EP4658153A1

EP4658153A1 - Highly integrated glucose sensor device

Info

Publication number: EP4658153A1
Application number: EP24702766.7A
Authority: EP
Inventors: Mathias Reichl
Original assignee: Glucomat GmbH
Current assignee: Glucomat GmbH
Priority date: 2023-01-31
Filing date: 2024-01-30
Publication date: 2025-12-10
Also published as: KR20250154397A; CN120957652A; WO2024160808A1

Abstract

The present disclosure relates to highly integrated sensor devices such as implantable devices, continuous monitoring devices and portable smart devices for determining a physiological parameter in a bodily fluid and/or tissue of a subject. Further, the present disclosure relates to methods for determining a physiological parameter in a bodily fluid and/or tissue of a subject.

Description

Highly integrated glucose sensor device

Description

Background

In the year 2016, about 415 million people suffered from diabetes. For 2040, an increase to more than 640 million people can be expected. Since people with diabetes are at risk for complications such as blindness, kidney diseases, heart diseases and stroke, there is a need to control the disease by closely monitoring blood glucose level.

Presently, determination of blood glucose is mainly based on invasive system and methods, wherein either a blood sample is taken and subsequently subjected to an in vitro test, or a sensor is implanted for determining the glucose level in vivo. These invasive systems and methods are disadvantageous in that they are painful or inconvenient.

WO 2021/032629 and WO 2022/090503 disclose non-invasive systems for determining a physiological parameter, particularly glucose, in a bodily fluid of a subject comprising a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation into a body part of said subject, a sensing unit for detecting emitted IR radiation from the irradiated body part of said subject, said IR radiation having (i) at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and (ii) having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject, and an analyzing unit for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit. The system may be used for non-invasively determining a physiological parameter such as glucose in the blood of a subject. Further, methods for non-invasively determining a physiological parameter, particularly glucose in a bodily fluid of a subject are disclosed. The contents of these documents are herein incorporated by reference in their entirety.

There is a need for developing highly integrated systems and methods, which allow an improved non-invasive determination of glucose and other physiological parameters.

Summary of the invention

According to the present disclosure, a simple, rapid and reliable determination of a physiological parameter is feasible using non-invasive systems and methods. These systems and methods involve irradiation of a body part of a subject, particular a human subject, with visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm or about 500 nm to about 1500 nm and detecting emitted IR radiation from the irradiated body part of said subject in the range of about 5 pm to about 12 pm. Surprisingly, the present inventor has found that irradiating a body part with shortwavelength radiation and detecting emitted long-wavelength radiation from the irradiated body part allows determination for physiological parameters such as glucose in a bodily fluid such as blood.

Irradiation of a body part with VIS/NIR radiation according to the present invention causes energy absorption within an area of the irradiated body part. Energy absorption in this irradiated area, i.e. , the absorption area, results in a local increase of tissue temperature within the irradiated body part, particularly within the absorption area, which again causes an increased emission of IR radiation from the irradiated body part, particularly from the absorption area, including an increased emission of IR radiation in the range of about 5 pm to about 12 pm. Further, by means of the local temperature increase in the irradiated absorption area, the IR radiation emitted from the absorption area shifts away from the corresponding IR absorption maxima of the molecules of the physiological parameter, e.g., from the glucose molecules. Thus, detection of emitted IR radiation from the irradiated body part is facilitated and substantially improved.

A first aspect of the present disclosure is an implantable device comprising:

- an outer housing adapted for implantation enclosing a system for determining a physiological parameter, e.g., glucose, in a tissue and/or bodily fluid of a body part of a subject, e.g., a human subject, the system comprising:

- a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

- a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject,

- a control unit adapted for controlling the measurement procedure and optionally for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, a power source, and - optionally at least one status indicator.

This aspect also includes a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the implantable device as described above.

A further aspect of the present disclosure is a non-invasive continuous monitoring device, e.g., a continuous glucose monitoring device comprising:

- an outer housing enclosing a non-invasive system for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a body part of a subject, e.g., a human subject and attachment means for holding the housing permanently to the body part, the system comprising:

- a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, - a control unit adapted for controlling the measurement procedure and optionally for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit,

- a power source, and

- optionally at least one status indicator.

This aspect also includes a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the continuous monitoring device as described above.

A further aspect of the present disclosure is a portable smart device, e.g., a smart phone comprising:

- an outer casing comprising a front face and a back face, wherein the front face comprises a screen and a keypad and the back face comprises a recess for receiving a body part, e.g., a fingertip, of a subject, e.g., a human subject and a non-invasive system for determining a physiological parameter, e.g., glucose in the bodily fluid and/or tissue of the body part integrated into the recess on the back face, the system comprising:

- a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, and

- a control unit adapted for controlling the measurement procedure and optionally for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit,

- optionally at least one status indicator.

This aspect also includes a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the smart device as described above.

A further aspect of the present disclosure is a non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose comprising:

- an outer housing enclosing a non-invasive system for determining ethanol or simultaneously determining ethanol and glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, the system comprising:

- a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm, a sensing unit wherein said sensing unit is adapted for (i) separately detecting a first parameter-specific IR radiation having a first wavelength or wavelength range and a second parameter-specific IR radiation having a second wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of glucose and/or ethanol and the intensity of the emitted IR radiation increases with a decreasing concentration of glucose and/or ethanol; wherein the first parameter-specific IR radiation has a wavelength of about 9.2 pm and wherein the second parameter-specific IR radiation includes a wavelength range from about 9.2 pm to about 9.6 pm, and wherein said sensing unit is further adapted for (ii) detecting reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, and

- a control unit adapted for the qualitative and/or quantitative determination of both glucose and ethanol based on the IR radiation detected in the sensing unit.

This aspect of the present disclosure refers to a detection of ethanol and a combined detection of ethanol and glucose in the tissue and/or bodily fluid of a subject, particularly in the blood of a human subject. This is achieved by detecting a first parameter-specific IR radiation having a wavelength of about 9.2 pm which does not include a wavelength of about 9.4 pm and which does not include a wavelength of about 9.6 pm and a second parameter-specific IR radiation including a wavelength range from about 9.2 pm to about 9.6 pm. A separate determination of ethanol optionally together with a determination of glucose is possible due to a characteristic change in the signal ratio between the first parameter-specific IR radiation at a wavelength of about 9.2 pm and the second parameter-specific IR radiation including a wavelength range from about 9.2 pm to about 9.6 pm which includes a wavelength of about 9.4 pm. In this aspect, a reference IR radiation may be determined at a first wavelength of about 8.8 pm or a first wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm, and/or a second wavelength range between about 9.7 pm and about 10.4 pm.

This aspect also includes a method for determining ethanol or both glucose and ethanol in a bodily fluid and/or tissue of a body part using the device as described above.

A further aspect of the present disclosure is a non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising:

- an outer casing comprising a non-invasive system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a subject, e.g. a human subject, the system comprising:

- a radiation source adapted for emitting visual (VIS)/near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

- a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting a parameter-specific IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting a reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, and

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of a plurality of individual measurements.

This aspect refers to a measurement sequence consisting of a plurality of measurements, e.g., about 100 to about 2000, about 200 to about 1000, or about 250 to about 500 individual measurements. An individual measurement may take about 1 ms to about 500 ms, about 2 ms to about 200 ms or about 5 ms to about 100 ms. A measurement sequence of a plurality of measurements may take about 0.2 s to about 60 s, about 0.5 s to about 30 s or about 1 s to about 10 s.

In certain embodiments, the temperature of the irradiated body part is monitored during the measurement sequence and individual measurements performed when the temperature of the body part increases are excluded from the determination. In these embodiments, the temperature of the irradiated body part is monitored , e.g. by a separate temperature sensor which may be a thermopile or a pyrometer sensor .

This aspect also includes a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the device as described above.

A further aspect of the present disclosure is a non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising: an outer casing comprising a non-invasive system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a subject, e.g. a human subject, the system comprising: - a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the radiation source is adapted of emitting visual (VlS)Znear-infrared (NIR) radiation into the body for a predetermined irradiation period and the sensing unit is adapted to perform a measurement of IR radiation emitted from the body part within the subsequent dissipation period.

Emission of visual (VlS)Znear-infrared (NIR) radiation by the radiation source into the body part will cause energy transfer into the body part resulting in a local increase in temperature. When the radiation source is shut off, a dissipation period begins where the energy dissipates throughout the irradiated body part.

This aspect of the present disclosure refers to a measurement of IR radiation emitted from the body part by the sensing unit within the dissipation period which starts after shutting off the radiation source. Measuring IR radiation emitted from the body part during this dissipation period may lead to substantial improvement in determining a physiological parameter, e.g., glucose. In certain embodiments, determining the physiological parameter is exclusively based on the measurement of IR radiation emitted from the body part within a time period when the IR radiation is shut off. The measurement with a dissipation period may be single measurement or a measurement sequence consisting of a plurality of individual measurements, particularly a measurement sequence as described above.

Typically, the measurement within the dissipation period takes place within about 2 s, about 1 .5 s, about 1 s, about 500 ms or about 200 ms after the radiation source is shut off.

In certain embodiments, the device is adapted for performing a single cycle consisting of irradiation period and measurement within the subsequent dissipation period. In further embodiments, the device is adapted for performing two or more cycles of irradiation/dissipation.

This aspect also includes a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the device as described above. Detailed description

The present disclosure involves determination of a physiological parameter by detecting IR radiation from previously irradiated body parts of a subject, particularly a human subject in the wavelength range of about 5 pm to about 12 pm, particularly in the range of about 8 pm to about 10 pm. More particularly, the present invention involves determination of a physiological parameter by its absorption of IR radiation emitted from a previously irradiated body part of a subject in the wavelength range of about 5 pm to about 12 pm, particularly in the range of about 8 pm to about 10 pm. The signal of the emitted IR radiation at the measurement wavelength decreases with an increasing concentration of the physiological parameter and the signal of the emitted IR radiation at the measurement wavelength increases with a decreasing concentration of the physiological parameter. The physiological parameter may be any compound having characteristic absorption bands in this wavelength range. For example, the physiological parameter is glucose or another clinically relevant analyte such as lactate or troponin.

In a certain embodiment of the invention, the system is adapted for the non-invasive determination of glucose in blood. In this embodiment, IR radiation is detected at a glucose-specific wavelength or wavelength range where glucose has a characteristic absorption band and where the intensity of the detected IR radiation is dependent from the concentration of glucose in the blood. More particularly, the glucose-specific wavelength or wavelength range is selected from a wavelength of about 9.2 pm, a wavelength of about 9.4 pm, a wavelength of about 9.6 pm, a wavelength range comprising at least two of the wavelengths of about 9.2 pm, about 9.4 pm and about

9.6 pm, a wavelength range comprising all three of the wavelengths of about 9.2 pm, about 9.4 pm and about 9.6 pm or any combination thereof. Additionally, IR radiation is detected at a reference wavelength or wavelength range where glucose has no characteristic absorption band and particularly an absorption minimum and where the intensity of the detected IR radiation is substantially independent from the concentration of glucose in blood. More particularly, the reference wavelength or wavelength range is selected from a wavelength or wavelength range between about

8.7 pm to about 9.0 pm, a wavelength or a wavelength range between about 9.7 pm to about 10.2 pm or any combination thereof. In particular embodiments of all aspects as described above, the system is adapted for sensing a reference wavelength of about 8.8 pm or a reference wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm.

In further particular embodiments of all aspects as described above, the system is adapted for sensing a reference wavelength of about 10.2 pm or a reference wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm.

In still further particular embodiments of all aspects as described above, the system is adapted for sensing a first reference wavelength of about 8.8 pm or a reference wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm and a second reference wavelength of about 10.2 pm or a reference wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm.

As outlined above, the invention is based on the irradiation of body tissue with electromagnetic radiation in the wavelength range between about 400 nm to about 1500 nm (VIS/NIR radiation) and detection of electromagnetic radiation emitted from the irradiated body part in the wavelength range between about 5 pm to about 15 pm (IR radiation). Irradiation of the body part with VIS/NIR radiation results in an enhanced self-emission of IR radiation from said body part due to local energy absorption, which causes a local increase in temperature. Thus, self-emission of IR radiation from the irradiated body part is increased by previous irradiation of said body part with VIS/NIR radiation. Consequently, irradiation of the body part with an external source of IR radiation in the wavelength range between about 5 pm to about 15 pm is not required. Thus, in certain embodiments, the system of the invention does not include an IR radiation source, particularly in certain embodiments the system of the invention does not include an IR radiation source adapted to irradiate the body part from which the detected IR radiation is emitted.

An absorption wavelength band of a physiological parameter typically has a width of 100 pm to 200 pm. Thus, the term “about” is understood to include this width of the absorption wavelength band. In certain embodiments, the term “about” is intended to include a value of ± 0.1 pm or ± 0.05 pm around the indicated wavelength, e.g., a wavelength of 9.2 pm ± 0.1 pm or 9.2 pm ± 0.05 pm.

Figure 1 shows the penetration depth of electromagnetic radiation into body tissue [mm] depending on the wavelength [nm]. It can be seen that the penetration depth is dependent from the wavelength. In the visual (VlS)Znear-infrared (NIR) wavelength range between about 400 nm to about 1500 nm, particularly in the range of about 500 nm to about 1500 nm or in the range of about 400 nm to about 1200 nm, more particularly in the range of about 550 nm to about 1200 nm, there is a penetration depth of about 1 mm or more, particularly about 3 mm or more. Thus, a body part irradiated with radiation will absorb electromagnetic energy resulting in a local increase of tissue temperature. This again results in an increased emission of longer-wavelength IR radiation, e.g., IR radiation in the wavelength range of about 5 pm to about 12 pm, where certain organic compounds present in bodily fluids, i.e. physiological parameters, show absorption bands. This allows a quantitative or qualitative determination of such parameters according to the above aspects of the present invention.

In certain embodiments, the VIS/NIR radiation emitted into the body part is in the range of about 550 nm to about 1000 nm, particularly in the range of about 800 nm to about 820 nm, e.g., about 810 nm, and/or in the range of about 590 nm to about 660 nm, e.g., at about 600 nm, and/or in the range of about 920 nm to about 980 nm, e.g., at about 940 nm. In certain embodiments, the VIS/NIR radiation emitted into the body is in the range of about 450 nm to about 800 nm.

Figure 2 shows relative absorption coefficients of certain compounds present in the human body depending on the wavelength in the range between 400 nm and 1100 nm. The wavelengths of about 600 nm and about 810 nm, at which radiation may be emitted into the body part, are specifically indicated. In the wavelength range of about 500 nm to about 1050 nm, there is a relatively low absorption of water (H2O). Further, the major blood constituents hemoglobin (Hb) and oxyhemoglobin (Hboxy) show similar absorption coefficients. The skin pigment melamine shows an absorption coefficient which decreases with increasing wavelength. The system or device of the invention comprises a radiation source (a) adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm into a body part of said subject, wherein the body part is particularly selected from a fingertip, an earlobe, a wrist, a forearm, a palm and an upper arm.

In an embodiment of the invention, the radiation source (a) is adapted for emitting VIS/NIR radiation in the range of about 920 nm to about 960 nm, e.g., about 940 nm into a body part. This irradiation wavelength may be used alone or in combination with at least one further irradiation wavelength. As shown in Figure 3, glucose has an absorption band at a wavelength of 940 nm. Thus, irradiation at a wavelength of about 940 nm leads to a selective excitation of glucose molecules and may result in a stronger absorption of glucose molecules in the IR wavelength range, particularly in the wavelength range of about 5 pm to about 12 pm.

According to an embodiment of the invention, the radiation source (a) is adapted for emitting VIS/NIR radiation in the range of about 920 nm to about 980 nm, e.g., about 940 nm into a body part of said subject, and the sensing unit (b) is further adapted for detecting VIS/NIR radiation having a wavelength of about 940 nm, where the intensity of the detected VIS/NIR radiation is dependent from the concentration of glucose. The measurement signal in the VIS/NIR wavelength range may be combined with the measurement signals in the IR range as described above, e.g., by means of a comparator.

In a still further embodiment, VIS/NIR irradiation occurs at a combination of at least 2 different wavelengths, particularly at a combination of a first wavelength of about 800 nm to about 820 nm, e.g., about 810 nm, and a second wavelength of about 920 nm to about 980 nm, e g., about 940 nm.

The radiation source (a) is adapted for emitting VIS/NIR radiation in the range of about 400 nm to about 1500 nm, particularly in the range of about 500 nm to about 1500 nm. The VIS/NIR radiation may be emitted continuously or intermittently throughout a predetermined time interval. In a certain embodiment, the radiation source is adapted to cause a local increase in the temperature of the irradiated body part, e.g., a fingertip, and particularly a local increase in the temperature of the absorption area within the irradiated body part. The local increase in temperature may be in the range of between about 1 °C to about 15°C, particularly about 2°C to about 10°C, and more particularly in the range of about 3°C to about 5°C. The locally increased temperature of the irradiated body part, e.g., a fingertip, may be in temperature range up to about 45°C, up to about 40°C or up to about 37°C, for example in the temperature range between about 30°C to about 35°C or about 30°C to about 32°C. This local temperature increase results in an enhanced self-emission of IR radiation from the irradiated body part and particularly from the absorption area within the irradiated body part.

In a certain embodiment, the radiation source (a) may be adapted for emitting radiation continuously at a power of about 10 mW to about 1 W, particularly for about 20 mW to about 500 mW, more particularly of about 50 mW to about 250 mW, and even more particularly of about 100 mW to about 200 mW, e.g. about 150 mW, for a time interval of about 0.1 to about 20 s, particularly of about 0.2 s to about 5 s, and more particularly of about 0.5 s to about 2 s, e.g. about 1 s.

In a further embodiment, the radiation source (a) may be adapted for emitting radiation intermittently at a power of about 10 mW to about 5 W, particularly of about 20 mW to about 1 W, and more particularly of about 50 mW to about 500 mW for a time interval of about 0.1 s to about 20 s, particularly of about 0.2 s to about 5 s, and more particularly of about 0.5 s to about 2 s. The radiation may be emitted intermittently with a pulse frequency of about 1 Hz to about 1 MHz.

In a further embodiment, the radiation source (a) is adapted for emitting radiation continuously or intermittently for a time period of at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s.

In a further embodiment, the radiation source (a) may be adapted to emit VIS/NIR radiation at a plurality of different wavelengths, e.g., at 2, 3, 4, 5, 6, 7, 8 or even more different wavelengths. For example, the radiation source may be multi-LED chip. The use of a multi-wavelength radiation source allows adjusting a predetermined penetration depth of electromagnetic radiation into the tissue of the irradiated body part depending on specific characteristics of the body part, e.g., pigmentation, skin thickness, presence, or absence of homy skin. As shown in Figure 1 , supra, the penetration depth into body tissue varies with the wavelength and the use of VIS/NIR radiation with different wavelengths or with combinations of different wavelengths can be adapted for each subject and/or each body part individually, if desired.

In certain embodiments, the radiation source (a) is a multi-wavelength radiation source is adapted to emit VIS/NIR radiation at several different wavelengths or wavelength ranges, for example, between about 400 nm to about 1200 nm, more particularly between about 450 nm and about 900 nm, e.g., at least 2, 3, 4, 6 or 8 wavelengths which may be selected from wavelengths at about 470 nm, about 520 nm, about 590 nm, about 650 nm, about 750 nm and about 810 nm.

The system or device of the invention comprises a sensing unit (b) for detecting emitted IR radiation from the irradiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range in the range of about 5 pm to about 12 pm, where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and for (ii) detecting IR radiation having at least one wavelength or wavelength range in the range of about 5 pm to about 12 pm, where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject.

In certain embodiments, the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein during at least a part of said time period, e.g. at least about 60% or at least about 80% or at least about 90% of said time period, the body part is irradiated by VIS/NIR radiation, wherein said time period may be at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s.

In certain embodiments, the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, e.g. a time period as described above, wherein during at least a part of said time period, e.g. at least about 60% or at least about 80% or at least about 90% of said time period, the temperature of the irradiated body part, particularly the absorption area, in the irradiated body part is higher than the surrounding tissue, e.g. at least 1 °C, at least 2°C, at least 5°C and up to 10°C higher than the surrounding tissue.

In certain embodiments, the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, e.g. a time period as described above, wherein during at least a part of said time period, e.g. at least about 60% or at least about 80% or at least about 90% of said time period, the temperature of the irradiated body part, particularly the absorption area, is increasing. The increase in temperature may about 2°C to about 10°C, particularly in the range of about 3°C to about 5°C.

The sensing unit (b) comprises at least one sensor adapted for detecting emitted IR radiation from the irradiated body part. In the sensing unit (b) of the invention, at least one sensor may be an analyte-specific sensor, i.e. a sensor which is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and at least on sensor may be a reference sensor, i.e. a sensor which is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject.

In certain embodiments, the sensing unit (b) is adapted for detecting self-emitted IR radiation from the previously irradiated body part, i.e. IR radiation generated by the body heat of the subject without irradiation by an external IR source. Further, the sensing unit (b) may be adapted for detecting emitted IR radiation from an absorption area within the previously VIS/NIR-irradiated body part wherein the absorption area has a locally increased temperature and exhibits an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm. In certain embodiments, at least one further sensor may be present, e.g. a sensor which (i) is adapted for detecting unspecific IR radiation, (ii) is adapted for detecting unspecific VIS/NIR radiation, (iii) is adapted for detecting VIS/NIR radiation having a wavelength, where the intensity of the detected VIS/NIR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and/or (iv) a temperature sensor for measuring the temperature of the body part.

In certain embodiments, the sensing unit (b) is further adapted for a temperature measurement, e.g., with a precision of at least about 1 °C, of at least about 0.1 °C or of at least about 0.01 °C. The sensing unit may be adapted for measuring and optionally monitoring the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of individual sensors within the sensing unit (b) and/or the temperature of an electronics component of the sensing unit (b), e.g., the temperature of a circuit board. In those embodiments, the sensing unit (b) may comprise at least one temperature sensor, particularly a plurality of temperature sensors, e.g. 2, 3 or 4 temperature sensors for measuring the skin temperature, and optionally at least one further temperature sensor, e.g., a sensor for measuring the environmental temperature, at least one sensor for measuring the temperatures of individual sensors within the sensing unit and/or a sensor for measuring the temperature of an electronics component of the sensing unit e.g. the temperature of a circuit board of the sensing unit (b).

In certain embodiments, the sensing unit (b) further comprises a gesture sensor adapted for detecting movement during the measurement. The gesture sensor may operate in the same wavelength range as the other sensors. By using a gesture sensor, measurements undertaken when the body part is moving may be identified and optionally excluded.

In certain embodiments, the sensing unit (b) further comprises an accelerometer, e.g., a microelectromechanical systems (MEMS) accelerator. By using an accelerometer, measurements undertaken when the body part is moving may be identified and optionally excluded. In certain embodiments, the sensing unit (b) comprises at least one further analytespecific sensor, i.e. , a sensor, which is adapted for detecting VIS/NIR radiation having at least one wavelength or wavelength range where the intensity of the detected VIS/NIR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject. For example, at least one further sensor adapted for detecting VIR/NIR radiation having a wavelength of about 940 nm may be present.

In certain embodiments of the invention, the radiation source (a) and the sensing unit (b) are located in positions relative to the irradiated body part, which are defined by an angle of at least 90° or more. In certain embodiments, the radiation source (a) and the sensing unit (b) are located on opposite sides of the irradiated body part.

The system or device of the invention comprises an analyzing or control unit (c) for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit (b). The analyzing unit may comprise, for example, an A/D converter and/or a microcontroller. The analysis of the measured signal may be based on the intensity and/or the decay time.

In particular embodiments, the analyzing or control unit (c) is adapted for a timedependent analysis of the detected IR radiation, wherein a measurement signal is recorded over a time period, particularly over a time period of at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s.

In further particular embodiments, the analyzing or control unit (c) is adapted for a temperature-compensated analysis of the detected IR radiation. A temperature- compensated analysis comprises a temperature compensation wherein the measurement signal is subject to a temperature correction. Particularly, the temperature compensation is based on the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of components of the sensing unit, e.g., the temperatures of individual sensors within the sensing unit and/or the temperature of an electronics component of the sensing unit. In still further particular embodiments, the analyzing or control unit (c) is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation as described above.

Figure 4 shows an embodiment of a system described in WO 2022/090503. A body part (1 ), e.g., a fingertip, is placed into contact with the system, which is adapted to irradiate an absorption area (2) within the body part (1 ).

The system comprises a cover (3) which is at least partially made of a material, which is optically transparent. For example, the cover is at least partially made of CaF2 and/or BaF2 or of a plastic material which is transparent in the IR wavelength range of about 5 pm to about 12 pm or a sub-range thereof, e.g., of about 8 pm to about 12 pm, and which is optionally transparent in the VIS/NIR wavelength range of about 400 nm to about 1500 nm or a sub-range thereof. Suitable IR-transparent plastic materials are e.g., the PolyIR plastic materials commercially available from Fresnel Technologies, Fort Worth, Texas, USA. In certain embodiments, the cover may have a thickness of about 0.2 mm to about 2 mm, particularly of about 0.3 mm to about 1.5 mm, more particularly about 1 mm.

The system further comprises at least one sensor (4) which may be provided with a filter element (5) and optionally a lens element (not shown), which e.g., may be arranged between a sensor (4) and a filter element (5). The sensor (4) may be mounted on a circuit board (6). Further, the system comprises at least one radiation source (9, 9a). For example, the system may comprise a radiation source (9) located on the same side as the sensor (4) and/or a radiation source (9a) located on an opposite side of the body part (1 ) with regard to the sensor (4). If desired, a further sensor (4) may be provided without filter element (5) for monitoring the exact skin temperature of the subject.

The system contains one or more sensors (4). In the embodiment of Figure 4, the system comprises four different sensors (4). The sensor may be an optical detector, particularly an optical photovoltaic detector, e.g., an InAsSb-based detector, which may be used in combination with a lock-in amplifier, if desired. A photovoltaic detector, e.g., an InAsSb-based detector has a rise time of only few nanoseconds and is particularly useful in a set-up wherein the body part is irradiated intermittently. In other embodiments, the sensor may be a heat detector, e.g., a thermopile or a bolometer. Suitable sensors include a photovoltaic detector (e.g., Hamamatsu P13894), a thermopile (e.g., Heimann HCS C21 F8-14) or other types of IR sensors (e.g., Sensirion STS21 or Melexis MLX90632). If desired, a sensor (4) may be provided with a filter element (5) capable of selectively transmitting radiation of a desired wavelength or wavelength range. The filter element may have narrow bandwidth, e.g., of about 50 to 100 nm, or a broader bandwidth, e.g., of about 400 nm or more. A filter may be made from germanium or other filter materials, which are optically transmissive for the respective wavelengths. Further, a sensor may be provided with a lens element, e.g., a micro-lens capable of focusing the light falling onto the sensor.

In certain embodiments, the sensor surface may be coated with a noble metal such as Au or Ag, particularly Au, in order to increase its sensitivity. Such a coating which may be shaped as a Bundt baking-pan is described by Awad (Nature Scientific Reports 9:12197 (2019)), the content of which is herein incorporated by reference.

In certain embodiments, the sensor is a miniaturized sensor having an area of about 1 mm² to about 10,000 mm², e.g., of about 10 mm² to about 1 ,000 mm². In certain embodiments, the sensor may be even more miniaturized, e.g., an ASIC (applicationspecific integrated circuit).

Further, the device may comprise a circuit board (7) on which the light source (9) is mounted and an active and/or passive heat sink (8).

The VIS/NIR radiation source (9, 9a, 9b) may be adapted for emitting collimated radiation, e.g., a laser-based light source, and/or adapted for emitting non-collimated radiation, e.g., an LED-based light source. For example, the light source may be selected from an LED, a laser diode, a VCSEL (vertical-cavity surface-emitting laser) or a laser. In certain embodiments, a broadband VIS/NIR radiation emitter is used which may be adapted for emitting VIS/NIR radiation in the range of about 650 nm to about 950 nm, particularly in the range of about 750 nm to about 850 nm and more particularly in the range of about 780 nm to about 820 nm. Suitable VIS/NIR emitters are e.g., the OSLON products from Osram such as OSLON SFH 4763. In certain embodiments of all aspects of the present disclosure, the device further comprises monitoring means for detecting fluctuations, e.g., power fluctuations in the radiation emitted by the radiation source. The monitoring means may comprise a photodiode, e.g., a photodiode integrated in the radiation source, or a photodiode separate from the radiation source. Detected fluctuations may be compensated by the sensing unit and/or the control unit, or the radiation source may be replaced.

A further embodiment of the system described in WO 2022/090503 is shown in Figure 5. Here, a single radiation source (9a) is provided on a side of the body part (1 ) which is opposite to a sensing unit comprising at least one sensor (4) provided with a filter (5) and a further sensor (4a) provided with a filter (5a). In certain embodiments, sensor (4a) is an optical sensor, e.g., a photodiode. It is adapted for a reference measurement of transmission radiation from radiation source (9a), e.g. for measuring radiation at a wavelength of about 600 nm and/or about 810 nm and/or about 940 nm. For this purpose, filter element (5a) may be a bandpass filter at about 600 nm and/or 810 nm and/or 940 nm.

Still a further embodiment described in WO 2022/090503 is shown in Figure 6. Here, a radiation source (9b) is provided on a side of the body part (1 ), e.g., a fingertip, wherein direct access to an absorption area (2) within the body part (1 ) is provided through the skin of the body part without the radiation passing through a cover structure of the device and/or without passing through a homy structure on the body surface, e.g., a fingernail and/or horny skin. Thereby, interference, e.g., interference from the cover structure or from keratinic homy skin or nail material and optionally nail varnish can be reduced or eliminated. According to this embodiment, a single radiation source (9b) or a plurality of radiation sources (9b), e.g., 2, 3, 4, 6 or 8 radiation sources may be provided at a position around the circumference of the body part (1 ), e.g., a fingertip. If a plurality of radiation sources is present, they are preferably adapted to emit radiation into a single absorption area (2) within the body part, which may be about 3 mm to about 5 mm below the body surface.

Still a further embodiment described in WO 2022/090503 is shown in Figure 7. In this embodiment, a cover (3) is provided which is adapted for focusing IR radiation emitted from the body part to the at least one sensor (4) of the sensing unit. Thereby, the radiation intensity on the sensor and thus the sensitivity and/or accuracy of the measurement may be increased. The cover (3) is made of a material, e.g., plastic, metal, metal oxide or composite material, which is substantially transparent for IR radiation in the wavelength range to be detected on the sensor, particularly for IR radiation in the wavelength range of about 5 pm to about 12 pm or a sub-range thereof, e.g., of about 8 pm to about 12 pm. Suitable materials are e.g., the PolyIR plastic materials, c.f. supra. In this embodiment, the cover (3) may comprise an IR Fresnel lens, i.e. , a lens of large aperture and short focal length capable of efficiently focusing IR radiation passing therethrough, or an array comprising a plurality e.g., up to 10 or more IR Fresnel lenses. In certain embodiments, the array may comprise IR Fresnel micro-lenses, e.g., up to 100 or 1000 micro-lenses, which may have diameters in the range of about 50 nm to about 500 pm. In certain embodiments, the IR Fresnel lens may have a back focal length of about 3 mm to about 10 mm, e.g., about 5 mm and may be manufactured from an IR-transparent plastic. For example, a suitable IR Fresnel lens, which is optically transparent in the wavelength range of 8-14 pm is commercially available from Edmund Optics (product family no. 2042).

Further, Figure 7 shows a radiation source (9a) provided on the opposite side of the body part with regard to the position of the sensing unit, which comprises a sensor (4). It should be noted, however, that one or more radiation sources may also be arranged in a circumferential arrangement around the body part (1 ), e.g., as shown in Figure 6. It should further be noted, that in this embodiment a plurality of different sensors may be present, e.g., as shown in Figure 4 and Figure 5.

As shown in Figure 4 and Figure 5, the system may comprise a plurality of different sensors (4). In certain embodiments, the system may comprise a plurality of analytespecific, e.g., glucose-specific sensors wherein a first sensor is adapted for detecting radiation at a first wavelength or wavelength range, e.g., at a wavelength of about 9.2 pm and at least another first sensor is adapted for detecting IR radiation at a second wavelength range which encompasses the first wavelength or wavelength range and further comprises another wavelength or wavelength range. For example, the other first sensor may be adapted for detecting IR radiation at a wavelength of about 9.2 pm and additionally at a wavelength of about 9.4 pm and/or about 9.6 pm, particularly at a wavelength of about 9.4 pm and a wavelength of about 9.6 pm. Further, the sensing unit may comprise a plurality of reference sensors adapted for detecting reference radiation at different wavelengths or wavelength ranges. For example, when determining glucose, a reference sensor may be adapted for detecting radiation having a wavelength range between about 8.6 pm and about 9.0 pm. Another reference sensor is adapted for detecting radiation at a wavelength or wavelength range between about 9.8 pm and about 10.2 pm.

Still a further embodiment described in WO 2022/090503 is shown in Figure 8. In this embodiment, a support (16) for the body part (1 ), e.g., a fingertip, is provided wherein said support (16) comprises an opening adapted to receive a portion (15) of the body part (1 ). For example, the support may comprise an annular structure with an opening, e.g., a substantially circular opening, in its center. The system is adapted for pressing the body part (1 ) onto the opening in the support (16) such that a portion (1 5) of the body part (1 ), e.g., a portion of the fingertip, is forced into the opening. Thus, the tissue including the blood vessels within portion (15) is compressed resulting in an enhanced amount of capillary blood within portion (15). Thereby, the signal intensity and thus the sensitivity and/or accuracy of the measurement may be increased.

Further, the system of Figure 8 includes a cover (3) which may be formed as an IR Fresnel lens as described above in the context of Figure 7. It should be noted, however, that other covers are also suitable. Furthermore, a radiation source (9a) is shown which is provided on the opposite side of the body part with regard to the position of the sensing unit, which comprises a sensor (4). It should be noted, however, that one or more radiation sources may also be arranged in a circumferential arrangement around the body part (1 ), e.g., as shown in Figure 6. It should further be noted, that in this embodiment a plurality of different sensors may be present, e.g., as shown in Figure 4 and Figure 5.

In Figure 9, measurement at a plurality of analyte-specific wavelengths/wavelength ranges and reference wavelengths/wavelength ranges is shown.

The absorption signal of glucose (24) has three different peaks at about 9.2 pm, at about 9.4 pm and about 9.6 pm. A first glucose-specific sensor may be adapted for measuring only the peak at 9.2 pm. Such a sensor would be adapted with a filter element capable of transmitting radiation only in a narrow range (22). Thus, the sensor is capable of selectively detecting radiation within this narrow range. A further glucosespecific sensor may be adapted for measuring radiation at a broader range between about 9.1 pm and about 9.7 pm, thereby encompassing the peaks at about 9.2 pm, 9.4 pm and 9.6 pm. This sensor may be adapted with a filter element capable of transmitting radiation in a broader range (21 ).

Two reference sensors may be provided, wherein said reference sensors are provided with filter elements capable of transmission of radiation with a wavelength in the range of about 8.6 pm and about 9.0 pm, particularly of about 8.8 pm - 8.9 pm (20) and/or radiation with a wavelength in the range of about 9.8 pm and about 10.2 pm, particularly of about 9.9 pm - 10.1 pm (23), respectively.

Parallel and separate measurements at a wavelength of about 9.2 pm on the one hand and at a wavelength range including the peak at 9.2 pm, but also at least one of the other peaks, particularly the peak at about 9.6 pm have a further advantage, since they allow determination whether the subject’s blood contains ethanol. Since ethanol and other alcohols have an absorption band at a wavelength of about 9.6 pm, but not at a wavelength of about 9.2 pm, the ratio between the peak at 9.2 pm and 9.6 pm may be used to determine and optionally correct a disturbance caused by blood alcohol.

In an alternative embodiment, a first glucose-specific sensor may be adapted for measuring only the peak at 9.6 pm. Such a sensor would be provided with a filter element capable of transmitting radiation only in a narrow range. A further glucosespecific sensor may be adapted for measuring radiation at a broader range between about 9.4 pm and about 9.6 pm, thereby encompassing the peaks at about 9.4 pm and about 9.6 pm and not encompassing the peak at 9.2 pm. This sensor may be provided with a filter element capable of transmitting radiation in a broader range.

In a further alternative embodiment, a reference sensor may be provided, which is provided with a filter element capable of transmission of radiation with a wavelength in the range of about 7.8 pm and about 8.2 pm, particularly of about 7.9 pm - 8.1 pm, optionally in combination with at least one further reference sensor, which is provided with a filter element capable of transmission of radiation with a wavelength in the range of about 8.8 pm - 9.2 pm and/or radiation with a wavelength of about 9.8 pm - 10.2 pm, respectively

In a still further embodiment, the system may comprise a sensor, which is adapted for a time-dependent detection of IR radiation having different wavelengths or wavelength ranges. In this embodiment, the system may be provided with a sensor comprising a plurality of filters adapted for transmitting IR radiation having different wavelengths or wavelength ranges wherein said filters may be placed on a sensor during different stages of a measurement cycle thereby allowing detection of different wavelengths or wavelength ranges within a measurement cycle. Such an embodiment described in WO 2022/090503 is shown in Figure 10. Here, a system is provided comprising a filter wheel (10) capable of rotating around an axis (11 ) and a shutter wheel (13) capable of rotating around an axis. The filter wheel and the shutter wheel are provided with illumination holes (15) through which light from the radiation source (not shown) may pass into the body part of the subject (not shown). Reflected light from the irradiated body part may pass through different holes (14) of the filter wheel (10) which may be provided with analyte-specific filter elements and/or reference filter elements as described above. The filter wheel's (10) and the shutter wheel's (13) position may be monitored with a magnet (12) in combination with a magnetic sensor. In operation, they may be rotated with predetermined frequencies, thereby allowing time-dependently passing of radiation from the radiation source into the body part and time-dependently passing of radiation emitted from the body part at predetermined time intervals through the different holes (14) of the filter wheel (10) to a sensor (not shown).

In an alternative embodiment (not shown), a sensor which is adapted for a timedependent detection of IR radiation having different wavelengths or wavelength ranges, may be a Fabry-Perot interferometer, e.g., a MEMS spectrometer for the desired IR wavelength range (cf. Tuohinieni et al., J. Micromech. Microeng. 22 (2012), 115004; Tuohinieni et al., J. Micromech. Microeng. 23 (2013), 075011 ).

In certain embodiments, the system comprises a single sensor, which is adapted for a time-dependent detection of IR radiation having different wavelengths or wavelength ranges. This sensor may be provided with different filters, e.g., with a filter wheel, or be a Fabry-Perot interferometer as described above.

A still further embodiment described in WO 2022/090503 is shown in Figure 11. The system of this embodiment is adapted for being permanently fixed to the subject's body. This system is particularly adapted for carrying out a plurality of measurements in predetermined time intervals. The system comprises a housing (30) and a strap (31 ) for fixing the housing around the body (33), e.g., a wrist or forearm. Further, the system comprises a radiation source for emitting VIS/NIR light into an absorption area (34) of the body part (33) and sensors for detecting IR radiation emitted from the irradiated body part.

A still further embodiment described in WO 2022/090503 is shown in Figure 12. The system of this embodiment is adapted for being permanently fixed to the subject's body and particularly adapted for carrying out a plurality of measurements in predetermined time intervals. The system comprises a housing (30) and a strap (31 ) for fixing the housing around the body (33), e.g., a wrist or forearm. Further, the system comprises a plurality of radiation sources, e.g., 2 radiation sources, for emitting VIS/NIR light into an absorption area (34) of the body part (33) and sensors for detecting IR radiation emitted from the irradiated body part. The light emitted from these sources may fall at angle, e.g., at an angle of about 30° to about 75° onto the surface of the body part (33).

In Figure 13, a schematic view of the system of Figure 4 is shown.

Figure 14 shows a heat map of a fingertip after irradiation with light of 810 nm for a time period of 2 s.

Figure 15 is diagram showing the time-dependent thermal power output in addition to the self-emission of a fingertip during intermittent irradiation with light of 810 nm with a power of 2 mW and a frequency of 0.1 Hz.

Figure 16a shows a block diagram of an embodiment of the sensing unit the present invention. A Region of Interest (ROI), i.e. , the skin tissue of a subject, particularly a human subject, is irradiated with a first light source emitting VIS/NIR radiation having a wavelength of 940 nm, a second light source emitting VIS/NIR radiation having a wavelength of about 810 nm and optionally a third light source emitting VIS/NIR radiation having a wavelength of about 600 nm. Radiation transmitted through the Region of Interest or reflected from the Region of Interest is analyzed by a sensing unit. Further, the device comprises a temperature sensor.

The sensing unit comprises a plurality of sensors, for example analyte-specific IR sensors (1 ) and (2) and reference sensors, e.g., IR sensor (4). For the determination of glucose, an IR sensor (1 ) may be provided with a first optical filter, which is transmissive for a wavelength of about 9.2 pm and an IR sensor (2) may be provided with a second optical filter, which is transmissive for a wavelength range between about 9.2 pm and about 9.6 pm. A reference sensor (4) may be provided with a fourth optical filter which is transmissive for a wavelength or wavelength range between about 8.6 pm and about 9.0 pm and/or a wavelength or wavelength range between about 9.8 pm and about 10.2 pm. Further, the sensing unit comprises an NIR sensor for detecting VIS/NIR radiation having a wavelength of about 940 pm where glucose has a strong absorption band. The NIR sensor is provided with a suitable optical filter, which is transmissive for this wavelength. Further, the sensing unit may comprise a temperature sensor for measuring the temperature of the skin tissue in the Region of Interest. The respective sensors may be coupled to amplifiers (AMP) for first signal amplification. Signals from individual sensors may be referenced with signals from other sensors by means of a comparator, thereby improving the measurement accuracy and/or signal quality. For example, the measurement signal from the NIR sensor at 940 nm may be referenced with the measurement signal from analyte-specific IR sensor (1 ). Alternatively or additionally, the measurement signal from the NIR sensor at 940 nm may be referenced with the measurement signals from analyte-specific IR sensor (1 ) and/or analyte-specific IR sensor (2) and/or reference IR sensor (4). The measured and optionally referenced signals are further amplified by a lock-in amplifier unit and transmitted to a microcontroller unit. A feedback control from the lock-in amplifier to the light sources may be provided. From the microcontroller unit, the signal and/or the result of internal algorithms may be transmitted to a display unit and/or another device, e.g., by a direct connection or via Bluetooth and/or WLAN. Figure 16b shows a block diagram of a further embodiment of the sensing unit of the present invention, which is similar to the sensing unit shown in Figure 16a. Here, additionally or alternatively, a multi-wavelength light source, e.g., a multi-wavelength LED comprising a plurality of individual diodes is provided. The multi-wavelength light source may e.g., have a wavelength range from 400 nm to about 700 nm is provided and may be operated by the microcontroller unit. Further, a temperature sensor coupled to an amplifier (AMP) is present. This temperature sensor may also be operated by the microcontroller unit.

In a still further embodiment of the invention, the system may comprise a spectral or line sensor or spectral or line sensor array, typically a bolometer or thermopile array, which is adapted for detecting an IR spectrum within the wavelength range of interest, e.g., including the range of about 7 pm to about 12 pm, particularly including the range of about 8 pm to about 10 pm. An IR spectrum may be generated by passing the IR radiation from the irradiated body part through a spectral splitting or diffracting device and then to the sensor or sensor array. Such an embodiment is shown in Figure 17. Emitted IR radiation (70) from the irradiated body part (71 ), e.g., a fingertip, is optionally focused by a focusing element (72) adapted for focusing IR radiation, e.g., a lens or concave mirror element, and then passed to a spectral splitting or diffracting element (73), e.g., a prism or a transmissive or reflective optical grating, where the IR radiation is split according to its wavelength. From there the diffracted radiation is passed to a spectral sensor or line sensor or sensor array (74), typically a bolometer or thermopile array, where an IR spectrum in the wavelength range of interest, e.g., between 8 pm and about 20 pm including analyte-specific wavelengths or wavelength ranges and reference wavelengths or wavelength ranges, e.g., as described above, is detected. The amount of the physiological parameter of interest, e.g., glucose may be determined by spectral analysis according to the relative intensities of predetermined analyte-specific and reference wavelengths.

The system and the method described herein allow qualitative and/or quantitative determination of the physiological parameter to be measured, particularly qualitative and/or quantitative determination of glucose in blood. In certain embodiments, the concentration of the physiological parameter, e.g., the concentration of glucose in blood, is quantitatively determined. In certain embodiments, the alteration rate of the measured amount of the physiological parameter, e.g., glucose, is determined. These embodiments may involve a non- quantitative measurement, e.g., a relative measurement of the alteration of the analyte amount per time unit, i.e. , the increase of the analyte amount or the decrease of the analyte amount per time unit. In case the alteration of the analyte amount into a single direction, i.e., increase or decrease, exceeds a predetermined level and/or time period, the system will provide an alert. This embodiment is particularly useful for systems as shown in Figure 11 and Figure 12, which may be permanently fixed at the body of the subject, e.g., around the wrist, forearm, or upper arm. This embodiment may be adapted for steady glucose level monitoring.

In certain embodiments, the system described herein is adapted for performing both non-quantitative measurements and quantitative measurements. For example, the system may be adapted for performing non-quantitative measurements, e.g., qualitatively measuring the alteration, e.g., the increase or decrease, of the analyte amount over time during standard operation. Non-quantitative measurements may e.g., be performed as continuous and/or intermittent monitoring measurements, as required. In case the alteration of the analyte amount exceeds a predetermined level and/or time period, the system is adapted to switch to a quantitative measurement in order to provide more detailed information. In these embodiments, a system adapted to be permanently fixed to the body, e.g., to an arm wrist, or to an ankle, may be used. Specific embodiments of such systems are shown in Figure 11 and Figure 12.

In certain embodiments, the system is adapted to perform non-quantitative measurements, e.g., continuous and/or intermittent monitoring measurements, and quantitative measurements on several different body parts. For example, the system may be adapted to perform non-quantitative measurements on a first body part, e.g., a body part to which the system may be permanently fixed, such as an arm wrist or an ankle, and to perform quantitative measurements on a second body part, e.g., a body part where capillary vessels are more accessible, such as an earlobe, a palm or a fingertip. For performing a measurement on the second body part, the system is removed from the first body part and brought into contact, particularly into direct contact with the second body part. After performing the measurement on the second body part, the system may be removed therefrom and brought again into contact with the first body part, e.g., by fixing the system to the first body part. In specific embodiments, the first body part is an arm wrist and/or the second body part is a fingertip.

A still further embodiment described in WO 2022/090503 is shown in Figure 18. Here, a device comprising a non-invasive system for determining a physiological parameter, e.g., glucose, in a bodily fluid of a subject is shown. The device comprises a casing

(80), which comprises a first face comprising a screen (81 ) which is at least partially made of a material which is optically transparent for NIR/VIS radiation emitted by a radiation source (82). Further, the device comprises a sensing unit (83) comprising at least two sensors (83a), (83b).

The device (80) may be a mobile device, e.g., a smart phone, a smart watch, a tablet or a fitness-tracker device. The device may be worn on the body of a subject, e.g., a wrist (84), and may be fixed by a band (85), e.g., a wrist band. A body part (86), e. g., a fingertip (or, alternatively, a plurality of fingertips or a palm) is placed upon screen

(81 ) for measurement. An absorption area (87) within body part (86) is irradiated by VIS/NIR radiation emitted by radiation source (82). The irradiated body part absorbs electromagnetic energy resulting in a local increase of local temperature and in an increased emission of IR radiation from the absorption area in the wavelength range of about 5 pm to about 12 pm. Molecules of the detected physiological parameter, e.g., glucose molecules, absorb the emitted IR radiation, present in the tissue of body part (86). Thus, at wavelengths or wavelength ranges corresponding to the absorption bands of the physiological parameter of interest, the signal of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the signal of the emitted IR radiation increases with a decreasing concentration of the physiological parameter.

Figure 19 shows a device described in WO 2022/090503 comprising a VIS/NIR radiation source (93), e.g., an LED, adapted for irradiating a body part, e.g., the fingertip (94) of a finger (90). The device comprises an IR temperature sensor (91 ), e.g., a bolometer, for measuring the temperature of the body part. Further, the device comprises four IR sensors (92a, 92b, 92c, 92d) provided with optical filters adapted for wavelength-specific measurement of the analyte to be determined, e.g., glucose. IR sensors (92a, 92b) may be adapted for measurements at analyte-specific wavelengths or wavelength ranges and IR sensors (92c, 92d) may be adapted for measurements at reference wavelengths or wavelength ranges. For example, sensor (92a) may be provided with an optical filter which is transmissive for a glucose-specific wavelength of about 9.2 pm and sensor (92b) may be provided with an optical filter, which is transmissive for a glucose-specific wavelength range between about 9.2 pm and about 9.6 pm; sensor (92c) may be provided with an optical filter which is transmissive for a reference wavelength or wavelength range between about 8.6 pm and about 9.0 pm and sensor (92d) may be provided with an optical filter which is transmissive for a reference wavelength or a wavelength range between about 9.8 pm and about 10.2 pm.

Figure 20 shows a further device described in WO 2022/090503 comprising a board (105) on which at least one VIS/NIR radiation source, e.g., two radiation sources (103a, 103b) and sensors (102a, 102b, 104) are mounted. The board is connected via means (101 ), e.g., a printed circuit (PCB) or printed circuit board assembly (PCBA), particularly a flexible or starrflex PCB or PCBA, to an analog-digital converter, a microcontroller or a processor (not shown). Radiation sources (103a, 103b) may be adapted to emit VIS/NIR radiation at the same wavelengths or at different wavelengths. For example, both radiation sources may emit radiation of a wavelength of about 810 pm or radiation at a wavelength of about 940 pm. Alternatively, one of the radiation sources may be adapted to emit radiation at a wavelength of about 810 pm and the other radiation source may be adapted to emit irradiation at a wavelength of about 940 pm. The device comprises an IR temperature sensor (104), e.g., a bolometer, for measuring the temperature of a body part (not shown). Further, the device comprises two IR sensors (102a, 102b) each comprising two separate sensing chips. Each sensing chip may be provided with a different optical filter. IR sensor (102a) may be adapted for measurements at analyte-specific wavelengths or wavelength ranges and IR sensor (102b) may be adapted for measurements at reference wavelengths or wavelength ranges. For example, a first chip on sensor (102a) may be provided with an optical filter which is transmissive for a glucose-specific wavelength of about 9.2 pm and a second chip on sensor (102a) may be provided with an optical filter, which is transmissive for a glucose-specific wavelength range between about 9.2 pm and about 9.6 pm; a first chip on sensor (102b) may be provided with an optical filter which is transmissive for a reference wavelength or wavelength range between about 8.6 pm and about 9.0 pm and a second chip on sensor (102b) may be provided with an optical filter which is transmissive for a reference wavelength or a wavelength range between about 9.8 pm and about 10.2 pm. In a further miniaturized embodiment, the device may comprise a single sensor step comprising at least 4 chips with 4 different optical filters (not shown). In a still further miniaturized embodiment, the device may be a single unit comprising all chips, all filters, all radiation sources and even the microelectronic components as analog-digital converters and microcontrollers in a single application-specific integrated circuit (ASIC) (not shown).

The device shown in Figure 20 (or any other device as described herein) may be provided as component for integration into a multi -function device, e.g., a smart device, such as a smart watch or a mobile phone. Alternatively, the device may be provided as stand-alone device.

Figure 21 shows a comparison of the glucose concentration measured by an invasive method (straight line), i.e., an amperometric measurement of blood samples with a conventional glucometer, and the relative (non-calibrated) glucose amount measured by the non-invasive method of the invention (dotted line), i.e., a measurement with a device as shown in Figure 13. The measurement was performed over a time period of 6 h. A high correlation between the conventional invasive glucose measurement and the inventive non-invasive glucose measurement was observed.

Further, a non-invasive system for determining glucose in blood is described, which allows identification and optional correction of disturbances caused by blood alcohol comprising a sensing unit for detecting emitted IR radiation from a body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation at a wavelength of about 9.2 pm and separately therefrom for detecting IR radiation at a wavelength of at least about 9.2 pm and about 9.6 pm, particularly at a wavelength range encompassing the wavelength of about 9.2 pm, about 9.4 pm and about 9.6 pm, and an analyzing unit for the separate determination of glucose from the above sensing units. A method for non-invasively determining glucose in blood of a subject using this system is also described herein.

Preferred features of these aspects are as previously indicated in the above specification.

Further described is the use of an InAsSb sensor, optionally in combination with a lock- in amplifier for the measure of IR radiation emitted from a body part.

Preferred features of this aspect are as previously indicated in the above specification.

Further described is a system and method for the non-quantitative measurement of glucose involving a plurality of measurements during a predetermined time interval and determining an alteration of the measurement signal indicating an alteration of the amount of analyte and providing an alter if the alteration of the glucose amount to one direction, i.e. , increase or decrease, exceeds a certain level in a predetermined time period. This system and method may be adapted for steady glucose level monitoring.

A first aspect of the present disclosure is an implantable device comprising:

- an outer housing adapted for implantation enclosing a system for determining a physiological parameter, e.g., glucose, in a tissue and/or bodily fluid of a body part, the system comprising:

- a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm, - a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject,

- a power source, and

- optionally at least one status indicator.

In certain embodiments, the device implanted into the subcutaneous fatty tissue and measures glucose there and/or in adjacent blood vessels, e.g., capillary blood vessels.

Figure 22 shows an embodiment of an implantable device including a system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue, e.g., subcutaneous fatty tissue, of a body part. In certain embodiments, the implantable device is needleless, i.e. , the device is completely enclosed by the housing such that no functional element is in direct contact with the surrounding tissue. In certain embodiments, the device has a size that it can be inserted into the subject's body with a suitable injection device. Alternatively, the device can be inserted surgically. The device may be implanted subcutaneously in the area of arms, legs, or belly. In certain embodiments, the implantable device is formed as an elongated capsule having a length of about 10-15 mm, particularly about 12-14 mm and a breadth of about 2-4 mm, particularly about 3 mm.

The implantable device comprises a housing (1 ) on the outside. The housing (1 ) is at least partially optically transparent to allow measurement of the desired physiological parameter, e.g., glucose by the system located within the housing. The housing is made from a physiologically compatible material, e.g., a physiologically compatible plastic, glass, or composite. In certain embodiments, the housing completely encloses the system.

The system of Figure 22 comprises at least one radiation source (9) adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part, e.g., bodily fluid and/or tissue (5) adjacent to the implanted device. In certain embodiments, the system comprises a plurality of radiation sources (9), e.g., 2, 3, 4, or 5 radiation sources.

The system of Figure 22 also comprises a sensing unit comprising at least one sensor (8), e.g., an optical and/or pyrometrical sensor, for detecting emitted IR radiation from the previously irradiated body part in the range of about 5 pm to about 12 pm. The sensing unit is adapted for (i) detecting IR radiation at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the irradiated body part (5), and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the irradiated body part (5). In certain embodiments, the system comprises a plurality of sensors (8), e.g., 2, 3, 4, or 5 sensors. A sensor (8) may be provided with an optical filter element (10) adapted for detection of IR radiation having the desired wavelength or wavelength range.

The system of Figure 22 comprises a control unit (3), particularly a highly integrated microcontroller, e.g., an ASIC. The control unit is adapted for controlling the measurement procedure. In certain embodiments, the control unit (3) is further adapted for analyzing the measurement result by qualitative and/or quantitative determination of the physiological parameter based on the measurement result. In certain embodiments, the control unit (3) comprises a communication means adapted for communicating with an external device (not shown), e.g., a smart phone or smart watch. The communication means may be adapted for transmitting a signal, e.g., a signal comprising the measurement result and/or the determination result, and or a signal comprising an identification code to the external device, and/or for receiving a signal from the external device. In certain embodiments, the system comprises communication means (4a, 4b), e.g., a Bluetooth antenna (4a) and/or an RFID antenna (4b).

Further, the system comprises a power source. In certain embodiments, the system comprises an internal power source that is rechargeable from an external power source. The power source may comprise a battery (6), e.g., a disposable or a rechargeable battery. In certain embodiments, the battery is rechargeable by wireless, e.g., capacitive charging, for example, using a charging coil (2). Further, the power source may comprise a capacitor (7), e.g., a supercapacitor or an ultracapacitor as a short-term power reservoir that provides power during power bursts when the radiation source (9) is actuated. In certain embodiments, the power source may also include a power harvesting device, e.g., a micro energy harvesting device, adapted for converting mechanical energy into electric energy.

In certain embodiments, the system comprises at least one status indicator (not shown) adapted to inform the wearer whether the parameter to be determined is inside or outside a physiologically acceptable range, particularly whether the glucose concentration is within the normoglycemic range or at a hypoglycemic or hyperglycemic value. The status indicator may also be adapted to alert the wearer of a device malfunction, e.g., caused by power supply shortage. In certain embodiments, the device may comprise an optical status indicator, e.g., a multicolor LED, an acoustic status indicator, e.g., a piezo loudspeaker element, and/or a haptic status indicator, e.g., a vibrator. The individual system elements of the implantable device are electrically connected with each other, if necessary. The electrical connections may be provided by a circuit board and/or wires, e.g., micro gold wires (not shown).

A further aspect of the present disclosure refers to a continuous monitoring device, e.g., a continuous glucose monitoring device comprising:

- an outer housing enclosing a non-invasive system for determining a physiological parameter, e.g., glucose in a tissue and/or bodily fluid of a body part and attachment means for holding the housing permanently to the body part, the system comprising:

- a power source, and

- optionally at least one status indicator.

This aspect also relates to a method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the continuous monitoring device as described above.

In certain embodiments, the continuous monitoring device measures glucose in the subcutaneous fatty tissue and/or in adjacent blood vessels, e.g., capillary blood vessels.

Figure 23 shows an embodiment of a continuous monitoring system, e.g., a continuous glucose monitoring system. This system may be permanently, e.g., for a time period of at least one week externally attached to a body part, e.g., the upper arm or belly (21 ). The system is adapted to perform continuous monitoring of a physiological parameter, e.g., glucose. In certain embodiments, the system is adapted to perform measurements in predetermined time intervals which may be constant or variable, as desired. For example, the time intervals may be in the range of about 1 min to about 2 h, or about 5 min to about 1 h, e.g., about 10 min. In certain embodiments, a user may selected appropriate time intervals in the control unit of the system.

The system may be held on the body part by an attachment means (22), e.g., a one- or two-sided adhesive tape. The attachment means may comprises one or several cutouts for allowing access of system elements, e.g., radiation source (38) and sensors (23, 35) to the subject's skin. The connection between the system and the attachment means may be provided by a suitable locking means (37), e.g., a bayonet lock.

The continuous monitoring system comprises a housing (26) on the outside. The housing (26) may be water-resistant or water-proof to protect system elements from water exposure. The housing may be made from a physiologically compatible material, e.g., a physiologically compatible metal, plastic, glass, or composite. In certain embodiments, the housing completely encloses the system.

The system comprises at least one radiation source (38) adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into tissue (39) of a body part (21 ) In certain embodiments, the system comprises a plurality of radiation sources (38), e.g., 2, 3, 4, or 5 radiation sources.

The system of Figure 23 comprises a sensing unit comprising at least one sensor (35), e.g., an optical and/or pyrometrical sensor, for detecting emitted IR radiation from the previously irradiated body part in the range of about 5 pm to about 12 pm as described herein. The sensing unit is adapted for (i) detecting IR radiation at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the irradiated body part (21 ), and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in a bodily fluid and/or tissue (39) of the irradiated body part (21 ). In certain embodiments, the system comprises a plurality of sensors (35), e.g., 2, 3, 4, or 5 sensors. A sensor (35) may be provided with an optical filter element (36) adapted for detection of IR radiation having the desired wavelength or wavelength range. In certain embodiments, the system further comprises a sensor (23) adapted to be in direct contact with the subject's skin. The sensor (23) may be a contact temperature sensor. The sensors may be mounted on a circuit board (24).

The system of Figure 23 also comprises a control unit, particularly a highly integrated microcontroller, e.g., an ASIC. The control unit may be mounted on a circuit board (33) which is attached to the circuit board (24) by rigid or flexible connecting element (25). The control unit is adapted for controlling the measurement procedure. In certain embodiments, the control unit is further adapted for analyzing the measurement result by qualitative and/or quantitative determination of the physiological parameter based on the measurement result. In certain embodiments, the control unit comprises a communication means, for communicating with an external device (not shown), e.g., a smart phone or smart watch. The communication means may be adapted for transmitting a signal, e.g., a signal comprising the measurement result and/or the determination result, and or a signal comprising an identification code to the external device, and/or for receiving a signal from the external device. In certain embodiments, the system comprises communication means (28, 31 ), e.g., a Bluetooth antenna (28) and/or an RFID antenna (31 ).

Further, the system of Figure 23 comprises a power source. In certain embodiments, the system comprises an internal power source that is rechargeable from an external power source. The power source may comprise a battery (34), e.g., a disposable or a rechargeable battery. In certain embodiments, the battery is rechargeable by wireless, e.g., capacitive charging, for example, using a charging coil (32). Further, the power source may comprise a capacitor (27), e.g., a supercapacitor or an ultracapacitor as a short-term power reservoir that provides power during power bursts when the radiation source (38) is actuated. In certain embodiments, the power source may also include a power harvesting device, e.g., a micro energy harvesting device, adapted for converting mechanical energy into electric energy.

In certain embodiments, the system comprises at least one status indicator adapted to inform the wearer whether the parameter to be determined is inside or outside a physiologically acceptable range, particularly whether the glucose concentration is within the normoglycemic range or at a hypoglycemic or hyperglycemic value. The status indicator may also be adapted to alert the wearer of a device malfunction, e.g., caused by power supply shortage. In certain embodiments, the device may comprise an optical status indicator (29), e.g., a multicolor LED, an acoustic status indicator (30), e.g., a piezo loudspeaker element, and/or a haptic status indicator (not shown), e.g., a vibrator.

The individual system elements of the implantable device are electrically connected with each other, if necessary. The electrical connections may be provided by a circuit board and/or wires, e.g., micro gold wires (not shown).

Preferred features of this aspect are as previously indicated in the above specification. A further aspect of the present disclosure refers to a portable smart device, e.g., a smart phone comprising:

- an outer casing comprising a front face and a back face, wherein the front face comprises a screen and a keypad and the back face comprises a recess for receiving a body part, e.g., a fingertip, and a non-invasive system for determining a physiological parameter, e.g., glucose in the bodily fluid and/or tissue of the body part integrated into the recess on the back face, the system comprising:

- a sensing unit for detecting emitted IR radiation from the previously IR-radiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, and a control unit adapted for controlling the measurement procedure and optionally for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, and - optionally at least one status indicator.

Figure 24 shows a further embodiment of the present disclosure, which is a portable smart device, e.g. , a smart phone, comprising a front face (not shown) and a back face. The front face comprises a screen and a keypad. Into the back face, a system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part wherein the system is integrated. Integrating the system into the back face of the device has certain advantages. There is no impairment of the display function of the screen. There is also no loss of energy since the radiation need not penetrate the screen. Further, the measurement can take place while operating the keypad on the front face.

The device shown in Figure 24 comprises a recess in the back face for receiving a body part, e.g., a fingertip. The recess comprises at least one radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into tissue of a body part. In certain embodiments, the system comprises a plurality of radiation sources, e.g., 2, 3, 4, or 5 radiation sources. In Figure 24, the device has 2 radiation sources, i.e. , the two small holes shown in the recess.

The system of Figure 24 comprises a sensing unit comprising at least one sensor, e.g., an optical and/or pyrometrical sensor, for detecting emitted IR radiation from the previously irradiated body part in the range of about 5 pm to about 12 pm as described herein. The sensing unit is adapted for (i) detecting IR radiation at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the irradiated body part (5), and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the tissue of the irradiated body part. In certain embodiments, the system comprises a plurality of sensors, e.g., 2, 3, 4, or 5 sensors. In Figure 24, the device has 3 sensors, i.e., the three large holes shown in the recess. Two of the sensor are dual sensor chips as described in Figure 20. A sensor may be provided with an optical filter element adapted for detection of IR radiation having the desired wavelength or wavelength range.

Below the recess, an electric connection to the control and/or power unit of the smart device is shown.

In the following, certain aspects and embodiments of the present disclosure are described as part of the specification. These embodiments particularly refer back to the aspects described in the appended claims.

Embodiments of the Specification

1 . A non-invasive system for determining a physiological parameter in a bodily fluid of a subject comprising:

(a) a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of tissue temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

(b) a sensing unit for detecting emitted IR radiation from the previously irradiated body part of said subject in the range of about 5 pm to about 12 pm, wherein said sensing unit is adapted for (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject, and

(c) an analyzing or control unit for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit (b). The system of embodiment 1 , which does not comprise a radiation source for emitting IR radiation in the wavelength range of about 5 pm to about 12 pm. The system of embodiment 1 or 2, wherein the physiological parameter is selected from compounds having at least one characteristic absorption band in the IR range of about 5 pm to about 12 pm, particularly in the range of about 8 pm to about 10 pm. The system of any one of the preceding embodiments, wherein the physiological parameter is glucose. The system of any one of the preceding embodiments, wherein the bodily fluid is blood. The system of any one of the preceding embodiments which is adapted for determining glucose in blood, wherein said sensing unit is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose in the blood of said subject, wherein said at least one wavelength or wavelength range is particularly selected from a wavelength of about 9.2 pm, a wavelength of about 9.4 pm, a wavelength of about 9.6 pm, a wavelength range comprising at least two of the wavelengths of about 9.2 pm, about 9.4 pm and about 9.6 pm, a wavelength range comprising all three of the wavelengths of about 9.2 pm, about 9.4 pm and about 9.6 pm or any combination thereof. The system of any one of the preceding embodiments which is adapted for determining glucose in blood, wherein said sensing unit is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of glucose in the blood of said subject, wherein said at least one wavelength or wavelength range is particularly selected from a wavelength or wavelength range between about 8.7 pm to about 9.0 pm, a wavelength or wavelength range between about 9.7 pm to about 10.2 pm or any combination thereof. The system of any one of the preceding embodiments, which comprises a single radiation source (a). The system of any one of embodiments 1 -7 which comprises a plurality of radiation sources (a), e.g., 2, 3, 4 or more and e.g., up to 10 individual radiation sources (a). The system of any one of the preceding embodiments, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation in the range of about 400 nm to about 1200 nm, particularly in the range of about 550 nm to about 1100 nm, particularly in the range of about 800 nm to about 820 nm, e.g. at about 810 nm, and/or in the range of about 590 nm to about 660 nm, e.g. at about 600 nm, and/or in the range of about 920 nm to about 980 nm, e.g. at about 940 nm. The system of any one of the preceding embodiments, wherein the radiation source (a) is adapted for emitting collimated radiation and/or adapted for emitting non-collimated radiation. The system of any one of the preceding embodiments, wherein the radiation source (a) is a LED, a laser diode, a vcsel (vertical-cavity surface-emitting laser) or a laser. The system of any one of the preceding embodiments, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation continuously or intermittently throughout a predetermined time interval. The system of any one of the preceding embodiments, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation to obtain a local increase in temperate in the irradiated body part, particularly in an absorption area within the irradiated body part in the range of about 2°C to about 10°C, particularly in the range of about 3°C to about 5°C. The system of embodiment 13 or 14, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation continuously at a power of about 10 mW to about 1 W, particularly of about 20 mW to about 500 mW, and more particularly of about 50 mW to about 250 mW. The system of embodiment 13, 14 or 15, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation continuously for a time interval of about 0.1 s to 20 s, particularly of about 1 s to about 5 s, and more particularly of about 0.5 s to about 2 s. The system of embodiment 13 or 14, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation intermittently at a power of about 10 mW to about 5 W, particularly of about 20 mW to about 1 W, and more particularly of about 50 mW to about 500 mW. The system of embodiment 13, 14 or 17, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation intermittently for a time interval of about 0.1 s to about 20 s, particularly of about 0.2 s to about 5 s, and more particularly of about 0.5 s to about 2 s. The system of embodiment 13, 14, 17 or 18, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation intermittently with a pulse frequency of about 1 Hz to about 1 MHz. The system of any one of the preceding embodiments, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation continuously or intermittently for a time period of at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The system of any one of the preceding embodiments, wherein the radiation source (a) is a multi-wavelength radiation source, particularly wherein the radiation source is adapted to emit VIS/NIR radiation at several, e.g. 2, 3, 4, 6, 8, 10 or more different wavelengths or wavelength ranges between about 400 nm to about 1200 nm, more particularly between about 450 nm and about 900 nm, e.g. at least 2, 3, 4, 6 or 8 wavelengths, which may be selected from about 470 nm, about 520 nm, about 590 nm, about 650 nm, about 750 nm and about 810 nm. The system of any one of the preceding embodiments, wherein the radiation source (a) and the sensing unit (b) are located in positions relative to the irradiated body part, which are defined by an angle of at least 90° or more. The system of any one of the preceding embodiments, wherein the radiation source (a) is provided on a side of the body part which is located opposite to the sensing unit (b). The system of any one of the preceding embodiments, wherein at least one radiation source (a) is provided on a side of the body part which allows for emitting radiation directly into the body part without passing through a part of the system. The system of any one of the preceding embodiments, wherein at least one radiation source (a) is provided on a side of the body part which allows for emitting radiation directly into the body part without passing through a homy part of the body surface, e.g., a fingernail. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for detecting self-emitted IR radiation from the previously irradiated body part. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for detecting emitted IR radiation from an absorption area within the previously irradiated body part wherein the absorption area has a locally increased temperature and exhibits an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm. The system of any one of the preceding embodiments, wherein the sensing unit (b) comprises at least one first sensor, at least one second sensor, and optionally at least one third sensor, wherein the at least one first sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the at least one second sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject, and wherein the at least one third sensor, if present, (i) is adapted for detecting unspecific IR radiation, (ii) is adapted for detecting unspecific VIS/NIR radiation, (iii) is adapted for detecting VIS/NIR radiation having a wavelength, where the intensity of the detected VIS/NIR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and/or (iv) is a temperature sensor for measuring the temperature of the body part. The system of embodiment 28, wherein the at least one first sensor and the at least one second sensor are each provided with filter elements and optionally lens elements which are optically transparent in a predetermined wavelength or wavelength range. The system of embodiment 28 or 29 comprising at least two different first sensors, which are adapted for detecting IR radiation having at least two different wavelengths or wavelength ranges. The system of embodiment 28, 29 or 30, wherein at least one first sensor is adapted for detecting IR radiation having a first wavelength or wavelength range and at least one other first sensor is adapted for detecting IR radiation having a second wavelength range wherein the second wavelength range comprises the first wavelength or wavelength range and further comprises another wavelength or wavelength range. The system of embodiment 31 for determining glucose in blood, wherein a first sensor is adapted for detecting IR radiation having a wavelength of about 9.2 pm and another first sensor is adapted for detecting IR radiation having a wavelength range between about 9.2 pm and about 9.6 pm. The system of embodiment 31 for determining glucose in blood, wherein a first sensor is adapted for detecting IR radiation having a wavelength of about 9.6 pm and another first sensor is adapted for detecting IR radiation having a wavelength range between about 9.4 pm and about 9.6 pm. The system of any one of embodiments 28-33 comprising at least two different second sensors, which are adapted for detecting IR radiation having at least two different wavelengths or wavelength ranges. The system of embodiment 33 for determining glucose in blood, wherein a second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 8.6 pm and 9.0 pm and another second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 9.8 pm and about 10.2 pm. The system of any one of embodiments 28-33 for determining glucose in blood, wherein a second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 7.8 pm and about 8.2 pm and optionally at least one further second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 8.6 pm and 9.0 pm and/or for detecting IR radiation having a wavelength or wavelength range between about 9.8 pm and about 10.2 pm. The system of any one of embodiments 28-36 for determining glucose in blood comprising at least one third sensor adapted for detecting VIS/NIR radiation, particularly VIS/NIR radiation having a wavelength of about 940 nm. The system of any of the preceding embodiments, wherein the sensing unit (b) comprises at least one sensor adapted for time-dependently and separately detecting IR radiation having different wavelengths or wavelength ranges, wherein in at least one first time interval the sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and wherein in at least one second time interval the sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject. The system of embodiment 38, wherein the sensing unit (b) comprises at least one sensor, which is provided with a plurality of filters adapted for transmitting IR radiation having different wavelengths or wavelength ranges. The system of embodiment 38 or 39, wherein the sensor is provided with a shutter wheel and/or a filter wheel. The system of embodiment 40, wherein the shutter wheel comprises a plurality of openings wherein at least some of said openings are provided with filter elements and optionally lens elements which are optically transparent in a predetermined wavelength or wavelength range. The system of embodiment 38, wherein the sensing unit (b) comprises at least one sensor, which is a Fabry-Perot interferometer. The system of any one of the preceding embodiments, wherein the sensing unit (b) comprises at least one spectral sensor or line sensor or a spectral or line sensor array. The system of any one of embodiments 38-42, wherein the sensing unit (b) comprises a single sensor. The system of any one of the preceding embodiments, wherein the sensing unit (b) comprises at least one sensor, which is an optical detector, particularly an optical photovoltaics detector, more particularly an InAsSb-based detector. The system of any one of the preceding embodiments, wherein the sensing unit (b) comprises at least one sensor, which is a thermopile or a bolometer. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein the body part is irradiated by VIS/NIR radiation during at least a part of said time period. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein during at least a part of said time period the temperature of the irradiated body part, particularly the absorption area, in the irradiated body part is higher than the surrounding tissue. The system of claim 48, wherein the temperature of the irradiated body part, particularly the absorption area, in the irradiated body part is at least 1 °C, at least 2°C, at least 5°C and up to 10°C higher than the surrounding tissue. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein during at least a part of said time period the temperature of the irradiated body part, particularly the absorption area, is increasing. The system of any one of the preceding embodiments, wherein the temperature is increasing in a range from about 2°C to about 10°C, particularly in a range of about 3°C to about 5°C. The system of any one of embodiments 47-51 , wherein the time period is at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The system of any one of the preceding embodiments, wherein the sensing unit (b) is further adapted for a temperature measurement, e.g. with a precision of at least about 1 °C, of at least about 0.1 °C or even of at least about 0.01 °C. The system of any one of the preceding embodiments, wherein the sensing unit (b) is adapted for measuring and optionally monitoring the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of individual sensors within the sensing unit (b) and/or the temperature of an electronics component of the sensing unit (b). The system of any one of the preceding embodiments, wherein the sensing unit (b) comprises at least one temperature sensor, particularly a plurality of temperature sensors, e.g. 2, 3 or 4 temperature sensors for measuring the skin temperature, and optionally at least one further temperature sensor, e.g. a sensor for measuring the environmental temperature, at least one sensor for measuring the temperatures of individual sensors within the sensing unit and/or a sensor for measuring the temperature of an electronics component of the sensing unit (b). The system of any one of the preceding embodiments, wherein the analyzing unit (c) comprises a microcontroller adapted for quantitatively determining the concentration of the physiological parameter and/or for non-quantitatively determining the alteration rate of the physiological parameter. The system of any one of the preceding embodiments, wherein the analyzing unit (c) is adapted for a time-dependent analysis of the detected IR radiation, wherein a measurement signal is recorded over a time period. The system of embodiment 57, wherein the time period is at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The system of any one of the preceding embodiments, wherein the analyzing unit (c) is adapted for a temperature-compensated analysis of the detected IR radiation. The system of embodiment 59, wherein the temperature-compensated analysis comprises a temperature compensation wherein the measurement signal is subject to a temperature correction. The system of embodiment 59 or 60, wherein the temperature compensation is based on the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of components of the sensing unit, e.g., the temperatures of individual sensors within the sensing unit and/or the temperature of an electronics component of the sensing unit. The system of any one of embodiments 57-61 , wherein the analyzing unit (c) is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation. The system of any one of the preceding embodiments, which is adapted for detecting IR radiation from a body part which is selected from a fingertip, an ear lobe, a wrist, a forearm, a palm and an upper arm. The system of any one of the preceding embodiments, wherein the radiation source (a) and the sensing unit (b) are arranged on the same side of the body part. The system of any one of the preceding embodiments, wherein the radiation source (a) and the sensing unit (b) are arranged on different sides, particularly on opposite sides of the body part. The system of any one of the preceding embodiments, wherein a first radiation source (a) is arranged on the same side of the body part as the sensing unit (b) and a further radiation source (a) is arranged on a different side, particularly on an opposite side of the body part as the sensing unit. The system of any one of the preceding embodiments further comprising a cover, wherein said cover is at least partially made of a material, which is optically transparent for VIS/NIR radiation emitted by the radiation source (a) and/or for IR radiation detected by the sensing unit (b). The system of embodiment 67, wherein the cover is at least partially made of CaF2 and/or BaF2 and/or of a plastic material, which is transparent for IR radiation and optionally transparent for VIS/NIR radiation. The system of embodiment 67 or 68, wherein the optically transparent material of the cover has a thickness of about 0.2 mm to about 2 mm, particularly of about 0.5 mm to about 1 .5 mm, more particularly about 1 mm. The system of any one of the preceding embodiments further comprising a cover, wherein said cover is at least partially made of a material which is optically transparent for IR radiation to be detected by the sensing unit, particularly in the IR wavelength range between about 5 pm to about 12 pm or a sub-range thereof and wherein said material is optionally substantially optically impermeable for VIS/NIR radiation emitted by the radiation source (a). The system of any one of the preceding embodiments further comprising a cover which focuses IR radiation from the body part to the sensing unit (b), particularly to the at least one sensor of the sensing unit (b). The system of embodiment 71 wherein the cover comprises an IR Fresnel lens or an array comprising a plurality of IR Fresnel lenses. Use of the system of any one of the preceding embodiments for non-invasively determining a physiological parameter in a bodily fluid of a subject. The use of embodiment 73, wherein the physiological parameter is glucose and the bodily fluid is blood. The use of embodiment 73 or 74, wherein the physiological parameter is quantitatively determined. The use of embodiment 73, 74 or 75, wherein the alteration rate of the physiological parameter rate is non-quantitatively determined. A method for non-invasively determining a physiological parameter in a bodily fluid of a subject comprising the steps:

(a) irradiating a body part of said subject with visual (VlS)Znear-infrared (NIR) radiation in the wavelength range of about 500 nm to about 1500 nm, or about 500 nm to about 1500 nm, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of tissue temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

(b) detecting emitted IR radiation from the previously irradiated body part of said subject in the wavelength range of about 5 pm to about 12 pm, comprising separately (i) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and

(ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject, and

(c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter. The method of embodiment 77, wherein the body part is not irradiated with a source of IR radiation in the wavelength range of about 5 pm to about 12 pm. The method of embodiment 77 or 78, wherein the physiological parameter is glucose, and the bodily fluid is blood. The method of embodiment 77, 78 or 79, wherein the physiological parameter is quantitatively determined. The method of any one of embodiments 77-80, wherein the alteration rate of the physiological parameter rate is non-quantitatively determined. A device comprising a non-invasive system for determining a physiological parameter in a bodily fluid of a subject, wherein the device comprises a casing, wherein the device includes:

(a) a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm into a body part of said subject, wherein the body part is particularly selected from a fingertip, a plurality of finger tips, and a palm, and wherein the radiation source is further adapted the irradiated body part absorbs electromagnetic energy resulting in a local increase of tissue temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

(c) an analyzing unit for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit (b), and wherein the casing comprises a first face comprising a screen, wherein the screen is at least partially made of a material, which is optically transparent for NIR/VIS radiation emitted by the radiation source (a) and for IR radiation detected by the sensing unit (b), wherein the radiation source (a), the sensing unit (b) and the analyzing unit (c) are incorporated within the casing. The device of embodiment 82, wherein the radiation source (a) is adapted for emitting radiation through the screen. The device of embodiment 82 or 83, wherein the sensing unit (b) is adapted for detecting radiation entering the casing through the screen. The device of any one of embodiments 82-84, wherein the screen has a size of about 1 cm² to about 500 cm², particularly about 2 cm² to about 200 cm². The device of any one of embodiments 82-85, wherein the screen is substantially planar. The device of any one of embodiments 82-86, which is adapted for displaying a contact position for the body part on the screen. The device of any one of embodiments 82-87, which is a mobile device. The device of any one of embodiments 82-88, which is selected from a smart phone, a smart watch, a tablet and a fitness tracker device. The device of any one of embodiments 82-89, wherein the optically transparent material is selected from an inorganic material such as CaF2 and/or BaF2 and from an organic material such as a plastic material. The device of any one of embodiments 82-90, wherein the optically transparent material has a thickness of about 0.2 mm to about 2 mm, particularly of about 0.3 mm to about 1 mm. The device of any one of embodiments 82-91 , which does not comprise a radiation source for emitting IR radiation in the wavelength range of about 5 pm to about 12 pm. The device of any one of embodiments 82-92, wherein the physiological parameter is glucose and the bodily fluid is glucose. The device of any one of embodiments 82-93, which is adapted for determining glucose in blood, wherein said sensing unit is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose in the blood of said subject, wherein said at least one wavelength or wavelength range is particularly selected from a wavelength of about 9.2 pm, a wavelength of about 9.4 pm, a wavelength of about 9.6 pm, a wavelength range comprising at least two of the wavelengths of about 9.2 pm, about 9.4 pm and about 9.6 pm, a wavelength range comprising the wavelengths of about 9.2 pm, about 9.4 pm and about 9.6 pm or any combination thereof. The device of any one of embodiments 82-94, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation in the range of about 550 nm to about 1200 nm, particularly in the range of about 800 nm to about 820 nm, e.g. at about 810 nm, and/or in the range of about 590 nm to about 610 nm, e.g. at about 600 nm, and/or in the range of about 920 nm to about 980 nm, e.g. at about 940 nm. The device of any one of embodiments 82-95, wherein the radiation source (a) is a LED, a laser diode, a vcsel (vertical-cavity surface-emitting laser) or a laser. The device of any one of embodiments 82-96, wherein the radiation source (a) is a multi-wavelength radiation source. The device of any one of embodiments 82-97, wherein the radiation source (a) is adapted for emitting VIS/NIR radiation continuously or intermittently for a time period of at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The device of any one of embodiments 82-98, wherein at least one first sensor is adapted for detecting IR radiation having a first wavelength or wavelength range and at least one other first sensor is adapted for detecting IR radiation having a second wavelength range, wherein the second wavelength range comprises the first wavelength or wavelength range and further comprises another wavelength or wavelength range, wherein the system is particularly adapted for determining glucose in blood, wherein a first sensor is adapted for detecting IR radiation having a wavelength of about 9.2 pm and another first sensor is adapted for detecting IR radiation having a wavelength range between about 9.2 pm and about 9.6 pm which comprises the first wavelength of about 9.2 pm and further comprises at least one wavelength of about 9.4 pm and about 9.6 pm, and particularly further comprises a wavelength of about 9.4 pm and about 9.6 pm. The device of any one of embodiments 82-99, which comprises at least two different second sensors adapted for detecting IR radiation having at least two different wavelengths or wavelength ranges, wherein the system is particularly adapted for determining glucose in blood, wherein a second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 8.6 pm and 9.0 pm and another second sensor is adapted for detecting IR radiation having a wavelength or wavelength range between about 9.8 pm and about 10.2 pm. The device of any one of embodiments 82-100, wherein the sensing unit (b) comprises at least one sensor adapted for time- dependently and separately detecting IR radiation having different wavelengths or wavelength ranges, wherein in at least one first time interval the sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid of said subject, and wherein in at least one second time interval the sensor is adapted for detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject. The device of any one of embodiments 82-101 , wherein the sensing unit (b) comprises a single sensor. The device of any one of embodiments 82-102, wherein the sensing unit (b) comprises at least one sensor which is an optical detector, particularly an optical photovoltaics detector, more particularly an InAsSb-based detector. The device of any one of embodiments 82-103, which further comprises lens element adapted for focusing IR radiation from the body part to the sensing unit (b), particularly to the at least one sensor of the sensing unit (b), wherein the lens element is incorporated within the casing and particularly wherein the lens element comprises an IR Fresnel lens or an array comprising a plurality of IR Fresnel lenses. The device of any one of embodiments 82-104, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein the body part is irradiated by VIS/NIR radiation during at least a part of said time period. The device of any one of embodiments 82-105, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein during at least a part of said time period the temperature of the irradiated body part, particularly the absorption area, in the irradiated body part is higher than the surrounding tissue. The device of embodiment 106, wherein the temperature of the irradiated body part, particularly the absorption area, in the irradiated body part is at least 1 °C, at least 2°C, at least 5°C and up to 10°C higher than the surrounding tissue. The device of any one of embodiments 82-107, wherein the sensing unit (b) is adapted for detecting IR radiation emitted from the irradiated body part over a time period, wherein during at least a part of said time period the temperature of the irradiated body part, particularly the absorption area, is increasing. The device of embodiment 108, wherein the temperature is increasing in a range from about 2°C to about 10°C, particularly in a range of about 3°C to about 5°C. The device of any one of embodiments 102-109, wherein the time period is at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The device of any one of embodiments 82-110, wherein the sensing unit (b) is further adapted for a temperature measurement, e.g. with a precision of at least about 1 °C, of at least about 0.1 °C or even of at least about 0.01 °C. The device of any one of embodiments 82-111 , wherein the sensing unit (b) is adapted for measuring and optionally monitoring the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of individual sensors within the sensing unit (b) and/or the temperature of an electronics component of the sensing unit (b). The device of any one of embodiments 82-112 wherein the sensing unit (b) comprises at least one temperature sensor, particularly a plurality of temperature sensors, e.g. 2, 3 or 4 temperature sensors for measuring the skin temperature, and optionally at least one further temperature sensor, e.g. a sensor for measuring the environmental temperature, at least one sensor for measuring the temperatures of individual sensors within the sensing unit and/or a sensor for measuring the temperature of an electronics component of the sensing unit (b). The device of any one of embodiments 82-113, wherein the analyzing unit (c) comprises a microcontroller adapted for quantitatively determining the concentration of the physiological parameter and/or for non-quantitatively determining the alteration rate of the physiological parameter. The device of any one of embodiments 81 -114, wherein the analyzing unit (c) is adapted for a time-dependent analysis of the detected IR radiation, wherein a measurement signal is recorded over a time period. The device of embodiment 115, wherein the time period is at least about 0.5 s, particularly of at least about 1 s to about 120 s and more particularly of at least about 2 s to about 20 s. The device of any one of embodiments 82-116, wherein the analyzing unit (c) is adapted for a temperature-compensated analysis of the detected IR radiation. The device of embodiment 117, wherein the temperature-compensated analysis comprises a temperature compensation wherein the measurement signal is subject to a temperature correction. The device of embodiment 117 or 118, wherein the temperature compensation is based on the skin temperature of the irradiated body part and optionally at least one further temperature such as the environmental temperature, the temperatures of components of the sensing unit, e.g. the temperatures of individual sensors within the sensing unit and/or the temperature of an electronics component of the sensing unit. The device of any one of embodiments 82-119, wherein the analyzing unit (c) is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation. Use of the device of any one of embodiments 82-120 for non-invasively determining a physiological parameter in a bodily fluid of a subject, wherein the physiological parameter is glucose, and the bodily fluid is blood, and wherein the alteration rate of the amount of glucose in blood is determined. A method for non-invasively determining a physiological parameter in a bodily fluid of a subject comprising the steps:

(a) irradiating a body part of said subject with visual (VlS)Znear-infrared (NIR) radiation in the wavelength range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of tissue temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

(ii) detecting IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid of said subject, and (c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter, wherein the radiation source (a), the sensing unit (b) and the analyzing unit (c) are incorporated within a casing, and wherein the casing comprises a first face comprising a screen, wherein the screen is at least partially made of a material, which is optically transparent for NIR/VIS radiation emitted by the radiation source (a) and for IR radiation detected by the sensing unit (b). The method of embodiment 122, wherein the body part is not irradiated with a source of IR radiation in the wavelength range of about 5 pm to about 12 pm. The method of embodiment 122 or 123, wherein the physiological parameter is glucose, and the bodily fluid is blood. The method of any one of embodiments 122-124, wherein the concentration of the physiological parameter is quantitatively determined, and/or wherein the alteration rate of the amount of the physiological parameter is determined, particularly non-quantitatively determined. The method of any one of embodiments 122-125, wherein step (b) further comprises (iii) carrying out a temperature measurement, and step (c) further comprises carrying a temperature-compensated analysis of the detected IR radiation. The system of any one of embodiments 1 - 72 or the device of any one of embodiments 82-120, wherein the sensing unit (b) comprises at least one sensor comprising a plurality of chips comprising different optical filter elements for detecting radiation at different wavelengths or wavelength ranges. The system of any one of embodiments 1 - 72 or the device of any one of embodiments 82-120, which is a single unit comprising the radiation source (a), the sensing unit (b) and the analyzing unit (c) in a single application-specific integrated circuit (ASIC). . A non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose comprising:

- a sensing unit wherein said sensing unit is adapted for (i) separately detecting a first parameter-specific IR radiation having a first wavelength or wavelength range and a second parameter-specific IR radiation having a second wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of glucose and/or ethanol and the intensity of the emitted IR radiation increases with a decreasing concentration of glucose and/or ethanol; wherein the first parameter-specific IR radiation has a wavelength of about 9.2 pm and wherein the second parameter-specific IR radiation includes a wavelength range from about 9.2 pm to about 9.6 pm, and wherein said sensing unit is further adapted for (ii) detecting reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, and

- a control unit adapted for the qualitative and/or quantitative determination of both glucose and ethanol based on the IR radiation detected in the sensing unit. . The device of embodiment 129, wherein the reference IR radiation has a wavelength of about 8.8 pm or wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm, and/or wherein the reference IR radiation has a wavelength of about 10.2 pm or wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm. . A method for non-invasively determining ethanol or glucose and ethanol in a bodily fluid of a subject comprising the steps:

(a) irradiating a body part of said subject with visual (VIS)/near-infrared (NIR) radiation in the wavelength range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of tissue temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

(b) detecting emitted IR radiation from the previously irradiated body part of said subject in the wavelength range of about 5 pm to about 12 pm, comprising (i) separately detecting a first parameter-specific IR radiation having a first wavelength or wavelength range and a second parameter-specific IR radiation having a second wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of glucose and/or ethanol and the intensity of the emitted IR radiation increases with a decreasing concentration of glucose and/or ethanol; wherein the first parameter-specific IR radiation has a wavelength of about 9.2 pm and wherein the second parameter-specific IR radiation includes a wavelength range from about 9.2 pm to about 9.6 pm, and and

(ii) detecting reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, and

(c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of both glucose and ethanol.

132. The method of embodiment 131 , wherein the reference IR radiation has a wavelength of about 8.8 pm or wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm, and/or wherein the reference IR radiation has a wavelength of about 10.2 pm or wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm.

133. A non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising:

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of a plurality of individual measurements. . The device of embodiment 133, wherein the control unit is adapted to monitor the temperature of the irradiated body part during the measurement procedure and to exclude individual measurements performed when the temperature of the body part from the determination. . A method for non-invasively determining a physiological parameter, e.g., a glucose comprising the steps:

(b) detecting emitted IR radiation from the previously irradiated body part of said subject in the wavelength range of about 5 pm to about 12 pm, comprising (i) detecting a parameter-specific IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with a decreasing concentration of the physiological parameter, and for (ii) detecting a reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of the physiological parameter in the bodily fluid and/or tissue of said subject, and

- (c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter by a measurement sequence consisting of a plurality of individual measurements.

136. The method of embodiment 135, wherein the temperature of the irradiated body part is monitored during the measurement procedure and individual measurements performed when the temperature of the body part increases are excluded from the determination.

137. A non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising: an outer casing comprising a non-invasive system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a subject, e.g. a human subject, the system comprising: - a radiation source adapted for emitting visual (VlS)Znear-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm into a body part of said subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase of temperature and in an increased emission of IR radiation in the wavelength range of about 5 pm to about 12 pm,

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the radiation source is adapted of emitting visual (VlS)Znear-infrared (NIR) radiation into the body for a predetermined irradiation period and the sensing unit is adapted to perform a measurement of IR radiation emitted from the body part within the subsequent dissipation period. . The device of embodiment 137, wherein the sensing unit is adapted to perform a measurement within a period of about 1 s, about 500 ms or about 200 ms after the radiation source is shut off. method for non-invasively determining a physiological parameter, e.g., a glucose comprising the steps:

(c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter, wherein the radiation source emits visual (VlS)Znear-infrared (NIR) radiation into the body for a predetermined irradiation period and a measurement of IR radiation emitted from the body part is carried out within the subsequent dissipation period. he method of embodiment 139, wherein the measurement is performed within a period of about 2 s, about 1.5 s, about 1 s, about 500 ms or about 200 ms after the radiation source is shut off. he device of any one of the preceding embodiments, which further comprises monitoring means, e.g., a photodiode, for detecting fluctuations, e.g., power fluctuations in the radiation emitted by the radiation source.

Claims

1 . An implantable device comprising:

2. The implantable device of claim 1 , which is a needleless device.

3. A method for determining a physiological parameter, e.g., glucose, in a bodily fluid and/or tissue of a body part using the implantable device of claim 1 or 2.

4. A continuous monitoring device, e.g., a continuous glucose monitoring device comprising:

- a power source, and

- optionally at least one status indicator.

5. A method for determining a physiological parameter, e.g., glucose, in a bodily fluid and/or tissue of a body part using the continuous monitoring device of claim 4.

6. A portable smart device, e.g., a smart phone comprising:

- an outer casing comprising a front face and a back face, wherein the front face comprises a screen and a keypad and the back face comprises a recess for receiving a body part, e.g., a fingertip, and a non-invasive system for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of the body part integrated into the recess on the back face, the system comprising:

- a control unit adapted for controlling the measurement procedure and optionally for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, and

- optionally at least one status indicator.

7. A method for determining a physiological parameter, e.g., glucose in a bodily fluid and/or tissue of a body part using the smart device of claim 6.

8. The system or method of cany one of claims 1 -7, which does not comprise a radiation source for emitting IR radiation in the wavelength range of about 5 pm to about 12 pm.

9. The system or method of cany one of the preceding claims, wherein the physiological parameter is glucose.

10. The system or method of any one of the preceding claims, wherein the control unit is adapted for a time-dependent analysis of the detected IR radiation, wherein a measurement signal is recorded over a time period, and/or wherein the control unit is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation.

11. A non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose comprising: - an outer housing enclosing a non-invasive system for determining ethanol or simultaneously determining ethanol and glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, the system comprising:

- a sensing unit wherein said sensing unit is adapted for (i) separately detecting a first parameter-specific IR radiation having a first wavelength or wavelength range and a second parameter-specific IR radiation having a second wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of glucose and/or ethanol and the intensity of the emitted IR radiation increases with a decreasing concentration of glucose and/or ethanol; wherein the first parameter-specific IR radiation has a wavelength of about 9.2 pm and wherein the second parameter-specific IR radiation includes a wavelength range from about 9.2 pm to about 9.6 pm, wherein said sensing unit is further adapted for (ii) detecting reference IR radiation having at least one wavelength or wavelength range where the intensity of the detected IR radiation is substantially independent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, and wherein the reference IR radiation particularly has a wavelength of about 8.8 pm or wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm, and/or wherein the reference IR radiation particularly has a wavelength of about 10.2 pm or wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm, and

12. A method for non-invasively determining ethanol or glucose and ethanol in a bodily fluid of a subject comprising the steps:

(b) detecting emitted IR radiation from the previously irradiated body part of said subject in the wavelength range of about 5 pm to about 12 pm, comprising (i) separately detecting a first parameter-specific IR radiation having a first wavelength or wavelength range and a second parameter-specific IR radiation having a second wavelength or wavelength range where the intensity of the detected IR radiation is dependent from the concentration of glucose and/or ethanol in the bodily fluid and/or tissue of said subject, wherein the intensity of the emitted IR radiation decreases with an increasing concentration of glucose and/or ethanol and the intensity of the emitted IR radiation increases with a decreasing concentration of glucose and/or ethanol; wherein the first parameter-specific IR radiation has a wavelength of about 9.2 pm and wherein the second parameter-specific IR radiation includes a wavelength range from about 9.2 pm to about 9.6 pm, wherein the reference IR radiation has particularly a wavelength of about 8.8 pm or wavelength range including a wavelength of about 8.8 pm, e.g., a wavelength range between about 7.5 pm and about 9.0 pm, and/or wherein the reference IR radiation has particularly a wavelength of about 10.2 pm or wavelength range including a wavelength of about 10.2 pm, e.g., a wavelength range between about 9.7 pm and about 10.5 pm, and

13. A non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising:

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of a plurality of individual measurements, wherein the control unit is particularly adapted to monitor the temperature of the irradiated body part during the measurement procedure and to exclude individual measurements performed when the temperature of the body part from the determination.

14. A method for non-invasively determining a physiological parameter, e.g., a glucose comprising the steps:

- (c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter by a measurement sequence consisting of a plurality of individual measurements, wherein the temperature of the irradiated body part is particularly monitored during the measurement procedure and individual measurements performed when the temperature of the body part increases are excluded from the determination.

15. A non-invasive monitoring device, for determining a physiological parameter, e.g., glucose in the tissue and/or bodily fluid of a subject, e.g., a human subject, comprising:

- a control unit adapted for the qualitative and/or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit, wherein the radiation source is adapted of emitting visual (VlS)Znear-infrared (NIR) radiation into the body for a predetermined irradiation period and the sensing unit is adapted to perform a measurement of IR radiation emitted from the body part within the subsequent dissipation period, wherein the sensing unit is particularly adapted to perform a measurement within a period of about 1 s, about 500 ms or about 200 ms after the radiation source is shut off.

16. A method for non-invasively determining a physiological parameter, e.g., a glucose comprising the steps:

(c) analyzing the detected IR radiation for the qualitative and/or quantitative determination of the physiological parameter, wherein the radiation source emits visual (VlS)Znear-infrared (NIR) radiation into the body for a predetermined irradiation period and a measurement of IR radiation emitted from the body part is carried out within the subsequent dissipation period, and wherein the measurement is particularly performed within a period of about 2 s, about 1 .5 s, about 1 s, about 500 ms or about 200 ms after the radiation source is shut off.