/cm and 16000/cm, and further temporarily between 15700/cm and 16000/cm.

It may also be provided that, in a measurement where the excitation beam is successively adjusted to different wavelengths and/or wavelength ranges, at least 5% and in particular at least 10% and at least 30% of the wavelength range covered are in areas of the spectrum which are insensitive to the substance to be detected, in particular glucose.

A range or point of the spectrum is considered insensitive for the purposes of this application for a substance to be detected in a sample if the absorption intensity of the sample in that range or point of the spectrum is independent of the amount and/or concentration of the substance in the sample, which usually means that the substance does not have any identifiable absorption bands in that range of the spectrum.

In addition, for the purpose of measurement to be as smooth and accurate as possible, provision may be made for at least one or two wavelength ranges or wavelength ranges without significant glucose absorption to be used to measure absorption, taking into account the absorption behaviour independent of glucose concentration of the sample or tissue.

For this purpose, it may be provided that at least one of the wave number ranges is between 1610 and 1695 cm-1 (Amid 1).

It may also be provided that at least one of the wave number ranges is between 1480 and 1575 cm-1 (Amid 2).

In addition, it may be provided that a depth range in the sample to be tested is first selected for measurement and that the beam of excitation is then controlled so that at least one period is allowed between time ranges (beams of excitation) in which the beam of excitation is emitted, corresponding to the diffusion time of a thermal wave required to travel the distance between the depth range in the sample to be tested and the surface of the sample.

This allows specific substances to be detected at specific depths or depths below the surface of the sample, as well as the concentration profile depending on the depth.

It may also be possible to measure the absorption intensity over time after the end of a time period in which the excitation beam is emitted, so that the phase position of the response signal can be taken into account in the evaluation, as an alternative or in addition to the absorption intensity.

In addition, it may be provided that a series of stored equidistant or non-equidistant settings, each determining a laser wavelength, are set in sequence to control a laser to produce the excitation beam, and that in particular at least 3 or 5 wavelengths of the absorption maximum of a substance to be detected are set. (lookup table)

It may also be provided that before and/or during and/or after a measurement, the mechanical pressure and/or force per unit area with which the optical medium in which the beam is reflected is pressed against the sample is recorded, so that effects of pressure on the sample or optical medium can be extrapolated from the measurement results or taken into account in the evaluation.

It may also be provided that, before and/or during and/or after a measurement, the ambient air humidity and/or a sample humidity content or the upper layers or surface humidity of the sample are determined.

This allows the effects of moisture in the sample or measuring device to be calculated from the measurement results or taken into account in the evaluation.

The invention also relates to a method for analyzing a substance whereby the method, using an excitation device, produces at least one electromagnetic excitation beam (EA) with at least one excitation wavelength by the consecutive operation of one or more or at least partially simultaneous operation of several laser emitters of a laser light source, Other a reaction signal (SR) is detected by a detection device and the substance is analysed on the basis of the detected reaction signal (SR).

The successive operation of one or more or at least partially simultaneous operation of several laser emitters may produce the different wavelengths which may be at or near absorption maxima at characteristic wavelengths of a substance detected in the substance.

In addition, the invention relates to a process by which the temperature of the laser emitter of the excitation device and/or the temperature of the detection device, in particular of an optical medium and/or a detection radiation source and/or an optical sensor, is kept constant during analysis, in particular at a specified temperature, and further, in particular, at a specified temperature above the human body temperature, preferably above 37 degrees Celsius, preferably above 38 or 40 degrees Celsius.

This measure allows the temperature to have a minimal impact on the measurement, and also avoids heating by body contact if the measuring device is kept at or above body temperature, at least during the measurement, by means of a temperature control device with a heating element and one or more sensors.

The invention also relates to a method whereby the temperature of the laser emitter of the excitation transmitter and/or the temperature of the detection device, in particular an optical medium and/or a detection radiation source and/or an optical sensor, is recorded during analysis and taken into account in the evaluation of the analysis by linking the measurement results with temperature correction values.

This method calculates the effects of temperature.

A further development of the invention may involve pressing the substance, in particular a body part, in particular a finger, against an optical medium which is part of the detection device, detecting the pressure exerted on the medium by the body part being pressed and, depending on the pressure exerted on the medium, switching on and/or off the stimulation device depending on a reduction in pressure, in particular below a certain threshold. In this way, a pressure sensor determines whether the measuring unit is being used and/or whether the optical medium is being covered by an object in the direction in which it is measured. In this case, the stimulation is released in the direction in which it is measured. This method prevents the greater part of the stimulation from reaching the optical or external environment even if no other measuring medium is used.

It may also be provided that the substance, in particular a body part, in particular a finger, is pressed against an optical medium which is part of the detection device, that a dimming of the medium is detected in the area of the body part being pressed and that dimming of the medium turns on and/or off the stimulation device by increasing the brightness in the medium, in particular above a certain threshold.

A brightness sensor/photodetector is used to determine whether the measuring device is in use and/or whether the optical medium is covered by an object being measured.

It may also be provided that the substance, in particular a body part, in particular a finger, is pressed against an optical medium which is part of the detection device, that a moisture level of the medium is recorded in the area of the pressed body part and that the stimulation device is switched on and/or off by reaching a specified moisture level at the medium, in particular by reducing the moisture level below a certain threshold.

In this constellation, a moisture sensor is used to determine whether the measuring device is in use and/or whether the optical medium is covered by an object being measured.

A further development of the invention may be that during the execution of the process a body part pressed on the optical medium is fixed to the medium, in particular by clamping the body part to the medium, gluing the body part to the medium, adhesion of the body part to the medium or vacuum suction of the body part to the medium.

This creates more stable measuring conditions, allowing a minimum time for measurement, and improves measurement accuracy and reliability.

In addition, it may be provided that the excitation beam ((SA)) is emitted with at least two or more excitation wavelengths or groups of excitation wavelengths, with a first excitation wavelength or group of excitation wavelengths allowing the detection of a substance to be detected in the substance, while at least one additional excitation wavelength or group of excitation wavelengths allows the detection of a reference substance different from a substance to be detected, and that profiles are determined and linked for at least two different substances with respect to their density distribution in the depth of the substance, and in particular a depth profile or at least one or more parameters of a depth profile of the reference substance in the substance are known.

This method takes advantage of the fact that the depth profile of several substances can be determined independently by appropriate selection of the excitation wavelengths, and if a depth profile of a substance introduced into the skin or already present there is known, the depth dimension of another measured substance can be adjusted according to physiological laws.

It may also be provided that the excitation beam (SA) is modulated, preferably in sequence with different modulation frequencies, by detecting response signals for different modulation frequencies or by analysing a time behaviour of the response signal when the intensity of the excitation beam changes, in particular when it is periodically switched on and off.

This measurement method allows the determination of the depth dimension from which the reaction signals come to the excitation beam without the use of different modulation frequencies or with only a few modulation frequencies. The reaction signals coming from different depths can be determined on the one hand by the dependence of their intensity on the modulation frequency, but also by the time behaviour of the reaction signals when a change in intensity of the excitation beam (e.g. when it is switched off).

Signals from lower depths follow the intensity changes of the excitation beam more quickly than signals from greater depths.

The modulation of the excitation beam (SA) may be provided by controlling a laser device (100) generating the excitation beam.

A further design of the invention may provide that the excitation beam is modulated with between 0 and 10 modulation frequencies, preferably with between 0 and 5 modulation frequencies, further preferably with between 1 and 3 modulation frequencies, further preferably with only one modulation frequency, and the time behaviour of the reaction signal, in particular a phase sensitive behaviour of the reaction signal, is analysed.

It may also be provided that the sensitivity of the excitation beam (SA) is between 3% and 60%, preferably between 3% and 50%, and preferably between 3% and 7%.

A further embodiment of the invention may provide that the power density of the excitation beam (SA) at the surface of the substance to be analyzed is less than 5 mW/mm2, in particular less than 2 mW/mm2, and further, in particular less than 1 mW/mm2.

This avoids heating of the substance to be analysed and saves the laser light source.

It may also be provided that the optical medium of the detection device is brought into contact with a body part, in particular a finger and/or a dialysate vessel and/or a blood vessel of a dialysis apparatus, and that in particular one or more excitation wavelengths are selected to detect urea, cholesterol, albumin, protein, creatinine, lactate or phosphates.

This allows both the dialysis process and the monitoring of dialysis patients to be carried out continuously with the measuring device of the invention.

Figures 1 to 24 show schematically different elements of the device and their elements in various embodiments, concepts of the invention and their application.

Figure 1 shows an example of a device 10 for the analysis of a substance 101 that preferably lies directly on an optical medium 108 which may be formed as an optically transparent crystal or glass body or plastic body or plastic crystal.

The device includes an excitation device 100 to emit one or more electromagnetic excitation beams SA, preferably in the form of excitation light beams with one or more excitation wavelengths, into a volume 103 located in the substance 101 below a first region 102 of the surface of the substance. The excitation device 100 is hereinafter also referred to briefly as the excitation light source 100. The excitation light source 100 may be a quantum cascade beam, in particular a laser-tunable one, which is tunable in wavelength; preferably, as described below, a light source line or light sources with at least two intermediate beams, in particular individual beams, each of which is equipped with a front half-wave, which are tuned in the same way.

In addition, a device 104 for modulating the intensity of the SA beam (s) shall be provided, preferably consisting of a modulating device for the light source, in particular its control, and/or at least a controlled mirror in the beam direction and/or a layer which is controllable in terms of its transparency and is in the beam direction.

The device shall also have a device 105 for the emission of an electromagnetic measuring beam 112, in particular a measuring beam, reflected, preferably totally, at the interface GF between the material 101 and the optical medium 108.

A detection device 106 is used to detect the reflected measuring beam 112 which forms a time-dependent response signal SR; the amplitude of the response signal SR is affected by the wavelength of the SA light and the intensity modulation of the SA light, as further explained below by examples.

The amplitude of the measuring signal depends on the wavelength of the control beam, the absorption properties of the sample and the thermal properties, in particular the thermal diffusivity and thermal conductivity of the sample and the optical element.

A device 107 for the analysis of the substance evaluates the detected SR response signals and generates an embodiment of a glucose or blood glucose indication BZA.

The operation of the device 10 described in Figure 1 and a method for analysing a substance 101 in the case of human or animal tissue, and for determining a BZA for glucose or blood glucose, are described below.

The apparatus 105 radiates an electromagnetic measuring beam 112, preferably a beam of light in the visible wavelength range or an infrared beam, into the optical medium 108 and this measuring beam 112 hits the boundary surface GF below the first area 102 of the surface of the fabric. At the boundary surface GF the measuring beam 112 is reflected and passes to the detection apparatus 106 which measures the reflected measuring beam 112.

The excitation light source 100 shall simultaneously generate one or more excitation rays SA, preferably infrared rays, the wavelength of which is preferably in the range of 3 μm to 20 μm, and preferably in the range of 8 μm to 11 μm.

The SA beams are intensity or amplitude modulated by the intensity modulation device 104. In one embodiment, the intensity modulation device 104 produces short pulses of light, preferably with a pulse frequency between 1 kHz and 10 MHz, further preferably between 1 kHz and 3 MHz, or pulse packs (double or multiple modulation), preferably with a frequency of the envelopes of 1 Hz to 10 kHz.

The modulated SA beams are coupled to the optical medium 108 and pass the GF interface into volume 103 within the tissue.

The wavelength of the SA stimulation beam is preferably chosen so that, in view of the blood glucose measurement described here, the SA stimulation beam is significantly absorbed by glucose or blood glucose. The following infrared wavelengths are particularly suitable for measuring glucose or blood glucose (vacuum wavelengths): 8.1 μm, 8.3 μm, 8.5 μm, 8.8 μm, 9.2 μm, 9.4 μm and 9.7 μm. In addition, glucose-tolerant wavelengths not absorbed by glucose can be used to detect other substances present and to exclude their influence on the measurement.

The absorption of the SA excitation beams in the tissue creates a local temperature increase in the volume 103 region, which generates heat transport and heat waves and consequently pressure waves towards the boundary surface GF; the resulting temperature and pressure fluctuations at the boundary surface GF modulate the refractive index or deformation, microstructure and reflection behaviour in the area 102 or the boundary surface GF region respectively and affect the radiation path of the measurement beams 112.

For example, assuming that the alignment between the device 105 and the detection device 106 is optimal without the SA excitation beam and maximum reception power is detected by the detection device 106, the absorption of the SA excitation beam in the volume 103 range and the heat transport and pressure waves may cause a (at least temporary) change in the amplitude or, in the case of periodic modulation, phase of the reflected measurement beam 112 or an intensity modulation of the reflected measurement beam 112.

The change in the reflection of the measuring beam 112 or the time-dependent change in the response signal SR shall be quantified by the detection device 106 and the detection result D shall be transmitted to the device 107.

The unit 107 may derive a BZA from previously performed calibration or comparison measurements, stored in an embodiment in the form of comparison tables or comparison curves in a storage tank 107a of the unit 107, on the basis of the current concentration of glucose or blood glucose within the tissue or volume 103 respectively, and produce an appropriate glucose or blood glucose indication.

Particularly preferred designs and variants of devices 10 for the analysis of a substance 101 are described below with reference to Figures 2 to 10.

The excitation device 100 for the emission of the excitation light beam or beams may be formed as an array as shown in Figure 2 and shall have at least 5, preferably at least 10, further preferably at least 15, or at least 50 or 100 individually controllable emitters 100a for each monochromatic light in the absorption spectrum of a substance to be analysed.

The array preferably produces beams of monochromatic light with one or more, and preferably all, of the following wavelengths (vacuum wavelengths): 8,1 μm, 8,3 μm, 8,5 μm, 8,8 μm, 9,2 μm, 9,4 μm and 9,7 μm, and if desired additional glucose tolerant wavelengths.

The device 105 for the emission of the measuring beam 112 and the detection device 106 may be arranged separately from the optical medium 108 as shown in Figure 1.In view of the minimum space required and the minimum installation effort, it is considered advantageous to have the device 105 for the emission of the measuring beam 112 and the detection device 106 mounted directly on the optical medium 108 preferably on opposite sections of the optical medium 108 108a and 108b, as shown in Figure 3.

The device 109 may be provided with a mechanical connection to the optical medium 108 directly or by means of an adjustment device 109 and preferably allows adjustment of the distance of the light source 100 from the optical medium 108 or adjustment in the direction of the beam and/or adjustment in the plane perpendicular to it (see Figure 4).

As shown in Figures 3, 4, 6, 7 and 8, the device 105 may be designed to emit the measuring beam 112 into the area of the optical medium 108 in contact with the first area 102 of the surface of the material, such an arrangement enabling the measuring beam 112 to be emitted at a flat angle and to produce a total reflection at the interface of the optical medium 108 with the material 101.

The mirage deflection can be made more effective by irradiation at a flat (small) angle (to the sample surface) similar to the well-known photothermal 'bouncing method', while reducing the deformation-related deflection of the measuring beam.

Conversely, by irradiating at steeper angles (to the surface of the material) the deflection can be made more effective by analogy with the well-known photothermal 'bouncing method', while at the same time reducing the mirage effect caused by the deflection of the measuring beam.

See the literature on this subject: Other - M. Bertolotti, G.L. Liakhou, R. Li Voti, S. Paolino, and C. Sibilia. Analysis of the photothermal deflection technique win the surface refection theme: theory and experiment.

The device 105 for the emission of the measuring beam 112 and/or the detection device 106 for the detection of the measuring beam 112 or the response signal SR may be mechanically fixed to the optical medium 108 directly or by means of an adjustment device and/or be coupled to it by means of one or more light-wave conductors 120.

It may also be provided, as shown in Figure 6, that the optical medium 108 carries directly an image optic 128 and/or an image optic 129 (each) in the form of a lens or other reflective or deflective medium and/or that an image optic is integrated into the optical medium 108. However, the image optic may also be integrated into the excitation device or the measuring beam generation device in the form of a lens or other reflective or deflective element, for example, if these are formed as integrated components and/or as semiconductor components. The image optic training source may be integrated into an output circuit by means of an additional element, such as a beam controller or a beam controller integrated into the measuring device.

It may also be provided, as shown in Figure 7, that the surface of the optical medium 108 has several inter-inclined sub-surfaces 110, 111 on which the measured beam 112 is reflected or refracted several times.

In addition, as shown in Figure 3, one or more mirror surfaces 113, 114 may be provided in or on the optical medium 108 to reflect the measuring beam 112 (and thus the response signal SR) by means of inhomogeneities within the optical medium 108 or its outer surfaces or by means of mirror elements integrated/fitting/infused or fixed to the optical medium, e.g. metallic or metallic coated, thereby extending the optical path of the surface light reflection of the measuring beam 112 in the optical medium 108 to the direction of detection 106, so that a measuring reflection of the optical medium 102 is reflected in the direction of detection 108, and then, after the first contact of the reflection with the detection medium 108, the optical reflection of the measuring beam 112 is reflected in the direction of detection 108, so that a signal reflection of the optical reflection of the measuring beam 102 is reflected in the direction of detection 108.

The detection device 106 may have several optically sensitive surfaces, such as optically sensitive semiconductor diodes, or may have several displaced openings 116, 117, 118 (Figure 5) in a connection body 119 at the end of which individual light-wave conductors 120 (Figure 4) are coupled to the light of the measuring beam 112 depending on its deflection. The light-wave conductors 120 are then connected to a connection body 119 which may be fixed to the optical medium 108 and direct the light to the part of the detection device 106 (Figure 4) located at the end of the light-wave conductor 120 as part of the detection device 106 for the measuring beam, as are the light-wave conductors 120.

For completeness, the excitation transmitter may also transmit the excitation, in whole or in part, to the surface of the material by means of one or more light-wave conductors. In one embodiment, the excitation transmitter may be directly coupled to one or more light-wave conductors coupled to the optical medium.

It may also be provided, as shown in Figure 8, that the stimulation device 100, the device 105 for the emission of the measuring beam 112 and the detection device 106 are attached directly to each other or to a common support 121. The support may consist of a plastic part, a circuit board or a metal sheet mounted in a housing 122. The support, which is shaped in the form of a U in the cross-section shown in Figure 8, may then at least partially encircle the optical medium 108 in one embodiment. The optical medium may also be attached to and adjusted to the support.

The support may also be formed by the housing 122 itself or by a part of the housing.

It may also be provided that the device with housing 122 is to be attached to the body 123 of a person, with the stimulation device 100 to emit one or more stimulation light beams SA, the device 105 to emit the measuring light beam 112 and the detection device 106 to detect the time-dependent response signal SR arranged and designed so that the measurement side (with a transparent window for stimulation) of the device is on the side of the device that is attached to the body, so that the substance to be analysed is on the body-facing side 124 of the housing 123 Page 122 To this end, Figure 8 shows that the sensing device 124 123 is a device which is used to detect the time-dependent response signal SR 125 by means of a device which is then mounted in the form of a device which is in an optical way, or which is mounted on the hand-facing side of the device, and which is then mounted on the side of the device, which is not adjustable to the body, and which is then moved by the walking device.

As shown in Figure 8, a dashed diagram of the fingerberry 126 can then be placed on the optical medium 108 and measured.

The optical medium 108 may be mounted within the housing 122 as well as the support 121 or directly to the housing 122. The optical medium 108 may also be directly connected to the support 121, with an adjustment device 127 to position the support 121 relative to the optical medium 108.

It is also conceivable to attach the excitation light source 100, the device 105 and the detection device 106 or even one or two of these elements directly to the optical medium 108 and the other element or elements to the vehicle 121.

Through the optical window in housing 122 and/or through the optical medium 108 other parameters of the fabric surface or the fingerprint 126 may be measured, such as a fingerprint in an embodiment. For this purpose, the housing may also include an optical detector 130 in the form of a camera, for example, attached to the support 121 which, through the optical medium 108, digitally captures an image of the fabric surface. This image is transmitted within a processing device 107 which is directly connected to the detection unit and also to the stimulation unit, and which may process the data from the detection unit 106. The processing device may also receive the measurement control information. It may also be separated from the other devices and communicate with them at least via a partial connection.

The image data from camera 130 can thus be processed inside the housing or via a radio connection outside the housing and compared with a personal identity database to retrieve calibration data of the identified person.

Such calibration data may also be stored remotely in a database, in an embodiment of a cloud, and the measurement data from the detection device 106 may be further processed both inside and outside the enclosure.

If data is processed outside the housing, the resulting data should preferably be radiated back to the device inside the housing for display.

In any case, the display may be fitted to the housing 122 and be read by the optical window, or in some embodiments, even partially by the optical medium. The display may also project a light indicator onto a display surface through the optical window and may have a projection device for this purpose. The display may display in one embodiment a measurement or analysis result, in particular a glucose concentration. The output may be a character or colour code in one embodiment. The display or a device parallel to it may in one embodiment suggest an insulin dose depending on other patient parameters (e.g. insulin factor sigma) or an automatic signal transmission in a direction of insulin delivery.

The device can be connected to and from an external data processing unit 131 by any standard, such as light, cable, radio (e.g. Bluetooth, WiFi), or ultrasonic or infrared signals.

Figure 9 shows a modulation device with a controller 132 modulating the stimulation device 100 to control the measuring beam.

Figure 10 shows an excitation light source 100 in front of which a mirror device, in particular a mirror device powered by a micro-electromechanical system (MEMS) 135 with one or more microspecs 133, 134 as known from optical image projection technology, is positioned to temporarily redirect the excitation light beam to a redirection 136.

Figure 11 shows an excitation light source 100 in front of which an optical layer 138 is placed in the excitation beam, controllable for transmission by a control device 137, in an embodiment with LCD cells.

In conclusion, the device and measurement procedure described above, especially when used to measure glucose in patients, save patients the painful and inconvenient invasive measurement and thus also allow regular and more frequent measurement.

The sensitivity of the measuring device is easily 30 to 300 mg/dL. Dependencies of the measurement results on substances other than glucose, such as alcohol or medications in the blood are minimal or nonexistent.

Err1:Expecting ',' delimiter: line 1 column 445 (char 444)

The photothermal detection method described in Figure 15 shall be used.

The laser beam (stimulation beam) penetrates the skin to a depth of up to 100 micrometers and reaches glucose molecules in the skin's interstitial fluid. As a result of the light absorption and associated energy transfer, a heat wave is generated, which travels to the skin surface and can be detected there with the photothermal detection element described above. This uses a detection or laser beam, the deflection of which in the optical medium depends on the heat effect of the heat wave in the optical medium. The deflection is recorded as an indicator of the absorption of the radiation by the glose.

The stimulation laser beam, when applied to the skin, penetrates the stratum corneum, i.e. the dead skin cells on the surface that do not contain current glucose levels. The stimulation beam reaches the stratum granulosum and stratum spinosum with relevant glucose proportions. The glucose level in these layers immediately follows the blood glucose level; the blood glucose level of the interstitial fluid is about 85-90% of the blood glucose level. This is especially true for well-circulated parts of the body, such as the fingertips, thumbs, earlobes and lips.

Some disturbances in measurements due to variations in the outermost skin layers may occur from subject to subject and may also be time-dependent.

To eliminate or minimize such disturbances, measurements are taken from different depths of the skin (distance ranges to the skin surface) and the infrared spectra are determined for several modulation frequencies of the stimulation beam (Figure 17, Figure 18) and used to eliminate upper skin effects by linking the spectra.

As a result, the method described for measuring glucose levels can compete with the previously used invasive methods in terms of accuracy and reliability (see Fig. 19).

Figure 20 shows a measuring device similar to those shown in Figure 8, with the same reference marks for the same functional elements.

Figure 20 shows various temperature sensors 150, 151 and 152, which may be used individually or in groups or all in a measuring device, with sensor 150 taking into account the temperature at the stimulation device 100, i.e. at a laser or laser array, temperature sensor 151 the temperature at an optical medium 108 and temperature sensor 152 the temperature at a detection device, e.g. at a photodetector. One or more partial temperatures may be taken into account in the analysis of the substance by means of correction coefficients for the radiation intensity of the stimulation device 100 or for the sensitivity of the entire or other parts of the detection medium at the external temperature of the device. The heat correction coefficient may be measured in the direction of a patient or in the direction of a table or in a temperature measuring instrument, but may not be so high as to be maintained by means of a short temperature change, e.g. at the temperature of the patient or in the direction of an electronic temperature control, or by means of a temperature change, which may be measured in the direction of a table or in the direction of a photodetector.

Figure 21 shows the use of a measuring device to measure a concentration of urea, the excitation light wavelengths being chosen to allow the detection of urea, i.e. the absorption wavelengths of urea. The measurement can be performed on a body part, but also on a dialysis line 15 or a blood line of a dialysis device.

Figure 22 shows a measuring device with a moisture sensor 155 to detect whether an object is exposed to the optical medium 108. Only when the moisture is high or when the moisture is detected in a specified value window, the stimulation device is released or activated to prevent the stimulation radiation from reaching the environment more than necessary, even if it is generally safe. The switch operated by the sensor 155 is marked with 156.

At the same time, a device for the suction of air 161, 162, 163 is shown in Figure 22 and 161 un d162 are used to indicate openings terminating at the front of the optical medium and connected to an intake channel. This intake channel may, for example, circle the area of the optical medium to which a body part is being pressed for measurement. The intake openings may also be circularly distributed.

Figure 23 shows a fixing device which creates a hollow in the optical medium into which, for example, a finger can be inserted.

The hollow is formed by a circular raised edge 164 as shown in Figure 23 which may consist of an elastic material or a cushion, in particular a inflatable cushion. A inflatable cushion may also be provided which is inflatable after the application of an object, in particular a finger, and which, when inflated, firmly grips the object (s) and the finger. The measuring device may then be connected to a device to control the pressure in the cushion.

Figure 23 also shows a pressure sensor 158, which may be located, for example, on the back of the optical medium, opposite the front side to which an object is pressed for measurement. e.g. the sensor 158 may have a spring with an approach/path switch and/or a piezo sensor, which generates a signal depending on the pressure being applied and/or a switch 160 to turn the stimulation device on and/or off.

In parallel, a brightness sensor 157 is shown in Figure 23 which can be a photosensor and which detects whether the front of the optical medium is covered by an object, in which case the stimulation device is switched on or off by the switch 159 or otherwise blocked.

Figure 24 shows two depth profiles of the density of two substances present in the substance/body part to be examined, taken or determined by the method and device of the invention. The two substances are detected by means of excitation beams with different wavelengths/groups of wavelengths, for example one or more wavelengths may be chosen as wavelengths at or near which the absorption maxima of the substances to be detected are located. The method of the invention allows the maximum density distribution 166, 167 IT to be determined depending on the depth of the surface to which the substance is applied.

This patent application, as already mentioned in the introduction, covers, in addition to the claims and examples described above, the following aspects: these aspects may be combined individually or in groups with features of the claims; the aspects may also be considered as separate inventions, or may be considered as separate inventions when combined with each other or with claims; the applicant reserves the right to claim these inventions at a later date, either in the context of this application or in subsequent partial or subsequent applications, subject to the priority of this application: 1) methods for analysing a substance in a body,The following shall be included: a beam of light with one or more specific excitation wavelengths passing through a first area of the body surface,intensity modulation of the beam of light with one or more frequencies, in particular in succession, by a component different from a mechanical chopper, in particular by electronic control of the excitation light source, a replacement device for a resonator of an excitation light source, a controller or a movable mirror device, a controllable deflector, a locking or mirror device coupled to a motor, stepper motor or MEMS, or a device for the transmission of a steady-state signal, such as a detector located outside the body of a detector, which is designed to reflect the effects of the radiation in the body, depending on the direction of propagation of the radiation.Other Modulation may be carried out in one embodiment by interference or by affecting the phase or polarization of the radiation of the stimulation device, in particular if it includes a laser light device. (2) Processes described in paragraph 1 by producing the stimulation beam by several emitters or multimeters, in particular in the form of a laser array, which emit light of different wavelengths simultaneously or in succession or in any pulse pattern. (3) Processes described in paragraph 1 or 2 by capturing an acoustic response signal by an acoustic sensor on the first area of the body surface. (4) Processes described in paragraphs 1 to 3 by producing an acoustic response signal by an infrared radiation sensor on the first area of the body surface.In particular, a thermocouple, bolometer or semiconductor detector, such as a quantum cascade detector, is detected.5) Process according to one of the following aspects 1 to 4, including the steps: making contact of an optical medium with a surface of a material such that at least one area of the surface of the optical medium is in contact with the first area of the surface of the body;sending an excitation beam of light of an excitation wavelength into a volume in the material below the first area of the surface, in particular through the area of the surface of the optical medium which is in contact with the first area of the surface of the material;measuring the temperature in the first area of the surface of the optical medium by an optical pyrometric procedure;Analyze the substance on the basis of the temperature increase detected depending on the wavelength of the excitation beam.6) Method according to Aspect 5, characterised by Other the emission of a measuring beam of light through the optical medium to the area of the surface, the optical medium, which is in direct contact with the surface of the material, such that the measuring beam and the excitation beam are immediately adjacent or overlap at the interface of the optical medium and the surface of the material on which the measuring beam is reflected; Other Direct or indirect detection of deflection of the reflected measuring beam depending on the wavelength of the excitation beam; and Other Analyze the substance based on the detected deflection of the measured beam of light depending on the wavelength of the excitation beam.(7) Processes according to one of Aspects 5 or 6 characterised by the measuring beam being produced by the same light source as the excitation beam.8) Processes according to one of Aspects 5, 6 or 7 characterised by the measuring beam being reflected once or more within the optical medium, outside the optical medium or partially within and partially outside the optical medium after the deflection and before detection.9) Processes according to Aspects 1 or any of the other preceding or following characterised by the measuring beam being a modulated intensity, particularly pulsed, excitation beam, particularly in the infrared spectral range, with a modulation rate between 1 Hz and 10 kHz, in particular.preferably between 10 Hz and 3000 Hz.10) process according to Aspect 1 or one of the other preceding or following processes, characterised by the light from the excitation beam (s) being produced by an integrated arrangement of several single lasers, in particular a laser array, simultaneously or successively or partially simultaneously and partially successively.11) process according to Aspect 1 or one of the other preceding or following processes, characterised by the determination of the intensity distribution of the response signal according to the depth below the surface of the reaction signal, according to the different modulation frequencies of the excitation beam.12) process according to Aspect 1 or other preceding or following processes, characterised by:that the phase position of the reaction signals relative to a modulated excitation beam at one or several modulation frequencies of the excitation beam results in a distribution of the intensity of the reaction signals according to the depth below the surface where the reaction signals originate.13) Method according to paragraph 11 or 12, characterised by weighting and interlinking the measurement results at different modulation frequencies to determine the distribution of the intensity of the reaction signals according to the depth below the surface.14) Method according to paragraph 11, 12 or 13, characterised by determining a specific intensity distribution over the depths of the body surface of a substance or a specific absorption density of light in a depth range of a substance or a specific absorption depth.15) procedures as described in paragraph 1 or any of the other preceding and following paragraphs, characterised by at least one biometric measurement on the body in the first area of the surface or immediately adjacent to it, in particular a fingerprint measurement, being carried out immediately before, after or during the detection of the reaction signal (s), and identifying the body, in particular a person, and by attributing reference values (calibration values) in particular to the detection of the reaction signal (s). Other a device to emit one or more excitation beams of one excitation wavelength each into a volume in the fabric below a first area of its surface, with a device to modulate an excitation beam,consisting of a radiation source modulation device, in particular its control, an interference device, a phase or polarization modulation device and/or at least a controlled mirror in the beam path and/or a beam path layer controllable in terms of transparency, and a detection device for: Other Detection of a time-dependent response signal depending on the wavelength of the excitation light and the intensity modulation of the excitation light and with a device for analysing the substance from the detected response signals.17) Device according to paragraph 16 with a device for detecting reaction signals separately according to different intensity modulation frequencies and/or with a device for detecting reaction signals depending on the phases of the respective response signal relative to the phase of modulation of the excitation beam,(a) a device for analysing a substance as defined in paragraph 16 or 17, with an optical medium to make contact of the surface of the optical medium with a first region of the surface of the substance, and Other A device for emitting an excitation beam of one or more excitation wavelengths into a volume in the fabric below the first surface area, in particular through the area of the surface of the optical medium in contact with the surface of the fabric, and a device for: Other Measure the temperature in the area of the surface of the optical medium in contact with the first area of the surface of the material by an optical process;and a device to analyse the substance by the temperature changes detected depending on the wavelength of the excitation beam and the intensity modulation of the excitation beam.19) device according to paragraph 18 is characterised by the fact that the excitation light source is mechanically fixed directly to the optical medium.20) device according to paragraph 18 is characterised by the fact that a device is provided for the emission of a measuring beam of light into the area of the optical medium in contact with the first area of the surface of the substance and that this device/detection device for the detection of the light beam is mechanically fixedly connected directly to the optical medium and/or coupled to this light beam by means of a measuring wave.(21) A device according to Aspect 18, 19 or 20 characterised by the optical medium having an optical reflector directly on it and/or an optical reflector incorporated in the optical medium.22) A device according to Aspect 18 or one of the other preceding or subsequent devices, characterised by the optical medium having several oppositely inclined surfaces on which the measuring beam is reflected several times.23) A process according to Aspect 18 or one of the other preceding or subsequent devices, characterised by the optical medium having one or more mirror surfaces for reflection of the light beam.24) A device according to Aspect 16 or 17 characterised by the detection device for detecting a detector signal, designed to detect the reaction of a substance to the measuring beam,The resonator may be open or closed. The quartz cable is preferably placed in or on the neck of the resonator (off-beam) or inside/outside the resonator (in-beam).25 Device according to paragraph 16, 17 or 18 is characterised by the fact that the detection device for detecting a time-dependent response signal is connected to a thermal radiation detector for detecting the thermal radiation at the surface of the material, in particular an infrared source, in particular a thermoelectric element, a bolt, or a semiconductor.26) Device according to paragraph 16 or 18 is connected to a common direction or to a direct line of contact, and the detection devices are indicated by the following:in particular, a device formed by a housing or part of a housing of the device.27) Device defined in one of the aspects 16 to 26 by the fact that the device has a portable housing which is adjustable to the body of a person, the device for emitting one or more excitation beams and the detection device for detecting a time-dependent response signal being so arranged and designed that the substance to be analysed is measured on the body-facing side of the housing.28) Device defined in one of the aspects 16 to 26 by the fact that the device has a portable housing which is adjustable to the body side of a person and that the direction of the device for emitting a light beam is set by the body-facing window on its intended position of orientation.29. a device for analysing a substance with an excitation device to produce at least one electromagnetic excitation beam, in particular an excitation light beam, with at least one excitation wavelength, a detection device to detect a reaction signal and a device for analysing the substance by the detected reaction signal.30. a device according to one of the preceding aspects 16 to 29 characterised by the fact that the detection device is designed to measure the deformation of a crystal. Other The deformation can be measured more effectively by choosing steeper (larger) angle of impact of the beam on the sample surface and minimizing the influence of mirage effect-related deflection of the beam. Other The following is a list of the Other The Commission has also examined the information provided by the Member States in the context of the investigation.Sibilia. Analysis of the photothermal deflection technique win the surface refection theme: Theory and Experiment. Journal of Applied Physics 83, 966 (1998) 31. Device according to one of the previous aspects 16 to 30, characterized by the fact that the stimulation device contains a probe laser or an LED, for example a NIR ((near-infrared)) LED.32. Device according to one of the previous aspects 16 to 31, characterized by the fact that the stimulation device has a sample element with a smaller or larger additional diameter than a Pump laser.33. Device according to one of the previous aspects 16 to 32, characterized by the fact that a special coating, in particular the optical element, is used to achieve a more favorable signal-to-noise ratio, i.e. IRE.Err1:Expecting ',' delimiter: line 1 column 103 (char 102)A device described in paragraph 35 above is characterised by the fact that the device has a retractor in the area of the detection surface, preferably next to the detection surface, to pre-treat the surface of the material and ensure a clean surface and/or in an embodiment, in the case of glucose measurement, to specifically indicate skin cleaning.37. A device according to paragraphs 16 to 36 above is characterised by the fact that the detection device is equipped with a calibration device to detect and detect certain fingerprints and/or fingerprints of a person and/or to detect the presence of a fingerprint and/or fingerprint.Err1:Expecting ',' delimiter: line 1 column 409 (char 408)Other Other the device is preferably configured to allow data transmission in encrypted form, in particular by fingerprint or other biometric data of the operator.40. Device according to one of the preceding aspects 16 to 39, characterised by the device being configured so that a suggestion of an insulin dose to be administered to the person can be determined by the device in combination with other data (e.g. insulin correction factor) and/or weight, body fat can be measured and/or manually indicated or transmitted to the device by other devices.41. Device according to one of the preceding aspects 16 to 40, characterised by the device being configured to increase the accuracy of the insulin dose to determine further parameters,in an embodiment with sensors for determining skin temperature, diffusivity, conductivity/moisture of the skin, for measuring the polarization of light (excluding water/sweat on the surface of the finger) or similar. Other Water and sweat on the surface of a human skin that may affect glucose measurement can be detected by a test stimulation with a stimulation radiation through the stimulation transmitter with the water bands at 1640 cm-1 (6.1 μm) and 690 cm-1 (15 μm). If the absorption exceeds a certain value, the measuring site/substance surface/skin surface is too wet for reliable measurement. Alternatively, the conductivity of the substance can be measured at the seam or directly at the measuring site.The device described in one of the previous two aspects 16 to 41 is characterised by having a cover in the beam gap of the pump and/or measuring laser beam, which can provide the required eye protection for living creatures.43. The device described in one of the previous two aspects 16 to 42 is characterised by having a variable detection surface.44. The device described in one of the previous two aspects 16 to 43 is characterised by having a reflected or roughened crystal as an optical medium, which allows the sample (e.g. finger) to be adjusted better.The measuring point on which the surface of the material to be analysed is placed is preferably unriveted and smooth.45. Device according to one of the preceding aspects 16 to 44 characterised by the use of a cylindrical TEMpl TEM00 mode for the measuring beam or other modes TEM01 (Dougnut) TEM02 or TEM03 instead of the cylindrical TEMpl TEM00. In particular, the latter have the advantage of being able to adjust their intensity to the sensitivity profile of the quadrant which is the detector for the directed vertical measuring beam (see figures). Furthermore, rectangular modes TEMmn TEM30 or TEM03 or higher can be used.46 Device according to one of the preceding aspects 16 to 45 characterized by the fact that the device measures not only at one point but in a grid. This may be done either by a shift of the pump or sample laser or the detection unit. Other In addition, the following aspects of the invention may also be inventions in themselves or in combination with one or more of them:47 A device designed to analyze a substance 101 with an excitation device 100 which produces at least one electromagnetic excitation beam (SA) of at least one excitation wavelength by the consecutive operation of one or more or at least partially simultaneous operation of several laser emitters of a laser light source.and Other a detection device 106 to detect a reaction signal (SR) and an analytical device to analyse the substance by means of the detected reaction signal (SR).48 A device as defined in paragraph 47 designed to maintain, by means of a temperature control device, the temperature of the laser beam of the stimulation device 100 and/or the temperature of the detection device 106, in particular of an optical medium (108) and/or a detection radiation source (105) and/or an optical sensor, constant during the analysis, in particular at a specified temperature, in particular at a specified temperature above the human body temperature, preferably above 37 °C, preferably below 38 °C or 40 °C.A device according to Aspect 47 or 48 designed to detect during analysis the temperature of the laser beam (s) of the stimulation device (100) and/or the temperature of the detection device (106), in particular of an optical medium (108) and/or a detection radiation source (105) and/or an optical sensor, by means of a temperature sensor and to take into account the analysis in the evaluation by linking the measured results with temperature correction values.50. A device according to Aspect 47, 48 or 49 designed to apply pressure, particularly to a part of the body, particularly a finger, against an optical medium (108), or to reduce the pressure exerted on the medium by means of the pressure exerted by the body by means of a medium (1008) and to control the pressure exerted on the body depending on the direction of movement of the medium (108);a device according to paragraph 47, 48, 49 or 50 designed to press the material, in particular a body part, in particular a finger, against an optical medium (108) which is part of the detection device, such that a dimming of the medium in the area of the body part being pressed is detected by a light sensor and that dimming the medium turns on the stimulation device (100) by means of a switch and/or turns it off by increasing the brightness in the optical medium, in particular over a certain threshold.52. A device according to paragraph 47, 49, 48, 50 or 51 designed so that the material,in particular, a body part, in particular a finger, is pressurised against an optical medium (108) which is part of the detection device, that a moisture level of the medium (108) is detected in the area of the pressurised body part by means of a moisture sensor and that, by reaching a specified moisture level on the medium, the stimulation transmitter (100) is switched on and/or off by a switch, either by reducing the moisture level, in particular below a certain threshold, or by increasing the moisture level above a certain threshold.53. device according to paragraph 47 or one of the following, which is so designed that a body can be fixed to the optical medium (108) during the procedure,In particular, by clamping the body part to the medium by means of a clamping device, bonding the body part to the medium by means of an adhesive layer, adhesion of the body part to the medium or by vacuum suction of the body part to the medium by means of a suction device.54. Device described in paragraph 47 designed to emit the excitation beam ((SA) with at least two excitation wavelengths or groups of excitation wavelengths, one of which allows detection of at least one substance to be detected in the substance, while at least one other excitation wave length or group of excitation wavelengths is connected to the detection of at least one different substance to be detected, and at least two different reference profiles are provided for the detection of the substance and its distribution between different profiles,and in particular, a depth profile or at least one or more parameters of a depth profile of the reference substance in the substance is known.55. Device according to paragraph 47 or any of the following, designed to modulate the excitation beam (SA), preferably modulated successively at different modulation frequencies by a modulation device, detecting reaction signals at different modulation frequencies by a detection device or analyzing the time behaviour of the reaction signal when the intensity of the excitation beam changes, in particular when it is periodically switched on and/or off.56. Device according to paragraph 55 designed to modulate the excitation beam (SA) by an illuminating device (100) of a laser-generating device.A device according to Aspect 47 or any of the following, which is so designed that the excitation beam is modulated at 0 to 10 modulation frequencies, preferably between 0 and 5 modulation frequencies, further preferably between 1 and 3 modulation frequencies, further preferably at one modulation frequency only, and the time behaviour of the reaction signal, in particular a phase-sensitive behaviour of the reaction signal, is analysed.58. A device according to Aspect 47 or any of the following, which is so designed that the sensitivity of the excitation beam (SA) is between 3 and 10%, preferably between 3 and 7%.59 A device according to Aspect 47 or any of the following, which is designed so that the power density of the excitant (SA) is less than 5 mm/W2 at the surface of the analyte.a device as described in paragraph 47 or any of the following, which is so designed that the optical medium (108) of the detection device is capable of being brought into contact with a body part, in particular a finger and/or a dialysate vessel and/or a blood vessel of a dialysis apparatus, and in particular that one or more excitation wavelengths are selected for the excitation beam to detect urea.

Other detection methods for detecting a response signal after emission of a stimulus beam may include: Other - Photoacoustic detection - photoacoustic detection by means of a tuning fork or other vibration element or: a slightly modified form of open cell QePAS (quartz enhanced photoacoustic spectroscopy). These methods allow pressure variations/vibrations at the surface of the material to be detected and evaluated as described above for the measured radiation deflection.

In principle, the values of a phase shift in the reaction signal compared to a periodic modulation of the excitation beam can be used for depth profiling (heating/cooling phases of the surface of the material should be evaluated more closely in terms of their course).

The device described may be fitted with a stock of adhesive strips to remove dead skin layers to allow measurements to be made on a human body as smoothly as possible, and thermal-conducting patches which can be applied regularly to the optical medium, which may be interchangeable if the other parts are properly fixed and adjusted.

The device may be intended and fitted for measurement not only on a person's finger but also on a lip or earlobe.

The measurement can also be performed in some versions without direct touch and application of the finger or other body part (at a distance), thus allowing for non-contact measurement.

The measurement can be improved by combining several of the described and explained measurement systems with similar error rates in terms of accuracy and reliability.

The DAQ and LockIn amplifiers in the evaluation can be combined in one device and the evaluation can be digitised as a whole.

The measurement may also be carried out on a moving fabric surface with the device, so that during a grid measurement, the light source and/or the measuring light source pass over the skin during the measurement in a grid, compensating or removing any skin irregularities.

The sensitivity of the detection device/deflection unit can be optimized by adjusting/varying the wavelength of the sample beam/light source, which can be variable in wavelength or include multiple laser light sources of different wavelengths to be selected or combined.

The pump/sample laser can be deflected in an optimal transverse mode (TEM).

The excitation device, measuring light source and detector can be constructed as a common array and the beams can be appropriately redirected in the optical medium to concentrate the emission and reception of all beams at one place.

A lens on or in the crystal of the optical medium may help to deflect the measured beam more strongly depending on the response signal.

In addition, the use of a gapfree photodiode for detection is conceivable, so that a lens could bundle the measuring beam after exit and thus allow a more accurate measurement.

The following concept is used to describe the additional design of the invention in accordance with the claims. This concept also constitutes, in itself, combined with the above aspects or with the claims, at least an independent invention. The applicant reserves the right to claim this invention or inventions at a later date, either in the context of this application or in subsequent partial or subsequent applications, claiming priority over this application.

Concept for non-invasive blood glucose measurement by determination of glucose in the skin by stimulation by quantum cascade lasers and measurement of the heat wave by radiant heat.

Figures 12 and 13 describe a method for determining the concentration of glucose or another substance in the interstitial fluid (ISF) of the skin. The skin area 102 (in this case the first area of the surface of the fabric) is irradiated with a focused beam of a quantum cascade laser reflected, if necessary, in a mirror or a hollow mirror 140 and gradually or continuously directed through a specific infrared region where glucose is specifically absorbed.The spectral range (or the individual wavelengths, typically 5 or more wavelengths) can be in particular between about 900 and about 1300 cm-1, where glucose has an absorption fingerprint, i.e. typical and representative absorption lines.2. The stimulation beam, designated SA, is used continuously (CW-L) or pulsed with high pulse recovery rate or modulated vibration. In addition, the stimulation beam is modulated at low frequencies, especially in the frequency range between 10 and 1000 Hz. The modulation may be periodic with different functions, in different lengths, or similar to certain types of sinusoidal or B-S.These stimulations from the vibrational level v0 to v1 return to the baseline state within a very short time; heat is released at this step.4. As a result of the heat development after (3), a heat wave is formed, which isotropically emanates from the absorption site. Depending on the thermal diffusion length determined by the low frequency modulation described under (2), the heat wave periodically reaches the surface of the skin with the modulation frequency.5. The periodic appearance of the heat wave at the surface corresponds to a periodic modulation of the thermal radiation property of the skin (substance surface of the sample).The periodic temperature rise described in (5) is recorded by means of a thermal radiation detector 139 i.e. an infrared detector i.e. a thermoelement, bolometer, semiconductor detector or similar pointed at the skin site of irradiation. It is dependent on the infrared radiation described in (1) and (2) and the absorption described in (3) and thus on the concentration of glucose. The thermal radiation SR (in this case the reaction signal) is collected by means of an optical element, in an embodiment of an infrared lens or mirror, in particular a paracavernous mirror 141, and directed to the detector in an embodiment of a convex mirror 141a via a convex reflector.The reaction signal can be processed in a lock-in amplifier 144 using a filter 143, which can be used to process the signal in a different way. By analysing the phase position between the activation signal and the thermal radiation signal (reaction signal) by means of a control and processing device 147, the depth information about the depth below the surface of the emission can be obtained, the results of which can be obtained in different ways. (8) The results of the analysis can also be obtained from different modulation frequencies and modulation methods for different types of substances (such as the frequency of the emission of the emission of the material) and the results can also be described.To make the detection of thermal radiation as sensitive as possible, the detection of thermal radiation according to (6) is used in spectral broadband for the entire infrared range concerned. Many areas of the Planck radiation curve are to be used. To make the detection insensitive to the intense stimulation radiation, the detection of thermal radiation is provided with notch filters 143 for these stimulation wavelengths. The wavelength range 148 passed through the notch filter 143 is also shown in Figure 13.h. the heat signal measured in (6-9) depends on the wavelength of the stimulus, and is therefore in an embodiment, if glucose is to be detected, first determined at non-glucose-relevant wavelengths of the stimulus beam (curve 145) of the background, then at (or including) different glucose wavelengths of the background, the difference in the background signal. The concentration of glucose in the skin is determined according to the different modes of production or distribution of the products (7) or (8) which are excluded from the background.

Although the invention has been illustrated and described in detail by preferred examples of embodiments, the invention is not limited by the examples disclosed and other variations may be derived from them by the professional without leaving the scope of the invention.

The following examples are also disclosed. Device (10) for analysing a substance (101) with An excitation device (100) to produce at least one electromagnetic excitation beam (SA), in particular an excitation light beam, with at least one excitation wavelength, a detection device (106, 139) to detect a reaction signal (SR) and a device (107, 147) to analyse the substance by the detected reaction signal (SR). Other characterised by: the excitation device is a radiation source, in one embodiment a monochromatic, in particular a polarized radiation source, and in another embodiment a laser light source,the device (10) has an optical medium (108) in direct contact with the fabric (101), in particular a first area (102) of the surface of the fabric,preferably arranged in such a way that the excitation device (100)that the emitted beam of excitation (SA) enters the optical medium (108) and leaves it at a predetermined point on the surface of the optical medium, andthe device comprises a device (105) for the emission of a measuring beam (112), in particular a measuring beam of light, arranged so that the emitted measuring beam (112) enters the optical medium (108) and preferably in operation the measuring beam (112) and the stimulating beam (SA) are located on an interface (GF) of the optical medium (108) and the surface of the material (101) at which the measuring beam (112) is reflected, overlapping, and the detection device (106) is a device that is a receiver (SR) of the measuring beam (112) and is designed to reflect or reflect a direct or indirect reflection of the measuring beam (112) and/or a detection device (112).The device is based on one of the examples above. Other characterised by: Other the apparatus (10) has an optical medium (108) in direct contact with the substance (101), in particular a first region (102) of the surface of the substance, and that the detection device (106) for detecting a reaction signal (SR) detects a change in the optical medium parameter, in particular in a region adjacent to the first region, as a result of the reaction signal, in particular a deformation and/or density change of the optical medium.4. Other characterised by: Other The detection device shall have a piezoelectric element connected to or integrated into the optical medium as a detector to detect distortion and/or density change.5.Other Other characterised by: Other the detection device has temperature sensors as detectors to capture the response signal. Other characterised by: The device has a device (104) for modulating the intensity of the excitation beam (SA) and the detection device (106) is suitable for detecting a time-dependent response signal (SR) depending on the wavelength of the excitation beam and/or the intensity modulation of the excitation beam.7. Other characterised by: Other The excitation device (100) radiates at least one electromagnetic excitation beam (SA) into a volume of material (103) which is below a first area (102) of the surface of the material (101).8. Other characterised by: Other the stimulation device (100) two or more transmitters (100a);"Software" specially designed or modified for the "development" or "production" of equipment specified in 1C001.a. or 1C001.b. Other characterised by: Other The two or more transmitters (100a) each generate a separate electromagnetic excitation beam and radiate it into the volume below the first range (102). Other characterised by: Other The wavelengths of the electromagnetic excitation beams of the two or more transmitters (100a) are different. Other characterised by: Other The excitation device comprises two or more lasers, in particular in the form of a one, two or several dimensional laser array, and/or two or several light-emitting diodes, in particular in the form of a one, two or several dimensional diode array.Other Other characterised by: Other the stimulation device is mechanically fixed, directly or indirectly by means of an adjustment device (109) to an optical medium (108) in direct contact with the fabric (101), in particular the first region (102) of the surface of the fabric (101). Other characterised by: Other 'intensity modulation device (104) ' means an electrical modulation device which is electrically connected to and electrically controlled by the stimulation device (100) or comprises or is formed by such a device.14. Other characterised by: Other The intensity modulation device (104) shall include at least one controlled mirror (133, 134) in the beam path.15.Other Other characterised by: Other the intensity modulation device (104) comprises or is formed by at least one layer (138) arranged in a beam direction, controllable in terms of transparency.16. Other characterised by: Other a device (105) designed to emit a measuring beam (112), in particular a measuring beam, into that region of an optical medium (108) which is in contact with the first region (102) of the surface of the fabric.17. Other characterised by: Other The device for transmitting a measuring beam and the detection device are so arranged that the detection device detects the measuring beam as the time-dependent response signal after it has been reflected at least once at the boundary surface (GF) of the optical medium (108);in contact with the fabric, in particular the first area (102) of the surface of the fabric (101). Other characterised by: Other The device for transmitting a measuring beam and/or the detection device and/or the stimulation device is mechanically fixed directly to the optical medium and/or coupled to it by means of a light-wave conductor (120). Other characterised by: Other the optical medium carries an image optic (128, 129) directly and/or an image optic (128, 129) is integrated into the optical medium. Other characterised by: Other The surface of the optical medium shall have several intersecting sub-surfaces (110, 111) on which the measuring beam (112),The measuring beam is reflected several times. Other characterised by: Other in or on the optical medium (108) one or more mirror surfaces (113, 114) are provided for reflecting the measuring beam (112), in particular the measuring beam.22. Other characterised by: Other the stimulation device (100) and/or the measuring beam device (105) and/or the detection device (106) are directly connected to each other or to a common support (121); Other characterised by: Other the support (121) is made up of a printed circuit board, metal or plastic plate or a housing (122) or part of the housing of the device.24.Other Other characterised by: Other The excitation transmitter shall comprise an integrated semiconductor device containing one or more laser elements and at least one micro-optical component and preferably an additional modulation element.25. Other characterised by: Other The modulation element shall have at least one moving and positionally controllable element relative to the other semiconductor component, in particular a mirror. Other characterised by: Other The modulation element has a layer whose radiation permeability can be controlled. Other characterised by: Other The modulation element shall have an electronic control circuit for modulating one or more laser elements. Other characterised by the fact that the stimulation device (100) is equipped to:The power output of the device is predominantly transmitted, in particular to more than 80% of the power output in the medium infrared wavelength range between 900/cm and 1650/cm.29. Other characterised by the fact that the stimulation device (100) is designed to emit between 20 and 100 wavelengths individually or successively, in particular between 20 and 70, in particular between 20 and 50, in particular between 30 and 50 wavelengths.30. Other The characteristic of the device is that, when measured, the majority of the excited wavelengths, in particular more than 50%, and in particular more than 80% of the wavelengths at absorption maxima, are in the range of basic vibrations of the glucose molecule.31.Other Other The characteristic of the device, in particular the excitation device, is that it is designed to modulate the excitation at a frequency between 1 Hz and 10 kHz, in particular between 10 and 1000 Hertz, and further, in particular between 20 and 500 Hertz.32. Other The device is designed to detect the response signal over time and to undergo a Fourier transformation, preferably after an excitation pulse of between 10 and 1000 ms duration, preferably between 50 and 500 ms duration, preferably between 50 and 150 ms duration.33. Other be characterised by the fact that the device is designed to:that the measurement is repeated 2-10 times and an average signal path of an integral transformation, in particular a Fourier transformation or a Wavlet transformation with an appropriate basic function, is given or an average of the individual integral transformations, in particular a Fourier transformation or a Wavlet transformation with an appropriate basic function, is performed. Other The test chemical is characterised by the presence of a device for adjusting the different angles of entry of the excitation beam into the substance being tested.35. Other The device shall be so designed that the measurement is repeated successively at different angles of entry of the stimulus beam and the results are linked, in particular subtracted, to eliminate the effects of the upper layers of the skin.A device according to one of the preceding examples, characterised by its calibration to the body temperature of the living organism, in particular 37 degrees Celsius, in particular by the fact that at least parts of the device are in direct or direct contact with the patient's body, either permanently or temporarily.37. A device according to one of the preceding examples, characterised by its design for determining the level of medicinal products in a body fluid, in particular for the determination of paracetamol, phenytoin, valproic acid, lamotrigine, phenobarbital, flecainide, digitoxin, digoxin, tacrolimus, subverolimus, amiodarone, aminoglycoside, theophylline, vancomycin, Lithium, azeximethyroxide, carboxylate, or methacrylate.38. A device according to the preceding examples, characterised by the presence of at least three extreme points in the distance between these two extremes, and by the fact that at least twenty of these are located in an extreme position.39. method for analysing a substance (101), wherein the method An excitation device (100) produces at least one electromagnetic excitation beam (SA) with at least one excitation wavelength by at least partially simultaneous or consecutive operation of several laser beams of a laser light source,a detection device (106) detects a reaction signal (SR) and analyses it independently of the detected reaction signal (SR) of the substance.40. The process described in example 39 is characterised by the sequential detection of reaction signals, in particular time-scale reaction signal paths, using different modulation frequencies of the excitation device, and by the linking of several reaction paths at different modulation sequences and by the obtaining of information in particular for a specific area under the surface of the substance.41.Other Other characterised by: Other The reaction signal paths at different modulation frequencies are determined for different wavelengths of the excitation beam and in particular specific information is obtained for a depth below the surface of the material.42. Other characterised by: Other when several modulation frequencies of the pump beam are used at the same time, the detected signal is separated according to its frequencies by an analytical method, preferably a Fourier transform, and Other The process of using one of the examples 39-42 above, Other characterised by: an optical medium (108) is brought into direct contact with the substance (101), in particular a first area (102) of the surface of the substance (101), the emitted stimulus beam (SA) is generated by the stimulation device (100) and is thus emitted,that it penetrates the optical medium (108) and leaves it at a predetermined point on the surface of the optical medium (108),is generated by a device (105) to emit a measuring beam (112) a measuring beam (112), in particular a measuring beam, so that it penetrates the optical medium (108) and that in particular the measuring beam (112) and the stimulation beam (SA) overlap in operation at an interface (GF) of the optical medium (108) and the surface of the material (101) at which the measuring beam (112) is reflected, and the detection device (106) directly or indirectly measures the response signal (SR) reflected by the measuring beam (112) or the measurement of the reflected beam.44 Procedure in one of the examples 39-43 Other characterised by: Other The excitation beam is periodically modulated with a first frequency amplitude and a frequency shift of the reaction signal relative to the first frequency is determined and a speed of movement of the measured substance is determined due to the Doppler effect.45. Other characterised by: Other depending on the concentration of the substance in the substance, a dosing device is controlled to deliver a substance into the substance, in particular into a patient's body, and/or an acoustic and/or optical signal is given and/or a signal is given by radio link to a processing device.46.that the excitation is predominantly, in particular at more than 80% of the power in the mid-infrared wavelength range at wavelengths between 900/cm and 1300/cm.47. Method according to Example 39 or one of the following, characterised by individual excitations of between 20 and 100 wavelengths, in particular between 20 and 70, further, in particular, between 20 and 50, further, in particular, between 30 and 50 wavelengths.48. Method according to Example 39 or one of the following, characterised by the majority of excited wavelengths, in particular, more than 50% further, in particular, more than 80% of the wavelengths at absorption maxima of ground vibrations of the glucose molecule49. Method according to Example 39 or one of the following,characterised by modulating the stimulation at a frequency between 1 Hz and 10 kHz, in particular between 10 and 1000 Hertz, and further, in particular between 20 and 500 Hertz50. Method according to example 39 or one of the following, characterised by recording the response signal over time and subjecting it to an integral transformation, for example a Fourier transformation or a wavelength transformation with an appropriate basic function, preferably after an excitation pulse of between 10 ms and 1000 ms duration, preferably between 50 and 500 ms duration, preferably between 50 and 150 ms duration51. Method according to example 50, characterised by repeating the measurement 2 to 10 times and by performing an average signal path of an integral transformation or an average of the individual integral transformations.52. the method described in Example 39 or one of the following, characterised by the measurement involving the reception of the response signal at at least one modulation frequency or time-resolved after a transmitted pulse and at one or more wavelengths, being repeated successively at different angles of entry of the excitation beam and the results being linked, in particular subtracted, to eliminate the effects of the upper skin layers.53. the method described in Example 39 or one of the following, characterised by the operation of the detection device's exhaust beam/measurement beam during the waveform at least temporarily in the wavelength range between 15000/cm and 16000/cm, in particular temporarily between 15500/cm and 16000/cm, and in particular temporarily between 15700/cm and 16000/cm.54. method according to example 39 or one of the following, characterised by the fact that, in a measurement where the excitation beam is successively adjusted to different wavelengths and/or wavelength ranges, at least 5% and in particular at least 10%, and at least 30% and at least 50% of the wavelength range covered are in areas of the spectrum which are insensitive to the substance to be detected, in particular glucose.55. method according to example 39 or one of the following, characterised by the fact that, in order to take into account the absorption behaviour of the sample or tissue independent of glucose concentration, at least one or two wavelengths or wavelengths without significant absorption by glucose ranges are provided for in which absorption is measured.56 Method 55 characterised by at least one of the wavelength ranges between 1610 and 1695 cm-1 (Amid 1).57 Method 55 or 56 characterised by at least one of the wavelength ranges between 1480 and 1575 cm-1 (Amid 2).58 Method 39 or one of the following characterised by first selecting a depth range in the sample to be examined for measurement and then controlling the excitation beam so that the time between the ranges (excitation pulses) in which the excitation beam is emitted is at least equal to the diffusion time of a thermal wave required to travel the distance between the depth range to be examined in the sample and the surface of the sample.Method according to example 39 or one of the following, characterised by measuring the absorption intensity time sequence after the end of a time period in which the excitation beam is emitted. (phase position of the response signal).60 Method according to example 39 or one of the following, characterised by setting a series of stored equidistant or non-equidistant settings, each determining a laser wavelength, in succession to control a laser to generate the excitation beam, and of which at least 3 in particular, at least 5 wavelengths of absorption maximum of a substance, are to be detected. (lookup table) 391.61.that, before and/or during and/or after a measurement, the mechanical pressure and/or pressure per unit area is recorded against the sample by which the optical medium in which the beam is reflected is pressed.61. Method, such as 39 or one of the following, characterised by determining, before and/or during and/or after a measurement, the humidity of the ambient air and/or a sample moisture content or the humidity of the upper layers or surface of the sample.62. Method for analysing a substance (101), where, in the method with an excitation terminal (100), at least one electromagnetic stimulation source (SA) with at least one excitation wave is produced by successive operation or at least one laser or a laser laser operated simultaneously,Other Other a detection device (106) detects a reaction signal (SR) and analyses the substance using the detected reaction signal (SR).63 Method according to one of Examples 39 to 62, characterised by keeping the temperature of the laser emitter of the stimulation device (100) and/or the temperature of the detection device (106), in particular of an optical medium (108) and/or a detection radiation source (105) and/or an optical sensor, constant, in particular at a given temperature, and in particular at a given temperature above human body temperature, preferably above 37 degrees Celsius, preferably above 38 or 40 degrees Celsius, during the analysis.64 Method according to an example of 39 to 63.characterised by the temperature of the laser emitter of the excitation device (100) and/or the temperature of the detection device (106), in particular of an optical medium (108) and/or a detection radiation source (105) and/or an optical sensor, being recorded during the analysis and taken into account in the analysis by linking the measurement results with temperature correction values.65. Method according to one of examples 39 to 64, characterised by the material, in particular a body part, in particular a finger, being pressed against an optical medium (108), which is part of the detection device, by the pressure exerted on the medium by the body pressed, being recorded and by the pressure exerted on the medium, depending on the pressure exerted on the medium (108) or by the pressure exerted on the medium (100), being reduced in the direction of this pressure, and by the pressure exerted on the medium, depending on the pressure exerted on the medium (108) or on the pressure exerted on the medium (100), and by the pressure exerted on the medium, being recorded in a different direction,The method described in one of examples 39 to 65 is characterised by pressing the substance, in particular a body part, in particular a finger, against an optical medium (108), which is part of the detection device, by detecting a dimming of the medium in the area of the body part being pressed and by dimming the medium by switching on and/or switching off the stimulation device (100) by increasing the brightness in the medium, in particular, above a certain threshold.the part of the detection device that detects a moisture content of the medium (108) in the area of the pressurised body part and that, by reaching a specified moisture content on the medium, switches on and/or deactivates the stimulation device (100) by reducing the moisture content, in particular below a certain threshold, or by increasing the moisture content, in particular above a certain threshold.68. Method according to one of the examples 39 to 67, characterised by a body pressurised on the optical medium (108) fixing itself to the medium (108) during the procedure, in particular by clamping the body part to the medium, partially bonding the body to the medium,Adhesion of the body part to the medium or by vacuum suction of the body part to the medium.69. Method according to one of examples 39 to 68 characterised by the emission of the excitation beam ((SA) with at least two excitation wavelengths or groups of excitation wavelengths, whereby a first excitation wavelength or group of excitation wavelengths allows the detection of a substance to be detected in the substance, while at least one further excitation wavelength or group of excitation wavelengths allows the detection of a different reference substance from a substance to be detected and that profiles are obtained for at least two different substances with respect to their diffuse distribution at depth and depth and with respect to each other, and in particular one or more profiles of a substance or group of substances at depth are known.Method according to example 69, where the excitation beam (SA) is modulated, preferably in succession with different modulation frequencies, whereby reaction signals are detected for different modulation frequencies or a time behaviour of the reaction signal is analyzed when the intensity of the excitation beam changes, in particular when it is periodically switched on and/or off.71. Method according to example 70, characterised by modulation of the excitation beam (SA) by controlling a laser beam (100) generating the excitation beam.72. Method according to examples 70 or 71, characterised by modulation of the excitation beam with 0 to 10 modulation frequencies, preferably between 0 and 5 modulation frequencies, preferably between 1 and 3 modulation frequencies,The method according to one of the examples 62 to 72 is characterised by the sensitivity of the excitation beam (SA) between 3 and 10%, preferably between 3 and 7%. The method according to one of the examples 62 to 73 is characterised by the power density of the excitation beam (SA) at the surface of the substance to be analysed being less than 5 mW/mm2, in particular less than 2 mW/mm2, in particular less than 1 mW/mm2.75. The method according to one of the examples 39 to 74 is characterised by the fact that the optical body of the detection device (108) is equipped with ain particular, a finger and/or a dialysate vessel and/or a blood vessel of a dialysis apparatus is brought into contact and in particular one or more excitation wavelengths are chosen to detect urea.

List of reference marks

10Device100Action device/action light source100A emitter/transmitter101Material102first area103Volume104Device105Device106Detection device107Processing device/evaluation device107A memory108Optical medium108A surface area108bSpace area109Adjustment device110Space area111Scale area112Measuring beam/measuring beam113Spectral area114Spectral beam116Opening area117Opening area118Off119Action device106Detection device120Spectral wave conductor121Carrier122Gluten-length detector122Gluten-signal detector12121212Signal detector1212F1212K14Signal detector1212K14Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector141Signal detector14Signal detector141Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector14Signal detector141Signal detector141Signal detector141Signal detector14Signal detector14Signal detector14Signal detector141Signal detector141Signal detector141Signal detector141S

Claims (15)

1. Device (10) for analysing a substance (101) with Other

   - an excitation device (100) for the production of at least one electromagnetic excitation beam (SA), in particular an excitation beam, with at least one excitation wavelength,

   - a detection device (106, 139) for detecting a response signal (SR), and

   - a device (107, 147) for analysing the substance by the detected reaction signal (SR).
2. Device according to claim 1, characterised by:

   - the stimulation device is a radiation source, in one embodiment a monochromatic source, in particular a polarized source, and furthermore in particular a laser light source,

   - the device (10) has an optical medium (108) in direct contact with the fabric (101), in particular a first area (102) of the surface of the fabric,

   - preferably the excitation transmitter (100) is so arranged that the emitted excitation beam (SA) enters the optical medium (108) and leaves it at a predetermined point on the surface of the optical medium, and

   - the device comprises a device (105) for the emission of a measuring beam (112), in particular a measuring beam, arranged so that the measuring beam (112) emitted penetrates the optical medium (108) and preferably overlaps the measuring beam (112) and the stimulation beam (SA) on an interface (GF) of the optical medium (108) and the surface of the material (101) on which the measuring beam (112) is reflected, when operating; and

   - the detection device (106) is a device for receiving the reflected measuring beam (112) forming the response signal (SR) and/or for directly or indirectly detecting a deflection of the reflected measuring beam (112).
3. a device meeting one of the above requirements, Other characterised by the fact that the device (10) has an optical medium (108) in direct contact with the substance (101), in particular a first region (102) of the surface of the substance, and that the detection device (106) for detecting a response signal (SR) detects a change in the optical medium parameter, in particular in a region adjacent to the first region, as a result of the response signal, in particular a distortion and/or density change of the optical medium; and/or Other where the detection device has a piezoelement connected to or integrated into the optical medium as a detector to detect deformation and/or density change and/or where the detection device has temperature sensors as a detector to detect the response signal.
4. a device meeting one of the above requirements, Other characterised by: Other the device (104) has a device (104) to modulate the intensity of the excitation beam (SA) and the detection device (106) to detect a time-dependent response signal (SR) depending on the wavelength of the excitation beam and/or the intensity modulation of the excitation beam, whereby the device (104) to modulate the intensity is preferably an electrical modulation device electrically connected to the excitation device (100) and controlled by such electrical control, or the device (104) to modulate the intensity of the voltage preferably includes at least one mirror (133, 134) located in the beam direction or one device (104) located in the direction or at least one such reflector located in the direction or in the direction of the beam direction (108) located in the first direction or in the direction of the beam direction, or at least one such controlled by such a material (103) located in the direction or in the direction of the beam direction or in the direction of the beam direction, or in the direction of the beam direction, and at least one such material (108) located in the first direction or in the direction of the beam direction, or in the direction of the beam direction, and controlled by such a material (102);
5. a device meeting one of the above requirements, Other characterised by the excitation transmitter (100) comprising two or more transmitting elements (100a), in particular in the form of a one-, two- or multi-dimensional array of transmitting elements, the transmitting elements being in particular laser or light-emitting diodes, and/or by the excitation transmitter (109) being mechanically fixed directly or indirectly by means of an adjustment device (109) to an optical medium (108) in direct contact with the fabric (101), in particular the first region (102) of the surface of the fabric (101).
6. a device meeting one of the above requirements, Other characterised by: Other The measuring beam and/or detection and/or stimulation device is mechanically fixed directly to the optical medium and/or coupled to it by means of a light-wave conductor (120), and/or Other that the stimulation device (100) and/or the device (105) for sending the measuring beam and/or the detection device (106) are directly attached to each other or to a common support (121) with the support (121) preferably consisting of a circuit board, metal plate or plastic plate or a housing (122) or part of the housing of the device, and/or that the optical medium directly bears an imaging optics (128, 129) and/or an imaging optics (128, 129) is integrated into the optical medium.
7. a device meeting one of the above requirements, Other characterised by the fact that the excitation transmitter (100) is designed to transmit predominantly, and in particular at more than 80% of its power, in the mean infrared wavelength range between 900/cm and 1650/cm, and/or that the excitation transmitter (100) is designed to transmit between 20 and 100 wavelengths individually or in succession, in particular between 20 and 70, and further, in particular between 20 and 50, and in particular between 30 and 50 wavelengths, in particular, in the presence of three characteristic interfacing extremes of a substance, in particular so that at least ten, or at least twenty, waves are emitted in the outer or upper two extremes, and/or that the measurement of the modulation of the wavelengths is carried out in a direction between 10 and 1000 kHz, in particular between 10 and 50% of the maximum frequency, and in particular between 10 and 500 kHz, in the direction of the maximum absorption, and in the direction of the maximum frequency, in particular between 50 and 50% of the maximum frequency, and in the direction of the maximum frequency, in the range of 10 kHz, and/or more, in particular, in the case of the device, the measurement is designed to transmit between 500 and 50% of the maximum frequency, in the direction of the transmitter, in the main transmitter and the main transmitter, in the main transmitter, and/or transmitter, and/or transmitter, in the main transmitter.
8. A device meeting one of the above requirements, characterised by the device being designed to detect the response signal time and undergo a Fourier transformation, preferably after an excitation pulse of between 10 ms and 1000 ms duration, preferably between 50 ms and 500 ms duration, preferably between 50 ms and 150 ms duration, and/or the device being designed to repeat the measurement 2-10 times and to undergo an average signal path of an integral transformation, in particular a Fourier transformation or a wavelet transformation with an appropriate basis function, or to perform a mediation of the individual integral transformations, in particular a Fourier transformation or a wavelet transformation with an appropriate basis function.
9. Method for analysing a substance (101), wherein the method Other

   - with an excitation device (100), at least one electromagnetic excitation beam (SA) of at least one excitation wavelength is produced by the operation of at least partly simultaneous or consecutive laser emitters of a laser light source,

   - a response signal (SR) is detected by a detection device (106) and

   - the substance is analysed on the basis of the detected reaction signal (SR).
10. The method described in claim 9 is characterised by the sequential detection of reaction signals, in particular time-scale reaction signals, using different modulation frequencies of the excitation device and by the linking of several reaction signal paths at different modulation frequencies and by the obtaining of information specific to a particular depth range below the surface of the material, preferably by detecting reaction signal paths at different modulation frequencies for different wavelengths of the excitation beam and by obtaining specific information for a depth range below the surface of the material, in particular by separating the signal at several modulation frequencies of the pumping current at the same time by means of a detection, prevention and transformation method. Other only the partial signal corresponding to the desired frequency is filtered out.
11. The method described in claim 9 or 10 is characterised by placing an optical medium (108) in direct contact with the material (101), in particular a first region (102) of the surface of the material (101), producing the emitted excitation beam (SA) with the excitation device (100) and emitting it in particular in such a way that it enters the optical medium (108) and leaves it at a predetermined point on the surface of the optical medium (108), by a device (105) to emit a beam (112) reflecting off a material (102), in particular a beam of light of the type produced by the measuring instrument (102) reflecting off the optical medium (108) and in particular by reflecting the measuring beam and the measuring beam (112) on the operating surface (SRF) of the optical instrument (102) or by direct reflection of the measuring beam (102) and/or by direct reflection of the measuring beam (102) on the operating surface (SRF) of the measuring instrument (101) and/or on the optical surface of the measuring instrument (102) and by reflecting off the measuring beam (102) and/or the measuring surface of the measuring instrument (102) and/or the measuring surface of the measuring instrument (102) and/or the measuring instrument (102) and the measuring surface of the measuring instrument (102) and the measuring instrument (102) and the measuring surface of the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring surface of the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the measuring instrument (102) and the meas Other depending on the concentration of the substance in the substance, a dosing device is controlled to deliver a substance into the substance, in particular into a patient's body, and/or an acoustic and/or optical signal is given and/or a signal is given by radio to a processing device.
12. a process according to one of claims 9 to 11 characterised by the predominance of the excitation, in particular more than 80% of the power, in the medium infrared wavelength range at wavelengths between 900/cm and 1300/cm, and/or by the individual excitation of between 20 and 100 wavelengths, in particular between 20 and 70, further, in particular, between 20 and 50, further, in particular, between 30 and 50 wavelengths, and/or by the majority of the excitation wavelengths, in particular more than 50%, in particular more than 80% of the wavelengths at absorption maxima of basic Glucosine pulses, and/or by the excitation of a frequency between 1 Hz and 10 kHz, in particular between 10 and 1000 Hz, in particular between 20 and 500 Hz, where a modulation of the frequency of the signal is desired, and by the pre-transformation of the signal, for example, between 50 and 50 ms, or by the integration of a frequency between 2 and 50 ms, or by a frequency between 50 and 50 ms, where the signal is modulated using a single signal transformation or a pre-transformation, for example, between 50 and 50 ms, or a frequency of integration, or a frequency between 50 and 50 ms, or more, or a frequency of integration, or a frequency between 50 and 50 ms, where the signal is modulated, or a frequency of integration is achieved by means of a pre-transformation or transformation, for example, between 2 and 50 and 50 ms, or more, or an integration of a frequency, or a frequency between 50 and 50 ms, or more, or more, or more, and a frequency of integration, or a frequency of 50 ms, or more, or more, or more, or less, or less, and a frequency, or less, and a frequency, and a frequency, or less, and a frequency, or less, and a frequency, or less, and a frequency, or less, and a frequency, or less, and a frequency, or less, or less, or less, and a frequency, or less, and a frequency, or less, or less, or less, and a, less, less, and a, less, less, less,
13. A process according to one of the claims 9 to 11 characterised by measuring the time course of the absorption intensity after the end of a time period in which the excitation beam is emitted and/or by measuring the mechanical pressure and/or pressure per unit area against which the optical medium reflecting the beam is pressed against the sample before and/or during and/or after a measurement of the humidity of the ambient air and/or a sample humidity or the humidity of the upper layers or surface of the sample.
14. A method for analysing a substance (101) whereby, in the process with an excitation transmitter (100), at least one electromagnetic excitation beam (SA) with at least one excitation wavelength is generated by the consecutive operation of one or more or at least partially simultaneous operation of several laser emitters of a laser source, a reaction signal (SR) is detected by a detection device (106) and analysed by the detected reaction signal (SR) of the substance, preferably the temperature of the laser beam (s) above the excitation transmitter (100) and/or the temperature of the detection medium (106), in particular an optical medium (108) and/or a detection beam (105) and/or an optical medium (105) is kept constant, in particular during an optical analysis, in a direction which is approximately 38 degrees Celsius (108) and/or 37 degrees Celsius (108) and in particular during the detection of the detection medium, and/or the temperature of the human body (106) and/or the temperature of the detector (108) and/or the optical medium (108) is kept constant, in particular during an optical analysis, in a direction which is approximately 38 degrees Celsius (108) and/or 40 degrees Celsius (108) and in particular during the detection of the detector (108) and/or the detector (105) and/or the detector.
15. a process according to one of claims 9 to 14 characterised by pressing the substance, in particular a body part, in particular a finger, against an optical medium (108) which is part of the detection device and by either sensing the pressure exerted on the medium by the body part being pressed and by switching on and/or off the stimulation device (100) depending on the pressure exerted on the medium (108), depending on the sensed pressure, or by sensing a dimming of the medium in the area of the body part being pressed and by switching on and/or off the stimulation device (100) depending on a reduction in the pressure, in particular below a certain threshold, or by sensing a dimming of the medium in the area of the body part being pressed and by switching on and/or off the control direction (100) depending on the dimming of the medium, depending on the luminance of the medium, in particular at the threshold,and/or the excitation beam (SA) is emitted with at least two excitation wavelengths or groups of excitation wavelengths, with a first excitation wavelength or group of excitation wavelengths allowing the detection of a substance to be detected in the substance, while at least one further excitation wavelength or group of excitation wavelengths allows the detection of a reference substance different from a substance to be detected, and with at least two different substances having profiles as to their density distribution in the depth of the substance and interconnected, and in particular a depth profile or at least one or more parameters of a depth of the reference substance in the substance being known, Other a width of not more than 50 mm,preferably modulated sequentially with different modulation frequencies, detecting response signals for different modulation frequencies or analysing a time behaviour of the response signal when the intensity of the excitation beam changes, in particular when it is periodically switched on and/or off.