Device and method for determining parameters regarding a content or property of biomolecules in biological tissues

1 . A device for determining one or more parameters regarding a content or property of biomolecules, in particular metabolites, in a biological tissue, the device comprising

at least one irradiation unit configured to irradiate the tissue with electromagnetic radiation exhibiting one or more wavelengths or wavelength ranges, in particular in the mid-infrared, near-infrared or visible spectral range,

at least one detection unit configured to detect, in a spatially resolved manner, first signals corresponding to optical, optoacoustic, or optothermal signals emanating from the tissue in response to irradiating the tissue with electromagnetic radiation, in particular in the near-infrared or visible spectral range, wherein the at least one irradiation unit and the at least one detection unit are located in the same half space above or adjacent to the irradiated tissue, and

a processing unit configured

i) to localize, based on the detected first signals, a location or region of interest on or within the tissue, at which at least one biomolecule, in particular metabolite, of interest is present or expected to be present,

ii) to control the at least one irradiation unit to irradiate the localized location or region of interest on or within the tissue with electromagnetic radiation exhibiting a time-varying intensity and one or more wavelengths or wavelength ranges in the mid-infrared spectral range,

iii) to control the at least one detection unit to detect second signals corresponding to optoacoustic or optothermal signals emanating from the irradiated location or region of interest on or within the tissue in response to irradiating the location or region of interest on or within the tissue with the electromagnetic radiation in the mid-infrared spectral range, and

iv) to determine, based on the detected second signals, one or more parameters regarding a content or property of the at least one biomolecule of interest at the location or region of interest on or within in the tissue.

2 . The device according to claim 1 , wherein the device is designed as or integrated in a portable or wearable device having a size, weight or form factor allowing the device to be carried or worn by a person.

3 . The device according to claim 1 , wherein the device is configured for non-invasively determining the one or more parameters regarding the content or property of biomolecules, in particular metabolites, in the biological tissue.

4 . The device according to claim 1 , wherein the at least one detection unit comprises

at least one sensitive element located so as to be close to or in contact with the tissue and configured to change at least one of its properties, in particular refractive index, temperature, reflectivity or polarizing properties, when interacting with the first signals or second signals emanating from the irradiated tissue or, respectively, from the irradiated location or region of interest on or within the tissue,

a probe beam source configured to generate a probe beam,

a probe beam guide unit configured to guide or direct the probe beam towards the at least one sensitive element, and

a probe beam detector configured to detect the probe beam after it has been at least partially reflected at or by the at least one sensitive element, wherein the detected probe beam corresponds to the first signals or second signals, respectively.

5 . The device according to claim 4 , wherein the probe beam guide unit comprises a coupler element configured to combine or co-align the probe beam with at least one beam of the electromagnetic radiation, with which the tissue is irradiated, so that the probe beam and the at least one beam of the electromagnetic radiation impinge on the same, or essentially the same, location on the tissue.

6 . The device according to claim 1 , wherein the at least one detection unit comprises

at least one sensitive element located so as to be close to or in contact with the tissue and configured to change at least one of its properties, in particular refractive index, temperature, reflectivity or polarizing properties, when interacting with the first signals or second signals emanating from the irradiated tissue or, respectively, from the irradiated location or region of interest on or within the tissue,

a probe beam source configured to generate a probe beam,

a probe beam encoding/decoding unit configured to encode and divide the probe beam into a reference probe beam and an active probe beam, and to generate probe beam signals based on the active probe beam and the reference probe beam after having been at least partially reflected at or by the at least one sensitive element, and

a probe beam guide unit configured to guide or direct the active probe beam and the reference probe beam towards the at least one sensitive element, wherein the probe beam guide unit comprises a coupler element configured

i) to combine or co-align the active probe beam with at least one beam of the electromagnetic radiation, with which the tissue is irradiated, so that the active probe beam and the at least one beam of the electromagnetic radiation impinge on the same, or essentially the same, location on the tissue, and

ii) to direct, in particular deflect or reflect, the reference probe beam to impinge on another location on the tissue, which is different or offset from the location on which the probe beam and the at least one beam of the electromagnetic radiation impinge,

wherein the processing unit is configured to derive the first signals or second signals, respectively, from the probe beam signals.

7 . The device according to claim 6 , wherein the probe beam encoding/decoding unit is configured

to divide the probe beam into the active probe beam and the reference probe beam and to encode the active probe beam and reference probe beam with respect to at least one physical property, in particular polarization direction or pattern, pulse duration, pulse repetition rate, intensity modulation or linewidth modulation, such that each of the active probe beam and reference probe beam has a distinctive encoding pattern, and

to recombine, in particular by interference, the active probe beam and the reference probe beam, after having been reflected at or by the at least one sensitive element, to obtain a recombined probe beam and to detect the recombined probe beam to generate the probe beam signals, or

to separately detect the active probe beam and the reference probe beam, after having been reflected at or by the at least one sensitive element, and to derive the probe beam signals based on, in particular by subtracting or dividing, the detected active probe beam and the detected reference probe beam.

8 . The device according to claim 1 , comprising at least one mid-infrared light guide element configured to guide the electromagnetic radiation exhibiting one or more wavelengths or wavelength ranges in the mid-infrared spectral range from the at least one irradiation unit to the location or region of interest on or within the tissue, wherein the mid-infrared light guide element comprises a solid body which is entirely or at least partially composed of at least one mid-infrared transparent material, in particular ZnS, ZnSe, CaF 2 , Ge, Si.

9 . The device according to claim 1 , wherein the at least one irradiation unit is configured to irradiate the tissue with at least two different types of electromagnetic radiation so as to obtain, for each of the at least two different types of electromagnetic radiation, unique optoacoustic or optothermal signals in response to irradiating the tissue with the at least two types of electromagnetic radiation, wherein each of the obtained optoacoustic or optothermal signals can be uniquely assigned to one of the at least two types of electromagnetic radiation by which the respective optoacoustic or optothermal signal has been caused.

10 . The device according to claim 9 , wherein the at least two different types of electromagnetic radiation differ from each other or are encoded with respect to at least one of the following properties of the electromagnetic radiation: polarization, pulse duration, pulse repetition rate, intensity modulation or linewidth modulation of the electromagnetic radiation.

11 . The device according to claim 1 , wherein the processing unit is configured to select, from the detected second signals, those second signals, which emanate from the location or region of interest on or within the tissue, and to determine, based on the selected second signals, the one or more parameters regarding the content or property of the at least one biomolecule of interest at the location or region of interest on or within in the tissue.

12 . The device according to claim 1 , wherein the at least one detection unit is configured to detect the second signals in a temporally resolved manner so as to obtain a series of second signals over time, and wherein the processing unit is configured to select second signals, which were detected at a particular time or during a particular time range and generated at the location of interest or within the region of interest, respectively, from the series of second signals, and to determine, based on the selected second signals, the one or more parameters regarding the content or property of the at least one biomolecule of interest at the location or region of interest on or within in the tissue.

13 . The device according to claim 12 , wherein the processing unit is configured to sum up or integrate the selected second signals, which were detected during a particular time range and generated within the region of interest, and to determine, based on the summed up or integrated selected second signals, the one or more parameters regarding the content or property of the at least one biomolecule of interest at the region of interest on or within in the tissue.

14 . The device according to claim 1 , wherein

the at least one irradiation unit is configured to subsequently irradiate the location or region of interest on or within the tissue with electromagnetic radiation at different wavelengths or wavelength ranges in the mid-infrared spectral range,

the at least one detection unit is configured to subsequently detect second signals corresponding to optoacoustic signals emanating from the irradiated location or region of interest on or within the tissue in response to subsequently irradiating the tissue with the electromagnetic radiation at the different wavelengths or wavelength ranges, respectively, and

the processing unit is configured to determine, based on the subsequently detected second signals, an optical absorption spectrum of the location or region of interest on or within the tissue.

15 . The device according to claim 1 , wherein

the at least one irradiation unit is configured to simultaneously irradiate the location or region of interest on or within the tissue with electromagnetic radiation at different wavelengths or wavelength ranges in the mid-infrared spectral range,

the at least one detection unit is configured to simultaneously detect second signals corresponding to optoacoustic signals emanating from the irradiated location or region of interest on or within the tissue in response to simultaneously irradiating the tissue with the electromagnetic radiation at the different wavelengths or wavelength ranges, respectively, and

the processing unit is configured to determine, based on the simultaneously detected second signals, an optical absorption spectrum of the location or region of interest on or within the tissue.

16 . The device according to claim 1 , wherein

the at least one irradiation unit is configured to subsequently irradiate the location or region of interest on or within the tissue with coherent electromagnetic radiation at different wavelengths or wavelength ranges in the mid-infrared spectral range,

the at least one detection unit is configured to subsequently detect second signals corresponding to incoherent optothermal signals emanating from the irradiated location or region of interest on or within the tissue in response to subsequently irradiating the tissue with the coherent electromagnetic radiation at the different wavelengths or wavelength ranges, respectively, wherein the at least one detection unit in particular comprises one or more bolometric or pyroelectric detector elements which are configured to detect thermal radiation, temperature, or temperature changes, and

the processing unit is configured to determine, based on the subsequently detected second signals, at least one optical absorption property or thermodynamic property of the location or region of interest on or within the tissue.

17 . The device according to claim 16 , the device further comprising an optical element provided between the at least one irradiation unit and the tissue and configured

to transmit the coherent electromagnetic radiation to the tissue so as to irradiate the location or region of interest on or within the tissue with the coherent electromagnetic radiation, and

to direct or reflect at least a part of the second signals corresponding to incoherent optothermal radiation signals emanating from the irradiated location or region of interest on or within the tissue towards the at least one detection unit.

18 . A method for determining one or more parameters regarding a content or property of biomolecules, in particular metabolites, in a biological tissue, the method comprising the following steps:

irradiating the tissue with electromagnetic radiation exhibiting one or more wavelengths or wavelength ranges, in particular in the near-infrared or visible spectral range,

detecting, in a spatially resolved manner, first signals corresponding to optical, optoacoustic, or optothermal signals emanating from the tissue in response to irradiating the tissue with the electromagnetic radiation,

localizing, based on the detected first signals, a location or region of interest on or within the tissue, at which at least one biomolecule of interest is present or expected to be present,

irradiating the localized location or region of interest on or within the tissue with electromagnetic radiation exhibiting a time-varying intensity and one or more wavelengths or wavelength ranges in the mid-infrared spectral range,

detecting second signals corresponding to optoacoustic or optothermal signals emanating from the irradiated location or region of interest on or within the tissue in response to irradiating the location or region of interest on or within the tissue with the electromagnetic radiation in the mid-infrared spectral range, and

determining, based on the detected second signals, one or more parameters regarding a content or property of the at least one biomolecule, in particular metabolite, of interest at the location or region of interest on or within in the tissue.