Highly integrated glucose sensor device

Abstract

The present disclosure relates to highly integrated sensor devices, such as implantable devices, continuous monitoring devices, and portable smart devices, for determining physiological parameters in bodily fluids and / or tissues of a subject. Additionally, the present disclosure relates to methods for determining physiological parameters in bodily fluids and / or tissues of a subject.

Description

[Technical Field]

[0001] The present disclosure relates to highly integrated sensor devices, such as implantable devices, continuous monitoring devices, and portable smart devices, for determining physiological parameters in bodily fluids and / or tissues of a subject. Additionally, the present disclosure relates to methods for determining physiological parameters in bodily fluids and / or tissues of a subject.

[0002] Background technology Approximately 415 million people had diabetes in 2016, a figure that is expected to increase to more than 640 million by 2040. Diabetics are at risk of complications such as blindness, kidney disease, heart disease, and stroke, so the disease must be controlled by closely monitoring blood sugar levels.

[0003] Currently, blood glucose measurement is primarily based on invasive systems and methods, which involve taking a blood sample and then subjecting it to in vitro testing or implanting a sensor to determine glucose levels in vivo. These invasive systems and methods have the disadvantage that they are painful or inconvenient.

[0004] WO 2021 / 032629 and WO 2022 / 090503 disclose noninvasive systems for determining physiological parameters, particularly glucose, in a subject's body fluid, the noninvasive systems comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation into a body part of the subject; a sensing unit for detecting IR radiation emitted from the irradiated body part of the subject, the IR radiation having (i) at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of the physiological parameter in the subject's body fluid, and (ii) at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the subject's body fluid; and an analysis unit for qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected in the sensing unit. The system can be used to noninvasively determine physiological parameters such as glucose in the subject's blood. Additionally, methods for non-invasively determining physiological parameters, particularly glucose, in the body fluids of a subject are disclosed, the contents of which are incorporated herein by reference in their entireties.

[0005] There is a need to develop highly integrated systems and methods that allow for improved non-invasive determination of glucose and other physiological parameters.

[0006] Summary of the Invention According to the present disclosure, simple, rapid, and reliable determination of physiological parameters can be achieved using noninvasive systems and methods. These systems and methods include irradiating a body part of a subject, particularly a human subject, with visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm or about 500 nm to about 1500 nm, and detecting IR radiation emitted from the irradiated body part of the subject in the range of about 5 μm to about 12 μm. Surprisingly, the inventors have found that by irradiating a body part with short-wavelength radiation and detecting long-wavelength radiation emitted from the irradiated body part, physiological parameters such as glucose in a body fluid such as blood can be determined.

[0007] Irradiation of a body part with VIS / NIR radiation according to the present invention causes energy absorption within the irradiated body part. This absorption of energy in the irradiated or absorbing region results in a local increase in tissue temperature within the irradiated body part, particularly within the absorbing region, which in turn causes an increase in IR radiation emission from the irradiated body part, particularly from the absorbing region, including an increase in IR radiation emission in the range of about 5 μm to about 12 μm. Furthermore, the local temperature increase in the irradiated absorbing region shifts the IR radiation emitted from the absorbing region away from the corresponding IR absorption maximum of molecules of physiological parameters, such as glucose molecules. Therefore, detection of IR radiation emitted from the irradiated body part is facilitated and substantially improved.

[0008] 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, such as glucose, in tissue and / or body fluid of a body part of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; -Power supply and - optionally at least one status indicator.

[0009] This aspect also includes a method of determining physiological parameters, such as glucose, in fluids and / or tissues of a body part using an implantable device as described above.

[0010] 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, such as glucose, in tissue and / or body fluid of a body part of a subject, e.g., a human subject, and attachment means for permanently holding the housing to the body part, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; -Power supply and and optionally at least one condition indicator.

[0011] This aspect also includes a method of determining a physiological parameter, such as glucose, in a body fluid and / or tissue of a body part using a continuous monitoring device as described above.

[0012] A further aspect of the present disclosure is a portable smart device, e.g., a smartphone, comprising: an outer casing having a front and a rear surface, the front surface comprising a screen and a keypad and the rear surface comprising a recess for receiving a body part, e.g. a fingertip, of a subject, e.g. a human subject, the outer casing comprising a non-invasive system for determining physiological parameters such as glucose in body fluids and / or tissue of the body part integrated into the front and rear surfaces and the recess of the rear surface, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; and optionally at least one status indicator.

[0013] This aspect also includes a method of determining a physiological parameter, such as glucose in a body fluid and / or tissue of a body part, using the smart device described above.

[0014] 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 tissue and / or bodily fluids of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit, the sensing unit is adapted to (i) separately detect first parameter-specific IR radiation having a first wavelength or wavelength range and second parameter-specific IR radiation having a second wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues, and wherein the intensity of the emitted IR radiation decreases as the concentration of glucose and / or ethanol increases and the intensity of the emitted IR radiation increases as the concentration of glucose and / or ethanol decreases; the first parameter-specific IR radiation has a wavelength of about 9.2 μm, and the second parameter-specific IR radiation includes a wavelength range of about 9.2 μm to about 9.6 μm; the sensing unit is further adapted to (ii) detect reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues; a control unit adapted for qualitative and / or quantitative determination of both glucose and ethanol based on IR radiation detected by the sensing unit.

[0015] This aspect of the present disclosure relates to the detection of ethanol and the combined detection of ethanol and glucose in the tissues and / or bodily fluids of a subject, particularly the blood of a human subject. This is achieved by detecting a first parameter-specific IR radiation having a wavelength of about 9.2 μm, excluding wavelengths at about 9.4 μm and excluding wavelengths at about 9.6 μm, and a second parameter-specific IR radiation having a wavelength range of about 9.2 μm to about 9.6 μm. Due to a characteristic change in the signal ratio between the first parameter-specific IR radiation having a wavelength of about 9.2 μm and the second parameter-specific IR radiation having a wavelength range of about 9.2 μm to about 9.6 μm, including a wavelength at about 9.4 μm, a separate determination of ethanol, optionally along with a determination of glucose, is possible.

[0016] In this embodiment, the reference IR radiation can be determined at a first wavelength of about 8.8 μm or a first wavelength range including a wavelength of about 8.8 μm, for example, a wavelength range between about 7.5 μm and about 9.0 μm, and / or a second wavelength range between about 9.7 μm and about 10.4 μm.

[0017] This aspect also includes a method for determining ethanol, or both glucose and ethanol, in fluids and / or tissues of a body part using the device described above.

[0018] A further aspect of the present disclosure is a non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter such as glucose in a body fluid and / or tissue of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being dependent on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for qualitative and / or quantitative determination of a physiological parameter based on IR radiation detected by the sensing unit, The control unit is adapted to perform a measurement sequence consisting of a plurality of individual measurements.

[0019] This embodiment refers to a measurement sequence consisting of multiple 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 multiple measurements may take about 0.2 seconds to about 60 seconds, about 0.5 seconds to about 30 seconds, or about 1 second to about 10 seconds.

[0020] In certain embodiments, the temperature of the irradiated body part is monitored during the measurement sequence, and individual measurements taken 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 by a separate temperature sensor, which may be, for example, a thermopile or pyrometer sensor.

[0021] This aspect also includes a method of determining a physiological parameter, such as glucose, in fluids and / or tissues of a body part using a device as described above.

[0022] A further aspect of the present disclosure is a non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter such as glucose in a body fluid and / or tissue of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being dependent on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for qualitative and / or quantitative determination of a physiological parameter based on IR radiation detected by the sensing unit, A non-invasive monitoring device comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation into the body for a predetermined irradiation period; and a control unit adapted to perform measurements of IR radiation emitted from the body part within a subsequent dissipation period.

[0023] The emission of visible (VIS) / near-infrared (NIR) radiation by a radiation source onto a body part causes energy transfer to the body part, resulting in a local increase in temperature. When the radiation source is shut off, a dissipation period begins during which the energy is dissipated throughout the irradiated body part.

[0024] This aspect of the disclosure relates to measuring IR radiation emitted from a body part by a sensing unit within a dissipation period that begins after blocking a radiation source. Measuring IR radiation emitted from a body part during this dissipation period can provide a substantial improvement in determining physiological parameters such as glucose. In certain embodiments, determining the physiological parameter is based solely on measuring IR radiation emitted from the body part during the period in which IR radiation is blocked. The measurement with the dissipation period can be a single measurement or a measurement sequence consisting of multiple individual measurements, particularly as described above.

[0025] Typically, measurements within the dissipation period are taken within about 2 seconds, about 1.5 seconds, about 1 second, about 500 ms, or about 200 ms after the radiation source is shut off.

[0026] In certain embodiments, the device is adapted to perform a single cycle consisting of an illumination period and a measurement within a subsequent dissipation period. In further embodiments, the device is adapted to perform two or more illumination / dissipation cycles.

[0027] This aspect also includes a method of determining a physiological parameter, such as glucose, in fluids and / or tissues of a body part using a device as described above. [Brief explanation of the drawings]

[0028] [Figure 1] It shows the penetration depth [mm] of electromagnetic radiation into body tissue as a function of wavelength [nm]. [Figure 2] It shows the relative absorption coefficients of certain compounds present in the human body as a function of wavelengths in the range of 400nm to 1100nm. [Figure 3] This shows the case where glucose has an absorption band at a wavelength of 940 nm. [Figure 4] 1 illustrates an embodiment of the system described in WO 2022 / 090503. [Figure 5] 1 shows a further embodiment of the system described in WO 2022 / 090503. [Figure 6] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 7] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 8] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 9]Measurements at multiple analyte-specific wavelengths / wavelength ranges and reference wavelengths / wavelength ranges are shown. [Figure 10] Such an embodiment is shown, as described in WO 2022 / 090503. [Figure 11] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 12] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 13] A schematic diagram of the system in Figure 4 is shown. [Figure 14] The heat map of a fingertip after 2 seconds of irradiation with 810 nm light is shown. [Figure 15] The time-dependent heat output is shown in addition to the self-emission of the fingertip during intermittent irradiation with 810 nm light at a power of 2 mW and a frequency of 0.1 Hz. [Figure 16a] 1 shows a block diagram of an embodiment of a sensing unit of the present invention; [Figure 16b] 16b shows a block diagram of a further embodiment of a sensing unit of the present invention, similar to the sensing unit shown in FIG. 16a. [Figure 17] 1 shows an embodiment of an IR spectrum. [Figure 18] 1 illustrates yet a further embodiment described in WO 2022 / 090503. [Figure 19] 1 shows a device as described in WO 2022 / 090503, comprising a VIS / NIR radiation source adapted to irradiate a body part. [Figure 20] 1 shows a further device as described in WO 2022 / 090503, comprising a substrate on which at least one VIS / NIR radiation source and a sensor are mounted. [Figure 21]A comparison is shown between the glucose concentration measured by an invasive method (solid line), i.e., amperometric measurement of a blood sample using a conventional glucometer, and the relative glucose amount measured by the non-invasive method of the present invention (dotted line). [Figure 22] 1 illustrates an embodiment of an implantable device that includes a system for determining a physiological parameter, such as glucose, in a body fluid and / or tissue of a body part, for example, subcutaneous adipose tissue.

[0029] MODE FOR CARRYING OUT THE INVENTION The present disclosure includes determining a physiological parameter by detecting IR radiation from a previously irradiated body part of a subject, particularly a human, in a wavelength range of about 5 μm to about 12 μm, particularly about 8 μm to about 10 μm. More specifically, the present invention includes determining a physiological parameter by absorbing IR radiation emitted from a previously irradiated body part of a subject in a wavelength range of about 5 μm to about 12 μm, particularly about 8 μm to about 10 μm. The signal of the emitted IR radiation at the measurement wavelength decreases as the concentration of the physiological parameter increases, and the signal of the emitted IR radiation at the measurement wavelength increases as the concentration of the physiological parameter decreases. The physiological parameter can be any compound with a characteristic absorption band in this wavelength range. For example, the physiological parameter can be glucose or another clinically relevant analyte such as lactate or troponin.

[0030] In a specific embodiment of the present invention, the system is adapted for noninvasive measurement of glucose in blood. In this embodiment, IR radiation is detected at a wavelength or wavelength range specific to glucose, where glucose has a characteristic absorption band and the intensity of the detected IR radiation depends on the concentration of glucose in the blood. More specifically, the glucose-specific wavelength or wavelength range is selected from a wavelength of about 9.2 μm, a wavelength of about 9.4 μm, a wavelength of about 9.6 μm, a wavelength range including at least two of the wavelengths of about 9.2 μm, about 9.4 μm, and about 9.6 μm, a wavelength range including all three of the wavelengths of about 9.2 μm, about 9.4 μm, and about 9.6 μm, or any combination thereof. Furthermore, IR radiation is detected at a reference wavelength or wavelength range where glucose does not have a characteristic absorption band, particularly an absorption minimum, and the intensity of the detected IR radiation is substantially independent of the concentration of glucose in the blood. More specifically, the reference wavelength or wavelength range is selected from a wavelength or wavelength range of about 8.7 μm to about 9.0 μm, a wavelength or wavelength range of about 9.7 μm to about 10.2 μm, or any combination thereof.

[0031] In certain embodiments of all of the above aspects, the system is adapted to sense a reference wavelength of about 8.8 μm, or a reference wavelength range that includes a wavelength of about 8.8 μm, for example, a wavelength range from about 7.5 μm to about 9.0 μm.

[0032] In further particular embodiments of all of the above aspects, the system is adapted to sense a reference wavelength of about 10.2 μm, or a reference wavelength range that includes a wavelength of about 10.2 μm, for example, a wavelength range from about 9.7 μm to about 10.5 μm.

[0033] In still further particular embodiments of all of the above aspects, the system is adapted to sense a first reference wavelength of about 8.8 μm, or a reference wavelength range including a wavelength of about 8.8 μm, e.g., a wavelength range of about 7.5 μm to about 9.0 μm, and a second reference wavelength of about 10.2 μm, or a reference wavelength range including a wavelength of about 10.2 μm, e.g., a wavelength range of about 9.7 μm to about 10.5 μm.

[0034] As outlined above, the present invention is based on irradiating body tissue with electromagnetic radiation in the wavelength range of about 400 nm to about 1500 nm (VIS / NIR radiation) and detecting electromagnetic radiation emitted from the irradiated body part in the wavelength range of about 5 μm to about 15 μm (IR radiation). Irradiating a body part with VIS / NIR radiation results in an enhanced self-emission of IR radiation from the body part due to local energy absorption, which causes a local increase in temperature. Therefore, the self-emission of IR radiation from the irradiated body part is increased by prior irradiation of the body part with VIS / NIR radiation. As a result, irradiation of the body part with an external source of IR radiation in the wavelength range of about 5 μm to about 15 μm is not required. Therefore, in certain embodiments, the systems of the present invention do not include an IR radiation source, and in particular, in certain embodiments, the systems of the present invention do not include an IR radiation source adapted to irradiate the body part from which the detected IR radiation is emitted.

[0035] The absorption wavelength band of a physiological parameter typically has a width of 100 μm to 200 μm. Therefore, the term "about" is understood to include this width of the absorption wavelength band. In certain embodiments, the term "about" is intended to include values ​​±0.1 μm or ±0.05 μm around the indicated wavelength, e.g., 9.2 μm ±0.1 μm or 9.2 μm ±0.05 μm.

[0036] FIG. 1 shows the penetration depth (mm) of electromagnetic radiation into body tissue as a function of wavelength (nm). It can be seen that the penetration depth depends on the wavelength. In the visible (VIS) / near-infrared (NIR) wavelength range between about 400 nm and 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 specifically 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, the irradiated body part absorbs the electromagnetic energy, resulting in a local increase in tissue temperature. This also results in an increase in the emission of longer-wavelength IR radiation, for example, in the wavelength range of about 5 μm to about 12 μm, where certain organic compounds present in body fluids, i.e., physiological parameters, exhibit absorption bands. This allows for quantitative or qualitative determination of such parameters according to the above-described embodiment of the present invention.

[0037] In certain embodiments, the VIS / NIR radiation emitted into the body part is in the range of about 550 nm to about 1000 nm, in particular 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., about 600 nm, and / or in the range of about 920 nm to about 980 nm, e.g., about 940 nm. In certain embodiments, the VIS / NIR radiation emitted inside the body is in the range of about 450 nm to about 800 nm.

[0038] Figure 2 shows the relative absorption coefficients of certain compounds present in the human body as a function of wavelength in the range of 400 nm to 1100 nm. Wavelengths of approximately 600 nm and approximately 810 nm, at which radiation can be emitted into body parts, are specifically shown. In the wavelength range of approximately 500 nm to approximately 1050 nm, the absorption of water (H2O) is relatively low. Furthermore, the major blood components, hemoglobin (Hb) and oxygenated hemoglobin (Hbxy), exhibit similar absorption coefficients. The skin pigment melamine exhibits an absorption coefficient that decreases with increasing wavelength.

[0039] The system or device of the present invention comprises a radiation source (a) adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm to a body part of said subject, the body part being selected from, inter alia, a fingertip, an earlobe, a wrist, a forearm, a palm and an upper arm.

[0040] In an embodiment of the present invention, the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 920 nm to about 960 nm, for example, about 940 nm, to a body part. This irradiation wavelength can be used alone or in combination with at least one additional irradiation wavelength. As shown in FIG. 3, glucose has an absorption band at a wavelength of 940 nm. Therefore, irradiation at a wavelength of about 940 nm can result in selective excitation of glucose molecules, resulting in stronger absorption of glucose molecules in the IR wavelength range, particularly in the wavelength range of about 5 μm to about 12 μm.

[0041] According to an embodiment of the present invention, the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 920 nm to about 980 nm, for example about 940 nm, onto the body part of the subject, and the sensing unit (b) is further adapted to detect VIS / NIR radiation having a wavelength of about 940 nm, the intensity of the detected VIS / NIR radiation depending on the concentration of glucose. The measurement signal in the VIS / NIR wavelength range can be combined with the measurement signal in the IR range as described above, for example by a comparator.

[0042] In still further embodiments, the VIS / NIR radiation occurs at a combination of at least two different wavelengths, particularly a first wavelength between about 800 nm and about 820 nm, e.g., about 810 nm, and a second wavelength between about 920 nm and about 980 nm, e.g., about 940 nm.

[0043] The radiation source (a) is adapted to emit 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 can be emitted continuously or intermittently over a predetermined time interval.

[0044] In certain embodiments, the radiation source is adapted to cause a local increase in temperature of the irradiated body part, e.g., a fingertip, particularly a local increase in temperature of an absorbing region within the irradiated body part. The local temperature increase can be in the range of about 1°C to about 15°C, particularly about 2°C to about 10°C, and more particularly about 3°C ​​to about 5°C. The locally increased temperature of the irradiated body part, e.g., a fingertip, can be in a temperature range of up to about 45°C, up to about 40°C, or up to about 37°C, e.g., in a temperature range of about 30°C to about 35°C or about 30°C to about 32°C. This local temperature increase results in enhanced self-emission of IR radiation from the irradiated body part, particularly from an absorbing region within the irradiated body part.

[0045] In certain embodiments, the radiation source (a) may be adapted to continuously emit radiation at a power of about 10 mW to about 1 W, particularly about 20 mW to about 500 mW, more particularly about 50 mW to about 250 mW, even more particularly about 100 mW to about 200 mW, for example about 150 mW, at a time interval of about 0.1 to about 20 seconds, particularly about 0.2 seconds to about 5 seconds, more particularly about 0.5 seconds to about 2 seconds, for example about 1 second.

[0046] In a further embodiment, the radiation source (a) may be adapted to emit radiation intermittently at a power of about 10 mW to about 5 W, particularly about 20 mW to about 1 W, more particularly about 50 mW to about 500 mW, at a time interval of about 0.1 seconds to about 20 seconds, particularly about 0.2 seconds to about 5 seconds, more particularly about 0.5 seconds to about 2 seconds. The radiation may be emitted intermittently at a pulse frequency of about 1 Hz to about 1 MHz.

[0047] In a further embodiment, the radiation source (a) is adapted to emit radiation continuously or intermittently over a period of at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0048] In further embodiments, the radiation source (a) can be adapted to emit VIS / NIR radiation at multiple different wavelengths, e.g., 2, 3, 4, 5, 6, 7, 8, or more different wavelengths. For example, the radiation source can be a multi-LED chip. Using a multi-wavelength radiation source makes it possible to tailor the predetermined penetration depth of the electromagnetic radiation into the tissue of the irradiated body part depending on the specific characteristics of the body part, such as pigmentation, skin thickness, and the presence or absence of keratinized skin. As shown in FIG. 1 above, the penetration depth into body tissue varies with wavelength, and the use of VIS / NIR radiation at different wavelengths or combinations of different wavelengths can be individually tailored to each subject and / or each body part, if desired.

[0049] In certain embodiments, the radiation source (a) is a multi-wavelength radiation source adapted to emit VIS / NIR radiation at at least 2, 3, 4, 6 or 8 wavelengths which may be selected from several different wavelengths or wavelength ranges, for example, from about 400 nm to about 1200 nm, more particularly from about 450 nm to about 900 nm, for example, from about 470 nm, about 520 nm, about 590 nm, about 650 nm, about 750 nm and about 810 nm.

[0050] The system or device of the present invention comprises a sensing unit (b) for detecting IR radiation emitted from the irradiated body part of the subject in the range of about 5 μm to about 12 μm, wherein the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or range of wavelengths in the range of about 5 μm to about 12 μm, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject, and (ii) detect IR radiation having at least one wavelength or range of wavelengths in the range of about 5 μm to about 12 μm, wherein the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in a body fluid of the subject.

[0051] In certain embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part over a period of time, wherein the body part is irradiated with VIS / NIR radiation for at least a portion of said period, such as at least about 60% or at least about 80% or at least about 90% of said period, and wherein said period may be at least about 0.5 seconds, in particular at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0052] In certain embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part over a period of time, such as a period as described above, and during at least a portion of said period, such as at least about 60% or at least about 80% or at least about 90% of said period, the temperature of the irradiated body part, in particular the absorbing region, is higher than the surrounding tissue, such as at least 1°C, at least 2°C, at least 5°C and up to 10°C higher than the surrounding tissue.

[0053] In certain embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part over a period of time, such as the period described above, and during at least a portion of said period, such as at least about 60% or at least about 80% or at least about 90% of said period, there is an increase in temperature of the irradiated body part, particularly the absorbing region. The increase in temperature may be in the range of about 2°C to about 10°C, particularly about 3°C ​​to about 5°C.

[0054] The sensing unit (b) comprises at least one sensor adapted to detect IR radiation emitted from the irradiated body part. In the sensing unit (b) of the present invention, at least one sensor may be an analyte-specific sensor, i.e., a sensor adapted to detect IR radiation having at least one wavelength or wavelength range, the intensity of which detected IR radiation depends on the concentration of a physiological parameter in the subject's body fluid, and at least the ON sensor may be a reference sensor, i.e., a sensor adapted to detect IR radiation having at least one wavelength or wavelength range, the intensity of which detected IR radiation is substantially independent of the concentration of a physiological parameter in the subject's body fluid.

[0055] In a particular embodiment, the sensing unit (b) is adapted to detect self-emitted IR radiation from the previously irradiated body part, i.e., IR radiation generated by the subject's body heat without irradiation by an external IR source. Furthermore, the sensing unit (b) may be adapted to detect IR radiation emitted from absorbing regions within the previously VIS / NIR irradiated body part, which absorbing regions exhibit a localized increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm.

[0056] In certain embodiments, there may be at least one further sensor, for example (i) a sensor adapted to detect non-specific IR radiation, (ii) a sensor adapted to detect non-specific VIS / NIR radiation, (iii) a sensor adapted to detect VIS / NIR radiation having a wavelength where the intensity of the detected VIS / NIR radiation depends on the concentration of a physiological parameter in the subject's body fluid, and / or (iv) a temperature sensor for measuring the temperature of a body part.

[0057] In certain embodiments, sensing unit (b) is further adapted for temperature measurement, for example, with an accuracy of at least about 1°C, at least about 0.1°C, or at least about 0.01°C. The sensing unit may be adapted to measure and optionally monitor the temperature of the skin of the irradiated body part, and optionally at least one further temperature, such as the environmental temperature, the temperature of individual sensors within sensing unit (b), and / or the temperature of electronic components of sensing unit (b), for example the temperature of a circuit board. In these embodiments, sensing unit (b) may include at least one temperature sensor, in particular multiple temperature sensors, for example two, three, or four temperature sensors for measuring the temperature of the skin, and optionally at least one further temperature sensor, for example a sensor for measuring the environmental temperature, at least one sensor for measuring the temperature of individual sensors within the sensing unit, and / or a sensor for measuring the temperature of electronic components of the sensing unit, for example the temperature of a circuit board of sensing unit (b).

[0058] In a particular embodiment, the sensing unit (b) further comprises a gesture sensor adapted to detect movement during the measurement. The gesture sensor may operate in the same wavelength range as the other sensors. By using the gesture sensor, measurements made when the body part is moving can be identified and optionally excluded.

[0059] In certain embodiments, the sensing unit (b) further comprises an accelerometer, for example a microelectromechanical systems (MEMS) accelerator, which can be used to identify and optionally exclude measurements made when the body part is in motion.

[0060] In certain embodiments, sensing unit (b) comprises at least one further analyte-specific sensor, i.e. a sensor adapted to detect VIS / NIR radiation having at least one wavelength or wavelength range, the intensity of which detected VIS / NIR radiation depends on the concentration of a physiological parameter in the subject's body fluid. For example, there may be at least one further sensor adapted to detect VIS / NIR radiation having a wavelength of about 940 nm.

[0061] In certain embodiments of the present invention, the radiation source (a) and the sensing unit (b) are positioned at positions defined by an angle of at least 90° relative to the irradiated body part, hi certain embodiments, the radiation source (a) and the sensing unit (b) are positioned on either side of the irradiated body part.

[0062] The system or device of the present invention comprises an analysis or control unit (c) for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit (b). The analysis unit may comprise, for example, an A / D converter and / or a microcontroller. The analysis of the measured signal may be based on intensity and / or decay time.

[0063] In a particular embodiment, the analysis or control unit (c) is adapted for a time-dependent analysis of the detected IR radiation, and the measurement signal is recorded over a period of time, in particular over a period of at least about 0.5 seconds, in particular over a period of at least about 1 second to about 120 seconds, more particularly over a period of at least about 2 seconds to about 20 seconds.

[0064] In a further particular embodiment, the analysis or control unit (c) is adapted for a temperature-compensated analysis of the detected IR radiation. The temperature-compensated analysis comprises temperature compensation, in which the measurement signal is corrected for temperature. In particular, the temperature compensation is based on the temperature of the skin of the irradiated body part and, optionally, on at least one further temperature, such as the ambient temperature, the temperatures of components of the sensing unit, e.g. the temperatures of individual sensors in the sensing unit, and / or the temperature of electronic components of the sensing unit.

[0065] In a still further particular embodiment, the analysis or control unit (c) is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation as described above.

[0066] Figure 4 shows an embodiment of the system described in WO 2022 / 090503. A body part (1), for example a fingertip, is placed in contact with the system, which is adapted to irradiate an absorbent area (2) inside the body part (1).

[0067] The system includes a cover (3) made at least partially of an optically transparent material. For example, the cover may be made at least partially of CaF2 and / or BaF2, or a plastic material that is transparent in the IR wavelength range of about 5 μm to about 12 μm or a subrange thereof, such as about 8 μm to about 12 μm, and optionally transparent in the VIS / NIR wavelength range of about 400 nm to about 1500 nm or a subrange thereof. A suitable IR-transparent plastic material is, for example, PolyIR plastic material commercially available from Fresnel Technologies, Fort Worth, Texas, USA. In certain embodiments, the cover can have a thickness of about 0.2 mm to about 2 mm, particularly about 0.3 mm to about 1.5 mm, and more particularly about 1 mm.

[0068] The system further includes at least one sensor (4), which may include a filter element (5) and, optionally, a lens element (not shown), which may be disposed, for example, between the sensor (4) and the filter element (5). The sensor (4) may be mounted on a circuit board (6). The system further includes at least one radiation source (9, 9a). For example, the system may include a radiation source (9) disposed on the same side as the sensor (4) and / or a radiation source (9a) disposed on the opposite side of the body part (1) relative to the sensor (4). If desired, an additional sensor (4) may be provided without a filter element (5) to monitor the subject's exact skin temperature.

[0069] The system includes one or more sensors (4). In the embodiment of FIG. 4, the system includes four different sensors (4). The sensors can be photodetectors, particularly photovoltaic detectors, such as InAsSb-based detectors, which can be used in combination with lock-in amplifiers if desired. Photovoltaic detectors, such as InAsSb-based detectors, have rise times of only a few nanoseconds and are particularly useful in settings where the body part is intermittently illuminated. In other embodiments, the sensors can be thermal detectors, such as thermopiles or bolometers. Suitable sensors include photovoltaic detectors (e.g., Hamamatsu P13894), thermopiles (e.g., Heimann HCS C21 F8-14), or other types of IR sensors (e.g., Sensirion STS21 or Melexis MLX90632). If desired, the sensors (4) can include filter elements (5) capable of selectively transmitting radiation of a desired wavelength or range of wavelengths. The filter elements can have narrow bandwidths, for example, about 50 to 100 nm, or broader bandwidths, for example, about 400 nm or greater. The filters can be made of germanium or other filter materials that are optically transparent to the respective wavelengths. Additionally, the sensor can include lens elements, such as microlenses, that can focus the light that strikes the sensor.

[0070] In certain embodiments, the sensor surface can be coated with a noble metal, such as Au or Ag, particularly Au, to enhance its sensitivity. Such a coating, which can be molded into a Bundt baking pan, is described in Awad (Nature Scientific Reports 9:12197 (2019)), the contents of which are incorporated herein by reference.

[0071] In certain embodiments, the sensor is about 1 mm 2 ~approx. 10,000mm 2 , for example, about 10 mm 2 ~approx. 1,000mm 2In certain embodiments, the sensor can be extremely small, for example an ASIC (Application Specific Integrated Circuit).

[0072] Additionally, 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).

[0073] The VIS / NIR radiation source (9, 9a, 9b) may be a laser-based light source that emits collimated radiation, and / or an LED-based light source that emits uncollimated radiation. 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 that can be adapted to emit 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, for example, OSLON products from Osram, such as the OSLON SFH 4763.

[0074] In certain embodiments of all aspects of the present disclosure, the device further comprises monitoring means for detecting fluctuations in the radiation emitted by the radiation source, e.g., power fluctuations. The monitoring means may include a photodiode, e.g., a photodiode integrated into the radiation source or a photodiode separate from the radiation source. The detected fluctuations may be compensated for by the sensing unit and / or the control unit, or the radiation source may be replaced.

[0075] 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 the side of the body part (1) opposite the sensing unit, which includes at least one sensor (4) equipped with a filter (5) and another sensor (4a) equipped with a filter (5a). In a specific embodiment, the sensor (4a) is an optical sensor, such as a photodiode, adapted for reference measurement of transmitted radiation from the radiation source (9a), for example, to measure radiation at wavelengths of about 600 nm, about 810 nm, and / or about 940 nm. For this purpose, the filter element (5a) can be a bandpass filter at about 600 nm, about 810 nm, and / or about 940 nm.

[0076] Yet another embodiment described in WO 2022 / 090503 is shown in Figure 6. Here, a radiation source (9b) is provided on the side of the body part (1), e.g., on a fingertip, and direct access to the absorption region (2) within the body part (1) is provided through the skin of the body part, without the radiation passing through the device's cover structure and / or through keratinized structures on the body surface, e.g., fingernails and / or keratinized skin. This reduces or eliminates interference, e.g., from the cover structure, or from keratinized skin or nail material, and optionally, nail polish. According to this embodiment, a single radiation source (9b) or multiple radiation sources (9b), e.g., 2, 3, 4, 6, or 8 radiation sources, can be provided at positions around the body part (1), e.g., around the fingertip. When multiple radiation sources are present, they are preferably adapted to emit radiation to a single absorption region (2) within the body part, which may be approximately 3 mm to approximately 5 mm below the body surface.

[0077] A further embodiment, as described in WO 2022 / 090503, is shown in FIG. 7. In this embodiment, a cover (3) is provided that is adapted to focus IR radiation emitted from the body part onto at least one sensor (4) of the sensing unit. This can increase the intensity of the radiation to the sensor and, therefore, the sensitivity and / or accuracy of the measurement. The cover (3) is made of a material, such as plastic, metal, metal oxide, or composite material, that is substantially transparent to IR radiation in the wavelength range detected on the sensor, particularly IR radiation in the wavelength range of about 5 μm to about 12 μm or a subrange thereof, such as about 8 μm to about 12 μm. Suitable materials include, for example, the PolyIR plastic material listed above. In this embodiment, the cover (3) can include an IR Fresnel lens, i.e., a lens with a large aperture and short focal length that can efficiently focus IR radiation passing therethrough, or an array including multiple, e.g., up to 10 or more, IR Fresnel lenses. In certain embodiments, the array can include IR Fresnel microlenses, e.g., up to 100 or 1000 microlenses, and can have diameters ranging from about 50 nm to about 500 μm. In certain embodiments, the IR Fresnel lenses can have a back focal length of about 3 mm to about 10 mm, e.g., about 5 mm, and can be fabricated from an IR-transmitting plastic. For example, suitable IR Fresnel lenses that are optically transparent in the 8-14 μm wavelength range are commercially available from Edmund Optics (Product Family No. 2042).

[0078] Furthermore, Figure 7 shows the radiation source (9a) provided on the opposite side of the body part with respect to the position of the sensing unit comprising the sensor (4). However, it should be noted that one or more radiation sources may be arranged in a circumferential arrangement around the body part (1), for example as shown in Figure 6. It should further be noted that in this embodiment there may be multiple different sensors, for example as shown in Figures 4 and 5.

[0079] As shown in Figures 4 and 5, the system can include multiple different sensors (4). In certain embodiments, the system can include multiple analyte-specific, e.g., glucose-specific, sensors, where a first sensor is adapted to detect radiation at a first wavelength or wavelength range, e.g., a wavelength of about 9.2 μm, and at least another first sensor is adapted to detect IR radiation at a second wavelength range that encompasses the first wavelength or wavelength range and further includes another wavelength or wavelength range. For example, the other first sensor can be adapted to detect IR radiation at a wavelength of about 9.2 μm, as well as at about 9.4 μm and / or about 9.6 μm, particularly at about 9.4 μm and about 9.6 μm.

[0080] Additionally, the sensing unit can include multiple reference sensors adapted to detect reference radiation at different wavelengths or wavelength ranges. For example, when determining glucose, a reference sensor can be adapted to detect radiation having a wavelength range of about 8.6 μm to about 9.0 μm. Another reference sensor is adapted to detect radiation at a wavelength or wavelength range of about 9.8 μm to about 10.2 μm.

[0081] A further embodiment described in WO 2022 / 090503 is shown in Figure 8. In this embodiment, a support (16) for a body part (1), e.g., a fingertip, is provided, the support (16) including an opening adapted to receive a portion (15) of the body part (1). For example, the support (16) may include an annular structure having an opening, e.g., a substantially circular opening, at its center. The system is adapted to press the body part (1) against the opening of the support (16) so that the portion (15) of the body part (1), e.g., a portion of the fingertip, is pressed into the opening. Thus, tissue, including blood vessels, inside the portion (15) is compressed, increasing the amount of capillary blood inside the portion (15). This can increase the signal strength and, therefore, the sensitivity and / or accuracy of the measurement.

[0082] Furthermore, the system of Fig. 8 includes a cover (3) which may be formed as an IR Fresnel lens as described above in the context of Fig. 7. However, it should be noted that other covers are also suitable. Furthermore, a radiation source (9a) is shown provided on the opposite side of the body part with respect to the position of the sensing unit comprising the sensor (4). However, it should be noted that one or more radiation sources may be arranged in a circumferential arrangement around the body part (1), as shown for example in Fig. 6. It should further be noted that in this embodiment, there may be multiple different sensors, as shown for example in Figs. 4 and 5.

[0083] FIG. 9 shows measurements at multiple analyte-specific wavelengths / wavelength ranges and a reference wavelength / wavelength range.

[0084] The absorption signal of glucose (24) has three distinct peaks at approximately 9.2 μm, approximately 9.4 μm, and approximately 9.6 μm. A first glucose-specific sensor can be adapted to measure only the 9.2 μm peak. Such a sensor is fitted with a filter element that is only capable of transmitting radiation in a narrow range (22). Thus, the sensor can selectively detect radiation within this narrow range. A further glucose-specific sensor can be adapted to measure radiation in a wider range from approximately 9.1 μm to approximately 9.7 μm, thereby encompassing the peaks at approximately 9.2 μm, 9.4 μm, and 9.6 μm. This sensor can be fitted with a filter element that is only capable of transmitting radiation in a wider range (21).

[0085] Two reference sensors may be provided, each comprising a filter element capable of transmitting radiation having a wavelength in the range of about 8.6 μm and about 9.0 μm, in particular in the range of about 8.8 μm to 8.9 μm (20) and / or radiation having a wavelength in the range of about 9.8 μm and about 10.2 μm, in particular in the range of about 9.9 μm to 10.1 μm (23).

[0086] Parallel and separate measurements, one of which is at a wavelength of about 9.2 μm and a wavelength range that includes the 9.2 μm peak, but also at least one of the other peaks, particularly the 9.6 μm peak, have a further advantage because they allow for a determination of whether a subject's blood contains ethanol. Because ethanol and other alcohols have an absorption band at a wavelength of about 9.6 μm but not at a wavelength of about 9.2 μm, the ratio of the 9.2 μm and 9.6 μm peaks can be used to determine, and optionally correct for, disturbances caused by blood alcohol.

[0087] In an alternative embodiment, a first glucose-specific sensor may be adapted to measure only the 9.6 μm peak. Such a sensor may include a filter element that is only capable of transmitting radiation in a narrow range. A further glucose-specific sensor may be adapted to measure radiation in a broader range from about 9.4 μm to about 9.6 μm, thereby encompassing the peak from about 9.4 μm to about 9.6 μm and not the 9.2 μm peak. This sensor may include a filter element that is capable of transmitting radiation in the wider range.

[0088] In a further alternative embodiment, a reference sensor may be provided, comprising a filter element capable of transmitting radiation with wavelengths in the range of approximately 7.8 μm and approximately 8.2 μm, in particular with wavelengths in the range of approximately 7.9 μm to 8.1 μm, optionally in combination with at least one further reference sensor, each comprising a filter element capable of transmitting radiation with wavelengths in the range of approximately 8.8 μm to 9.2 μm and / or radiation with wavelengths in the range of approximately 9.8 μm to 10.2 μm.

[0089] In yet a further embodiment, the system can include a sensor adapted for time-dependent detection of IR radiation having different wavelengths or wavelength ranges. In this embodiment, the system can include a sensor with multiple filters adapted to transmit IR radiation having different wavelengths or wavelength ranges, and the filters can be positioned on the sensor during different phases of a measurement cycle, thereby enabling detection of different wavelengths or wavelength ranges within the measurement cycle. Such an embodiment, described in WO 2022 / 090503, is shown in FIG. 10. Here, a system is provided that includes a filter wheel (10) rotatable about an axis (11) and a shutter wheel (13) rotatable about an axis. The filter wheel and shutter wheel are provided with illumination apertures (15) that allow light from a radiation source (not shown) to pass through to a body part of a subject (not shown). Reflected light from the illuminated body part can pass through different apertures (14) in the filter wheel (10), which can include analyte-specific and / or reference filter elements as described above. The positions of the filter wheel (10) and the shutter wheel (13) can be monitored with a magnet (12) combined with a magnetic sensor. In operation, they can be rotated at a predetermined frequency, thereby allowing radiation from the radiation source to pass in a time-dependent manner to the body part, and radiation emitted from the body part at predetermined time intervals to pass in a time-dependent manner through different holes (14) in the filter wheel (10) to a sensor (not shown).

[0090] In an alternative embodiment (not shown), the sensor adapted for time-dependent 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 (see Tuohinieni et al., J. Micromech. Microeng. 22 (2012), 115004; Tuohinieni et al., J. Micromech. Microeng. 23 (2013), 075011).

[0091] In certain embodiments, the system comprises a single sensor adapted for the time-dependent detection of IR radiation having different wavelengths or wavelength ranges, which may comprise different filters, e.g., a filter wheel, or may be a Fabry-Perot interferometer as described above.

[0092] A further embodiment described in WO 2022 / 090503 is shown in Figure 11. The system of this embodiment is adapted to be permanently fixed to the subject's body. The system is particularly adapted to perform multiple measurements at predetermined time intervals. The system comprises a housing (30) and a strap (31) for fastening the housing around the body (33), for example, the wrist or forearm. Furthermore, the system comprises a radiation source for emitting VIS / NIR light to an absorption region (34) of the body part (33) and a sensor for detecting IR radiation emitted from the irradiated body part.

[0093] A further embodiment described in WO 2022 / 090503 is shown in Figure 12. The system of this embodiment is adapted to be permanently fixed to the subject's body, particularly adapted to perform multiple measurements at predetermined time intervals. The system includes a housing (30) and a strap (31) for securing the housing around the body (33), for example, the wrist or forearm. The system further includes multiple radiation sources, for example, two radiation sources, for emitting VIS / NIR light to an absorption region (34) of the body part (33), and a sensor for detecting IR radiation emitted from the irradiated body part. The light emitted from these light sources may strike the surface of the body part (33) at an angle, for example, between about 30° and about 75°.

[0094] FIG. 13 shows a schematic diagram of the system of FIG.

[0095] Figure 14 shows the heat map of a fingertip after 2 seconds of irradiation with 810 nm light.

[0096] FIG. 15 shows the time-dependent heat output as well as the self-emission of the fingertip during intermittent irradiation with 810 nm light at a power of 2 mW and a frequency of 0.1 Hz.

[0097] 16a shows a block diagram of an embodiment of the sensing unit of the present invention. A region of interest (ROI), i.e., skin tissue of a subject, in particular a human subject, is illuminated by 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. The radiation transmitted through or reflected from the region of interest is analyzed by the sensing unit. Furthermore, the device includes a temperature sensor.

[0098] The sensing unit includes multiple sensors, e.g., analyte-specific IR sensors (1) and (2), and a reference sensor, e.g., IR sensor (4). For glucose measurement, IR sensor (1) may include a first optical filter transparent to a wavelength of approximately 9.2 μm, and IR sensor (2) may include a second optical filter transparent to a wavelength range of approximately 9.2 μm to approximately 9.6 μm. Reference sensor (4) may include a fourth optical filter transparent to a wavelength or wavelength range of approximately 8.6 μm to approximately 9.0 μm and / or a wavelength or wavelength range of approximately 9.8 μm to approximately 10.2 μm. Furthermore, the sensing unit includes an NIR sensor for detecting VIS / NIR radiation having a wavelength of approximately 940 μm, at which glucose has a strong absorption band. The NIR sensor is equipped with an appropriate optical filter transparent to this wavelength. Furthermore, the sensing unit may include a temperature sensor for measuring the temperature of the skin tissue in the area of ​​interest. Each sensor may be coupled to an amplifier (AMP) for first signal amplification. Signals from individual sensors may be referenced to signals from other sensors by a comparator, thereby improving measurement accuracy and / or signal quality. For example, the measurement signal from the 940 nm NIR sensor may be referenced to the measurement signal from the analyte-specific IR sensor (1). Alternatively or additionally, the measurement signal from the 940 nm NIR sensor may be referenced to the measurement signal from the analyte-specific IR sensor (1) and / or the analyte-specific IR sensor (2) and / or the reference IR sensor (4). The measured, optionally referenced, signal is further amplified by a lock-in amplifier unit and transmitted to the microcontroller unit. Feedback control from the lock-in amplifier to the light source may be provided. From the microcontroller unit, the signal and / or the result of the internal algorithm may be transmitted to a display unit and / or another device, for example, by direct connection or via Bluetooth and / or WLAN.

[0099] Figure 16b shows a block diagram of a further embodiment of a sensing unit of the present invention, similar to the sensing unit shown in Figure 16a. Here, additionally or alternatively, a multi-wavelength light source, e.g., a multi-wavelength LED including a plurality of individual diodes, is provided. The multi-wavelength light source may have a wavelength range of, for example, 400 nm to about 700 nm and may be provided and operated by a microcontroller unit. Furthermore, there is a temperature sensor coupled to the amplifier (AMP). This temperature sensor may also be operated by the microcontroller unit.

[0100] In yet further embodiments of the present invention, the system may include a spectral or line sensor or a spectral or line sensor array, typically an array of bolometers or thermopiles, adapted to detect an IR spectrum within a wavelength range of interest, including, for example, a range of about 7 μm to about 12 μm, particularly a range of about 8 μm to about 10 μm. The IR spectrum may be generated by passing IR radiation from an irradiated body part through a spectral splitting or diffracting device and then through a sensor or sensor array. Such an embodiment is shown in FIG. 17. IR radiation (70) emitted from an irradiated body part (71), e.g., a fingertip, is optionally focused by a focusing element (72), e.g., a lens or concave mirror element, adapted to focus the IR radiation, and then sent to a spectral splitting or diffracting element (73), e.g., a prism or a transmissive or reflective optical grating, to split the IR radiation according to its wavelength. From there, the diffracted radiation is passed to a spectral sensor or line sensor or sensor array (74), typically an array of bolometers or thermopiles, which detects the IR spectrum in a wavelength range of interest, e.g., 8 μm to about 20 μm, including an analyte-specific wavelength or wavelength range and a reference wavelength or wavelength range, e.g., as described above. The amount of a physiological parameter of interest, such as glucose, can be determined by spectral analysis according to the relative intensities of the predetermined analyte-specific wavelengths and the reference wavelength.

[0101] The systems and methods described herein allow for the qualitative and / or quantitative determination of measured physiological parameters, and in particular the qualitative and / or quantitative determination of glucose in blood.

[0102] In certain embodiments, the concentration of a physiological parameter, e.g., the concentration of glucose in blood, is determined quantitatively. In certain embodiments, the rate of change of a measured amount of a physiological parameter, such as glucose, is determined. These embodiments may include non-quantitative measurements, e.g., a relative measurement of the change in the amount of an analyte per unit time, i.e., an increase or decrease in the amount of an analyte per unit time. If the unidirectional change in the amount of an analyte, i.e., an increase or decrease, exceeds a predetermined level and / or time period, the system issues an alert. This embodiment is particularly useful for systems such as those shown in FIGS. 11 and 12, which may be permanently secured around the subject's body, e.g., the wrist, forearm, or upper arm. This embodiment may be adapted for monitoring steady-state glucose levels.

[0103] In certain embodiments, the systems described herein are adapted to perform both non-quantitative and quantitative measurements. For example, the system may be adapted to perform non-quantitative measurements, e.g., qualitatively measure changes in the amount of an analyte over time, e.g., increases or decreases, during standard operation. The non-quantitative measurements may be performed, for example, as continuous and / or intermittent monitoring measurements, as needed. If the change in the amount of the analyte exceeds a predetermined level and / or period, the system may be adapted to switch to quantitative measurements to provide more detailed information. In these embodiments, systems adapted to be permanently fixed to the body, e.g., the arm, wrist, or ankle, may be used. Specific embodiments of such systems are shown in Figures 11 and 12.

[0104] In certain embodiments, the system is adapted to perform non-quantitative measurements, e.g., continuous and / or intermittent monitoring measurements, as well as quantitative measurements for several different body parts. For example, the system may be adapted to perform non-quantitative measurements for a first body part, e.g., a body part to which the system may be permanently fixed, such as an arm, wrist, or ankle, and perform quantitative measurements for a second body part, e.g., a body part to which capillaries are more accessible, such as an earlobe, palm, or fingertip. To perform measurements for the second body part, the system is detached from the first body part and brought into contact, particularly direct contact, with the second body part. After performing measurements for the second body part, the system may be detached from the second body part and brought back into contact with the first body part, e.g., by fixing the system to the first body part. In certain embodiments, the first body part is an arm, wrist, and / or the second body part is a fingertip.

[0105] A further embodiment described in WO 2022 / 090503 is shown in Figure 18. Here, a device is shown that includes a non-invasive system for determining a physiological parameter, such as glucose, in a subject's body fluid. The device includes a casing (80) that includes a first surface that includes a screen (81) that is at least partially made of a material that is optically transparent to NIR / VIS radiation emitted by a radiation source (82). Furthermore, the device includes a sensing unit (83) that includes at least two sensors (83a), (83b).

[0106] The device (80) may be a mobile device, such as a smartphone, smartwatch, tablet, or fitness tracker device. The device may be worn on the subject's body, e.g., wrist (84), and secured by a band (85), e.g., a wristband. A body part (86), e.g., a fingertip (or multiple fingertips or the palm of a hand), is placed on the display (81) for measurement. An absorption region (87) within the body part (86) is illuminated by VIS / NIR radiation emitted by a radiation source (82). The irradiated body part absorbs the electromagnetic energy, resulting in a local increase in local temperature and an increase in the emission of IR radiation from the absorption region in the wavelength range of about 5 μm to about 12 μm. Molecules of the detected physiological parameter, such as glucose molecules, absorb the emitted IR radiation present in the tissue of the body part (86). Thus, at a wavelength or wavelength range corresponding to the absorption band of the physiological parameter of interest, the signal of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the signal of the emitted IR radiation increases with decreasing concentration of the physiological parameter.

[0107] Figure 19 shows the device described in WO 2022 / 090503, which includes a VIS / NIR radiation source (93), e.g., an LED, adapted to irradiate a body part, e.g., the fingertip (94) of a finger (90). The device includes an IR temperature sensor (91), e.g., a bolometer, for measuring the temperature of the body part. Furthermore, the device includes four IR sensors (92a, 92b, 92c, 92d) equipped with optical filters adapted for wavelength-specific measurement of the object to be determined, e.g., glucose. The IR sensors (92a, 92b) can be adapted for measurement at an analyte-specific wavelength or wavelength range, while the IR sensors (92c, 92d) can be adapted for measurement at a reference wavelength or wavelength range. For example, sensor (92a) may include an optical filter that is transparent to a glucose-specific wavelength of about 9.2 μm, sensor (92b) may include an optical filter that is transparent to a glucose-specific wavelength range of about 9.2 μm to about 9.6 μm, sensor (92c) may include an optical filter that transmits a reference wavelength or a wavelength range of about 8.6 μm to about 9.0 μm, and sensor (92d) may include an optical filter that transmits a reference wavelength or a wavelength range of about 9.8 μm to about 10.2 μm.

[0108] FIG. 20 shows a further device described in WO 2022 / 090503, comprising a substrate (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 substrate is connected to an analog-to-digital converter, microcontroller, or processor (not shown) via a means (101), e.g., a printed circuit (PCB) or printed circuit board assembly (PCBA), in particular a flexible or star-flex PCB or PCBA. The radiation sources (103a, 103b) can be adapted to emit VIS / NIR radiation at the same wavelength or at different wavelengths. For example, both radiation sources can emit radiation at a wavelength of approximately 810 μm or radiation at a wavelength of approximately 940 μm. Alternatively, one of the radiation sources may be adapted to emit radiation at a wavelength of approximately 810 μm, and the other radiation source may be adapted to emit radiation at a wavelength of approximately 940 μm. The device includes an IR temperature sensor (104), such as a bolometer, for measuring the temperature of a body part (not shown). Furthermore, the device includes two IR sensors (102a, 102b), each with two separate sensing tips. Each sensing tip may be equipped with a different optical filter. The IR sensor (102a) may be adapted to measure at an analyte-specific wavelength or wavelength range, and the IR sensor (102b) may be adapted to measure at a reference wavelength or wavelength range. For example, the first chip-on sensor (102a) may include an optical filter that is transparent to a glucose-specific wavelength of about 9.2 μm, the second chip-on sensor (102a) may include an optical filter that is transparent to a glucose-specific wavelength range of about 9.2 μm to about 9.6 μm, the first chip-on sensor (102b) may include an optical filter that transmits a reference wavelength or a wavelength range of about 8.6 μm to about 9.0 μm, and the second chip-on sensor (102b) may include an optical filter that transmits a reference wavelength or a wavelength range of about 9.8 μm to about 10.2 μm. In a further miniaturized embodiment, the device may include a single sensor stage including at least four chips with four different optical filters (not shown).In an even more miniaturized embodiment, the device may be a single unit containing all chips, all filters, all radiation sources, and even microelectronic components such as analog-to-digital converters and a microcontroller in a single application specific integrated circuit (ASIC) (not shown).

[0109] 20 (or any other device described herein) may be provided as a component for integration into a multifunction device, e.g., a smart device such as a smartwatch or mobile phone, or the device may be provided as a standalone device.

[0110] Figure 21 shows a comparison of glucose concentrations measured by an invasive method (straight line), i.e., amperometric measurement of a blood sample using a conventional glucometer, with the relative (uncalibrated) glucose amount measured by a non-invasive method of the present invention (dotted line), i.e., measurement using the device shown in Figure 13. Measurements were taken over a 6-hour period. A high correlation was observed between the conventional invasive glucose measurement and the non-invasive glucose measurement of the present invention.

[0111] Furthermore, a non-invasive system for determining glucose in blood is described, which allows identifying and optionally correcting disturbances caused by blood alcohol, comprising a sensing unit for detecting IR radiation emitted from a body part of said subject in the range of about 5 μm to about 12 μm, The sensing unit comprises (i) a sensing unit adapted to detect IR radiation at a wavelength of about 9.2 μm and separately to detect IR radiation at wavelengths of at least about 9.2 μm and about 9.6 μm, in particular in a wavelength range encompassing wavelengths of about 9.2 μm, about 9.4 μm and about 9.6 μm, and an analysis unit for determining glucose, separate from the sensing unit.

[0112] Also described herein is a method for using this system to non-invasively determine glucose in a subject's blood.

[0113] Preferred features of these embodiments are as already set out in the specification above.

[0114] The use of an InAsSb sensor, optionally in combination with a lock-in amplifier, for the measurement of IR radiation emitted from a body part is further described.

[0115] Preferred features of this embodiment are as already set out in the specification above.

[0116] Systems and methods are further described for non-quantitative measurement of glucose, which involve multiple measurements during a predetermined time interval, determining a change in a measurement signal indicative of a change in the amount of an analyte, and providing a change if the change in glucose amount is in one direction, i.e., an increase or decrease, beyond a certain level for a predetermined period of time. The systems and methods may be adapted for monitoring steady-state glucose levels.

[0117] Preferred features of this embodiment are as already set out in the specification above.

[0118] 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, such as glucose, in tissue and / or body fluid of a body part, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; -Power supply and - optionally at least one status indicator.

[0119] This aspect also includes a method of determining physiological parameters, such as glucose, in fluids and / or tissues of a body part using an implantable device as described above.

[0120] In certain embodiments, the device is implanted in subcutaneous adipose tissue and measures glucose therein and / or in adjacent blood vessels, eg, capillaries.

[0121] FIG. 22 illustrates an embodiment of an implantable device including a system for determining physiological parameters, such as glucose, in body fluids and / or tissues of a body part, e.g., subcutaneous adipose tissue. In certain embodiments, the implantable device is needleless, i.e., the device is completely enclosed by a housing so that the functional elements do not come into direct contact with surrounding tissue. In certain embodiments, the device is sized to be inserted into a subject's body using an appropriate injection device. Alternatively, the device may be inserted surgically. The device may be implanted subcutaneously in the arm, leg, or abdominal region. 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 width of about 2-4 mm, particularly about 3 mm.

[0122] The implantable device comprises an exterior housing (1). The housing (1) is at least partially optically transparent to allow measurement of a desired physiological parameter, such as glucose, by a system disposed within the housing. The housing is made of a physiologically compatible material, such as a physiologically compatible plastic, glass, or composite material. In certain embodiments, the housing completely encloses the system.

[0123] The system of Figure 22 comprises at least one radiation source (9) adapted to emit visible (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, e.g., bodily fluids and / or tissues (5) adjacent to the implanted device. In certain embodiments, the system includes multiple radiation sources (9), e.g., 2, 3, 4, or 5 radiation sources.

[0124] The system of Figure 22 also includes a sensing unit including at least one sensor (8), e.g., an optical and / or calorimetric sensor, for detecting IR radiation emitted from the previously irradiated body part in the range of about 5 μm to about 12 μm. The sensing unit is adapted to (i) detect IR radiation of at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in the irradiated body part (5), and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in the irradiated body part (5). In certain embodiments, the system includes multiple sensors (8), e.g., two, three, four, or five sensors. The sensor (8) may include an optical filter element (10) adapted to detect IR radiation having a desired wavelength or wavelength range.

[0125] The system of Fig. 22 comprises a control unit (3), in particular a highly integrated microcontroller, e.g., an ASIC. The control unit is adapted to control the measurement procedure. In certain embodiments, the control unit (3) is further adapted to analyze the measurement results by qualitative and / or quantitative determination of physiological parameters based on the measurement results. In certain embodiments, the control unit (3) comprises communication means adapted to communicate with an external device (not shown), e.g., a smartphone or a smartwatch. The communication means may be adapted to transmit signals, e.g., signals including the measurement results and / or determination results and / or signals including an identification code, to the external device and / or receive signals 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).

[0126] The system further comprises a power source. In certain embodiments, the system includes 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 rechargeable battery. In certain embodiments, the battery is rechargeable wirelessly, e.g., by capacitive charging using a charging coil (2). Furthermore, the power source may comprise a capacitor (7), such as a supercapacitor or ultracapacitor, as a short-term power reservoir to provide power during power bursts when the radiation source (9) is activated. In certain embodiments, the power source may also include a power harvesting device, e.g., a micro-energy harvesting device, adapted to convert mechanical energy into electrical energy.

[0127] In certain embodiments, the system includes at least one status indicator (not shown) adapted to inform the wearer whether the determined parameter is inside or outside a physiologically acceptable range, in particular 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 to a malfunction of the device caused, for example, by a power outage. In certain embodiments, the device may comprise an optical status indicator, e.g., a multicolored LED, an acoustic status indicator, e.g., a piezoelectric speaker element, and / or a tactile status indicator, e.g., a vibrator.

[0128] The individual system elements of the implantable device are electrically connected to one another as needed, which may be provided by a circuit board and / or wires, such as microgold wires (not shown).

[0129] Preferred features of this embodiment are as already set out in the specification above.

[0130] A further aspect of the present disclosure is 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, such as glucose, in tissue and / or body fluid of a body part, and attachment means for permanently holding the housing to the body part, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; -Power supply and and optionally at least one status indicator.

[0131] This aspect also relates to a method of determining a physiological parameter, such as glucose, in a body fluid and / or tissue of a body part using a continuous monitoring device as described above.

[0132] In certain embodiments, the continuous monitoring device measures glucose in subcutaneous adipose tissue and / or adjacent blood vessels, such as capillaries.

[0133] FIG. 23 illustrates an embodiment of a continuous monitoring system, e.g., a continuous glucose monitoring system. The system may be permanently worn externally on a body part, e.g., the upper arm or abdomen, for a period of at least one week (21). The system is adapted to perform continuous monitoring of a physiological parameter, such as glucose. In certain embodiments, the system is adapted to perform measurements at predetermined time intervals, which may be fixed or variable, as desired. For example, the time interval may range from about 1 minute to about 2 hours, or from about 5 minutes to about 1 hour, e.g., about 10 minutes. In certain embodiments, a user may select an appropriate time interval in the system's control unit.

[0134] The system may be held to the body part by attachment means (22), such as, for example, single-sided or double-sided adhesive tape. The attachment means may comprise one or more cutouts to allow system elements, such as, for example, the radiation source (38) and sensors (23, 35), access to the subject's skin. The connection between the system and the attachment means may be provided by a suitable locking means (37), such as a bayonet lock.

[0135] The continuous monitoring system includes an exterior housing 26. The housing 26 may be water-resistant or waterproof to protect the system components from exposure to water. The housing may be made from a physiologically compatible material, such as a physiologically compatible metal, plastic, glass, or composite material. In certain embodiments, the housing completely encloses the system.

[0136] The system includes at least one radiation source (38) adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, to tissue (39) of the body part (21). In certain embodiments, the system includes multiple radiation sources (38), for example, two, three, four, or five radiation sources.

[0137] The system of FIG. 23 includes a sensing unit including at least one sensor (35), e.g., an optical and / or calorimetric sensor, for detecting emitted IR radiation from a previously irradiated body part in the range of about 5 μm to about 12 μm, as described herein. The sensing unit is adapted to (i) detect IR radiation of at least one wavelength or wavelength range, the intensity of which depends on the concentration of a physiological parameter in the irradiated body part (21), and (ii) detect IR radiation having at least one wavelength or wavelength range, the intensity of which is substantially independent of the concentration of a physiological parameter in the body fluids and / or tissues (39) of the irradiated body part (21). In certain embodiments, the system includes multiple sensors (35), e.g., two, three, four, or five sensors. The sensor (35) may include an optical filter element (36) adapted to detect IR radiation having a desired wavelength or wavelength range. In certain embodiments, the system further includes a sensor (23) adapted for direct contact with the subject's skin. The sensor 23 may be a contact temperature sensor and may be mounted on a circuit board 24.

[0138] The system of FIG. 23 also includes a control unit, particularly a highly integrated microcontroller, e.g., an ASIC. The control unit may be attached to a circuit board (33), which is attached to the circuit board (24) by a rigid or flexible connecting element (25). The control unit is adapted to control the measurement procedure. In certain embodiments, the control unit is further adapted to analyze the measurement results by qualitative and / or quantitative determination of physiological parameters based on the measurement results. In certain embodiments, the control unit includes communication means for communicating with an external device (not shown), such as, for example, a smartphone or a smartwatch. The communication means may be adapted to transmit signals to and / or receive signals from the external device, e.g., signals including the measurement results and / or determination results and / or signals including an identification code. In certain embodiments, the system includes communication means (28, 31), such as, for example, a Bluetooth antenna (28) and / or an RFID antenna (31).

[0139] The system of FIG. 23 further comprises a power source. In certain embodiments, the system includes an internal power source that is rechargeable from an external power source. The power source may comprise a battery (34), such as a disposable or rechargeable battery. In certain embodiments, the battery is rechargeable wirelessly, such as by capacitive charging using a charging coil (32). Additionally, the power source may include a capacitor (27), such as a supercapacitor or ultracapacitor, as a short-term power reservoir to provide power during power bursts when the radiation source (38) is activated. In certain embodiments, the power source may also include a power harvesting device, such as a micro-energy harvesting device, adapted to convert mechanical energy into electrical energy.

[0140] In certain embodiments, the system includes at least one status indicator adapted to inform the wearer whether the determined parameter is inside or outside a physiologically acceptable range, in particular whether the glucose concentration is within the normoglycemic range or at a hypoglycemic or hyperglycemic level. The status indicator may also be adapted to alert the wearer to a malfunction of the device caused, for example, by a power outage. In certain embodiments, the device may comprise an optical status indicator (29), for example a multicolored LED, an acoustic status indicator (30), for example a piezoelectric speaker element, and / or a tactile status indicator (not shown), for example a vibrator.

[0141] The individual system elements of the implantable device are electrically connected to one another as needed, which may be provided by a circuit board and / or wires, such as microgold wires (not shown).

[0142] Preferred features of this embodiment are as already set out in the specification above.

[0143] A further aspect of the present disclosure is a portable smart device, e.g., a smartphone, comprising: an outer casing having a front and a rear surface, the front surface comprising a screen and a keypad and the rear surface comprising a recess for receiving a body part, for example a fingertip, the outer casing comprising a non-invasive system for determining physiological parameters such as glucose in body fluids and / or tissue of a body part integrated into the recess on the front and rear surface, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for controlling the measurement procedure and, optionally, for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit; and optionally at least one status indicator.

[0144] This aspect also includes a method of determining a physiological parameter, such as glucose in a body fluid and / or tissue of a body part, using the smart device described above.

[0145] FIG. 24 shows a further embodiment of the present disclosure, which is a portable smart device, e.g., a smartphone, with a front face (not shown) and a back face. The front face includes a screen and a keypad. The back face incorporates a system for determining physiological parameters, such as glucose, in fluids and / or tissues of a body part. Integrating the system into the back face of the device has certain advantages: it does not interfere with the display function of the screen; and there is no energy loss, as radiation does not need to penetrate the screen. Furthermore, measurements can be performed while operating the keypad on the front face.

[0146] The device shown in Figure 24 includes a recess on the back for receiving a body part, e.g., a fingertip. The recess includes at least one radiation source adapted to emit visible (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 the tissue of the body part. In certain embodiments, the system includes multiple radiation sources, e.g., two, three, four, or five radiation sources. In Figure 24, the device has two radiation sources, i.e., two small holes shown in the recess.

[0147] The system of FIG. 24 includes a sensing unit including at least one sensor, e.g., an optical and / or calorimetric sensor, for detecting IR radiation emitted from a previously irradiated body part in the range of about 5 μm to about 12 μm, as described herein. The sensing unit is adapted to (i) detect IR radiation of at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in the irradiated body part (5), and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in the tissue of the irradiated body part. In certain embodiments, the system includes multiple sensors, e.g., two, three, four, or five sensors. In FIG. 24, the device has three sensors, i.e., three large holes shown in the recesses. Two of the sensors are dual sensor chips, as described in FIG. 20. The sensors may include optical filter elements adapted to detect IR radiation having a desired wavelength or wavelength range.

[0148] Below the recess are shown the electrical connections to the control and / or power supply unit of the smart device.

[0149] Preferred features of this embodiment are as already set out in the specification above.

[0150] Certain aspects and embodiments of the present disclosure are described below as part of this specification, and these embodiments refer in particular to the aspects set forth in the appended claims.

[0151] Embodiments of the specification 1. A non-invasive system for determining a physiological parameter in a body fluid of a subject, comprising: (a) a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, to a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) a sensing unit for detecting IR radiation emitted from the previously irradiated body part of the subject in a range of about 5 μm to about 12 μm, the sensing unit (i) detecting IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject; Detecting, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and wherein the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) a sensing unit adapted to detect IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in a body fluid of the subject; (c) an analysis or control unit for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit (b); Non-invasive systems, including:

[0152] 2. The system of embodiment 1, wherein the system does not include a radiation source for emitting IR radiation in the wavelength range of about 5 μm to about 12 μm.

[0153] 3. The system according to 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 μm to about 12 μm, in particular in the range of about 8 μm to about 10 μm.

[0154] 4. A system according to any one of embodiments 1 to 3, wherein the physiological parameter is glucose.

[0155] 5. The system of any one of embodiments 1 to 4, wherein the bodily fluid is blood.

[0156] 6. The system of any one of embodiments 1 to 5, adapted to determine glucose in blood, wherein the sensing unit is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose in the subject's blood, and wherein the at least one wavelength or wavelength range is specifically selected from a wavelength of about 9.2 μm, a wavelength of about 9.4 μm, a wavelength of about 9.6 μm, a wavelength range comprising at least two of the wavelengths of about 9.2 μm, about 9.4 μm, and about 9.6 μm, a wavelength range comprising all three of the wavelengths of about 9.2 μm, about 9.4 μm, and about 9.6 μm, or any combination thereof.

[0157] 7. The system of any one of embodiments 1 to 6, adapted to determine glucose in blood, wherein the sensing unit is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose in the subject's blood, and wherein the at least one wavelength or wavelength range is specifically selected from a wavelength or wavelength range of about 8.7 μm to about 9.0 μm, a wavelength or wavelength range of about 9.7 μm to about 10.2 μm, or any combination thereof.

[0158] 8. The system of any one of embodiments 1 to 7, comprising a single radiation source (a).

[0159] 9. The system according to any one of the preceding claims, comprising a plurality of radiation sources (a), such as 2, 3, 4 or more, such as up to 10 individual radiation sources (a).

[0160] 10. The system according to any one of the preceding claims, wherein the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 400 nm to about 1200 nm, in particular in the range of about 550 nm to about 1100 nm, in particular in the range of about 800 nm to about 820 nm, such as about 810 nm, and / or in the range of about 590 nm to about 660 nm, for example about 600 nm, and / or in the range of about 920 nm to about 980 nm, for example about 940 nm.

[0161] 11. The system of any one of embodiments 1 to 10, wherein the radiation source (a) is adapted to emit collimated radiation and / or adapted to emit non-collimated radiation.

[0162] 12. A system according to any one of the preceding embodiments, wherein the radiation source (a) is an LED, a laser diode, a vcsel (vertical cavity surface emitting laser) or a laser.

[0163] 13. The system of any one of embodiments 1 to 12, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently over a predetermined time interval.

[0164] 14. The system according to any one of the preceding claims, wherein the radiation source (a) is adapted to emit VIS / NIR radiation to obtain a local increase in temperature in the irradiated body part, in particular in an absorption area within the irradiated body part, in the range of about 2°C to about 10°C, in particular in the range of about 3°C ​​to about 5°C.

[0165] 15. The system according to embodiment 13 or 14, wherein the radiation source (a) is adapted to continuously emit VIS / NIR radiation at a power of about 10 mW to about 1 W, in particular about 20 mW to about 500 mW, more in particular about 50 mW to about 250 mW.

[0166] 16. The system according to embodiment 13, 14 or 15, wherein the radiation source (a) is adapted to continuously emit VIS / NIR radiation at a time interval of about 0.1 seconds to 20 seconds, particularly about 1 second to about 5 seconds, more particularly about 0.5 seconds to about 2 seconds.

[0167] 17. The system according to embodiment 13 or 14, wherein the radiation source (a) is adapted to intermittently emit VIS / NIR radiation at a power of about 10 mW to about 5 W, particularly about 20 mW to about 1 W, more particularly about 50 mW to about 500 mW.

[0168] 18. The system according to embodiment 13, 14 or 17, wherein the radiation source (a) is adapted to emit VIS / NIR radiation intermittently at a time interval of from about 0.1 seconds to about 20 seconds, particularly from about 0.2 seconds to about 5 seconds, more particularly from about 0.5 seconds to about 2 seconds.

[0169] 19. The system of embodiment 13, 14, 17 or 18, wherein the radiation source (a) is adapted to intermittently emit VIS / NIR radiation at a pulse frequency of about 1 Hz to about 1 MHz.

[0170] 20. The system of any one of embodiments 1 to 19, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently over a period of at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0171] 21. The system according to any one of embodiments 1 to 20, wherein the radiation source (a) is a multi-wavelength radiation source, in particular 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 from about 400 nm to about 1200 nm, more particularly from about 450 nm to about 900 nm, for example 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.

[0172] 22. A system according to any one of the preceding embodiments, wherein the radiation source (a) and the sensing unit (b) are positioned at a position defined by an angle of at least 90° or more relative to the irradiated body part.

[0173] 23. A system according to any one of the preceding embodiments, wherein the radiation source (a) is provided on a side of the body part opposite the sensing unit (b).

[0174] 24. A system according to any one of the preceding embodiments, wherein at least one radiation source (a) is provided on the side of the body part, allowing radiation to be emitted directly to the body part without passing through part of the system.

[0175] 25. A system according to any one of the preceding claims, wherein at least one radiation source (a) is provided on the side of a body part that allows radiation to be emitted directly to the body part without passing through a keratinized part of the body surface, for example, a fingernail.

[0176] 26. A system according to any one of embodiments 1 to 25, wherein the sensing unit (b) is adapted to detect self-emitted IR radiation from a previously irradiated body part.

[0177] 27. The system of any one of embodiments 1 to 26, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an absorbing region within the previously irradiated body part, the absorbing region having a locally elevated temperature and exhibiting an increased emission of IR radiation in the wavelength range of about 5 μm to about 12 μm.

[0178] 28. The sensing unit (b) comprises at least one first sensor, at least one second sensor, and optionally at least one third sensor; at least one first sensor adapted to detect IR radiation having at least one wavelength or range of wavelengths, wherein an intensity of the detected IR radiation depends on a concentration of a physiological parameter in a body fluid of the subject; at least one second sensor adapted to detect IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in the subject's body fluid; 28. The system of any one of embodiments 1 to 27, wherein the at least one third sensor, if present, is (i) adapted to detect non-specific IR radiation, (ii) adapted to detect non-specific VIS / NIR radiation, (iii) adapted to detect VIS / NIR radiation having a wavelength, the intensity of the detected VIS / NIR radiation depending on the concentration of a physiological parameter in the subject's body fluid, and / or (iv) a temperature sensor for measuring the temperature of a body part.

[0179] 29. The system of embodiment 28, wherein the at least one first sensor and the at least one second sensor each comprise a filter element and optionally a lens element that are optically transparent at a predetermined wavelength or wavelength range.

[0180] 30. The system of embodiment 28 or 29, comprising at least two different first sensors adapted to detect IR radiation having at least two different wavelengths or wavelength ranges.

[0181] 31. The system of embodiment 28, 29, or 30, wherein at least one first sensor is adapted to detect IR radiation having a first wavelength or wavelength range, and at least one other first sensor is adapted to detect IR radiation having a second wavelength range, the second wavelength range encompassing the first wavelength or wavelength range and further including another wavelength or wavelength range.

[0182] 32. The system of embodiment 31 for determining glucose in blood, wherein a first sensor is adapted to detect IR radiation having a wavelength of about 9.2 μm, and another first sensor is adapted to detect IR radiation having a wavelength range of about 9.2 μm to about 9.6 μm.

[0183] 33. The system of embodiment 31 for determining glucose in blood, wherein a first sensor is adapted to detect IR radiation having a wavelength of about 9.4 μm and another first sensor is adapted to detect IR radiation having a wavelength range of about 9.6 μm to about 9.6 μm.

[0184] 34. A system according to any one of embodiments 28 to 33, comprising at least two different second sensors adapted to detect IR radiation having at least two different wavelengths or wavelength ranges.

[0185] 35. The system of embodiment 33 for determining glucose in blood, wherein a second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 8.6 μm to 9.0 μm, and another second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 9.8 μm to about 10.2 μm.

[0186] 36. A system for determining glucose in blood described in any one of embodiments 28 to 33, wherein the second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 7.8 μm to about 8.2 μm, and optionally at least one further second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 8.6 μm to 9.0 μm and / or to detect IR radiation having a wavelength or wavelength range of about 9.8 μm to about 10.2 μm.

[0187] 37. A system described in any one of embodiments 28 to 36 for determining glucose in blood, comprising at least one third sensor adapted to detect VIS / NIR radiation, in particular VIS / NIR radiation having a wavelength of approximately 940 nm.

[0188] 38. The sensing unit (b) comprises at least one sensor adapted to time-dependently and separately detect IR radiation having different wavelengths or wavelength ranges; During at least one first time interval, the sensor is adapted to detect IR radiation having at least one wavelength or range of wavelengths, wherein an intensity of the detected IR radiation depends on a concentration of a physiological parameter in a body fluid of the subject; 38. The system of any one of embodiments 1 to 37, wherein, during at least one second time interval, the sensor is adapted to detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in the subject's body fluid.

[0189] 39. The system of embodiment 38, wherein the sensing unit (b) comprises at least one sensor equipped with a plurality of filters adapted to transmit IR radiation having different wavelengths or wavelength ranges.

[0190] 40. A system according to embodiment 38 or 39, wherein the sensor comprises a shutter wheel and / or a filter wheel.

[0191] 41. The system of embodiment 40, wherein the shutter wheel comprises a plurality of apertures, at least some of which comprise filter elements and optionally lens elements that are optically transparent at a predetermined wavelength or range of wavelengths.

[0192] 42. The system of embodiment 38, wherein the sensing unit (b) comprises at least one sensor that is a Fabry-Perot interferometer.

[0193] 43. A system according to any one of embodiments 1 to 42, wherein the sensing unit (b) comprises at least one spectral or line sensor or a spectral or line sensor array.

[0194] 44. The system of any one of embodiments 38 to 42, wherein the sensing unit (b) comprises a single sensor.

[0195] 45. The system of any one of embodiments 1 to 44, wherein the sensing unit (b) comprises at least one sensor that is a photodetector, in particular a photovoltaic detector, more particularly an InAsSb-based detector.

[0196] 46. ​​A system according to any one of embodiments 1 to 45, wherein the sensing unit (b) comprises at least one sensor that is a thermopile or a bolometer.

[0197] 47. A system described in any one of embodiments 1 to 46, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a period of time, the body part being irradiated by VIS / NIR radiation during at least a portion of said period of time.

[0198] 48. The system of any one of embodiments 1 to 47, wherein the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part over a period of time, and wherein during at least a portion of said period, the temperature of the irradiated body part, particularly the absorbing regions, is higher than the surrounding tissue.

[0199] 49. The system according to claim 48, wherein the temperature of the irradiated body part, in particular the absorbing 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.

[0200] 50. A system according to any one of the preceding embodiments, wherein the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part for a period of time, and during at least part of said period, the temperature of the irradiated body part, in particular the absorbing region, is increased.

[0201] 51. A system according to any one of the preceding embodiments, wherein the temperature is increased in the range of about 2°C to about 10°C, in particular in the range of about 3°C ​​to about 5°C.

[0202] 52. A system described in any one of embodiments 47 to 51, wherein the period is at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0203] 53. The system of any one of embodiments 1 to 52, wherein the sensing unit (b) is further adapted for temperature measurement, for example, with an accuracy of at least about 1°C, at least about 0.1°C, or at least about 0.01°C.

[0204] 54. A system described in any one of embodiments 1 to 53, wherein the sensing unit (b) is adapted to measure and optionally monitor the temperature of the skin of the irradiated body part, and optionally at least one further temperature, such as the environmental temperature, the temperature of an individual sensor within the sensing unit (b), and / or the temperature of an electronic component of the sensing unit (b).

[0205] 55. A system according to any one of embodiments 1 to 54, wherein the sensing unit (b) comprises at least one temperature sensor, in particular a plurality of temperature sensors, e.g. two, three or four temperature sensors for measuring the temperature of the skin, and optionally at least one further temperature sensor, e.g. a sensor for measuring the ambient temperature, at least one sensor for measuring the temperature of individual sensors in the sensing unit, and / or a sensor for measuring the temperature of electronic components of the sensing unit, e.g. the temperature of a circuit board of the sensing unit (b).

[0206] 56. The system of any one of embodiments 1 to 55, wherein the analysis unit (c) comprises a microcontroller adapted for quantitatively determining the concentration of the physiological parameter and / or for non-quantitatively determining the rate of change of the physiological parameter.

[0207] 57. A system according to any one of the preceding embodiments, wherein the analysis unit (c) is adapted for time-dependent analysis of the detected IR radiation, and the measurement signal is recorded over a period of time.

[0208] 58. The system of embodiment 57, wherein the period is at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0209] 59. The system of any one of embodiments 1 to 58, wherein the analysis unit (c) is adapted for temperature-compensated analysis of the detected IR radiation.

[0210] 60. The system of embodiment 59, wherein the temperature compensation analysis includes temperature compensation in which the measurement signal is corrected for temperature.

[0211] 61. A system described in embodiment 59 or 60, wherein temperature compensation is based on the temperature of the skin of the irradiated body part and, optionally, at least one further temperature, such as the environmental temperature, the temperature of a component of the sensing unit, e.g., the temperature of an individual sensor within the sensing unit, and / or the temperature of an electronic component of the sensing unit.

[0212] 62. The system of any one of embodiments 57 to 61, wherein the analysis unit (c) is adapted for time-dependent and temperature-compensated analysis of the detected IR radiation.

[0213] 63. A system described in any one of embodiments 1 to 62, adapted to detect IR radiation from a body part selected from a fingertip, an earlobe, a wrist, a forearm, a palm, and an upper arm.

[0214] 64. A system according to any one of embodiments 1 to 63, wherein the radiation source (a) and the sensing unit (b) are positioned on the same side of the body part.

[0215] 65. A system according to any one of the preceding embodiments, wherein the radiation source (a) and the sensing unit (b) are positioned on different sides, in particular on opposite sides, of the body part.

[0216] 66. A system according to any one of the preceding embodiments, wherein the first radiation source (a) is arranged on the same side of the body part as the sensing unit (b), and the further radiation source (a) is arranged on a different side, in particular on the opposite side of the body part from the sensing unit.

[0217] 67. The system of any one of embodiments 1 to 66, further comprising a cover, said cover being at least partially made of a material that is optically transparent to the VIS / NIR radiation emitted by the radiation source (a) and / or the IR radiation detected by the sensing unit (b).

[0218] 68. The system of embodiment 67, wherein the cover is made at least in part of CaF2 and / or BaF2, and / or a plastic material that is transparent to IR radiation and optionally transparent to VIS / NIR radiation.

[0219] 69. 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 about 0.5 mm to about 1.5 mm, and more particularly about 1 mm.

[0220] 70. The system of any one of embodiments 1 to 69, further comprising a cover, said cover being at least partially made of a material that is optically transparent to IR radiation detected by the sensing unit, particularly in the IR wavelength range between about 5 μm and about 12 μm or a subrange thereof, and said material is optionally substantially optically opaque to VIS / NIR radiation emitted by radiation source (a).

[0221] 71. A system according to any one of the preceding embodiments, further comprising a cover for focusing IR radiation from the body part onto the sensing unit (b), in particular onto at least one sensor of the sensing unit (b).

[0222] 72. The system of embodiment 71, wherein the cover comprises an IR Fresnel lens or an array comprising multiple IR Fresnel lenses.

[0223] 73. Use of a system according to any one of embodiments 1 to 72 for non-invasively determining physiological parameters in the body fluids of a subject.

[0224] 74. The use according to embodiment 73, wherein the physiological parameter is glucose and the body fluid is blood.

[0225] 75. The use according to embodiment 73 or 74, wherein the physiological parameter is determined quantitatively.

[0226] 76. The use according to embodiment 73, 74 or 75, wherein the rate of change of the physiological parameter is determined non-quantitatively.

[0227] 77. A method for non-invasively determining a physiological parameter in a body fluid of a subject, comprising: (a) irradiating a body part of the subject with visible (VIS) / near-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 an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting IR radiation emitted from the previously irradiated body part of the subject in a wavelength range of about 5 μm to about 12 μm; (i) detecting IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject; Detecting, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and wherein the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the subject's bodily fluid; and (c) analyzing the detected IR radiation for qualitative and / or quantitative determination of the physiological parameter.

[0228] 78. The method of embodiment 77, wherein the body part is not irradiated with an IR radiation source in the wavelength range of about 5 μm to about 12 μm.

[0229] 79. The method of embodiment 77 or 78, wherein the physiological parameter is glucose and the body fluid is blood.

[0230] 80. The method of embodiment 77, 78 or 79, wherein the physiological parameter is determined quantitatively.

[0231] 81. The method of any one of embodiments 77 to 80, wherein the rate of change of the physiological parameter is determined non-quantitatively.

[0232] 82. A device comprising a non-invasive system for determining a physiological parameter of a body fluid of a subject, the device comprising: a casing; (a) a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm to a body part of the subject, wherein the body part is particularly selected from a fingertip, fingertips, and a palm, and the radiation source is further adapted such that the irradiated body part absorbs electromagnetic energy resulting in an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) a sensing unit for detecting IR radiation emitted from the previously IR-irradiated body part of the subject in a range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation depends on the concentration of a physiological parameter in the subject's body fluid, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the subject's body fluid; (c) an analysis unit for qualitative and / or quantitative determination of physiological parameters based on the IR radiation detected by the sensing unit (b); the casing comprises a first surface comprising a screen, the screen being at least partially made from a material that is optically transparent to the NIR / VIS radiation emitted by the radiation source (a) and the IR radiation detected by the sensing unit (b); The radiation source (a), the sensing unit (b) and the analysis unit (c) are housed within a casing.

[0233] 83. The apparatus of embodiment 82, wherein the radiation source (a) is adapted to emit radiation through the screen.

[0234] 84. The device of embodiment 82 or 83, wherein the sensing unit (b) is adapted to detect radiation entering the casing through the screen.

[0235] 85. The screen is approximately 1 cm 2 ~about 500cm 2 , especially about 2 cm 2 ~about 200cm 2 85. The device according to any one of embodiments 82 to 84, having a size of

[0236] 86. A device described in any one of embodiments 82 to 85, wherein the screen is substantially planar.

[0237] 87. A device described in any one of embodiments 82 to 86, adapted to display the contact position of the body part on a screen.

[0238] 88. The apparatus of any one of embodiments 82 to 87, which is a mobile device.

[0239] 89. The device described in any one of embodiments 82 to 88, selected from a smartphone, a smartwatch, a tablet, and a fitness tracker device.

[0240] 90. A device according to any one of embodiments 82 to 89, wherein the optically transparent material is selected from inorganic materials such as CaF2 and / or BaF2 and organic materials such as plastic materials.

[0241] 91. A device according to any one of embodiments 82 to 90, wherein the optically transparent material has a thickness of about 0.2 mm to about 2 mm, in particular about 0.3 mm to about 1 mm.

[0242] 92. The device of any one of embodiments 82 to 91, which does not include a radiation source for emitting IR radiation in the wavelength range of about 5 μm to about 12 μm.

[0243] 93. A device according to any one of embodiments 82 to 92, wherein the physiological parameter is glucose and the body fluid is glucose.

[0244] 94. The device of any one of embodiments 82 to 93, adapted to determine glucose in blood, wherein the sensing unit is adapted to detect IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation depending on the concentration of glucose in the subject's blood, and wherein the at least one wavelength or wavelength range is specifically selected from a wavelength of about 9.2 μm, a wavelength of about 9.4 μm, a wavelength of about 9.6 μm, a wavelength range comprising at least two of the wavelengths of about 9.2 μm, about 9.4 μm and about 9.6 μm, a wavelength range comprising wavelengths of about 9.2 μm, about 9.4 μm and about 9.6 μm, or any combination thereof.

[0245] 95. The device according to any one of embodiments 82 to 94, wherein the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 550 nm to about 1200 nm, in particular in the range of about 800 nm to about 820 nm, for example about 810 nm, and / or in the range of about 590 nm to about 610 nm, for example about 600 nm, and / or in the range of about 920 nm to about 980 nm, for example about 940 nm.

[0246] 96. An apparatus according to any one of embodiments 82 to 95, wherein the radiation source (a) is an LED, a laser diode, a vcsel (vertical cavity surface emitting laser) or a laser.

[0247] 97. An apparatus comprising: 97. The apparatus of any one of embodiments 82 to 96, wherein the radiation source (a) is a multi-wavelength radiation source.

[0248] 98. An apparatus according to any one of embodiments 82 to 97, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently for a period of at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, more particularly at least about 2 seconds to about 20 seconds.

[0249] 99. At least one first sensor is adapted to detect IR radiation having a first wavelength or wavelength range, and at least one other first sensor is adapted to detect IR radiation having a second wavelength range; the second wavelength range includes the first wavelength or wavelength range and further includes another wavelength or wavelength range; 99. The device of any one of embodiments 82 to 98, wherein the system is particularly adapted to determine glucose in blood, and wherein the first sensor is adapted to detect IR radiation having a wavelength of about 9.2 μm, and another first sensor is adapted to detect IR radiation having a wavelength range of about 9.2 μm to about 9.6 μm, including a first wavelength of about 9.2 μm, and further including at least one wavelength of about 9.4 μm and about 9.6 μm, and particularly further including wavelengths of about 9.4 μm and about 9.6 μm.

[0250] 100. A method of detecting IR radiation comprising: providing at least two different second sensors adapted to detect IR radiation having at least two different wavelengths or wavelength ranges; An apparatus described in any one of embodiments 82 to 99, wherein the system is particularly adapted to determine glucose in blood, and wherein the second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 8.6 μm to 9.0 μm, and another second sensor is adapted to detect IR radiation having a wavelength or wavelength range of about 9.8 μm to about 10.2 μm.

[0251] 101. The sensing unit (b) comprises at least one sensor adapted to time-dependently and separately detect IR radiation having different wavelengths or wavelength ranges; During at least one first time interval, the sensor is adapted to detect IR radiation having at least one wavelength or range of wavelengths, wherein an intensity of the detected IR radiation depends on a concentration of a physiological parameter in a body fluid of the subject; An apparatus described in any one of embodiments 82 to 100, wherein during at least one second time interval, the sensor is adapted to detect IR radiation having at least one wavelength or wavelength range in which the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter in the subject's body fluid.

[0252] 102. The device of any one of embodiments 82 to 101, wherein the sensing unit (b) comprises a single sensor.

[0253] 103. The device according to any one of embodiments 82 to 102, wherein the sensing unit (b) comprises at least one sensor that is a photodetector, in particular a photovoltaic detector, more particularly an InAsSb-based detector.

[0254] 104. Further comprising a lens element adapted to focus IR radiation from the body part onto the sensing unit (b), in particular onto the at least one sensor of the sensing unit (b); An apparatus according to any one of embodiments 82 to 103, wherein the lens element is incorporated within the casing, and in particular the lens element comprises an IR Fresnel lens or an array comprising a plurality of IR Fresnel lenses.

[0255] 105. An apparatus according to any one of embodiments 82 to 104, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a period of time, the body part being irradiated by VIS / NIR radiation during at least a portion of said period of time.

[0256] 106. A device according to any one of embodiments 82 to 105, wherein the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part over a period of time, and during at least a part of said period, the temperature of the irradiated body part, in particular the absorbing regions, is higher than the surrounding tissue.

[0257] 107. The device according to embodiment 106, wherein the temperature of the irradiated body part, in particular the absorbing 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.

[0258] 108. A device described in any one of embodiments 82 to 107, wherein the sensing unit (b) is adapted to detect IR radiation emitted from the irradiated body part for a period of time, and during at least part of said period, the temperature of the irradiated body part, in particular the absorbing area, increases.

[0259] 109. The device according to embodiment 108, wherein the temperature is increased in the range of about 2°C to about 10°C, in particular in the range of about 3°C ​​to about 5°C.

[0260] 110. A device according to any one of embodiments 102 to 109, wherein the period is at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, more particularly at least about 2 seconds to about 20 seconds.

[0261] 111. A device according to any one of embodiments 82 to 110, wherein the sensing unit (b) is further adapted for measuring temperature with an accuracy of, for example, at least about 1°C, at least about 0.1°C, or at least about 0.01°C.

[0262] 112. A device described in any one of embodiments 82 to 111, wherein the sensing unit (b) is adapted to measure and optionally monitor the temperature of the skin of the irradiated body part, and optionally at least one further temperature, such as the environmental temperature, the temperature of an individual sensor within the sensing unit (b), and / or the temperature of an electronic component of the sensing unit (b).

[0263] 113. A device described in any one of embodiments 82 to 112, wherein the sensing unit (b) comprises at least one temperature sensor, in particular a plurality of temperature sensors, for example two, three or four temperature sensors for measuring the temperature of the skin, and optionally at least one further temperature sensor, for example a sensor for measuring the ambient temperature, at least one sensor for measuring the temperature of individual sensors in the sensing unit, and / or a sensor for measuring the temperature of electronic components of the sensing unit, for example the temperature of a circuit board of the sensing unit (b).

[0264] 114. An apparatus according to any one of embodiments 82 to 113, wherein the analysis unit (c) comprises a microcontroller adapted for quantitatively determining the concentration of the physiological parameter and / or for non-quantitatively determining the rate of change of the physiological parameter.

[0265] 115. An apparatus according to any one of embodiments 81 to 114, wherein the analysis unit (c) is adapted for time-dependent analysis of the detected IR radiation, and the measurement signal is recorded over a period of time.

[0266] 116. The device of embodiment 115, wherein the period is at least about 0.5 seconds, particularly at least about 1 second to about 120 seconds, and more particularly at least about 2 seconds to about 20 seconds.

[0267] 117. An apparatus according to any one of embodiments 82 to 116, wherein the analysis unit (c) is adapted for temperature-compensated analysis of the detected IR radiation.

[0268] 118. The apparatus of embodiment 117, wherein the temperature compensation analysis includes temperature compensation in which the measurement signal is corrected for temperature.

[0269] 119. An apparatus as described in embodiment 117 or 118, wherein temperature compensation is based on the temperature of the skin of the irradiated body part and, optionally, at least one further temperature, such as the environmental temperature, the temperature of a component of the sensing unit, e.g., the temperature of an individual sensor within the sensing unit, and / or the temperature of an electronic component of the sensing unit.

[0270] 120. An apparatus according to any one of embodiments 82 to 119, wherein the analysis unit (c) is adapted for time-dependent and temperature-compensated analysis of the detected IR radiation.

[0271] 121. Use of a device described in any one of embodiments 82 to 120 for non-invasively determining a physiological parameter in a body fluid of a subject, wherein the physiological parameter is glucose, the body fluid is blood, and the rate of change of the amount of glucose in the blood is determined.

[0272] 122. A method for non-invasively determining a physiological parameter in a body fluid of a subject, comprising: (a) irradiating a body part of the subject with visible (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 an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting IR radiation emitted from the previously irradiated body part of the subject in a wavelength range of about 5 μm to about 12 μm; (i) detecting IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation depends on the concentration of a physiological parameter in a body fluid of the subject; Detecting, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and wherein the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the subject's bodily fluid; and (c) analyzing the detected IR radiation for qualitative and / or quantitative determination of the physiological parameter; The radiation source (a), the sensing unit (b) and the analyzing unit (c) are housed in a casing; The method, wherein the casing comprises a first surface comprising a screen, the screen being made at least in part of a material that is optically transparent to the NIR / VIS radiation emitted by the radiation source (a) and the IR radiation detected by the sensing unit (b).

[0273] 123. The method of embodiment 122, wherein the body part is not irradiated with IR radiation in the wavelength range of about 5 μm to about 12 μm.

[0274] 124. The method according to embodiment 122 or 123, wherein the physiological parameter is glucose and the body fluid is blood.

[0275] 125. The method according to any one of embodiments 122 to 124, wherein the concentration of a physiological parameter is quantitatively determined and / or the rate of change of a physiological parameter is determined, in particular non-quantitatively.

[0276] 126. A method according to any one of embodiments 122 to 125, wherein step (b) further comprises (iii) performing temperature measurements, and step (c) further comprises performing a temperature-compensated analysis of the detected IR radiation.

[0277] 127. A system described in any one of embodiments 1 to 72, or an apparatus described in any one of embodiments 82 to 120, wherein the sensing unit (b) comprises at least one sensor comprising multiple chips with different optical filter elements for detecting radiation of different wavelengths or wavelength ranges.

[0278] 128. A system described in any one of embodiments 1 to 72 or an apparatus described in any one of embodiments 82 to 120, which is a single unit including a radiation source (a), a sensing unit (b), and an analysis unit (c) in a single application-specific integrated circuit (ASIC).

[0279] 129. 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 tissue and / or bodily fluids of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit, the sensing unit is adapted to (i) separately detect first parameter-specific IR radiation having a first wavelength or wavelength range and second parameter-specific IR radiation having a second wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues, and wherein the intensity of the emitted IR radiation decreases as the concentration of glucose and / or ethanol increases and the intensity of the emitted IR radiation increases as the concentration of glucose and / or ethanol decreases; the first parameter-specific IR radiation has a wavelength of about 9.2 μm, and the second parameter-specific IR radiation includes a wavelength range of about 9.2 μm to about 9.6 μm; the sensing unit is further adapted to (ii) detect reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues; a control unit adapted for qualitative and / or quantitative determination of both glucose and ethanol based on IR radiation detected by the sensing unit.

[0280] 130. The reference IR radiation has a wavelength of about 8.8 μm or a wavelength range including a wavelength of about 8.8 μm, for example, a wavelength range of about 7.5 μm to about 9.0 μm; and / or An apparatus as described in embodiment 129, wherein the reference IR radiation has a wavelength of about 10.2 μm or a wavelength range including a wavelength of about 10.2 μm, for example, a wavelength range of about 9.7 μm to about 10.5 μm.

[0281] 131. A method for non-invasively determining ethanol or glucose and ethanol in a body fluid of a subject, comprising: (a) irradiating the subject's body part with visible (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 the electromagnetic energy, resulting in a local increase in tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting emitted IR radiation from the previously irradiated body part of the subject in a wavelength range of about 5 μm to about 12 μm; (i) separately detecting first parameter-specific IR radiation having a first wavelength or wavelength range and second parameter-specific IR radiation having a second wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of glucose and / or ethanol increases and the intensity of the emitted IR radiation increases as the concentration of glucose and / or ethanol decreases; the first parameter-specific IR radiation has a wavelength of about 9.2 μm, and the second parameter-specific IR radiation includes a wavelength range of about 9.2 μm to about 9.6 μm; (ii) detecting reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues; and (c) analyzing the detected IR radiation for a qualitative and / or quantitative determination of both glucose and ethanol.

[0282] 132. The reference IR radiation has a wavelength of about 8.8 μm or a wavelength range including a wavelength of about 8.8 μm, for example, a wavelength range of about 7.5 μm to about 9.0 μm; and / or 132. The method of embodiment 131, wherein the reference IR radiation has a wavelength of about 10.2 μm or a wavelength range including a wavelength of about 10.2 μm, for example, a wavelength range of about 9.7 μm to about 10.5 μm.

[0283] 133. A non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter such as glucose in a body fluid and / or tissue of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being dependent on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for qualitative and / or quantitative determination of a physiological parameter based on IR radiation detected by the sensing unit, A non-invasive monitoring device comprising: a control unit adapted to perform a measurement sequence consisting of a plurality of individual measurements.

[0284] 134. The device described in embodiment 133, wherein the control unit is adapted to monitor the temperature of the irradiated body part during the measurement procedure and to exclude from the judgment individual measurements made when the temperature of the body part.

[0285] 135. A method for non-invasively determining a physiological parameter, such as glucose, comprising: (a) irradiating a body part of the subject with visible (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 an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting IR radiation emitted from the previously irradiated body part of the subject in a wavelength range of about 5 μm to about 12 μm; (i) detecting parameter-specific IR radiation having at least one wavelength or range of wavelengths, the intensity of the detected IR radiation depending on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter of a body fluid and / or tissue of the subject; and (c) analyzing the detected IR radiation for qualitative and / or quantitative determination of the physiological parameter by a measurement sequence consisting of a plurality of individual measurements.

[0286] 136. The method according to embodiment 135, in which the temperature of the irradiated body part is monitored during the measurement procedure, and individual measurements made when the temperature of the body part is elevated are excluded from the determination.

[0287] 137. A non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter such as glucose in a body fluid and / or tissue of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy, resulting in a local increase in temperature and an increase in the emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in the range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being dependent on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of the detected IR radiation being substantially independent of the concentration of the physiological parameter in a body fluid and / or tissue of the subject; a control unit adapted for qualitative and / or quantitative determination of a physiological parameter based on IR radiation detected by the sensing unit, A non-invasive monitoring device comprising: a radiation source adapted to emit visible (VIS) / near infrared (NIR) radiation into the body for a predetermined irradiation period; and a control unit adapted to perform measurements of IR radiation emitted from the body part within a subsequent dissipation period.

[0288] 138. The apparatus of embodiment 137, wherein the sensing unit is adapted to perform measurements within a period of about 1 second, about 500 ms, or about 200 ms after the radiation source is shut off.

[0289] 139. A method for non-invasively determining a physiological parameter, such as glucose, comprising: (a) irradiating a body part of the subject with visible (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 an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting IR radiation emitted from the previously irradiated body part of the subject in a wavelength range of about 5 μm to about 12 μm; (i) detecting parameter-specific IR radiation having at least one wavelength or range of wavelengths, the intensity of the detected IR radiation depending on the concentration of a physiological parameter in a body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of a physiological parameter of a body fluid and / or tissue of the subject; and (c) analyzing the detected IR radiation for qualitative and / or quantitative determination of the physiological parameter; A method in which a radiation source emits visible (VIS) / near infrared (NIR) radiation into a body for a predetermined irradiation period, and measurements of IR radiation emitted from the body part are taken within a subsequent dissipation period.

[0290] 140. The method of embodiment 139, wherein the measurement is performed within a period of about 2 seconds, about 1.5 seconds, about 1 second, about 500 ms, or about 200 ms after the radiation source is shut off.

[0291] 141. An apparatus according to any one of the preceding embodiments, further comprising monitoring means, e.g., a photodiode, for detecting fluctuations in the radiation emitted by the radiation source, e.g., power fluctuations.

Claims

1. 1. An implantable device comprising: a system for determining a physiological parameter, such as glucose, in tissue and / or fluid of a body part, the system including an outer housing adapted for implantation that encloses the system; a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from said previously IR-irradiated body part of said subject in said range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of the physiological parameter in the body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for controlling the measuring procedure and optionally for the qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected by the sensing unit; Power supply and and optionally at least one status indicator.

2. 10. The implantable device of claim 1, which is a needle-free device.

3. 3. A method for determining physiological parameters such as glucose in body fluids and / or tissues of a body part using an implantable device according to claim 1 or 2.

4. A continuous monitoring device, for example a continuous glucose monitoring device, comprising:

1. A non-invasive system for determining a physiological parameter, such as glucose, in tissue and / or fluid of a body part, comprising: an outer housing enclosing said housing; and attachment means for permanently holding said housing to said body part, said system comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from said previously IR-irradiated body part of said subject in said range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of the physiological parameter in the body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for controlling the measuring procedure and optionally for the qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected by the sensing unit; Power supply and and optionally at least one status indicator.

5. A method for determining physiological parameters such as glucose of body fluids and / or tissues of a body part using a continuous monitoring device according to claim 4.

6. A portable smart device, such as a smartphone, an outer casing including a front and a rear surface, said front surface comprising a screen and a keypad, and said rear surface comprising a recess for receiving a body part, for example a fingertip, and an outer casing including a non-invasive system for determining physiological parameters, such as glucose, in body fluids and / or tissue of said body part integrated into said recess on said rear surface, said system comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from said previously IR-irradiated body part of said subject in a range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of the physiological parameter in the body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for controlling the measuring procedure and optionally for the qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected by the sensing unit; and optionally at least one status indicator.

7. A method for determining physiological parameters such as glucose of body fluids and / or tissues of a body part using a smart device according to claim 6.

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

9. 9. The system or method of claim 1, wherein the physiological parameter is glucose.

10. 10. A system or method according to any one of claims 1 to 9, wherein the control unit is adapted for a time-dependent analysis of the detected IR radiation, and measurement signals are recorded over a period of time, and / or the control unit is adapted for a time-dependent and temperature-compensated analysis of the detected IR radiation.

11. 1. A non-invasive device for determining ethanol, or for simultaneously determining ethanol and glucose, comprising: a non-invasive system for determining ethanol, or simultaneously determining ethanol and glucose, in tissue and / or bodily fluids of a subject, e.g., a human subject, the system comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; A sensing unit, the sensing unit is adapted to (i) separately detect first parameter-specific IR radiation having a first wavelength or wavelength range and second parameter-specific IR radiation having a second wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the body fluid and / or tissue of the subject, and wherein the intensity of the emitted IR radiation decreases as the concentration of glucose and / or ethanol increases and the intensity of the emitted IR radiation increases as the concentration of glucose and / or ethanol decreases; the first parameter-specific IR radiation has a wavelength of about 9.2 μm, and the second parameter-specific IR radiation includes a wavelength range of about 9.2 μm to about 9.6 μm; the sensing unit is further adapted to (ii) detect reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose and / or ethanol in the body fluid and / or tissue of the subject; The reference IR radiation has, in particular, a wavelength of about 8.8 μm or a wavelength range including a wavelength of about 8.8 μm, for example a wavelength range from about 7.5 μm to about 9.0 μm; and / or a sensing unit, wherein the reference IR radiation has, in particular, a wavelength of about 10.2 μm or a wavelength range including a wavelength of about 10.2 μm, for example, a wavelength range from about 9.7 μm to about 10.5 μm; a control unit adapted for the qualitative and / or quantitative determination of both glucose and ethanol based on the IR radiation detected by the sensing unit.

12. 1. A method for non-invasively determining ethanol, or glucose and ethanol, in a bodily fluid of a subject, comprising: (a) irradiating the subject's body part with visible (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 in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting emitted IR radiation from the previously irradiated body part of the subject in the wavelength range of about 5 μm to about 12 μm; (i) separately detecting first parameter-specific IR radiation having a first wavelength or wavelength range and second parameter-specific IR radiation having a second wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases as the concentration of glucose and / or ethanol increases and the intensity of the emitted IR radiation increases as the concentration of glucose and / or ethanol decreases; the first parameter-specific IR radiation has a wavelength of about 9.2 μm, and the second parameter-specific IR radiation includes a wavelength range of about 9.2 μm to about 9.6 μm; The reference IR radiation has, in particular, a wavelength of about 8.8 μm or a wavelength range including a wavelength of about 8.8 μm, for example a wavelength range of about 7.5 μm to about 9.0 μm; and / or Detecting, in particular, the reference IR radiation has a wavelength of about 10.2 μm or a wavelength range including a wavelength of about 10.2 μm, for example a wavelength range from about 9.7 μm to about 10.5 μm; and (ii) detecting reference IR radiation having at least one wavelength or range of wavelengths, wherein the intensity of the detected IR radiation is substantially independent of the concentration of glucose and / or ethanol in the body fluid and / or tissue of the subject; and (c) analyzing said detected IR radiation for said qualitative and / or quantitative determination of both glucose and ethanol.

13. 1. A non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter, such as glucose, in a body fluid and / or tissue of a subject, e.g., a human subject, said system comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from said previously IR-irradiated body part of said subject in a range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of which depends on the concentration of the physiological parameter in the body fluid of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of which of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for the qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected by the sensing unit, the control unit is adapted to perform a measurement sequence consisting of a plurality of individual measurements; A non-invasive monitoring device comprising: a control unit that is specifically adapted to monitor the temperature of the irradiated body part during the measurement procedure and to exclude from the determination individual measurements made at that temperature of the body part.

14. 1. A method for non-invasively determining a physiological parameter, such as glucose, comprising: (a) irradiating the subject's body part with visible (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 in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting emitted IR radiation from the previously irradiated body part of the subject in the wavelength range of about 5 μm to about 12 μm; (i) detecting parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of which is dependent on the concentration of the physiological parameter in the body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting reference IR radiation having at least one wavelength or wavelength range, the intensity of which is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the 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, and analyzing, wherein the temperature of the irradiated body part is specifically monitored during the measurement procedure, and individual measurements taken when the temperature of the body part increases are excluded from the determination.

15. 1. A non-invasive monitoring device for determining a physiological parameter, such as glucose, in tissue and / or body fluid of a subject, e.g., a human subject, comprising: an outer casing containing a non-invasive system for determining a physiological parameter, such as glucose, in a body fluid and / or tissue of a subject, e.g., a human subject, said system comprising: a radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm, or about 500 nm to about 1500 nm, onto a body part of the subject, wherein the irradiated body part absorbs electromagnetic energy resulting in a local increase in temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; a sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of said subject in said range of about 5 μm to about 12 μm, the sensing unit is adapted to (i) detect parameter-specific IR radiation having at least one wavelength or wavelength range, the intensity of which depends on the concentration of the physiological parameter in the body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter, and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter, and (ii) detect reference IR radiation having at least one wavelength or wavelength range, the intensity of which of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; a control unit adapted for the qualitative and / or quantitative determination of the physiological parameter based on the IR radiation detected by the sensing unit, The radiation source is adapted to emit visible (VIS) / near infrared (NIR) radiation into the body for a predetermined irradiation period, and the sensing unit is adapted to perform measurements of IR radiation emitted from the body part within a subsequent dissipation period; and a control unit, wherein the sensing unit is specifically adapted to perform measurements within a period of about 1 second, about 500 ms, or about 200 ms after the radiation source is shut off.

16. 1. A method for non-invasively determining a physiological parameter, such as glucose, comprising: (a) irradiating a body part of the subject with visible (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 an increase in local tissue temperature and an increase in emission of IR radiation in the wavelength range of about 5 μm to about 12 μm; (b) detecting IR radiation emitted from the previously irradiated body portion of the subject in the wavelength range of about 5 μm to about 12 μm; (i) detecting parameter-specific IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of the physiological parameter in the body fluid and / or tissue of the subject, wherein the intensity of the emitted IR radiation decreases with increasing concentration of the physiological parameter and the intensity of the emitted IR radiation increases with decreasing concentration of the physiological parameter; and (ii) detecting reference IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation is substantially independent of the concentration of the physiological parameter in the body fluid and / or tissue of the subject; (c) analyzing the detected IR radiation for the qualitative and / or quantitative determination of the physiological parameter; the radiation source emits visible (VIS) / near infrared (NIR) radiation into the body for a predetermined exposure period, and measurements of IR radiation emitted from the body part are taken within a subsequent dissipation period; The method, wherein the measurement is particularly performed within a period of about 2 seconds, about 1.5 seconds, about 1 second, about 500 ms, or about 200 ms after the radiation source is shut off.

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