Optical configuration for dermis spectroscopy

Abstract

A spectrometer (110) and a method for skin-layer specific spectroscopy is disclosed. The spectrometer (110) comprises at least one illumination source (112) for illuminating a sample (114) of a subject with at least one illumination light beam (116) having at least one wavelength in an optical spectral range; at least one detector (122) sensitive to light in the optical spectral range, wherein the detector (122) is configured for detecting light from at least two spatially separated light detection spots (126, 130); at least one dispersive element (124) arranged in front of the detector (122) in a direction of a light beam from the sample (114) to the detector, wherein the illumination source (112) is separated from a first light detection spot (126) of the detector (122) by a first baseline (128), wherein the illumination source (112) is separated from a second light detection spot (130) of the detector (122) by a second baseline (132), wherein the detector (122) comprises at least one first optical receiving fiber configured for receiving at least one first incident light beam from the first light detection spot (126) generated by the sample (114) upon interaction with the illumination light beam (116) and for transferring the first incident light beam to the dispersive element (124), and wherein the detector (122) comprises at least one second optical receiving fiber configured for receiving at least one second incident light beam from the second light detection spot (130) generated by the sample (114) upon interaction with the illumination light beam (116) and for transferring the second incident light beam to the dispersive element (124).

Description

[0001] 240508W001

[0002] Optical Configuration for Dermis Spectroscopy

[0003] Technical Field

[0004] The invention relates to a spectrometer and a method for skin-layer specific spectroscopy. The invention further relates to a computer program, a computer-readable storage medium and to non-transient computer-readable medium for performing the method. Such devices and methods can, in general, be used for investigating or monitoring purposes, in particular, in the infrared (IR) spectral region, especially in the near-infrared (NIR) spectral region, e.g. for investigating or monitoring of spectroscopic properties of one or more skin layers. However, further application are also feasible.

[0005] Background art

[0006] Spectrometers are known to be efficient tools for obtaining information on the spectral properties of an object, when emitting, irradiating, reflecting and / or absorbing light. Spectrometers, thus, may assist in analyzing samples or other tasks in which information on the spectral properties of an object is of interest.

[0007] For example, near infrared (NIR) spectroscopy in a wavelength range of 750 to 2500 nm is a known technique used for analyzing molecular vibrations and rotations, as well as combinations and overtones of the molecular vibrations and rotations. NIR spectroscopy may allow for a nondestructive analysis of solid, liquid, and gaseous samples, and may be used in various fields of technology, such as pharmaceuticals, food and agriculture, material science, biomedical research and the like. In general, NIR spectroscopy may be used to analyze the composition of the skin, including lipids, collagen, and elastin level. Alternatively, NIR spectroscopy is known to measure biomarkers in various biological samples, such as skin, blood, urine, and saliva. These techniques can e.g. be used to quantify biomarkers related to disease diagnosis, monitoring of treatment efficacy, and assessment of physiological processes in the body or the like.

[0008] Despite the advantages achieved by known methods and devices, several technical challenges remain. The use of spectroscopic techniques for analyzing biomarkers in the skin of a human or animal body may still be technically challenging. Specifically, the NIR spectrum of skin may show many dependencies and variabilities, such as inter-subject and intra-subject variabilities. The isolation of spectral features of low-concentration skin biomarkers over a broadly varying spectral background using proper optical combination of sensors, optical setup or chemometrics tools may therefore pose a technical challenge. In particular, assessing the skin structure via spectroscopic techniques may be associated with several technical challenges. The skin is a multilayered tissue with various components, such as lipids, proteins, and water, which may affect the accuracy of spectroscopic biomarker measurement. Specifically, the skin can be modeled by an epidermis layer, a dermis layer and a subcutaneous layer. For spectroscopic biomarker measurement, signals from the subcutaneous layer may be envisaged since blood 240508W001

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[0010] vessels are present in this skin layer. However, the penetration depth of light, specifically of near infrared light, may be limited to few hundred micrometers, which is generally not enough to sample the subcutaneous layer. Thus, blood vessels in the subcutaneous may not be sampled by known spectroscopic techniques, such as NIR spectroscopy, when light is collected from the identical position as the position where skin is illuminated.

[0011] US 2015 / 011850 A1 discloses a noninvasive analyzer apparatus and method of use thereof comprising a near-infrared source, a detector, and a photon transport system configured to direct photons from the source to the detector via an analyzer-sample optical interface. The photon transport system includes a dynamically position light directing unit used to, within a measurement time period for a single analyte concentration determination, change any of: radius, energy, intensity, position, incident angle, solid angle, and / or depth of penetration of a beam of photons entering skin of a subject.

[0012] US 2016 / 242682 A1 discloses a noninvasive analyzer apparatus and method of use thereof for spatially separating light having noninvasively probed a tissue volume into groups, which narrows standard deviations of pro bed tissue path length for each of the groups. Reduction in tissue path length uncertainty subsequently enhances noninvasive analyte concentration determination accuracy. Control of individual detector distance from an illumination zone in combination with control of area of a detection zone coupled to an individual detector yields intensity control of the various groups. The intensity control is optionally aided using several intensity control elements including: control of detector response shape, hardware gain settings set as function of distance from the illumination zone, varying numerical aperture of light collection optics as a function of position from the illumination zone, multiple illumination-detector linked bundles, micro-optics, segmented spacers, arcs of detector elements, and / or outlier analysis based on detected intensity as a function of position.

[0013] US 2019 / 195790 A1 discloses a device for measuring radiation backscattered by a sample including: at least one light source that is configured to emit a light beam, along an axis of incidence, towards a surface of the sample so as to form, on said surface, an elementary illumination zone; an image sensor for forming an image of the radiation backscattered by the sample when the latter is illuminated by the light source, the image sensor lying in a detection plane; a bundle of optical fibers, extending, along an extension axis, between a proximal surface and a distal surface, the proximal surface being applied against the image sensor, the distal surface being configured to be applied against the surface of the sample; wherein the light source is arranged around the bundle of optical fibers, and wherein the distance between the light source and the bundle of optical fibers is less than 1 mm.

[0014] Problem to be solved

[0015] It is therefore desirable to provide devices and method which at least partially address aboveidentified technical challenges. Specifically, a spectrometer and a method for skin-layer specific 240508W001

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[0017] spectroscopy shall be proposed which allow for subcutaneous sampling via spectroscopic techniques, such as NIR spectroscopy.

[0018] Summary

[0019] This problem is addressed by a spectrometer, a method for skin-layer specific spectroscopy and by a computer program, a computer-readable storage medium and a non-transient computer-readable medium with the features of the independent claims. Advantageous embodiments which might be realized in an isolated fashion or in any arbitrary combinations are listed in the dependent claims as well as throughout the specification.

[0020] In a first aspect, a spectrometer, specifically a near infrared spectrometer, is disclosed. The spectrometer comprises:

[0021] at least one illumination source for illuminating a sample of a subject with at least one illumination light beam having at least one wavelength in an optical spectral range;

[0022] at least one detector sensitive to light in the optical spectral range, wherein the detector is configured for detecting light from at least two spatially separated light detection spots; at least one dispersive element arranged in front of the detector in a direction of a light beam from the sample to the detector,

[0023] wherein the illumination source is separated from a first light detection spot of the detector by a first baseline, wherein the illumination source is separated from a second light detection spot of the detector by a second baseline, wherein the detector comprises at least one first optical receiving fiber configured for receiving at least one first incident light beam from the first light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the first incident light beam to the dispersive element, and wherein the detector comprises at least one second optical receiving fiber configured for receiving at least one second incident light beam from the second light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the second incident light beam to the dispersive element.

[0024] The term “spectrometer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical device configured for acquiring at least one item of spectral information on at least one object. Specifically, the at least one item of spectral information may refer to at least one optical property or optically measurable property which is determined as a function of a wavelength, for one or more different wavelengths. More specifically, the optical property or optically measurable property, as well as the at least one item of spectral information, may relate to at least one property characterizing at least one of a transmission, an absorption, a reflection and an emission of the at least one object, either by itself or after illumination with external light. The at least one optical property may be determined for one or more wavelengths. The spectrometer specifically may form an apparatus which is capable of recording a signal intensity with respect to the corresponding wavelength of a spectrum or a partition thereof, such as a wavelength interval, 240508W001

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[0026] wherein the signal intensity may, specifically, be provided as an electrical signal which may be used for further evaluation. The spectrometer may specifically be a near infrared spectrometer, more specifically a device capable of recording a signal intensity at least in the near infrared spectral range. The near infrared spectrometer may specifically comprise an instrument configured for recording diffusive reflectance near infrared spectra.

[0027] The spectrometer, as an example, may be or may comprise a device which allows for a measurement of at least one spectrum, e.g. for the measurement of a spectral flux, specifically as a function of a wavelength or detection wavelength. The spectrum may be acquired, as an example, in absolute units or in relative units, e.g. in relation to at least one reference measurement. Thus, as an example, the acquisition of the at least one spectrum specifically may be performed either for a measurement of the spectral flux (unit W / nm) or for a measurement of a spectrum relative to at least one reference material (unit 1), which may describe the property of a material, e.g., reflectance over wavelength. Additionally or alternatively, the reference measurement may be based on a reference light source, an optical reference path, a calculated reference signal, e.g. a calculated reference signal from literature, and / or on a reference device.

[0028] Specifically, the at least one spectrometer may be a diffusive reflective spectrometer configured for acquiring spectral information from the light which is diffusively reflected by the at least one object, e.g. the at least one sample. Additionally or alternatively, the at least one spectrometer may be or may comprise an absorption- and / or transmission spectrometer. In particular, measuring a spectrum with the spectrometer may comprise measuring absorption in a transmission configuration. Specifically, the spectrometer may be configured for measuring absorption in a transmission configuration. As outlined above, however, other types of spectrometers are also feasible.

[0029] The at least one spectrometer, specifically and as will be outlined in further detail below, may comprise at least one illumination source which, as an example, may comprise at least one of a tunable light source, a light source having at least one fixed emission wavelength and a broadband light source. The spectrometer, as will be outlined in further detail below, further comprises at least one detector configured for detecting light, such as light which is at least one of transmitted, reflected or emitted from the at least one object. The spectrometer further may comprise, as will be outlined in further detail below, at least one dispersive element, such as at least one of a grating, a prism and a filter, e.g. a length variable filter having varying transmission properties over its lateral extension. The dispersive element may be used for separating incident light into a spectrum of constituent wavelength signals whose respective intensities are determined by employing the detector, such as a detector having a detector array as described below in more detail.

[0030] The spectrometer, specifically, may be a portable spectrometer. The term “portable” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term spe- 240508W001

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[0032] cifically may refer, without limitation, to the property of at least one object of being moved by human force, such as by a single user. Specifically, the object characterized by the term “portable” may have a weight not exceeding 10 kg, specifically not exceeding 5 kg, more specifically not exceeding 1 kg or even not exceeding 500 g. Additionally or alternatively, the dimensions of the object characterized by the term “portable” may be such that the object ex-tends by no more than 0.3 m into any dimension, specifically by no more than 0.2 m into any dimension. The object, specifically, may have a volume of no more than 0.03 m3, specifically of no more than 0.01 m3, more specifically no more than 0.001 m3or even no more than 500 mm3. In particular, as an example, the portable spectrometer may have dimensions of e.g. 10 mm by 10 mm by 5 mm. Specifically, the portable spectrometer may be part of a mobile device or may be attachable to a mobile device, such as a notebook computer, a tablet, a cell phone, such as a smart phone, a smartwatch and / or a wearable computer, also referred to as “wearable”, e.g. a body borne computer such as a wrist band or a watch. In particular, a weight of the spectrometer, specifically the portable spectrometer, may be in the range from 1 g to 100 g, more specifically in the range from 1 g to 10 g.

[0033] The spectrometer may be configured for acquiring at least one item of spectral information on at least one object. The term “spectroscopic information”, also referred to as “spectral information” or as “an item of spectral information”, as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an item of information, e.g. on at least one object and / or radiation emitted by at least one object, characterizing at least one optical property of the object, more specifically at least one item of information characterizing, e.g. qualifying and / or quantifying, at least one of a transmission, an absorption, a reflection and an emission of the at least one object. As an example, the at least one item of spectral information may comprise at least one intensity information, e.g. information on an intensity of light being at least one of transmitted, absorbed, reflected or emitted by the object, e.g. as a function of a wavelength or wavelength sub-range over one or more wavelengths, e.g. over a range of wavelengths. Specifically, the intensity information may correspond to or be derived from the signal intensity, specifically the electrical signal, recorded by the spectrometer device with respect to a wavelength or a range of wavelengths of the spectrum.

[0034] The spectrometer specifically may be configured for acquiring at least one spectrum or at least a part of a spectrum of detection light propagating from the object to the spectrometer. The spectrum may describe the radiometric unit of spectral flux, e.g. given in units of watt per nanometer (W / nm), or other units, e.g. as a function of the wavelength of the detection light. Thus, the spectrum may describe the optical power of light, e.g. in the NIR spectral range, in a specific wavelength band. The spectrum may contain one or more optical variables as a function of the wavelength, e.g. the power spectral density, electric signals derived by optical measurements and the like. The spectrum may indicate, as an example, the power spectral density and / or the spectral flux of the object, e.g. of a sample, e.g. relative to a reference sample, such as a transmittance and / or a reflectance of the object, specifically of the sample. 240508W001

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[0036] The spectrum, as an example, may comprise at least one measurable optical variable or property of the detection light and / or of the object, specifically as a function of the illumination light and / or the detection light. As an example, the at least one measurable optical variable or property may comprise at least one at least one radiometric quantity, such as at least one of a spectral density, a power spectral density, a spectral flux, a radiant flux, a radiant intensity, a spectral radiant intensity, an irradiance, a spectral irradiance. Specifically, as an example, the spectrometer, specifically the detector, may measure the irradiance in Watt per square meter (W / m2), more specifically the spectral irradiance in Watt per square meter per nanometer (W / m2 / nm). Based on the measured quantity the spectral flux in Watt per nanometer (W / nm) and / or the radiant flux in Watt (W) may be determined, e.g. calculated, by taking into account an area of the detector. The spectrum may specifically comprise a near infrared spectrum. The near infrared spectrum may be a diffusive reflectance near infrared spectrum given in units of absorbance a with a = - og10(reflectance). The reflectance R may specifically be a background-corrected reflectance spectrum R = (S - BG) / (R — BG). The sample measurement S may be a raw detector signal over wavelength that is recorded from the sample of the subject with the spectrometer, specifically with the near infrared spectrometer. The reference measurement R may be a raw detector signal over wavelength that is recorded from a reference sample, such as a sample with known reflectance over wavelength, e.g. of 100% or 2%. The background measurement BG may be for a raw detector signal over wavelength of an instrument background that is recorded with the spectrometer, specifically with the near infrared spectrometer, using either an open port or a very dark reflectance target e.g. with reflectance of below 0.1%.

[0037] As outlined above, the spectrometer comprises the at least one illumination source for illuminating a sample of a subject with at least one illumination light beam having at least one wavelength in an optical spectral range.

[0038] As used herein, the term “light” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to electromagnetic radiation in the optical spectral range. The term “optical spectral range” may refer, without limitation, to one or more of the infrared, the visible and the ultraviolet spectral range. As further used herein, the term “wavelength” may refer, without limitation to a distance between consecutive corresponding points of the same phase of the electromagnetic radiation.

[0039] Further, the term “ultraviolet spectral range”, generally, refers to electromagnetic radiation having a wavelength of 1 nm to 380 nm, preferably of 100 nm to 380 nm. Further, in partial accordance with standard ISO-21348 in a valid version at the date of this document, the term “visible spectral range”, generally, refers to a spectral range of 380 nm to 760 nm. The term “infrared spectral range” (I R) generally refers to electromagnetic radiation of 760 nm to 1000 pm, wherein the range of 760 nm to 1.5 pm is usually denominated as “near infrared spectral range” (NIR) while the range from 1.5 pm to 15 pm is denoted as “mid infrared spectral range” (MidlR) and the range from 15 pm to 1000 pm as “far infrared spectral range” (FIR). Preferably, light used for the typical purposes of the present invention is light in the infrared (IR) spectral range, more 240508W001

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[0041] preferred, in the near infrared (NIR) and / or the mid infrared spectral range (MidlR), especially the light having a wavelength of 800 nm to 5 pm, preferably of 800 nm to 3 pm. This is due to the fact that many material properties or properties on the chemical constitution of many objects may be derived from the near infrared spectral range. It shall be noted, however, that spectroscopy in other spectral ranges is also feasible and within the scope of the present invention.

[0042] The term “illumination source” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary device configured for generating or providing light in the sense of the above-mentioned definition. The illumination source specifically may be or may comprise at least one electrical light source, such as an electrically driven light source. The illumination source may specifically be a broad band light source emitting light in the optical spectral range, specifically in the near infrared spectral range.

[0043] The term “illuminating” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of exposing at least one object to light. The process of exposing the at least one object to light may specifically comprise generating light and directing the generated light to the at least one object, such as by controlling a direction of propagation of the light, e.g. by generating a light beam. Thus, specifically, the illumination source may be configured for generating a light beam such that the generated light is directed to the at least one object.

[0044] The term “light beam” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an amount of light emitted and / or reflected into a specific direction. Thus, the light beam may be a bundle of light rays having a predetermined extension in a direction perpendicular to a direction of propagation of the light beam. Preferably, the light beam may be or may comprise one or more Gaussian light beams, such as a linear combination of Gaussian light beams, which may be characterized by one or more Gaussian beam parameters, such as one or more of a beam waist, a Rayleighlength or any other beam parameter or combination of beam parameters suited to characterize a development of a beam diameter and / or a beam propagation in space. As used herein, the term “ray” generally refers to a line that is perpendicular to wavefronts of light which points in a direction of energy flow. As used herein, the term “beam” generally refers to a collection of rays. In the following, the terms “ray” and “beam” will be used as synonyms. Thus, specifically, the term “light beam” generally refers to an amount of light, specifically an amount of light traveling essentially in the same direction, including the possibility of the light beam having a spreading angle or widening angle. The light beam may have a spatial extension. Specifically, the light beam may have a Gaussian beam profile. Consequently, the term “illumination light beam”, as used herein, may refer, without limitation, to a light beam generated by the illumination source. 240508W001

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[0046] The illumination light beam may specifically comprise a light beam propagating from the illumination source to the sample of the subject.

[0047] The illumination light beam may have a wavelength from 800 nm to 3000 nm, preferably from 1250 nm to 2500 nm, more preferably from 1700 nm to 1800 nm and / or from 2200 nm to 2400 nm. Thus, preferably, the optical spectral range may be a skin-layer specific spectral range, specifically a near infrared spectral range.

[0048] The term “subject” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary living object. The subject may be or may comprise one or more living beings and / or one or more parts thereof, such as one or more body parts of a human being, e.g. a user, and / or an animal.

[0049] The term “sample” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a part of the subject which may fully or partially be analyzed by spectroscopic methods. The sample may specifically refer to a sample that is investigated by the spectrometer or the method. For example, the sample of the subject may comprise a skin, more specifically a skin of a human being, e.g. of a user of the spectrometer. However, other samples are also feasible.

[0050] The illumination source may further comprise at least one light source configured for generating the illumination light beam. The illumination source may comprise at least one optical sending fiber configured for transmitting the light beam from the light source to the sample. Thus, in this example, the optical sending fiber may define a position of the illumination source with respect to the sample of the subject. The light source may comprise at least one light source selected from the group consisting of: an incandescent lamp; a light emitting diode (LED); a laser; a laser diode; a solid-state laser; a gas laser; a quantum cascade laser; a plasma light source; a gas discharge lamp, such as low pressure discharge lamps and / or high pressure lamps. As an example, the light source may comprise at least one light-emitting diode and at least one luminescent material for light-conversion of primary light generated by the light-emitting diode. For example, the luminescent material may comprise phosphor. Thus, the light source may be or may comprise a phosphor LED.

[0051] As further outlined above, the spectrometer comprises the at least one detector sensitive to light in the optical spectral range, wherein the detector is configured for detecting light from at least two spatially separated light detection spots.

[0052] The term “detecting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of at least one 240508W001

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[0054] of determining, measuring and monitoring at least one parameter, qualitatively and / or quantitatively, such as at least one of a physical parameter, a chemical parameter and a biological parameter. Specifically, the physical parameter may be or may comprise an electrical parameter. Consequently, the term “detector” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary device configured for detecting, i.e. for at least one of determining, measuring and monitoring, at least one parameter, qualitatively and / or quantitatively, such as at least one of a physical parameter, a chemical parameter and a biological parameter. The detector may be configured for generating at least one detector signal, more specifically at least one electrical detector signal, such as an analogue and / or a digital detector signal, the detector signal providing information on the at least one parameter measured by the detector. The detector signal may directly or indirectly be provided by the detector to an evaluation unit, such that the detector and the evaluation unit may be directly or indirectly connected. The detector signal may be used as a “raw” detector signal and / or may be processed or preprocessed before further used, e.g. by filtering and the like. Thus, the detector may comprise at least one processing device and / or at least one preprocessing device, such as at least one of an amplifier, an analogue / digital converter, an electrical filter and a Fourier transformation. The detector may specifically comprise a detector sensitive to near infrared light, e.g. comprising PbS or PbSe.

[0055] The detector may be or may comprise at least one optical detector. The optical detector may be configured for determining at least one optical parameter, such as an intensity and / or a power of light by which at least one sensitive area of the detector is irradiated. More specifically, the optical detector may comprise at least one photosensitive element and / or at least one optical sensor, such as at least one of a photodiode, a photocell, a photosensitive resistor, a phototransistor, a thermophile sensor, a photoacoustic sensor, a pyroelectric sensor, a photomultiplier and a bolometer. The detector, thus, may be configured for generating at least one detector signal, more specifically at least one electrical detector signal, in the above-mentioned sense, providing information on at least one optical parameter, such as the power and / or intensity of light by which the detector or a sensitive area of the detector is illuminated.

[0056] The detector may comprise one single optically sensitive element or area or a plurality of optically sensitive elements or areas. Specifically, the detector may be or may comprise at least one detector array, more specifically an array of photosensitive elements. Each of the photosensitive elements may comprise at least a photosensitive area which may be adapted for generating an electrical signal depending on the intensity of the incident light, wherein the electrical signal may, in particular, be provided to the evaluation unit, as will be outlined in further detail below.

[0057] The photosensitive area as comprised by each of the optically sensitive elements may, especially, be a single, uniform photosensitive area which is configured for receiving the incident light which impinges on the individual optically sensitive elements. However, other arrangements of the optically sensitive elements may also be conceivable. 240508W001

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[0059] The array of optically sensitive elements may be designed to generate detector signals, preferably electronic signals, associated with the intensity of the incident light which impinges on the individual optically sensitive elements. The detector signal may be an analogue and / or a digital signal. The electronic signals for adjacent pixelated sensors can, accordingly, be generated simultaneously or else in a temporally successive manner. By way of example, during a row scan or line scan, it is possible to generate a sequence of electronic signals which correspond to the series of the individual optically sensitive elements which are arranged in a line. In addition, the individual optically sensitive elements may, preferably, be active pixel sensors which may be adapted to amplify the electronic signals prior to providing it to the evaluation unit. For this purpose, the detector may comprise one or more signal processing devices, such as one or more filters and / or analogue-digital-converters for processing and / or preprocessing the electronic signals.

[0060] In case the detector comprises an array of optically sensitive elements, the detector, as an example, may be selected from any known pixel sensor, in particular, from a pixelated organic camera element, preferably, a pixelated organic camera chip, or from a pixelated inorganic camera element, preferably, a pixelated inorganic camera chip, more preferably from a CCD chip or a CMOS chip, which are, commonly, used in various cameras nowadays. As an alternative, the detector generally may be or comprise a photoconductor, in particular an inorganic photoconductor, especially PbS, PbSe, Ge, InGaAs, ext. InGaAs, InSb, or HgCdTe. As a further alternative it may comprise at least one of pyroelectric, bolometer or thermophile detector elements. Thus, a camera chip having a matrix of 1 x N pixels or of M x N pixels may be used here, wherein, as an example, M may be < 10 and N may be in the range from 1 to 50, preferably from 2 to 20, more preferred from 5 to 10. Further, a monochrome camera element, preferably a monochrome camera chip, may be used, wherein the monochrome camera element may be differently selected for each optically sensitive element, especially, in accordance with the varying wavelength along the series of the optical sensors.

[0061] Thus, the array may be adapted to provide a plurality of the electrical signals which may be generated by the photosensitive areas of the optically sensitive elements comprised by the array. The electrical signals as provided by the array of the spectrometer device may be forwarded to the evaluation unit.

[0062] Alternatively or additionally, the detector may comprise at least one photosensitive element configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light. The detector may comprise an array of photosensitive elements, wherein each of the photosensitive elements may be configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light. The spectrometer may specifically be configured such that the photosensitive elements are sensitive to differing spectral ranges of the detection light. The photosensitive element may comprise at least one photoconductive material selected from the group consisting of lead sulfide (PbS); lead selenide (PbSe); mercury cadmium telluride (HgCdTe); cadmium sulfide (CdS); cadmium 240508W001

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[0064] selenide (CdSe); indium antimonide (InSb); indium arsenide (InAs); indium gallium arsenide (In-GaAs); silicon (Si); silicon germanium (SiGe); an extrinsic semiconductor; an organic semiconductor.

[0065] The term “light detection spot” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a light collection area. Specifically, the light detection spot may comprise an area on the sample of the subject from where light is collected for being detected by the detector. Thus, specifically, detection light may be traveling from the light detection spots to the detector for being detected by the detector. The light detection spots may be defined by appropriate means of the spectrometer configured for receiving light, specifically detection light, from the sample of the subject, such as light which is diffusively reflected by the sample of the subject. For example, the spectrometer may comprise at least one optical element, such as an aperture, a lens, an optical fiber or the like, configured for receiving light from a spatially limit area. The at least two light detection spots are spatially separated.

[0066] The term “spatially separated” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a different location in space. Specifically, the two spatially separated detection light spots may comprise a different location in space with respect to each other. The spatial separation of the two or more light detection spots may be a complete separation. Thus, specifically the at least two spatially separated light spots may comprise two or more distinct light detection spots. In other words, the at least two spatially separated light detection spots may be non-overlapping light detection spots.

[0067] The first light detection spot may be spatially separated by the second light detection spot by a centroid distance of 100 pm to 1000 pm, specifically of 200 pm to 500 pm, more specifically of 250 pm. The term “centroid” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a geometric center of a plane figure. Specifically, the centroid of the first and second light detection spot may be the geometric center of the first and second light detection spot, respectively. For example, the first and second light detection spot may be of circular geometry. The centroid of the first and second light detection spot may be the center of the respective circle. Consequently, the term “centroid distance”, as used herein, may refer, without limitation, to a distance between two centroids. For example, the centroid distance between the first light detection spot and the second light detection spot may be a distance between the centroid of the first light detection spot and the centroid of the second light detection spot.

[0068] The detector further comprises at least one first optical receiving fiber configured for receiving at least one first incident light beam from the first light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the first incident light beam 240508W001

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[0070] to the dispersive element. Further, the detector comprises at least one second optical receiving fiber configured for receiving at least one second incident light beam from the second light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the second incident light beam to the dispersive element. Thus, the position of the first and second optical receiving fiber may define a position of the first and second light detection spot, respectively.

[0071] As further outlined above, the spectrometer comprises the at least one dispersive element arranged in front of the detector in a direction of a light beam from the sample to the detector. The term “dispersive element” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary optical element which interacts with differing spectral portions of incident light in a different manner, e.g. by having at least one wavelength-dependent optical property, such as at least one wave-length-dependent optical property selected from the list consisting of: a degree of reflection, a direction of reflection, a degree of refraction, a direction of refraction, an absorption, a transmission, an index of refraction. Specifically, the dispersive element may be an optical element configured for splitting light into different wavelengths, such as a grating, a filter or the like.

[0072] The dispersive element may specifically be selected from the group of a tunable dispersive element and a dispersive element having a fixed transmission spectrum. By using a tunable dispersive element, as an example, differing wavelength ranges may be selected sequentially, whereas, by using a dispersive element having a fixed transmission spectrum, the selection of the wavelength ranges may be fixed and may, however, be dependent e.g. on a detection position, thereby allowing for simultaneously exposing different detectors and / or different photosensitive elements of the detector to differing spectral ranges of light.

[0073] The at least one dispersive element may comprise at least one of a filter, a grating, a prism, a plasmonic filter, a diffractive optical element and a metamaterial. More specifically, the spectrometer may comprise at least one filter element disposed in a beam path of the light from the subject, i.e. in the beam path of the detection light, wherein the filter element, specifically may be configured such that each of the photosensitive elements is exposed to an individual spectral range of the light from the object. As an example, a variable filter element may be used, the transmission of which depends on a position on the filter element, such that, when the variable filter element is placed on top of the array of photosensitive elements, the individual photosensitive elements are exposed to differing spectral ranges of the incident light, specifically the detection light from the sample. Additionally or alternatively, the at least one dispersive element may comprise at least one of the following elements: an array of individual bandpass filters, an array of patterned filters, a MEMS-lnterferometer, a MEMS-Fabry Perot interferometer. Further elements are feasible.

[0074] The term “arranged in front of’ as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or 240508W001

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[0076] customized meaning. The term specifically may refer, without limitation, to an arrangement ahead of an element or device in a defined direction. Specifically, the arrangement of the dispersive element in front of the detector may comprise the dispersive element arranged ahead of the detector in the direction of the light beam from the sample to the detector. Thus, specifically, the detection light traveling from the sample to the detector may pass the dispersive element prior to the detector.

[0077] As further outlined above, the illumination source is separated from a first light detection spot of the detector by a first baseline, wherein the illumination source is separated from a second light detection spot of the detector by a second baseline. As used herein, the terms “first” and “second” are used for nomenclature only and, in particular, do not give any information about an order and / or about whether, for example, other elements are present.

[0078] The term “baseline” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a distance between the illumination source and a light detection spot. Specifically, the first baseline may be a distance between the illumination source and the first light detection spot. The second baseline may be a distance between the illumination source and the second light detection spot. The baseline may specifically be a distance in a plane defined by the sample of the subject. The baseline may be a distance between a position where the illumination light beam propagating from the illumination source to the sample of the subject impinges on the sample of the subject and a light detection spot, such as an area on the sample of the subject from where light is collected for being detected by the detector. The baseline may be defined between a centroid of the position where the illumination light beam impinges on the sample of the subject and the respective light detection spot.

[0079] The first baseline may be from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.25 mm. Alternatively or additionally, the second baseline may be from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.5 mm. For example, the first baseline may be 2.25 mm and the second baseline may be 2.5 mm. This combination may specifically be advantageously for sampling the skin layer as dermis sampling remains constant while subcutaneous sampling doubles according to Monte-Carlo simulation of NIR-sampling in skin samples based on Henyey-Greenstein description of each skin layer, as e.g. described in H. Arimoto, M.

[0080] Egawa, and Y. Yamada, “Depth profile of diffuse reflectance near-infrared spectroscopy for measurement of water content in skin”, Skin Research and Technology, Vol. 11, No. 1, pp. 27-35, 2005.

[0081] The first baseline and the second baseline may specifically be in the same spatial direction. Thus, for example, the illumination source, the first light detection spot and the second light detection spot may be located on a common straight line. In other words, the illumination source, the first light detection spot and the second light detection spot may define a one-dimensional arrangement, wherein the position where the illumination light beam impinges on the sample of 240508W001

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[0083] the subject, the first and second light detection spots may be distributed along the one-dimensional arrangement.

[0084] Alternatively or additionally, the first baseline may be equal to the second baseline. The first light detection spot and the second light detection spot may be on a perimeter of the illumination source. Thus, in this example, the first light detection spot and the second light detection may be arranged in an arbitrary fashion around the illumination source with the first baseline being equal to the second baseline, such as on the perimeter of the light source with the first and second baseline as a radius of the perimeter.

[0085] The spectrometer may further comprise at least one evaluation device configured for evaluating at least one first detection signal generated by the detector upon detecting detection light from the first light detection spot and for evaluating at least one second detection signal generated by the detector upon detecting detection light from the second light detection spot. The term “to evaluate”, as used herein, is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to the process of processing at least one first item of information in order to generate at least one second item of information thereby. Consequently, the term “evaluation unit”, as used herein, is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary device or a combination of devices configured to evaluate or process at least one first item of information, in order to generate at least one second item of information thereof. Thus, specifically, the evaluation unit may be configured for processing at least one input signal and to generate at least one output signal thereof. The at least one input signal, as an example, may comprise at least one of the first and second detector signals provided directly or indirectly by the at least one detector.

[0086] As an example, the evaluation unit may be or may comprise one or more integrated circuits, such as one or more application-specific integrated circuits (ASICs), and / or one or more data processing devices, such as one or more of computers, digital signal processors (DSP), field programmable gate arrays (FPGA) preferably one or more microcomputers and / or microcontrollers. Additional components may be comprised, such as one or more preprocessing devices and / or data acquisition devices, such as one or more devices for receiving and / or preprocessing of the detector signals, such as one or more AD-converters and / or one or more filters. Further, the evaluation unit may comprise one or more data storage devices. Further, the evaluation unit may comprise one or more interfaces, such as one or more wireless interfaces and / or one or more wire-bound interfaces.

[0087] The evaluation device may be configured, such as by software programming and / or by hardware means, for using the first detection signal as a reference signal for evaluating the second detection signal to derive at least one item of spectral information on a subcutaneous region of the sample. The reference signal may specifically be or may comprise a spectral background. 240508W001

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[0089] The spectral background may be a spectrum, specifically a near infrared spectrum, of the sample of the subject, e.g. of the skin, when the relevant biomarker is absent. Thus, specifically, the reference signal may be used to determine an absorbance contrast. The absorbance contrast may be a difference between the absorbance at two or more different wavelengths.

[0090] Further, the item of spectral information on the subcutaneous region of the sample may be used for determining at least one biomarker. The biomarker may be at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g. aldehyde, collagen level, skin hydration, sebum (fat) concentration. The biomarkers may specifically be evaluated in a chemometric approach, such as by using multivariate data analysis together with biomarker information from reference methods, e.g., the analysis of blood samples. Alternatively or additionally, classification or quantification algorithms can be applied, e.g., principle component analysis, least square regression, multiple linear regression.

[0091] The biomarker may specifically comprise at least one of a body biomarker and a skin biomarker. The body biomarker may be at least one measurable substance, characteristic, and / or molecule concentration in the body of the subject serving as an indicator of normal or disturbed biological processes in the body, specifically in the human body. The body biomarker may comprise at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, metabolic products of ethanol, e.g., aldehyde, collagen level, skin hydration, sebum (fat) concentration. The skin biomarker may be a body biomarker that can be measured at the skin surface or through the skin of the subject. The skin biomarker may comprise at least one biomarker selected from the group consisting of: a concentration of an abundant molecule, e.g., water, glucose, lactate, or ethanol. For example, the biomarker may comprise a blood alcohol concentration. The blood alcohol concentration may be a concentration of ethanol in the blood of the subject given in units volume per volume (%o).

[0092] In a further aspect of the present invention, a method for skin-layer specific spectroscopy, specifically for skin-layer specific near infrared spectroscopy, is disclosed. The method comprises using at least one spectrometer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further details below. Thus, for possible embodiments of the spectrometer and / or definitions of terms, reference is made to the description of the spectrometer above. The method may specifically comprise using a near infrared spectrometer.

[0093] The method comprises the following steps that may be performed in the given order. However, a different order may also be possible. In particular, one, more than one or even all of the method steps may be performed once or repeatedly. Further, the method steps may be performed successively or, alternatively, one or more of the method steps may be performed in a timely 240508W001

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[0095] overlapping fashion or even in a parallel fashion and / or in a combined fashion. The method may further comprise additional method steps that are not listed.

[0096] The method comprises the following steps:

[0097] a. illuminating a sample of a subject with at least one illumination light beam having at least one wavelength in an optical spectral range, specifically in a near infrared spectral range, by using the illumination source;

[0098] b. detecting light generated by the sample upon interaction with the illumination light beam and impinging on the detector from at least two spatially separated light detection spots thereby obtaining at least one first detector signal for at least one first light detection spot and at least one second detector signal for at least one second light detection spot; c. evaluating the first and second detector signal to derive at least one item of spectral information on a subcutaneous region of the sample.

[0099] The sample of the subject may specifically comprise a skin sample. For example, the sample of the subject may comprise a skin sample of a living being, such as from a human being, e.g. from a user of the spectrometer, and / or from an animal.

[0100] Alternatively or additionally, the first detection signal may be used as a reference signal for evaluating the second detection signal to derive the at least one item of spectral information on the subcutaneous region of the sample. The item of spectral information on the subcutaneous region of the sample may be used for determining at least one biomarker. The biomarker may be at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g., aldehyde, collagen level, skin hydration, sebum (fat) concentration. The biomarkers may specifically be evaluated in a chemometric approach, such as by using multivariate data analysis together with biomarker information from reference methods, e.g., the analysis of blood samples. Alternatively or additionally, classification or quantification algorithms can be applied, e.g., principle component analysis, least square regression, multiple linear regression.

[0101] Alternatively or additionally, the method specifically may be performed on-line, e.g. in the field. The spectrometer, specifically, may be a portable spectrometer which specifically may be used in the field. In particular, the spectrometer may be part of a mobile device or may be attachable to a mobile device, such as a notebook computer, a tablet, a cell phone, such as a smart phone, a smartwatch and / or a wearable computer, also referred to as “wearable”, e.g. a body borne computer.

[0102] The method may fully or partially be computer-implemented. Thus, at least step c. of the method may be computer-implemented.

[0103] The method may be at least one method selected from the group consisting of: an in-vivo method; an ex-vivo method; an in-vitro method. The in-vivo method may specifically comprise a 240508W001

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[0105] measurement of biomarker, specifically of body or skin biomarkers, on a living organism, e.g. on an animal or a human being. The ex-vivo method may specifically comprise a measurement of biomarker, specifically of body or skin biomarkers, on tissue of actual but not living organism. The in-vitro method may specifically comprise a measurement or experiment conducted outside of a living organism, typically in a controlled laboratory environment, using isolated cells or tissue or extracted tissue from an animal or human tissue. Alternatively or additionally, the method may also be performed on a skin phantom, such as on a system that imitates properties of human skin in terms of skin’s NIR spectrum. In particular, the skin phantom may be configured for mimicking NIR absorption and scattering properties of real skin.

[0106] In a further aspect of the present invention, a computer program is disclosed, comprising instructions which, when the program is executed by the spectrometer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further details below, cause the spectrometer to perform the method according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further details below.

[0107] In a further aspect of the present invention, a computer-readable storage medium is disclosed, comprising instructions which, when the instructions are executed by the spectrometer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further details below, cause the spectrometer to perform the method according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further details below.

[0108] As used herein, the term “computer-readable storage medium” specifically may refer to non-transitory data storage means, such as a hardware storage medium having stored thereon computer-executable instructions. The computer-readable storage medium specifically may be or may comprise a storage medium such as a random-access memory (RAM) and / or a read-only memory (ROM). The computer-readable storage medium may also be referred to as “computer-readable data carrier”.

[0109] In a further aspect of the present invention, a non-transient computer-readable medium is disclosed, including instructions that, when executed by one or more processors, cause the one or more processors to perform the method according to the present invention, such as according to any one of the embodiment disclosed above and / or according to any one of the embodiments disclosed in further detail below.

[0110] In a further aspect of the present invention, a use of a spectrometer according to the present invention, such as according to any one of the embodiment disclosed above and / or according to any one of the embodiments disclosed in further detail below, is disclosed, for skin-layer specific near infrared spectroscopy. 240508W001

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[0112] As used herein, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.

[0113] Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically are used only once when introducing the respective feature or element. In most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” are not repeated, nonwithstanding the fact that the respective feature or element may be present once or more than once.

[0114] Further, as used herein, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.

[0115] The devices and the method according to the present invention may provide a large number of advantages over known methods and devices. Specifically, the devices and the method according to the present invention allow for subcutaneous sampling via spectroscopic techniques, such as NIR spectroscopy. The spectrometer according to the present invention may provide a spatial separation of illumination source and the detector to sample deeper skin layers, especially the dermis layer and the subcutaneous layer. The spectrometer may specifically provide an optical configuration using two separate light detetction spots that are separated e.g. by 250 pm and are located e.g. 2.5 mm away from the illumination source. With this optical configuration, it may be expected that dermis sampling remains constant while subcutaneous sampling doubles. Thus, when using signals from both light detection spots, the detector signal from the first light detection spot may be used as a spectral reference for the detector signal from the second light detection spot, which, specifically may contain higher sampling of the subcutaneous layer, e.g. with above-identified configuration 20% instead of 10% subcutaneous sampling. 240508W001

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[0117] By comparing common and differing spectral features in the detector signals, information from the subcutaneous layer can be isolated and evaluated.

[0118] Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

[0119] Embodiment 1 : A spectrometer, specifically a near infrared spectrometer, comprising

[0120] at least one illumination source for illuminating a sample of a subject with at least one illumination light beam having at least one wavelength in an optical spectral range;

[0121] at least one detector sensitive to light in the optical spectral range, wherein the detector is configured for detecting light from at least two spatially separated light detection spots;

[0122] at least one dispersive element arranged in front of the detector in a direction of a light beam from the sample to the detector,

[0123] wherein the illumination source is separated from a first light detection spot of the detector by a first baseline, wherein the illumination source is separated from a second light detection spot of the detector by a second baseline.

[0124] Embodiment 2: The spectrometer according to the preceding embodiment, wherein the first baseline is from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.25 mm.

[0125] Embodiment 3: The spectrometer according to any one of the preceding embodiments, wherein the second baseline is from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.5 mm.

[0126] Embodiment 4: The spectrometer according to any one of the preceding embodiments, wherein the first baseline is 2.25 mm and the second baseline is 2.5 mm.

[0127] Embodiment 5: The spectrometer according to the preceding embodiments, wherein the first baseline and the second baseline are in the same spatial direction.

[0128] Embodiment 6: The spectrometer according to any one of the preceding embodiments, wherein the first baseline is equal to the second baseline, wherein the first light detection spot and the second light detection spot are on a perimeter of the illumination source.

[0129] Embodiment 7: The spectrometer according to any one of the preceding embodiments, wherein the first light detection spot is spatially separated by the second light detection spot by a centroid distance of 100 pm to 1000 pm, specifically of 200 pm to 500 pm, more specifically of 250 pm. 240508W001

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[0131] Embodiment 8: The spectrometer according to any one of the preceding embodiments, wherein the at least two spatially separated light detection spots are non-overlapping light detection spots.

[0132] Embodiment 9: The spectrometer according to any one of the preceding embodiments, wherein the detector comprises at least one first optical receiving fiber configured for receiving at least one first incident light beam from the first light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the first incident light beam to the dispersive element.

[0133] Embodiment 10: The spectrometer according to any one of the preceding embodiments, wherein the detector comprises at least one second optical receiving fiber configured for receiving at least one second incident light beam from the second light detection spot generated by the sample upon interaction with the illumination light beam and for transferring the second incident light beam to the dispersive element.

[0134] Embodiment 11 : The spectrometer according to any one of the preceding embodiments, wherein the illumination source comprises at least one light source configured for generating the illumination light beam, wherein the illumination source comprises at least one optical sending fiber configured for transmitting the light beam from the light source to the sample.

[0135] Embodiment 12: The spectrometer according to the preceding embodiment, wherein the light source comprises at least one light source selected from the group consisting of: an incandescent lamp; a light emitting diode (LED); a laser; a laser diode; a solid-state laser; a gas laser; a quantum cascade laser; a plasma light source; a gas discharge lamp, such as low pressure discharge lamps and / or high pressure lamps.

[0136] Embodiment 13: The spectrometer according to any one of the two preceding embodiments, wherein the light source comprises at least one light-emitting diode and at least one luminescent material for light-conversion of primary light generated by the light-emitting diode.

[0137] Embodiment 14: The spectrometer according to any one of the preceding embodiments, wherein the illumination light beam has a wavelength from 800 nm to 3000 nm, preferably from 1250 nm to 2500 nm, more preferably from 1700 nm to 1800 nm and / or from 2200 nm to 2400 nm.

[0138] Embodiment 15: The spectrometer according to any one of the preceding embodiments, wherein the optical spectral range is a skin-layer specific spectral range, specifically a near infrared spectral range. 240508W001

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[0140] Embodiment 16: The spectrometer according to any one of the preceding embodiments, wherein the spectrometer comprises at least one evaluation device configured for evaluating at least one first detection signal generated by the detector upon detecting detection light from the first light detection spot and for evaluating at least one second detection signal generated by the detector upon detecting detection light from the second light detection spot.

[0141] Embodiment 17: The spectrometer according to the preceding embodiment, wherein the evaluation device is configured for using the first detection signal as a reference signal for evaluating the second detection signal to derive at least one item of spectral information on a subcutaneous region of the sample.

[0142] Embodiment 18: The spectrometer according to the preceding embodiment, wherein the item of spectral information on the subcutaneous region of the sample is used for determining at least one biomarker, wherein the biomarker is at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g. aldehyde, collagen level, skin hydration, sebum (fat) concentration.

[0143] Embodiment 19: The spectrometer according to any one of the preceding embodiments, wherein the detector comprises at least one photosensitive element configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light.

[0144] Embodiment 20: The spectrometer according to any one of the preceding embodiments, wherein the detector comprises an array of photosensitive elements, wherein each of the photosensitive elements is configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light.

[0145] Embodiment 21 : The spectrometer according to the preceding embodiment, wherein the spectrometer is configured such that the photosensitive elements are sensitive to differing spectral ranges of the detection light.

[0146] Embodiment 22: The spectrometer according to any one of the two preceding embodiments, wherein the photosensitive element comprises at least one photoconductive material selected from the group consisting of lead sulfide (PbS); lead selenide (PbSe); mercury cadmium telluride (HgCdTe); cadmium sulfide (CdS); cadmium selenide (CdSe); indium antimonide (InSb); indium arsenide (InAs); indium gallium arsenide (InGaAs); silicon (Si); silicon germanium (SiGe); an extrinsic semiconductor; an organic semiconductor. 240508W001

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[0148] Embodiment 23: The spectrometer according to any one of the preceding embodiments, wherein the dispersive element is selected from the group of a tunable dispersive element and a dispersive element having a fixed transmission spectrum.

[0149] Embodiment 24: A method for skin-layer specific spectroscopy, specifically for skin-layer specific near infrared spectroscopy, using at least one spectrometer according to any one of the preceding embodiments, specifically a near infrared spectrometer, comprising the following steps:

[0150] a. illuminating a sample of a subject with at least one illumination light beam having at least one wavelength in an optical spectral range, specifically in a near infrared spectral range, by using the illumination source;

[0151] b. detecting light generated by the sample upon interaction with the illumination light beam and impinging on the detector from at least two spatially separated light detection spots thereby obtaining at least one first detector signal for at least one first light detection spot and at least one second detector signal for at least one second light detection spot;

[0152] c. evaluating the first and second detector signal to derive at least one item of spectral information on a subcutaneous region of the sample.

[0153] Embodiment 25: The method according to the preceding embodiment, wherein the sample of the subject comprises a skin sample.

[0154] Embodiment 26: The method according to any one of the preceding embodiments referring to a method, wherein the first detection signal is used as a reference signal for evaluating the second detection signal to derive the at least one item of spectral information on the subcutaneous region of the sample.

[0155] Embodiment 27: The method according to the preceding embodiment, wherein the item of spectral information on the subcutaneous region of the sample is used for determining at least one biomarker, wherein the biomarker is at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g., aldehyde, collagen level, skin hydration, sebum (fat) concentration.

[0156] Embodiment 28: A computer program comprising instructions which, when the program is executed by the spectrometer according to any one of the preceding embodiments referring to a spectrometer, cause the spectrometer to perform the method according to any one of the preceding embodiments referring to a method. 240508W001

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[0158] Embodiment 29: A computer-readable storage medium comprising instructions which, when the instructions are executed by the spectrometer according to any one of the preceding embodiments referring to a spectrometer cause the spectrometer to perform the method according to any one of the preceding embodiments referring to a method.

[0159] Embodiment 30: A non-transient computer-readable medium including instructions that, when executed by one or more processors, cause the one or more processors to perform the method according to any one of the preceding embodiments referring to a method.

[0160] Embodiment 31 : A use of a spectrometer according to any one of the preceding embodiments referring to a spectrometer for skin-layer specific near infrared spectroscopy.

[0161] Short description of the Figures

[0162] Further optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be realized in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements.

[0163] In the Figures:

[0164] Figure 1 shows an embodiment of a spectrometer according to the present invention in a schematic view;

[0165] Figure 2A and 2B show diagrams of simulations of spectral measurements; and

[0166] Figure 3 shows a flow chart of an embodiment of a method for skin-layer specific spectroscopy.

[0167] Detailed description of the embodiments

[0168] Figure 1 shows an embodiment of a spectrometer 110 according to the present invention in a schematic view. The spectrometer 110 may specifically be a near infrared spectrometer and, thus, may be configured for recording diffusive reflectance near infrared spectra. However, other spectrometers 110 are also feasible.

[0169] The spectrometer 110 comprises at least one illumination source 112 for illuminating a sample 114 of a subject with at least one illumination light beam 116 having at least one wavelength in an optical spectral range. For example, the sample 114 of the subject may be a skin of the user 240508W001

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[0171] of the spectrometer 110. The illumination light beam 116 may have a wavelength from 800 nm to 3000 nm, preferably from 1250 nm to 2500 nm, more preferably from 1700 nm to 1800 nm and / or from 2200 nm to 2400 nm. Thus, preferably, the optical spectral range may be a skinlayer specific spectral range, specifically a near infrared spectral range. For example, the illumination source 112 may comprise at least one light source 118 comprising at least one light-emitting diode and at least one luminescent material for light-conversion of primary light generated by the light-emitting diode. The LED, via the luminescent material, may be configured for emitting light in a wavelength range from 800 nm to 3000 nm.

[0172] Further, as shown in Figure 1, the spectrometer 110 may comprise at least one sample interface 120, such as at least one window being made from at least one transparent material configured for transmitting the illumination light beam 116 to the sample 114 of the subject.

[0173] The spectrometer 110 further comprises at least one detector 122 sensitive to light in the optical spectral range, wherein the detector 122 is configured for detecting light from at least two spatially separated light detection spots. The spectrometer 110 further comprises at least one dispersive element 124 arranged in front of the detector 122 in a direction of a light beam 124 from the sample 114 to the detector 122.

[0174] As an example, the detector 122 may comprise at least one photosensitive element configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light. The detector 122 may comprise an array of photosensitive elements, wherein each of the photosensitive elements may be configured for generating at least one detector signal dependent on an illumination of its light-sensitive region with detection light. The spectrometer 110 may specifically be configured such that the photosensitive elements are sensitive to differing spectral ranges of the detection light. The photosensitive element may comprise at least one photoconductive material selected from the group consisting of lead sulfide (PbS); lead selenide (PbSe); mercury cadmium telluride (HgCdTe); cadmium sulfide (CdS); cadmium selenide (CdSe); indium antimonide (InSb); indium arsenide (InAs); indium gallium arsenide (InGaAs); silicon (Si); silicon germanium (SiGe); an extrinsic semiconductor; an organic semiconductor. Further, in this example, the dispersive element 124 may comprise a variable filter element, the transmission of which depends on a position on the filter element, such that, when the variable filter element is placed on top of the array of photosensitive elements, the individual photosensitive elements are exposed to differing spectral ranges of the incident light, specifically the detection light from the sample 114. Other examples are also feasible.

[0175] Further, as indicated by the arrows in Figure 1 , the illumination source 112 is separated from a first light detection spot 126 of the detector 122 by a first baseline 128, wherein the illumination source 112 is separated from a second light detection spot 130 of the detector 122 by a second baseline 132. For example, the first baseline 128 may be 2.25 mm and the second baseline 132 may be 2.5 mm. This combination may specifically be advantageously for sampling the skin layer as dermis sampling remains constant while subcutaneous sampling doubles according to 240508W001

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[0177] Monte-Carlo simulation of NIR-sampling in skin samples based on Henyey-Greenstein description of each skin layer.

[0178] In the exemplary embodiment of Figure 1 , the first baseline 128 and the second baseline 132 may specifically be in the same spatial direction. Thus, for example, the illumination source 112, the first light detection spot 126 and the second light detection spot 130 may be located on a common straight line. In other words, the illumination source 112, the first light detection spot 126 and the second light detection spot 130 may define a one-dimensional arrangement, wherein the position where the illumination light beam 116 impinges on the sample 114 of the subject, the first and second light detection spots 126, 130 may be distributed along the onedimensional arrangement. However, other arrangements are also feasible.

[0179] The spectrometer 110 may further comprise at least one evaluation device 134 configured for evaluating at least one first detection signal generated by the detector 122 upon detecting detection light from the first light detection spot 126 and for evaluating at least one second detection signal generated by the detector 122 upon detecting detection light from the second light detection spot 130. The evaluation device 134 may be configured, such as by software programming and / or by hardware means, for using the first detection signal as a reference signal for evaluating the second detection signal to derive at least one item of spectral information on a subcutaneous region of the sample 114. The reference signal may specifically be or may comprise a spectral background. The spectral background may be a spectrum, specifically a near infrared spectrum, of the sample 114 of the subject, e.g. of the skin, when the relevant biomarker is absent. Thus, specifically, the reference signal may be used to determine an absorbance contrast. The absorbance contrast may be a difference between the absorbance at two or more different wavelengths.

[0180] Further, the item of spectral information on the subcutaneous region of the sample 114 may be used for determining at least one biomarker. The biomarker may be at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g. aldehyde, collagen level, skin hydration, sebum (fat) concentration. The biomarkers may specifically be evaluated in a chemometric approach, such as by using multivariate data analysis together with biomarker information from reference methods, e.g., the analysis of blood samples. Alternatively or additionally, classification or quantification algorithms can be applied, e.g., principle component analysis, least square regression, multiple linear regression.

[0181] Figure 2A and 2B show diagrams of simulations of spectral measurements using the spectrometer 110. Specifically, Figure 2A shows a total power 136 in arbitrary units (a.u.) of the light beam from the sample 114 to the detector 122 as a function of penetration depth 138 in millimeter (mm) in the sample 114. In Figure 2A, the penetration depth of skin for varying distance between illumination source 112 and detection spots were obtained for NIR-sampling, extracted in a Monte-Carlo simulation, based on Henyey-Greenstein description of each skin layer. Further, 240508W001

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[0183] Figure 2A illustrates the sample 114 of the subject together with the position where the illumination light beam 116 illuminates the sample 114 and the first and second light detection spots 126, 130.

[0184] Further, Figure 2B shows a contribution 140 Ptof the different skin layers to the total power Ptotas a function of a distance 142 between the illumination source 112 and a light detection spot 126, 130. Specifically, based on the simulation of Figure 2A, the time spent by the photons in each skin layer is analyzed for varying distances 142. Therein, reference number 136 denotes the total power as in Figure 2A, reference number 146 denotes the distribution of photons from the epidermis layer, reference number 144 denotes the distribution of photons from the dermis layer, and reference number 148 denotes the distribution of photons from the subcutaneous layer. Accordingly, the bars above Figure 2B show the distance ranges for epidermis sampling 150, dermis sampling 152 and subcutaneous sampling 154. As shown in Figure 2B, choosing the first baseline 128 as 2.25 mm and the second baseline 132 as 2.5 mm may be of particular advantage to sample the subcutaneous layer of the skin as dermis sampling remains constant while subcutaneous sampling doubles. Thus, the first detector signal from the first light detection spot 126 can be used as the reference signal for the second detector signal from the second light detection spot 130.

[0185] Figure 3 shows a flow chart of an embodiment of a method for skin-layer specific spectroscopy. The method comprises using at least one spectrometer 110 according to the present invention, such as according to the exemplary embodiment of Figure 1 and / or according to any other embodiment disclosed herein. Thus, for a description of the spectrometer 110, reference is made to the description of Figure 1.

[0186] The method comprises the following steps that may be performed in the given order. However, a different order may also be possible. In particular, one, more than one or even all of the method steps may be performed once or repeatedly. Further, the method steps may be performed successively or, alternatively, one or more of the method steps may be performed in a timely overlapping fashion or even in a parallel fashion and / or in a combined fashion. The method may further comprise additional method steps that are not listed.

[0187] The method comprises the following steps:

[0188] a. (denoted by reference number 156) illuminating a sample 114 of a subject with at least one illumination light beam 116 having at least one wavelength in an optical spectral range, specifically in a near infrared spectral range, by using the illumination source 112; b. (denoted by reference number 158) detecting light generated by the sample 114 upon interaction with the illumination light beam 116 and impinging on the detector 122 from at least two spatially separated light detection spots 126, 130 thereby obtaining at least one first detector signal for at least one first light detection spot 126 and at least one second detector signal for at least one second light detection spot 130;

[0189] c. (denoted by reference number 160) evaluating the first and second detector signal to derive at least one item of spectral information on a subcutaneous region of the sample 114. 240508W001

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[0191] As outlined above, the sample 114 of the subject may specifically comprise a skin sample. For example, the sample 114 of the subject may comprise a skin sample from a user of the spectrometer 110. Further, alternatively or additionally, the first detection signal may be used as a reference signal for evaluating the second detection signal to derive the at least one item of spectral information on the subcutaneous region of the sample 114. The item of spectral information on the subcutaneous region of the sample 114 may be used for determining at least one biomarker. The biomarker may be at least one biomarker selected from the group consisting of: body temperature, body hydration, hemoglobin oxygenation, concentration of glucose, concentration of lactate, concentration of ethanol, concentration of metabolic products of ethanol, e.g., aldehyde, collagen level, skin hydration, sebum (fat) concentration. The biomarkers may specifically be evaluated in a chemometric approach, such as by using multivariate data analysis together with biomarker information from reference methods, e.g., the analysis of blood samples. Alternatively or additionally, classification or quantification algorithms can be applied, e.g., principle component analysis, least square regression, multiple linear regression.

[0192] For example, the method may comprise obtaining a first spectrum Ai at the first light detection spot 126 and a second spectrum A2 at the second light detection spot 130. The first spectrum A1 and / or the second spectrum A2 may be pre-processed, e.g. using a baseline correction and / or a standard normal variate (SNV) and / or other correction or normalization methods. The method may further comprise a calculation of a difference spectrum Adeita=Ai-A2. The difference spectrum Adeita may specifically comprise a signal contribution from the subcutaneous layer of the skin sample of the subject. Thus, in this example, the difference spectrum Adeita may be used to determine a presence and / or a concentration of the biomarker in the subject. However, other options of evaluation are also feasible. 240508W001

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[0194] List of reference numbers

[0195] 110 spectrometer

[0196] 112 illumination source

[0197] 114 sample

[0198] 116 illumination light beam

[0199] 118 light source

[0200] 120 sample interface

[0201] 122 detector

[0202] 124 dispersive element

[0203] 126 first light detection spot

[0204] 128 first baseline

[0205] 130 second light detection spot

[0206] 132 second baseline

[0207] 134 evaluation device

[0208] 136 total power

[0209] 138 penetration depth

[0210] 140 contribution

[0211] 142 distance

[0212] 144 dermis layer

[0213] 146 epidermis layer

[0214] 148 subcutenous layer

[0215] 150 epidermis sampling

[0216] 152 dermis sampling

[0217] 154 subcutaneous sampling

[0218] 156 illuminating a sample

[0219] 158 detecting light

[0220] 160 evaluating the first and second detector signal

Claims

240508W001- 29 -Claims1. A spectrometer (110) comprisingat least one illumination source (112) for illuminating a sample (114) of a subject with at least one illumination light beam (116) having at least one wavelength in an optical spectral range;at least one detector (122) sensitive to light in the optical spectral range, wherein the detector (122) is configured for detecting light from at least two spatially separated light detection spots (126, 130);at least one dispersive element (124) arranged in front of the detector (122) in a direction of a light beam from the sample (114) to the detector (122),wherein the illumination source (112) is separated from a first light detection spot (126) of the detector (122) by a first baseline (128), wherein the illumination source (112) is separated from a second light detection spot (130) of the detector (122) by a second baseline (132), wherein the detector (122) comprises at least one first optical receiving fiber configured for receiving at least one first incident light beam from the first light detection spot (126) generated by the sample (114) upon interaction with the illumination light beam (116) and for transferring the first incident light beam to the dispersive element (124), and wherein the detector (122) comprises at least one second optical receiving fiber configured for receiving at least one second incident light beam from the second light detection spot (130) generated by the sample (114) upon interaction with the illumination light beam (116) and for transferring the second incident light beam to the dispersive element (124).

2. The spectrometer (110) according to the preceding claim, wherein the first baseline (128) is from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.25 mm.

3. The spectrometer (110) according to any one of the preceding claims, wherein the second baseline (132) is from 1 mm to 10 mm, preferably from 2 mm to 3 mm, more preferably is 2.5 mm.

4. The spectrometer (110) according to any one of the preceding claims, wherein the first baseline (128) is 2.25 mm and the second baseline (132) is 2.5 mm.

5. The spectrometer (110) according to the preceding claims, wherein the first baseline (128) and the second baseline (132) are in the same spatial direction and / or wherein the first baseline (128) is equal to the second baseline (132), wherein the first light detection spot (126) and the second light detection spot (130) are on a perimeter of the illumination source (112).

6. The spectrometer (110) according to any one of the preceding claims, wherein the first light detection spot (126) is spatially separated by the second light detection spot (130) by240508W001- 30 -a centroid distance of 100 pm to 1000 pm, specifically of 200 pm to 500 pm, more specifically of 250 pm.

7. The spectrometer (110) according to any one of the preceding claims, wherein a first position of the first optical receiving fiber defines the first position of the first light detection spot (126), and wherein a second position of the second optical receiving fiber defines a the second position of the second light detection spot (130).

8. The spectrometer (110) according to any one of the preceding claims, wherein the illumination source (112) comprises at least one light source (118) configured for generating the illumination light beam (116), wherein the illumination source (112) comprises at least one optical sending fiber configured for transmitting the illumination light beam (116) from the light source (118) to the sample (114).

9. The spectrometer (110) according to any one of the preceding claims, wherein the spectrometer (110) comprises at least one evaluation device (134) configured for evaluating at least one first detection signal generated by the detector (122) upon detecting detection light from the first light detection spot (126) and for evaluating at least one second detection signal generated by the detector (122) upon detecting detection light from the second light detection spot (130), wherein the evaluation device (134) is configured for using the first detection signal as a reference signal for evaluating the second detection signal to derive at least one item of spectral information on a subcutaneous region of the sample (114).

10. A method for skin-layer specific spectroscopy using at least one spectrometer (110) according to any one of the preceding claims, comprising the following steps:a. illuminating a sample (114) of a subject with at least one illumination light beam (116) having at least one wavelength in an optical spectral range by using the illumination source (112);b. detecting light generated by the sample (114) upon interaction with the illumination light beam (116) and impinging on the detector (122) from at least two spatially separated light detection spots (126, 130) thereby obtaining at least one first detector signal for at least one first light detection spot (126) and at least one second detector signal for at least one second light detection spot (130);c. evaluating the first and second detector signal to derive at least one item of spectral information on a subcutaneous region of the sample (114).

11. A computer program comprising instructions which, when the program is executed by the spectrometer (110) according to any one of claims 1 to 9, cause the spectrometer (110) to perform the method according to any one of the preceding claims referring to a method.

12. A computer-readable storage medium comprising instructions which, when the instructions are executed by the spectrometer (110) according to any one of claims 1 to 9, cause240508W001- 31 -the spectrometer (110) to perform the method according to any one of the preceding claims referring to a method.

13. A non-transient computer-readable medium including instructions that, when executed by one or more processors, cause the one or more processors to perform the method according to claim 10.

14. A use of a spectrometer (110) according to any one of claims 1 to 9 for skin-layer specific near infrared spectroscopy.

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