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 a bodily fluid and / or tissue of a subject. In addition, the present disclosure relates to a method for determining a physiological parameter in a bodily fluid and / or tissue of a subject.

Description

Technical Field

[0001] This disclosure relates to highly integrated sensor devices, such as implantable devices, continuous monitoring devices, and portable smart devices, for determining physiological parameters in the body fluids and / or tissues of a subject. Furthermore, this disclosure relates to methods for determining physiological parameters in the body fluids and / or tissues of a subject. Background Technology

[0002] In 2016, approximately 415 million people had diabetes. By 2040, the number of people with diabetes is projected to increase to over 640 million. Because people with diabetes are at risk of complications such as blindness, kidney disease, heart disease, and stroke, it is necessary to manage the disease by closely monitoring blood glucose levels.

[0003] Currently, blood glucose determination primarily relies on invasive systems and methods, which involve collecting blood samples and subsequently testing them in vitro, or implanting sensors within the body to determine glucose levels. The drawback of these invasive systems and methods is that they are painful or inconvenient.

[0004] WO 2021 / 032629 and WO 2022 / 090503 disclose a non-invasive system for determining physiological parameters (particularly glucose) in the body fluids of a subject. This non-invasive system includes a radiation source suitable for emitting visible (VIS) / near-infrared (NIR) radiation onto 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 fluids, and (ii) 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 fluids); and an analysis unit for qualitatively and / or quantitatively determining the physiological parameter based on the IR radiation detected in the sensing unit. This system can be used to non-invasively determine physiological parameters such as glucose in the blood of a subject. In addition, methods for non-invasively determining physiological parameters (particularly glucose) in the body fluids of subjects have been disclosed. The contents of these documents are incorporated herein by reference in their entirety.

[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. Summary of the Invention

[0006] According to this disclosure, it is feasible to determine physiological parameters simply, rapidly, and reliably using non-invasive systems and methods. These systems and methods involve emitting 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 a subject (specifically a human subject) and detecting IR radiation in the range of about 5 µm to about 12 µm emitted from a previously irradiated body part of the subject. Surprisingly, the inventors have discovered that irradiating a body part with short-wavelength radiation and detecting long-wavelength radiation emitted from the irradiated body part allows for the determination of physiological parameters (such as glucose) in bodily fluids (such as blood).

[0007] According to the present invention, irradiation of a body part with VIS / NIR radiation causes energy absorption in a region of the irradiated body part. This energy absorption in the irradiated region, i.e., the absorption region, leads to an increase in local tissue temperature within the irradiated body part (specifically, in the absorption region), which again causes an increase in the emission of IR radiation from the irradiated body part (specifically, from the absorption region), including an increase in the emission of IR radiation ranging from about 5 µm to about 12 µm. Furthermore, due to the increase in local temperature in the irradiated absorption region, the IR radiation emitted from the absorption region is far removed from the corresponding IR absorption maximum of molecules with physiological parameters (e.g., glucose molecules). Therefore, the detection of IR radiation emitted from the irradiated body part is facilitated and significantly improved.

[0008] The first aspect of this disclosure is an implantable device comprising:

[0009] - An implantable outer shell that surrounds a system for determining physiological parameters, such as glucose, in tissues and / or body fluids of a subject, such as a human subject, the system comprising:

[0010] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0011] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0012] 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues.

[0013] - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0014] - Power supply, and

[0015] - Optionally, at least one status indicator.

[0016] This also includes a method for determining physiological parameters, such as glucose, in body fluids and / or tissues of a body site using an implantable device as described above.

[0017] Another aspect of this disclosure is a non-invasive continuous monitoring device, such as a continuous glucose monitoring device, comprising:

[0018] - An outer housing surrounding a non-invasive system and an attachment device, the non-invasive system for determining physiological parameters, such as glucose, in tissues and / or bodily fluids of a body part of a subject, such as a human subject, and the attachment device for permanently retaining the housing to the body part, the system comprising:

[0019] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0020] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0021] 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues.

[0022] - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0023] - Power supply, and

[0024] - Optionally, at least one status indicator.

[0025] This also includes a method for determining physiological parameters, such as glucose, in body fluids and / or tissues of a body part using a continuous monitoring device as described above.

[0026] Another aspect of this disclosure is a portable smart device, such as a smartphone, comprising:

[0027] - A housing comprising a front and a back, wherein the front includes a screen and a keyboard and the back includes a recess for accommodating a body part, such as a fingertip, of a subject, such as a human subject, and the housing includes a non-invasive system integrated into the recess on the back, the non-invasive system being used to determine physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part, the system comprising:

[0028] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0029] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0030] 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 within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range is substantially independent of the concentration of a physiological parameter in the subject's body fluids and / or tissues.

[0031] - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0032] - Optionally, at least one status indicator.

[0033] This also includes a method for determining physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part using the smart device described above.

[0034] Another aspect of this disclosure is a non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose, comprising:

[0035] - An outer housing surrounding a non-invasive system for determining ethanol in the tissues and / or body fluids of a subject, such as a human subject, or simultaneously determining ethanol and glucose in the tissues and / or body fluids of a subject, such as a human subject, the system comprising:

[0036] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0037] - Sensing unit

[0038] The sensing unit is adapted to (i) detect IR radiation with a first parameter specific having a first wavelength or a first wavelength range and IR radiation with a second parameter specific having a second wavelength or a second wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the body fluids and / or tissues 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.

[0039] The first parameter-specific IR radiation has a wavelength of approximately 9.2 µm, and the second parameter-specific IR radiation includes a wavelength range from approximately 9.2 µm to approximately 9.6 µm.

[0040] The sensing unit is also adapted to (ii) detect 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 glucose and / or ethanol in the subject's body fluids and / or tissues, and

[0041] - A control unit adapted to qualitatively and / or quantitatively determine both glucose and ethanol based on IR radiation detected in the sensing unit.

[0042] This aspect of the disclosure relates to the detection of ethanol in the tissues and / or bodily fluids of a subject (specifically, in the blood of a human subject) and the combined detection of ethanol and glucose. This is achieved by detecting a first parameter-specific IR radiation and a second parameter-specific IR radiation having a wavelength of about 9.2 µm and excluding wavelengths of about 9.4 µm and excluding wavelengths of about 9.6 µm, and the second parameter-specific IR radiation including a wavelength range from about 9.2 µm to about 9.6 µm. Due to the characteristic variation in the signal ratio between the first parameter-specific IR radiation at a wavelength of about 9.2 µm and the second parameter-specific IR radiation including a wavelength of about 9.4 µm, the separate determination of ethanol may optionally be made together with glucose.

[0043] In this regard, the reference IR radiation may be determined at a wavelength of about 8.8 µm or in a first wavelength range including about 8.8 µm, such as in a wavelength range between about 7.5 µm and about 9.0 µm, and / or in a second wavelength range between about 9.7 µm and about 10.4 µm.

[0044] This also includes a method for determining ethanol or glucose and ethanol in bodily fluids and / or tissues of a body part using the device described above.

[0045] Another aspect of this disclosure is a non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, including:

[0046] - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising:

[0047] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0048] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0049] The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues.

[0050] - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameter based on IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of multiple individual measurements.

[0051] This involves measurement sequences consisting of multiple measurements, such as approximately 100 to approximately 2000, approximately 200 to approximately 1000, or approximately 250 to approximately 500 individual measurements. A single measurement may take approximately 1 ms to approximately 500 ms, approximately 2 ms to approximately 200 ms, or approximately 5 ms to approximately 100 ms. A measurement sequence of multiple measurements may take approximately 0.2 s to approximately 60 s, approximately 0.5 s to approximately 30 s, or approximately 1 s to approximately 10 s.

[0052] In some embodiments, the temperature of the irradiated body part is monitored during the measurement sequence, and separate measurements performed as the temperature of the body part increases are excluded from the determination. In these embodiments, the temperature of the irradiated body part is monitored, for example, by a separate temperature sensor, which may be a thermopile or a pyrometer sensor.

[0053] This also includes a method for determining physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part using the device described above.

[0054] Another aspect of this disclosure is a non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, including:

[0055] - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising:

[0056] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0057] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0058] The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues.

[0059] - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0060] The radiation source is adapted to emit visible (VIS) / near-infrared (NIR) radiation into the body during a predetermined irradiation period, and the sensing unit is adapted to perform a measurement of the IR radiation emitted from the body part during a subsequent dissipation period.

[0061] When a radiation source emits visible (VIS) / near-infrared (NIR) radiation into a body part, it causes energy to transfer to that body part, resulting in a local increase in temperature. When the radiation source is turned off, a dissipation phase begins, during which energy is dissipated through the irradiated body part.

[0062] This aspect of the disclosure relates to the measurement of IR radiation emitted from a body part by a sensing unit during a dissipation period, wherein the dissipation period begins after the radiation source is turned off. Measuring IR radiation emitted from the body part during this dissipation period may result in a significant increase in the determination of physiological parameters such as glucose. In some embodiments, the determination of physiological parameters is based solely on measurements of IR radiation emitted from the body part during a time period when the IR radiation is turned off. The measurement during the dissipation period may be a single measurement or a sequence of measurements consisting of multiple individual measurements, specifically the measurement sequence described above.

[0063] Typically, measurements during the dissipation period occur within approximately 2 seconds, 1.5 seconds, 1 second, 500 ms, or 200 ms after the radiation source is turned off.

[0064] In some embodiments, the device is adapted to perform a single cycle consisting of an irradiation period and measurements during a subsequent dissipation period. In other embodiments, the device is adapted to perform two or more irradiation / dissipation periods.

[0065] This also includes a method for determining physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part using the device described above. Detailed Implementation

[0066] This disclosure relates to determining a physiological parameter by detecting IR radiation emitted from a previously irradiated body part of a subject, particularly a human subject, in the range of about 5 µm to about 12 µm, and particularly in the range of about 8 µm to about 10 µm. More specifically, the invention relates to determining the physiological parameter by the absorption of IR radiation emitted from a previously irradiated body part of the subject in the range of about 5 µm to about 12 µm, and particularly in the range of about 8 µm to about 10 µm. The signal of the emitted IR radiation at the measurement wavelength decreases with increasing concentration of the physiological parameter, and increases with decreasing concentration of the physiological parameter. The physiological parameter can be any compound having a characteristic absorption band in that wavelength range. For example, the physiological parameter is glucose or another clinically relevant analyte, such as lactate or troponin.

[0067] In one embodiment of the invention, the system is adapted for non-invasive determination of glucose in blood. In this embodiment, IR radiation is detected at a glucose-specific wavelength or wavelength range in which 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 wavelengths of about 9.2 µm, about 9.4 µm, about 9.6 µm, including at least two of wavelengths of about 9.2 µm, about 9.4 µm, and about 9.6 µm, including all three of wavelengths of about 9.2 µm, about 9.4 µm, and about 9.6 µm, or any combination thereof. Additionally, IR radiation is detected at a reference wavelength or wavelength range in which glucose does not have a characteristic absorption band and specifically has a minimum absorption value, and 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 between about 8.7 µm and about 9.0 µm, a wavelength or wavelength range between about 9.7 µm and about 10.2 µm, or any combination thereof.

[0068] In all aspects of the specific embodiments described above, the system is suitable for sensing a reference wavelength of about 8.8 µm or a reference 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.

[0069] In all aspects of the further embodiments described above, the system is suitable for sensing a reference wavelength of about 10.2 µm or a reference wavelength range including a wavelength of about 10.2 µm, for example, a wavelength range between about 9.7 µm and about 10.5 µm.

[0070] In all aspects of the further embodiments described above, the system is suitable for sensing a first reference wavelength of about 8.8 µm or a reference 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 for sensing a second reference wavelength of about 10.2 µm or a reference wavelength range including a wavelength of about 10.2 µm, for example, a wavelength range between about 9.7 µm and about 10.5 µm.

[0071] As summarized above, the present invention is based on irradiating body tissue with electromagnetic radiation (VIS / NIR radiation) in the wavelength range of about 400 nm to about 1500 nm and detecting electromagnetic radiation (IR radiation) emitted from the irradiated body part in the wavelength range of about 5 µm to about 15 µm. Irradiation of the body part with VIS / NIR radiation results in enhanced self-emission of IR radiation from the body part due to local energy absorption, which leads to an increase in local temperature. Therefore, the self-emission of IR radiation from the irradiated body part is increased by the prior irradiation of the body part with VIS / NIR radiation. Therefore, it is not necessary to irradiate the body part with an external IR radiation source in the wavelength range of about 5 µm to about 15 µm. Therefore, in some embodiments, the system of the present invention does not include an IR radiation source, specifically in some embodiments, the system of the present invention does not include an IR radiation source suitable for irradiating the body part emitting the detected IR radiation.

[0072] 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 the width of this absorption wavelength band. In some embodiments, the term "about" is intended to include values ​​of ±0.1 µm or ±0.05 µm around the indicated wavelength, such as wavelengths of 9.2 µm ± 0.1 µm or 9.2 µm ± 0.05 µm.

[0073] Figure 1The diagram shows the penetration depth [mm] of electromagnetic radiation into body tissue according to wavelength [nm]. It can be seen that the penetration depth depends on the wavelength. In the visible (VIS) / near-infrared (NIR) wavelength range of about 400 nm to about 1500 nm, specifically in the range of about 500 nm to about 1500 nm or 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 greater, specifically about 3 mm or greater. Therefore, the irradiated body part will absorb electromagnetic energy, which leads to an increase in local tissue temperature. This, in turn, leads to an increase in the emission of longer wavelength IR radiation (e.g., IR radiation in the wavelength range of about 5 µm to about 12 µm), in which certain organic compounds present in body fluids (e.g., physiological parameters) exhibit absorption bands. According to the above aspects of the invention, this allows for the qualitative or quantitative determination of such parameters.

[0074] In some embodiments, the VIS / NIR radiation emitted into the body part is in the range of about 550 nm to about 1000 nm, specifically 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 some embodiments, the VIS / NIR radiation emitted into the body is in the range of about 450 nm to about 800 nm.

[0075] Figure 2 The relative absorption coefficients of certain compounds present in the human body are shown based on wavelengths ranging from 400 nm to 1100 nm. As explicitly indicated, radiation at wavelengths of approximately 600 nm and approximately 810 nm can be emitted into body parts. Water (H₂O) exhibits relatively low absorption in the wavelength range of approximately 500 nm to approximately 1050 nm. Furthermore, hemoglobin (Hb) and oxyhemoglobin (Hboxy), the main components of blood, show similar absorption coefficients. Skin pigment melanin shows an absorption coefficient that decreases with increasing wavelength.

[0076] The system or device of the present invention includes a radiation source (a) suitable for emitting 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 specifically selected from the fingertip, earlobe, wrist, forearm, palm and upper arm.

[0077] In one embodiment of the invention, the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 920 nm to about 960 nm (e.g., about 940 nm) onto a body part. This irradiation wavelength can be used alone or in combination with at least one other irradiation wavelength. Figure 3 As shown, glucose has an absorption band at a wavelength of 940 nm. Therefore, irradiation at a wavelength of approximately 940 nm causes selective excitation of glucose molecules and may lead to stronger absorption of glucose molecules in the IR wavelength range (specifically in the wavelength range of approximately 5 µm to approximately 12 µm).

[0078] According to one embodiment of the invention, a radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 920 nm to about 980 nm (e.g., about 940 nm) into a body part of the subject, and a sensing unit (b) is further adapted to detect VIS / NIR radiation having a wavelength of about 940 nm, wherein the intensity of the detected VIS / NIR radiation depends on the concentration of glucose. As described above, the measurement signal in the VIS / NIR wavelength range can be used in conjunction with a measurement signal in the IR range, for example, by means of a comparator.

[0079] In another embodiment, VIS / NIR irradiation occurs in a combination of at least two different wavelengths, specifically in a combination of a first wavelength of about 800 nm to about 820 nm (e.g., about 810 nm) and a second wavelength of about 920 nm to about 980 nm (e.g., about 940 nm).

[0080] The radiation source (a) is suitable for emitting VIS / NIR radiation with a range of about 400 nm to about 1500 nm, specifically about 500 nm to about 1500 nm. The VIS / NIR radiation can be emitted continuously or intermittently at predetermined time intervals.

[0081] In one embodiment, the radiation source is adapted to cause a localized temperature increase in an irradiated body part (e.g., a fingertip), and specifically, a localized temperature increase in an absorbing region within the irradiated body part. The localized temperature increase can be in the range of about 1°C to about 15°C, specifically between about 2°C and about 10°C, and more specifically between about 3°C ​​and about 5°C. The locally elevated temperature of the irradiated body part (e.g., a fingertip) can be in a temperature range up to about 45°C, up to about 40°C, or up to about 37°C, for example, in the temperature range of about 30°C to about 35°C or about 30°C to about 32°C. This localized temperature increase results in enhanced self-emission of IR radiation from the irradiated body part, and specifically, enhanced self-emission of IR radiation from the absorbing region within the irradiated body part.

[0082] In one embodiment, the radiation source (a) may be adapted to continuously emit radiation with a power of about 10 mW to about 1 W, specifically about 20 mW to about 500 mW, more specifically about 50 mW to about 250 mW, and even more specifically about 100 mW to about 200 mW (e.g., 150 mW) over time intervals of about 0.1 s to about 20 s, specifically about 0.2 s to about 5 s, and more specifically about 0.5 s to about 2 s, for example, about 1 s.

[0083] In another embodiment, the radiation source (a) may be adapted to intermittently emit radiation with a power of about 10 mW to about 5 W, specifically about 20 mW to about 1 mW, and more specifically about 50 mW to about 500 mW, over time intervals of about 0.1 s to about 20 s, specifically about 0.2 s to about 5 s, and more specifically about 0.5 s to about 2 s. The radiation may be emitted intermittently at a pulse frequency of about 1 Hz to about 1 MHz.

[0084] In another embodiment, the radiation source (a) is adapted to emit radiation continuously or intermittently over a period of at least about 0.5 s, specifically over a period of at least about 1 s to about 120 s and more specifically over a period of at least about 2 s to about 20 s.

[0085] In another embodiment, 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 even more different wavelengths). For example, the radiation source can be a multi-LED chip. The use of a multi-wavelength radiation source allows for adjusting the predetermined penetration depth of electromagnetic radiation into the tissue of the irradiated body part according to specific characteristics of the body part (e.g., pigmentation, skin thickness, presence or absence of keratinized skin). Figure 1 As shown above (supra), if desired, the penetration depth into body tissue varies with wavelength, and the use of VIS / NIR radiation with different wavelengths or combinations of different wavelengths can be applied individually to each subject and / or each body part.

[0086] In some embodiments, the radiation source (a) is a multi-wavelength radiation source suitable for emitting VIS / NIR radiation at several different wavelengths or wavelength ranges, for example, between about 400 nm and about 1200 nm, more specifically between about 450 nm and about 900 nm, for example, at least 2, 3, 4, 6 or 8 wavelengths can be selected from wavelengths of about 470 nm, about 520 nm, about 590 nm, about 650 nm, about 750 nm and about 810 nm.

[0087] The system or device of the present invention includes a sensing unit (b) for detecting IR radiation emitted from an 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 wavelength range in the range of about 5 µm to about 12 µm, wherein the intensity of the detected IR radiation in the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids, and the sensing unit is adapted to (ii) detect IR radiation having at least one wavelength or wavelength range in the range of about 5 µm to about 12 µm, wherein the intensity of the detected IR radiation in the at least one wavelength or wavelength range is substantially independent of the concentration of a physiological parameter in the subject's body fluids.

[0088] In some embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein the body part is irradiated with VIS / NIR radiation during at least a portion of the time period (e.g., during at least about 60%, at least about 80%, or at least about 90% of the time period), wherein the time period may be at least 0.5 s, specifically at least about 1 s to about 120 s, and more specifically at least about 2 s to about 20 s.

[0089] In some embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part within a time period, such as the time period described above, wherein during at least a portion of the time period (e.g., during at least about 60%, at least about 80%, or at least about 90% of the time period), the temperature of the irradiated body part (specifically, the absorbing region) is higher in the irradiated body part than the temperature of the surrounding tissue, for example, at least 1°C, at least 2°C, at least 5°C, and up to 10°C higher than the temperature of the surrounding tissue.

[0090] In some embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, such as the time period described above, wherein during at least a portion of the time period (e.g., during at least about 60%, at least about 80%, or at least about 90% of the time period), the temperature of the irradiated body part (specifically, the absorbing region) rises. The temperature rise may be from about 2°C to about 10°C, specifically in the range of about 3°C ​​to about 5°C.

[0091] The sensing unit (b) includes at least one sensor suitable for detecting IR radiation emitted from an irradiated body part. In the sensing unit (b) of the present invention, the at least one sensor may be an analyte-specific sensor, i.e., a sensor suitable for detecting 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 fluids, and the at least one sensor may be a reference sensor, i.e., a sensor suitable for detecting 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 fluids and / or tissues.

[0092] In some embodiments, the sensing unit (b) is adapted to detect IR radiation emitted from a previously irradiated body part, i.e., IR radiation generated by the subject's body heat without external IR source irradiation. Furthermore, the sensing unit (b) can be adapted to detect IR radiation emitted from an absorption region in a body part previously irradiated by VIS / NIR, wherein the absorption region has a locally elevated temperature and exhibits an increase in IR radiation emission in the wavelength range of about 5 µm to about 12 µm.

[0093] In some embodiments, at least one other sensor may also be present, such as a sensor (i) suitable for detecting non-specific IR radiation, (ii) suitable for detecting non-specific VIS / NIR radiation, (iii) suitable for detecting VIS / NIR radiation having a wavelength in which the intensity of the VIS / NIR radiation detected depends on the concentration of physiological parameters in the subject's body fluids, and / or (iv) a temperature sensor for measuring the temperature of a body part.

[0094] In some embodiments, the sensing unit (b) is also adapted for temperature measurement, for example, having an accuracy of at least 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 skin temperature of an irradiated body part, and optionally at least one other temperature, such as ambient temperature, the temperature of the various sensors in the sensing unit (b), and / or the temperature of the electronic components of the sensing unit (b), such as the temperature of a circuit board. In those embodiments, the sensing unit (b) may include at least one temperature sensor, specifically multiple temperature sensors, such as two, three, or four temperature sensors for measuring skin temperature, and optionally at least one other temperature sensor, such as a sensor for measuring ambient temperature, at least one sensor for measuring the temperature of the various sensors in the sensing unit, and / or a sensor for measuring the temperature of the electronic components of the sensing unit (e.g., the temperature of the circuit board of the sensing unit (b)).

[0095] In some embodiments, the sensing unit (b) further includes an attitude sensor adapted to detect movement during measurement. The attitude sensor can operate within the same wavelength range as other sensors. By using the attitude sensor, measurements taken while the body part is moving can be identified and optionally excluded.

[0096] In some embodiments, the sensing unit (b) further includes an accelerometer, such as a microelectromechanical system (MEMS) accelerometer. By using the accelerometer, measurements taken during body part movement can be identified and optionally excluded.

[0097] In some embodiments, the sensing unit (b) further includes at least one analyte-specific sensor, i.e., a sensor suitable for detecting VIS / NIR radiation having at least one wavelength or wavelength range, the intensity of which depends on the concentration of a physiological parameter in the subject's body fluids. For example, at least one other sensor suitable for detecting VIR / NIR radiation having a wavelength of approximately 940 nm may be present.

[0098] In some embodiments of the invention, the radiation source (a) and the sensing unit (b) are located relative to the irradiated body part, the location being defined by an angle of at least 90° or greater. In some embodiments, the radiation source (a) and the sensing unit (b) are located on the opposite side of the irradiated body part.

[0099] The system or device of the present invention includes an analysis unit or control unit (c) for qualitatively and / or quantitatively determining physiological parameters based on IR radiation detected in a sensing unit (b). The analysis unit may include, for example, an A / D converter and / or a microcontroller. The measured signal may be analyzed based on intensity and / or decay time.

[0100] In a particular embodiment, the analysis unit or control unit (c) is adapted to perform time-dependent analysis of the detected IR radiation, wherein the measurement signal is recorded over a time period, specifically over a time period of at least about 0.5 s, specifically over a time period of at least about 1 s to about 120 s, and more specifically over a time period of at least about 2 s to about 20 s.

[0101] In another specific embodiment, the analysis unit or control unit (c) is adapted to perform temperature-compensated analysis of the detected IR radiation. The temperature-compensated analysis includes temperature compensation, in which the measured signal is affected by temperature correction. Specifically, the temperature compensation is based on the skin temperature of the irradiated body part and at least one other temperature, such as the ambient temperature, the temperature of components of the sensing unit (e.g., the temperature of the various sensors in the sensing unit), and / or the temperature of the electronic components of the sensing unit.

[0102] In another specific embodiment, the analysis unit or control unit (c) is adapted for time-dependent analysis and temperature-compensated analysis of the detected IR radiation as described above.

[0103] Figure 4 An embodiment of the system described in WO 2022 / 090503 is shown. A body part (1) (e.g., a fingertip) is placed in contact with the system, which is adapted to irradiate an absorption area (2) in the body part (1).

[0104] The system includes a cover (3) that is at least partially made of an optically transparent material. For example, the cover is at least partially made 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 (e.g., about 8 µm to about 12 µm), and optionally in the VIS / NIR wavelength range of about 400 nm to about 1500 nm or a subrange thereof. Suitable IR-transparent plastic materials are, for example, PolyIR plastic materials available from Fresnel Technologies (Fort Worth, Texas, USA). In some embodiments, the cover may have a thickness of about 0.2 mm to about 2 mm, specifically about 0.3 mm to about 1.5 mm, and more specifically about 1 mm.

[0105] The system also includes at least one sensor (4), which may be provided with a filter element (5) and optionally a lens element (not shown), which may be arranged, for example, between the sensor (4) and the filter element (5). The sensor (4) may be mounted on a circuit board (6). In addition, the system includes at least one radiation source (9, 9a). For example, the system may include a radiation source (9) located on the same side as the sensor (4) and / or a radiation source (9a) located on the opposite side of the body part relative to the sensor (4). If necessary, another sensor (4) without a filter element (5) may be provided for monitoring the precise skin temperature of the subject.

[0106] The system contains one or more sensors (4). Figure 4In one embodiment, the system includes four different sensors (4). The sensors can be optical detectors, specifically optical photovoltaic detectors, such as InAsSb-based detectors, which can be used in conjunction with a lock-in amplifier if needed. Photovoltaic detectors (e.g., InAsSb-based detectors) have rise times of only a few nanoseconds and are particularly useful in settings where body parts are intermittently irradiated. In other embodiments, the sensors can be thermal detectors, such as thermopile or bolometer. Suitable sensors include photovoltaic detectors (e.g., Hamamatsu P13894), thermopile detectors (e.g., Heimann HCS C21 F8-14), or other types of IR sensors (e.g., Sensirion STS21 or Melexis MLX90632). If needed, the sensors (4) can be provided with filter elements (5) capable of selectively transmitting radiation of a desired wavelength or wavelength range. The filter elements can have a narrow bandwidth, for example, from about 50 nm to about 100 nm, or a wider bandwidth, for example, about 400 nm or greater. The filter can be made of germanium or other light-filtering materials that are optically transmissive for all wavelengths. Furthermore, the sensor can also be provided with lens elements, such as microlenses capable of focusing light onto the sensor.

[0107] In some embodiments, the sensor surface may be coated with a precious metal such as gold or silver, especially gold, to increase its sensitivity. Awad (Nature Scientific Reports 9:12197 (2019)) describes such a coating that can be shaped into a Bundt baking pan, the contents of which are incorporated herein by reference.

[0108] In some embodiments, the sensor is approximately 1 mm in diameter. 2 Approximately 10,000 mm 2 (For example, about 10 mm) 2 Approximately 1000mm 2 Miniaturized sensors with smaller surface areas. In some embodiments, the sensors can be even smaller, for example, ASICs (Application-Specific Integrated Circuits).

[0109] In addition, the device may include a circuit board (7) with a light source (9) mounted on it and an active and / or passive heat sink (8).

[0110] The VIS / NIR radiation source (9, 9a, 9b) can be suitable for emitting collimated radiation (e.g., laser-based sources) and / or for emitting non-collimated radiation (e.g., LED-based sources). For example, the source can be selected from LEDs, laser diodes, VCSELs (vertical-cavity surface-emitting lasers), or lasers. In some embodiments, a broadband VIS / NIR radiation emitter is used, suitable for emitting VIS / NIR radiation in the range of about 650 nm to about 950 nm, specifically in the range of about 750 nm to about 850 nm, and more specifically 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.

[0111] In some embodiments of all aspects of this disclosure, the device further includes a monitoring device for detecting fluctuations (e.g., power fluctuations in radiation emitted by a radiation source). The monitoring device may include a photodiode, for example, a photodiode integrated into the radiation source or a photodiode separate from the radiation source. Detected fluctuations may be compensated for by a sensing unit and / or a control unit, or the radiation source may be replaced.

[0112] Figure 5 Another embodiment of the system described in WO 2022 / 090503 is shown. Here, a single radiation source (9a) is provided on the side of the body part (1) opposite to the sensing unit, which includes at least one sensor (4) provided with a filter (5) and another sensor (4a) provided with a filter (5a). In some embodiments, the sensor (4a) is an optical sensor, such as a photodiode. The sensor (4a) is suitable for reference measurement of transmitted radiation from the radiation source (9a), for example, for measuring radiation with wavelengths of about 600 nm and / or about 810 nm and / or about 940 nm. For this purpose, the filter element (5a) may be a bandpass filter of about 600 nm and / or about 810 nm and / or about 940 nm.

[0113] Figure 6Another embodiment described in WO 2022 / 090503 is shown. Here, a radiation source (9b) is provided on one side of a body part (1) (e.g., a fingertip), wherein a direct channel is provided through the skin of the body part to the absorption area (2) in the body part (1) without the radiation penetrating the cover structure of the device and / or the keratinous structure of the body surface (e.g., nail plate and / or keratinized skin). This reduces or eliminates interference, for example, 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 a location around the circumference of the body part (1) (e.g., a fingertip). If multiple radiation sources are present, the radiation sources are preferably adapted to emit radiation to a single absorption area (2) in the body part, which may be about 3 mm to about 5 mm below the body surface.

[0114] Figure 7 Another embodiment described in WO 2022 / 090503 is shown. In this embodiment, the cover (3) is provided to focus IR radiation emitted from a body part onto at least one sensor (4) of the sensing unit. This increases the radiation intensity on the sensor and thus improves 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 within the wavelength range to be detected on the sensor, specifically to IR radiation in the wavelength range of about 5 µm to about 12 µm or its sub-ranges (e.g., about 8 µm to about 12 µm). Suitable materials are, for example, PolyIR plastic material, see above. In this embodiment, the cover (3) may include an IR Fresnel lens, i.e., a large-aperture, short-focal-length lens capable of effectively focusing IR radiation passing through it, or an array comprising multiple (e.g., up to 10 or more) IR Fresnel lenses. In some embodiments, the array may include IR Fresnel microlenses, for example, up to 100 or 1000 microlenses, which may have a diameter in the range of about 50 nm to about 500 µm. In some embodiments, the IR Fresnel lenses may have a back focal length of about 3 mm to about 10 mm (e.g., about 5 mm) and may be made of IR-transparent plastic. For example, suitable IR Fresnel lenses that are optically transparent in the 8-14 µm wavelength range are available from Edmund Optics (Product Series No. 2042).

[0115] also, Figure 7A radiation source (9a) is shown provided on the side of the body part (1) opposite to the position of the sensing unit, which includes a sensor (4). However, it should be noted that one or more radiation sources may also be arranged circumferentially around the body part (1), for example, as shown in the diagram. Figure 6 As shown. It should also be noted that in this embodiment, multiple different sensors may exist, for example, such as... Figure 4 and Figure 5 As shown.

[0116] like Figure 4 and Figure 5 As shown, the system may include multiple different sensors (4). In some embodiments, the system may include multiple analyte-specific (e.g., glucose-specific) sensors, wherein a first sensor is adapted to detect radiation within a first wavelength or wavelength range (e.g., about 9.2 µm) and at least another first sensor is adapted to detect IR radiation within a second wavelength range that includes the first wavelength or wavelength range and also includes another wavelength or wavelength range. For example, other first sensors may be adapted to detect IR radiation at a wavelength of about 9.2 µm and additionally detect IR radiation at wavelengths of about 9.4 µm and / or about 9.6 µm (particularly at wavelengths of about 9.4 µm and about 9.6 µm).

[0117] Furthermore, the sensing unit may include multiple reference sensors suitable for detecting radiation at different wavelengths or wavelength ranges. For example, in determining glucose, a reference sensor may be suitable for detecting radiation with a wavelength range between approximately 8.6 µm and 9.0 µm. Another reference sensor may be suitable for detecting radiation with wavelengths or wavelength ranges between approximately 9.8 µm and approximately 10.2 µm.

[0118] Figure 8 Another embodiment described in WO 2022 / 090503 is shown. In this embodiment, a support (16) is provided for a body part (1) (e.g., a fingertip), wherein the support (16) includes an opening adapted to receive a portion (15) of the body part (1). For example, the support 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 in the support (16) such that a portion (15) of the body part (1) (e.g., a portion of a fingertip) is pressed into the opening. As a result, tissue including blood vessels in the portion (15) is compressed, thereby increasing the amount of capillary blood in the portion (15). This can thereby improve signal strength and the sensitivity and / or accuracy of the measurement.

[0119] also, Figure 8 Systems that can be formed as such Figure 7The IR Fresnel lens cover (3) described in the context. However, it should be noted that other covers are also suitable. Furthermore, a radiation source (9a) provided on the side of the body part opposite to the position of the sensing unit, which includes a sensor (4), is shown. However, it should be noted that one or more radiation sources may also be arranged circumferentially around the body part (1), for example, as... Figure 6 As shown. It should also be noted that in this embodiment, multiple different sensors may exist, for example, such as... Figure 4 and Figure 5 As shown.

[0120] exist Figure 9 The measurements are shown in the diagram for specific wavelength / wavelength ranges and reference wavelength / wavelength ranges for multiple analytes.

[0121] 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 peak at 9.2 µm. Such a sensor can be tuned to have a filter element capable of transmitting only radiation within a narrow range (22). Thus, the sensor is capable of selectively detecting radiation within this narrow range. Another glucose-specific sensor can be adapted to measure a wider range of radiation between approximately 9.1 µm and approximately 9.7 µm, thereby including peaks at approximately 9.2 µm, 9.4 µm, and 9.6 µm. This other glucose-specific sensor can be tuned to have a filter element capable of transmitting radiation within a wider range (21).

[0122] Two reference sensors may be provided, wherein the reference sensors are provided with filter elements that are respectively capable of transmitting radiation in the wavelength range of about 8.6µm to about 9.0µm (specifically about 8.8µm-8.9µm (20)) and / or radiation in the wavelength range of about 9.8µm to about 10.2µm (specifically about 9.9µm-10.1µm (23)).

[0123] Parallel and independent measurements at approximately 9.2 µm wavelength and in a wavelength range including at least one of the peaks at 9.2 µm and others (specifically, a peak at approximately 9.6 µm) offer further advantages, as they allow determination of whether a subject's blood contains ethanol. Since ethanol and other alcohols have absorption bands at approximately 9.6 µm but not at approximately 9.2 µm wavelength, the ratio of the peak at 9.2 µm to the peak at 9.6 µm can be used to determine, and optionally correct for, interference caused by ethanol in the blood.

[0124] In an alternative embodiment, the first glucose-specific sensor can be adapted to measure only the peak at 9.6 µm. Such a sensor can be provided with a filter element capable of transmitting only radiation within a narrow range. Another glucose-specific sensor can be adapted to measure a wider range of radiation between about 9.4 µm and about 9.6 µm, thereby including peaks at about 9.4 µm and about 9.6 µm but excluding the peak at 9.2 µm. This other glucose-specific sensor can be provided with a filter element capable of transmitting radiation over a wider range.

[0125] In another alternative embodiment, the reference sensor may be provided with filter elements capable of transmitting radiation with wavelengths in the range of about 7.8 µm to about 8.2 µm (specifically about 7.9 µm to 8.1 µm). The reference sensor may optionally be provided in combination with at least one other reference sensor, which is provided with filter elements respectively capable of transmitting radiation with wavelengths in the range of about 8.8 µm to 9.2 µm and / or radiation with wavelengths in the range of about 9.8 µm to 10.2 µm.

[0126] In another embodiment, the system may include a sensor suitable for time-dependent detection of IR radiation with different wavelengths or wavelength ranges. In this embodiment, the system may be provided with multiple filters suitable for transmitting IR radiation with different wavelengths or wavelength ranges, wherein the filters may be placed on the sensor at different stages of a measurement cycle, thereby allowing detection of different wavelengths or wavelength ranges within a single measurement cycle. Figure 10 An embodiment described in WO2022 / 090503 is shown. Here, the system is provided to include 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 to have an illumination hole (15) through which light from a radiation source (not shown) enters a body part (not shown) of the subject. Light reflected from the irradiated body part can pass through different holes (14) of the filter wheel (10), which can be provided with analyte-specific filter elements and / or reference filter elements as described above. The positions of the filter wheel (10) and the shutter wheel (13) can be monitored using a magnet (12) in conjunction with a magnetic sensor. In operation, the filter wheel and shutter wheel can rotate at a predetermined frequency, thereby allowing radiation from the radiation source to enter the body part in a time-dependent manner and allowing radiation emitted from the body part to reach the sensor (not shown) through the different holes (14) of the filter wheel (10) at predetermined time intervals.

[0127] In an alternative embodiment (not shown), the sensor suitable for time-dependent detection of IR radiation with different wavelengths or wavelength ranges can be a Fabry-Perot interferometer, for example, 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).

[0128] In some embodiments, the system includes a single sensor suitable for time-dependent detection of IR radiation with different wavelengths or wavelength ranges. This sensor may be provided with different filters, for example, having a filter wheel, or a Fabry-Perot interferometer as described above.

[0129] Figure 11 Another embodiment described in WO 2022 / 090503 is shown. The system of this embodiment is suitable for permanent attachment to a subject's body. Specifically, the system is suitable for performing multiple measurements at predetermined time intervals. The system includes a housing (30) and a strap (31) for securing the housing around a body (33) (e.g., a wrist or forearm). Furthermore, the system includes a radiation source for emitting VIS / NIR light into an absorption region (34) of the body part (33) and a sensor for detecting IR radiation emitted from the irradiated body part.

[0130] Figure 12 Another embodiment described in WO 2022 / 090503 is shown. This embodiment's system is suitable for permanent attachment to a subject's body and specifically for performing multiple measurements at predetermined time intervals. The system includes a housing (30) and a strap (31) for securing the housing around a body (33) (e.g., wrist or forearm). Furthermore, the system includes multiple radiation sources, e.g., two radiation sources, for emitting VIS / NIR light into an absorption region (34) of the body part (33). Light emitted from these sources can fall onto the surface of the body part (33) at an angle, for example, from about 30° to about 75°.

[0131] Figure 13 It shows Figure 4 A schematic diagram of the system.

[0132] Figure 14 The image shows a thermal image of the fingertip after being illuminated with 810 nm light for 2 seconds.

[0133] Figure 15This is a graph showing the time-dependent thermal power output, excluding 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.

[0134] Figure 16a A block diagram of one embodiment of the sensing unit of the present invention is shown. The region of interest (ROI), i.e., the skin tissue of a subject (specifically a human subject), is illuminated using a first light source emitting VIS / NIR radiation with a wavelength of 940 nm, a second light source emitting VIS / NIR radiation with a wavelength of approximately 810 nm, and optionally a third light source emitting VIS / NIR radiation with a wavelength of approximately 600 nm. Radiation transmitted through or reflected from the ROI is analyzed by the sensing unit. Furthermore, the device includes a temperature sensor.

[0135] The sensing unit includes multiple sensors, such as an analyte-specific IR sensor (1) and an analyte-specific IR sensor (2), and a reference sensor (e.g., an IR sensor (4)). To determine glucose, the IR sensor (1) may be provided with a first optical filter that transmits a wavelength of approximately 9.2 µm, and the IR sensor (2) may be provided with a second optical filter that transmits a wavelength range between approximately 9.2 µm and approximately 9.6 µm. The reference sensor (4) may be provided with a fourth optical filter that transmits a wavelength or wavelength range between approximately 8.6 µm and approximately 9.0 µm and / or a wavelength or wavelength range between approximately 9.8 µm and 10.2 µm. Furthermore, the sensing unit includes an NIR sensor for detecting VIS / NIR radiation at a wavelength of approximately 940 µm, where glucose has a strong absorption band. The NIR sensor is provided with a suitable optical filter that transmits this wavelength. Additionally, the sensing unit may include a temperature sensor for measuring the temperature of skin tissue in the region of interest. Each sensor may be coupled to an amplifier (AMP) for initial signal amplification. Signals from individual sensors can be compared with signals from other sensors using a comparator, thereby improving measurement accuracy and / or signal quality. For example, a measurement signal at 940 nm from an NIR sensor can be compared with a measurement signal from an analyte-specific IR sensor (1). Alternatively or additionally, a measurement signal at 940 nm from an NIR sensor can be compared with measurement signals from an analyte-specific IR sensor (1) and / or an analyte-specific IR sensor (2) and / or a reference IR sensor (4). The measured signals, as well as optionally referenced signals, are amplified by a lock-in amplifier and transmitted to the microcontroller unit. Feedback control from the lock-in amplifier to the light source can be provided. The signals and / or the results of internal algorithms can be transmitted from the microcontroller unit to a display unit and / or other devices, for example, via a direct connection or via Bluetooth and / or a wireless LAN.

[0136] Figure 16b A block diagram of another embodiment of the sensing unit of the present invention is shown, and... Figure 16a The sensing unit shown is similar. Here, additionally or alternatively, a multi-wavelength light source is provided, for example, a multi-wavelength LED comprising multiple individual diodes. The multi-wavelength light source may have a wavelength range, for example, from 400 nm to about 700 nm, and may be operated by a microcontroller unit. Furthermore, a temperature sensor is present, coupled to an amplifier (AMP). This temperature sensor may also be operated by a microcontroller unit.

[0137] In another embodiment of the invention, the system may include a spectral sensor or line sensor or array of spectral or line sensors suitable for detecting IR spectra in a range of wavelengths of interest (e.g., including a range of about 7 µm to about 12 µm, specifically including a range of about 8 µm to about 10 µm), typically a radiative thermal estimator or thermopile array. IR spectra can be generated by passing IR radiation from an irradiated body part through a spectral separation or diffraction device and then to the sensor or sensor array. Figure 17 An embodiment is illustrated. 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) suitable for focusing the IR radiation, and then passed to a spectral separation or diffraction element (73) (e.g., a prism or a transmission or reflection grating), at which the IR radiation is separated according to its wavelength. The radiation diffracted from the spectral separation or diffraction element (73) is passed to a spectral sensor or line sensor or sensor array (74) (typically a radiative thermal estimator or thermopile array), at which an IR spectrum in the range of wavelengths of interest (e.g., between 8 µm and about 20 µm, including, for example, an analyte-specific wavelength or wavelength range and a reference wavelength or wavelength range as described above) is detected at the spectral sensor or line sensor or sensor array (74). The amount of a physiological parameter of interest (e.g., glucose) can be determined by spectral analysis based on the relative intensities of the predetermined analyte-specific wavelength and reference wavelength.

[0138] The systems and methods described herein allow for the qualitative and / or quantitative determination of a physiological parameter to be measured, specifically, the qualitative and / or quantitative determination of glucose in the blood.

[0139] In some embodiments, the concentration of a physiological parameter, such as the concentration of glucose in the blood, is quantitatively determined. In some embodiments, the rate of change of a measured amount of a physiological parameter, such as glucose, is determined. These embodiments may involve non-quantitative measurements, such as relative measurements of the change in analyte amount per unit time, i.e., an increase or decrease in analyte amount per unit time. If the change in analyte amount in a unidirectional direction (i.e., an increase or decrease) exceeds a predetermined level and / or time period, the system will provide an alarm. This embodiment specifically addresses... Figure 11 and Figure 12 The system shown can be permanently attached to the subject's body (e.g., around the wrist, forearm, or upper arm). This embodiment can be applied to the monitoring of stable glucose levels.

[0140] In some embodiments, the system described herein is suitable for performing both non-quantitative and quantitative measurements. For example, the system may be adapted to perform non-quantitative measurements, such as quantitatively measuring changes in the amount of an analyte over time during standard operation, e.g., increases or decreases. Non-quantitative measurements may be performed as needed, e.g., as continuous and / or intermittent monitoring measurements. If the change in the amount of the analyte exceeds a predetermined level and / or time period, the system is adjusted to switch to quantitative measurements to provide more detailed information. In these embodiments, systems suitable for permanent attachment to the body (e.g., to the wrist or ankle) may be used. Figure 11 and Figure 12 Specific embodiments of this type of system are shown.

[0141] In some embodiments, the system is adapted to perform non-quantitative measurements (e.g., continuous and / or intermittent monitoring measurements) and quantitative measurements on several different body parts. For example, the system may be adapted to perform non-quantitative measurements on a first body part (e.g., a body part to which the system may be permanently attached, such as the wrist or ankle) and quantitative measurements on a second body part (e.g., a body part where capillaries are more accessible, such as the earlobe, palm, or fingertip). To perform a measurement on the second body part, the system is displaced from the first body part and brought into contact with the second body part, specifically in direct contact. After performing a measurement on the second body part, the system can be displaced from the second body part and brought back into contact with the first body part, for example, by attaching the system to the first body part. In a particular embodiment, the first body part is the wrist and / or the second body part is the fingertip.

[0142] Figure 18 Another embodiment is shown in WO 2022 / 090503. Here, a device comprising a non-invasive system for determining physiological parameters (e.g., glucose) in a subject's bodily fluids is shown. The device includes a housing (80) comprising a first surface comprising a screen (81) made of a material at least partially optically transparent to NIR / VIS radiation emitted by a radiation source (82). Furthermore, the device includes a sensing unit (83) comprising at least two sensors (83a) and (83b).

[0143] The device (80) can be a mobile device, such as a smartphone, smartwatch, tablet, or health tracker device. The device can be worn on the subject's body, for example, on the wrist (84), and can be secured by a strap (85), such as a wristband. A body part (86), such as a fingertip (or alternatively, multiple fingertips or a palm), is placed on a screen (81) for measurement. An absorption region (87) within the body part (86) is irradiated with VIS / NIR radiation emitted by a radiation source (82). The irradiated body part absorbs electromagnetic energy, resulting in a localized increase in 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 (e.g., glucose molecules) absorb the emitted IR radiation present in the tissue of the body part (86). Therefore, in the wavelength or wavelength range corresponding to the absorption band of the physiological parameter of interest, the emitted IR radiation signal decreases with increasing concentration of the physiological parameter and increases with decreasing concentration of the physiological parameter.

[0144] Figure 19 The apparatus described in WO 2022 / 090503 is shown, which includes a VIS / NIR radiation source (93), such as an LED, suitable for irradiating a body part (e.g., the fingertip (94) of a finger (90)). The apparatus includes an IR temperature sensor (91), such as a radiative thermal analyzer, for measuring the temperature of the body part. Furthermore, the apparatus includes four IR sensors (92a, 92b, 92c, 92d) provided with optical filters suitable for wavelength-specific measurements of an analyte to be determined (e.g., glucose). The IR sensors (92a, 92b) can be used for measurements at an analyte-specific wavelength or wavelength range, and the IR sensors (92c, 92d) can be used for measurements at a reference wavelength or wavelength range. For example, sensor (92a) may be provided with an optical filter that transmits a glucose-specific wavelength of about 9.2 µm, and sensor (92b) may be provided with an optical filter that transmits a glucose-specific wavelength range between about 9.2 µm and about 9.6 µm; sensor (92c) may be provided with an optical filter that transmits a reference wavelength or wavelength range between about 8.6 µm and about 9.0 µm, and sensor (92d) may be provided with an optical filter that transmits a reference wavelength or wavelength range between about 9.8 µm and about 10.2 µm.

[0145] Figure 20Another device described in WO 2022 / 090503 is shown, comprising a board (105) on which sensors (102a, 102b, 104) and at least one VIS / NIR radiation source (e.g., two radiation sources (103a, 103b)) are mounted. The board is connected via a device (101) (e.g., a printed circuit board (PCB) or printed circuit board assembly (PCBA), specifically a flexible or starrflex PCB or PCBA) to an analog-to-digital converter, a microcontroller, or a processor (not shown). The radiation sources (103a, 103b) may be adapted to emit VIS / NIR radiation at the same wavelength or at different wavelengths. For example, both radiation sources may emit radiation at a wavelength of approximately 810 µm or at a wavelength of approximately 940 µm. Alternatively, one radiation source 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), for measuring the temperature of a body part (not shown), e.g., a radiative thermal estimator. Furthermore, the device includes two IR sensors (102a, 102b), each comprising two separate sensing chips. Each sensing chip can be equipped with a different optical filter. The IR sensor (102a) can be used for measurements at a specific wavelength or wavelength range of the analyte, and the IR sensor (102b) can be used for measurements at a reference wavelength or wavelength range. For example, the first chip on sensor (102a) can be equipped with an optical filter that transmits at a glucose-specific wavelength of approximately 9.2 µm, and the second chip on sensor (102a) can be equipped with an optical filter that transmits at a glucose-specific wavelength range between approximately 9.2 µm and approximately 9.6 µm; the first chip on sensor (102b) can be equipped with an optical filter that transmits at a reference wavelength or wavelength range between approximately 8.6 µm and approximately 9.0 µm, and the second chip on sensor (102b) can be equipped with an optical filter that transmits at a reference wavelength or wavelength range between approximately 9.8 µm and approximately 10.2 µm. In another miniaturized embodiment, the device may include a single sensor step comprising at least four chips (not shown) with four different optical filters. In yet another miniaturized embodiment, the device may be a single unit comprising all the chips, all the filters, all the radiation sources, and even microelectronic components (not shown) as an analog-to-digital converter and microcontroller within a single application-specific integrated circuit (ASIC).

[0146] Figure 20The device shown (or any other device described herein) may be provided as a component for integration into a multifunctional device, such as a smart device, like a smartwatch or mobile phone. Alternatively, the device may be provided as a stand-alone device.

[0147] Figure 21 The diagram illustrates glucose concentration (linear) measured by an amperometric measurement of a blood sample using an invasive method (conventional blood glucose meter) and by a non-invasive method of the present invention (conventional blood glucose meter). Figure 13 The comparison shows a relative (uncalibrated) glucose level measured by the device shown. Measurements were performed over a 6-hour period. A high correlation can be observed between conventional invasive blood glucose measurements and the non-invasive blood glucose measurement of this invention.

[0148] Furthermore, a non-invasive system for determining permissible glucose in the blood and optionally correcting for interference caused by blood ethanol is described. This non-invasive system includes a sensing unit for detecting IR radiation emitted from a 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 at a wavelength of about 9.2 µm and separately detect IR radiation at wavelengths of at least about 9.2 µm and about 9.6 µm, specifically in a wavelength range including about 9.2 µm, about 9.4 µm, and about 9.6 µm, and includes an analysis unit for separately determining glucose from the aforementioned sensing unit.

[0149] This article also describes a method for non-invasively determining glucose levels in a subject's blood using this system.

[0150] These preferred features are as described in the above specification.

[0151] The use of an InAsSb sensor, optionally combined with a lock-in amplifier, is also described for measuring IR radiation emitted from body parts.

[0152] The preferred features in this regard are as described in the above specification.

[0153] A system and method for non-quantitative glucose measurement are also described, which involves multiple measurements over predetermined time intervals and determining changes in a measurement signal indicating a change in the amount of the analyte, providing an alarm if the glucose level changes in one direction (i.e., increase or decrease) exceeding a certain level within the predetermined time period. This system and method can be applied to the monitoring of stable glucose levels.

[0154] The preferred features in this regard are as described in the above specification.

[0155] The first aspect of this disclosure is an implantable device comprising:

[0156] - An implantable outer shell that surrounds a system for determining physiological parameters, such as glucose, in tissues and / or body fluids at a body site, the system comprising:

[0157] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0158] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0159] 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues.

[0160] - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0161] - Power supply, and

[0162] - Optionally, at least one status indicator.

[0163] This also includes methods for determining physiological parameters, such as glucose, in body fluids and / or tissues of body sites using implantable devices as described above.

[0164] In some embodiments, the device is implanted into subcutaneous adipose tissue and measures glucose in the subcutaneous adipose tissue and / or glucose in adjacent blood vessels, such as capillaries.

[0165] Figure 22Examples of implantable devices are shown, comprising systems for determining physiological parameters of body sites, such as glucose in body fluids and / or tissues (e.g., subcutaneous adipose tissue). In some embodiments, the implantable device is needle-free, i.e., the device is completely enclosed by a shell such that no functional elements are in direct contact with surrounding tissue. In some embodiments, the device is sized to be inserted into a subject's body using a suitable injection device. Alternatively, the device can be inserted surgically. The device can be implanted subcutaneously in the arm, leg, or abdominal region. In some embodiments, the implantable device is formed as an elongated capsule having a length of about 10-15 mm (specifically about 12-14 mm) and a width of about 2-4 mm (specifically about 3 mm).

[0166] The implantable device includes an external housing (1). The housing (1) is at least partially optically transparent to allow measurement of desired physiological parameters, such as glucose, by a system located within the housing. The housing is made of a physiologically compatible material, such as a physiologically compatible plastic, a biocompatible glass, or a biocompatible composite. In some embodiments, the housing completely surrounds the system.

[0167] Figure 22 The system includes 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 body parts such as bodily fluids and / or tissues (5) adjacent to an implantable device. In some embodiments, the system includes multiple radiation sources (9), for example, 2, 3, 4 or 5 radiation sources.

[0168] Figure 22 The system also includes a sensing unit comprising at least one sensor (8), such as an optical sensor and / or a high-temperature measurement sensor, for detecting IR radiation emitted from a 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 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 irradiated body part (5), and the sensing unit is adapted to (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 some embodiments, the system includes multiple sensors (8), for example, 2, 3, 4, or 5 sensors. The sensors (8) may be provided with an optical filter element (10) adapted to detect IR radiation having a desired wavelength or wavelength range.

[0169] Figure 22 The system includes a control unit (3), specifically a highly integrated microcontroller, such as an ASIC. The control unit is adapted to control the measurement process. In some embodiments, the control unit (3) is also adapted to analyze the measurement results by quantitatively and / or qualitatively determining physiological parameters based on the measurement results. In some embodiments, the control unit (3) includes a communication device (not shown) adapted to communicate with an external device, such as a smartphone or smartwatch. The communication device may be adapted to transmit signals to the external device (e.g., signals including measurement results and / or determination results, and / or signals including identification codes) and / or receive signals from the external device. In some embodiments, the system includes communication devices (4a, 4b), such as a Bluetooth antenna (4a) and / or an RFID antenna (4b).

[0170] In addition, the system includes a power source. In some embodiments, the system includes an internal power source that can be recharged from an external power source. The power source may include a battery (6), such as a disposable battery or a rechargeable battery. In some embodiments, the battery may be recharged wirelessly (e.g., by capacitor charging), for example, using a charging coil (2). Furthermore, the power source may include a capacitor (7) (e.g., a supercapacitor or ultracapacitor) as a short-term power storage device that provides power during power bursts when the radiation source (9) is excited. In some embodiments, the power source may also include a power harvesting device suitable for converting mechanical energy into electrical energy, such as a micro energy harvesting device.

[0171] In some embodiments, the system includes at least one status indicator (not shown) adapted to indicate to the wearer that a parameter to be determined is within or outside a physiologically acceptable range, specifically whether the glucose concentration is within the normal blood glucose range, or at a low or high blood glucose level. The status indicator may also be adapted to alert the wearer to device malfunctions, such as those caused by a power supply shortage. In some embodiments, the device may include an optical status indicator (e.g., a multi-color LED), an acoustic status indicator (e.g., a piezoelectric speaker element), and / or a tactile status indicator (e.g., a vibrator).

[0172] If necessary, the individual system components of the implantable device can be electrically connected to each other. The electrical connections can be provided by circuit boards and / or wires (e.g., micro gold wires) (not shown).

[0173] The preferred features in this regard are as described in the above specification.

[0174] Another aspect of this disclosure relates to a continuous monitoring device, such as a continuous glucose monitoring device, comprising:

[0175] - An outer housing surrounding a non-invasive system and an attachment device, the non-invasive system for determining physiological parameters such as glucose in tissues and / or fluids of a body site, and the attachment device for permanently retaining the housing to the body site, the system comprising:

[0176] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0177] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0178] 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues.

[0179] - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0180] - Power supply, and

[0181] - Optionally, at least one status indicator.

[0182] This also relates to methods for determining physiological parameters, such as glucose, in body fluids and / or tissues of body parts using continuous monitoring devices as described above.

[0183] In some embodiments, the continuous monitoring device measures glucose in subcutaneous adipose tissue and / or glucose in adjacent blood vessels, such as capillaries.

[0184] Figure 23Embodiments of a continuous monitoring system, such as a continuous glucose monitoring system, are shown. This system may be permanently (e.g., for a period of at least one week) externally attached to a body part, such as the upper arm or abdomen (21). The system is suitable for performing continuous monitoring of physiological parameters such as glucose. In some embodiments, the system is adapted to perform measurements at predetermined time intervals as needed, which may be constant or variable. For example, the time interval may range from about 1 minute to about 2 hours, or from about 5 minutes to about 1 hour, for example, about 10 minutes. In some embodiments, the user can select a suitable time interval at the system's control unit.

[0185] The system can be held in place on a body part by an attachment device (22) (e.g., single-sided or double-sided tape). The attachment device may include one or more slits to allow system components (e.g., radiation source (38) and sensors (23, 35)) to be close to the subject's skin. The connection between the system and the attachment device may be provided by a suitable locking device (37) such as a bayonet lock.

[0186] The continuous monitoring system includes an external housing (26). The housing (26) may be water-resistant or water-proof to protect system components from water exposure. The housing may be made of a biocompatible material, such as a biocompatible metal, biocompatible plastic, biocompatible glass, or biocompatible composite. In some embodiments, the housing completely surrounds the system.

[0187] The system includes at least one radiation source (38) suitable for emitting 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 tissue (39) of a body part (21). In some embodiments, the system includes multiple radiation sources (38), for example, 2, 3, 4 or 5 radiation sources.

[0188] Figure 23The system includes a sensing unit comprising at least one sensor (35), such as an optical sensor and / or a high-temperature measurement sensor, for detecting IR radiation emitted from a previously irradiated body part in a range of about 5 µm to about 12 µm, as described herein. 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 irradiated body part (21), and the sensing unit is adapted to (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 bodily fluids and / or tissues (39) of the irradiated body part (21). In some embodiments, the system includes multiple sensors (35), for example, 2, 3, 4, or 5 sensors. The sensors (35) may be provided with an optical filter element (36) adapted to detect IR radiation having a desired wavelength or wavelength range. In some embodiments, the system also includes a sensor (23) adapted for direct contact with the skin of a subject. The sensor (23) can be a contact temperature sensor. The sensor can be mounted on a circuit board (24).

[0189] Figure 23 The system also includes a control unit, specifically a highly integrated microcontroller, such as an ASIC. The control unit may be mounted on a circuit board (33) attached to a circuit board (24) via a rigid or flexible connecting element (25). The control unit is adapted to control the measurement process. In some embodiments, the control unit is also adapted to analyze the measurement results by quantitatively and / or qualitatively determining physiological parameters based on the measurement results. In some embodiments, the control unit includes a communication device (not shown) for communicating with an external device, such as a smartphone or smartwatch. The communication device may be adapted to transmit signals (e.g., signals including measurement results and / or determination results, and / or signals including identification codes) to and / or receive signals from the external device. In some embodiments, the system includes communication devices (28, 31), such as a Bluetooth antenna (28) and / or an RFID antenna (31).

[0190] also, Figure 23The system includes a power source. In some embodiments, the system includes an internal power source that can be recharged from an external power source. The power source may include a battery (34), such as a disposable battery or a rechargeable battery. In some embodiments, the battery may be recharged wirelessly (e.g., by capacitor charging), for example, using a charging coil (32). Furthermore, the power source may include a capacitor (27) (e.g., a supercapacitor or supercapacitor) as a short-term power storage device that provides power during power bursts when the radiation source (38) is excited. In some embodiments, the power source may also include a power harvesting device suitable for converting mechanical energy into electrical energy, such as a micro energy harvesting device.

[0191] In some embodiments, the system includes at least one status indicator adapted to indicate to the wearer whether a parameter to be determined is within or outside a physiologically acceptable range, specifically whether the glucose concentration is within the normal blood glucose range, or at a low or high blood glucose level. The status indicator may also be adapted to alert the wearer to device malfunctions, such as those caused by a power supply shortage. In some embodiments, the device may include an optical status indicator (29) (e.g., a multi-color LED), an acoustic status indicator (30) (e.g., a piezoelectric speaker element), and / or a tactile status indicator (not shown) (e.g., a vibrator).

[0192] If necessary, the individual system components of the implantable device can be electrically connected to each other. The electrical connections can be provided by circuit boards and / or wires (e.g., micro gold wires) (not shown).

[0193] The preferred features in this regard are as described in the above specification.

[0194] Another aspect of this disclosure also relates to a portable smart device, such as a smartphone, comprising:

[0195] - A housing comprising a front and a back, wherein the front includes a screen and a keyboard and the back includes a recess for accommodating body parts such as fingertips, and the housing includes a non-invasive system integrated into the recess on the back, the non-invasive system being used to determine physiological parameters such as glucose in bodily fluids and / or tissues of a body part, the system comprising:

[0196] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0197] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0198] 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 within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range is substantially independent of the concentration of a physiological parameter in the subject's body fluids and / or tissues.

[0199] - A control unit, adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on IR radiation detected in the sensing unit, and

[0200] - Optionally, at least one status indicator.

[0201] This also includes a method for determining physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part using the smart device described above.

[0202] Figure 24 Another embodiment of this disclosure is shown, which is a portable smart device, such as a smartphone, comprising a front (not shown) and a back. The front includes a screen and a keyboard. A system for determining physiological parameters, such as glucose, in bodily fluids and / or tissues of a body part is integrated into the back. Integrating the system into the back of the device has several advantages. There is no impairment to the screen's display function. There is also no energy loss because radiation does not need to penetrate the screen. Furthermore, measurements can be taken while operating the keyboard on the front.

[0203] Figure 24 The illustrated device includes a recess in its back for accommodating a body part, such as a fingertip. This 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 some embodiments, the system includes multiple radiation sources, for example, 2, 3, 4, or 5 radiation sources. Figure 24 In the middle, the device has two radiation sources, namely, the two small holes shown in the recess.

[0204] Figure 24 The system includes a sensing unit comprising at least one sensor, such as an optical sensor and / or a high-temperature measurement sensor, for detecting IR radiation emitted from a previously irradiated body part in a range of about 5 µm to about 12 µm, as described herein. 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 irradiated body part (5), and the sensing unit is adapted to (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 some embodiments, the system includes multiple sensors, for example, 2, 3, 4, or 5 sensors. Figure 24 The device has three sensors, namely the three large holes shown in the recess. Two of the sensors are... Figure 20 The dual-sensor chip described herein. The sensor can be provided with optical filter elements suitable for detecting IR radiation with a desired wavelength or wavelength range.

[0205] Below the recess, electrical connections to the control unit and / or power unit of the smart device are shown.

[0206] The preferred features in this regard are as described in the above specification.

[0207] In the following description, certain aspects and embodiments of this disclosure are depicted as part of the specification. These embodiments particularly relate to the aspects described in the appended claims.

[0208] Detailed implementation method of the instruction manual

[0209] 1. A non-invasive system for determining physiological parameters in a subject's body fluids, comprising:

[0210] (a) A radiation source suitable for emitting 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 localized increase in tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0211] (b) A sensing unit for detecting IR radiation emitted from a previously irradiated body part of the subject in a range of about 5 µm to about 12 µm.

[0212] 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 within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids.

[0213] 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.

[0214] The sensing unit is adapted to (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 physiological parameters in the subject's body fluids, and

[0215] (c) An analysis unit or control unit for qualitatively and / or quantitatively determining physiological parameters based on the IR radiation detected in the sensing unit (b).

[0216] 2. The system as described in Example 1, wherein the system does not include a radiation source for emitting IR radiation with a wavelength range of about 5 µm to about 12 µm.

[0217] 3. The system as described in Example 1 or 2, wherein the physiological parameters are selected from compounds having at least one characteristic absorption band in the IR range of about 5 µm to about 12 µm, specifically in the range of about 8 µm to about 10 µm.

[0218] 4. The system as described in any of the foregoing embodiments, wherein the physiological parameter is glucose.

[0219] 5. The system as described in any of the foregoing embodiments, wherein the bodily fluid is blood.

[0220] 6. The system as described in any of the foregoing embodiments for determining 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, wherein the at least one wavelength or wavelength range is specifically selected from about 9.2 µm, about 9.4 µm, about 9.6 µm, including at least two of about 9.2 µm, about 9.4 µm, and about 9.6 µm, including all three of about 9.2 µm, about 9.4 µm, and about 9.6 µm, or any combination thereof.

[0221] 7. A system as described in any of the foregoing embodiments for determining 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, wherein the at least one wavelength or wavelength range is specifically selected from a wavelength or wavelength range between about 8.7 µm and about 9.0 µm, a wavelength or wavelength range between about 9.7 µm and about 10.2 µm, or any combination thereof.

[0222] 8. The system as described in any of the foregoing embodiments, wherein the system includes a single radiation source (a).

[0223] 9. The system as described in any one of Examples 1-7, wherein the system includes a plurality of radiation sources (a), for example, 2, 3, 4 or more, and for example, up to 10 individual radiation sources (a).

[0224] 10. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is adapted to emit VIS / NIR radiation in the range of about 400 nm to about 1200 nm, specifically in the range of about 550 nm to about 1100 nm, specifically in the range of about 800 nm to about 820 nm (e.g., at about 810 nm), and / or in the range of about 590 nm to about 660 nm (e.g., at about 600 nm), and / or in the range of about 920 nm to about 980 nm (e.g., at about 940 nm).

[0225] 11. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is adapted to emit collimated radiation and / or to emit non-collimated radiation.

[0226] 12. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is an LED, a laser diode, a VCSEL (vertical cavity surface-emitting laser), or a laser.

[0227] 13. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently at predetermined time intervals.

[0228] 14. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is adapted to emit VIS / NIR radiation to obtain a local temperature increase in the irradiated body part, specifically an increase of about 2°C to about 10°C in the absorption region of the irradiated body part, specifically an increase of about 3°C ​​to about 5°C.

[0229] 15. The system as described in Example 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, specifically at a power of about 20 mW to about 500 mW and more specifically at a power of about 50 mW to about 250 mW.

[0230] 16. The system as described in Examples 13, 14 or 15, wherein the radiation source (a) is adapted to continuously emit VIS / NIR radiation for time intervals of about 0.1 s to about 20 s, specifically about 1 s to about 5 s and more specifically about 0.5 s to about 2 s.

[0231] 17. The system as described in Example 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, specifically at a power of about 20 mW to about 1 W and more specifically at a power of about 50 mW to about 500 mW.

[0232] 18. The system as described in Examples 13, 14 or 17, wherein the radiation source (a) is adapted to intermittently emit VIS / NIR radiation for time intervals of about 0.1 s to about 20 s, specifically about 0.2 s to about 5 s and more specifically about 0.5 s to about 2 s.

[0233] 19. The system as described in Examples 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.

[0234] 20. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently for a period of at least about 0.5 s, specifically for a period of at least about 1 s to about 120 s and more specifically for a period of at least about 2 s to about 20 s.

[0235] 21. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is a multi-wavelength radiation source, specifically wherein the radiation source is adapted to emit VIS / NIR radiation at several (e.g., 2, 3, 4, 6, 8, 10 or more) different wavelengths or wavelength ranges between about 400 nm and about 1200 nm, more specifically between about 450 nm and about 900 nm, for example, at least 2, 3, 4, 6 or 8 wavelengths may be selected from about 470 nm, about 520 nm, about 590 nm, about 650 nm, about 750 nm and about 810 nm.

[0236] 22. The system as described in any of the foregoing embodiments, wherein the radiation source (a) and the sensing unit (b) are located relative to the irradiated body part, the location being defined by an angle of at least 90° or greater.

[0237] 23. The system as described in any of the foregoing embodiments, wherein the radiation source (a) is provided on the side of the body part opposite to the sensing unit (b).

[0238] 24. The system as described in any of the foregoing embodiments, wherein at least one radiation source (a) is provided on one side of a body part that allows radiation to be emitted directly into the body part without passing through the system.

[0239] 25. The system as described in any of the foregoing embodiments, wherein at least one radiation source (a) is provided on a body part that allows radiation to be emitted directly into the body part without penetrating the keratinous portion of the body surface, such as one side of a nail.

[0240] 26. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to detect self-emitted IR radiation from a previously irradiated body part.

[0241] 27. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an absorption region in a previously irradiated body part, wherein the absorption region has a locally elevated temperature and exhibits an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0242] 28. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) includes at least one first sensor, at least one second sensor, and optionally at least one third sensor.

[0243] The at least one first sensor is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids.

[0244] The at least one second sensor is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range is substantially independent of the concentration of physiological parameters in the subject's body fluids, and

[0245] The at least one third sensor, if present, is (i) suitable for detecting nonspecific IR radiation, (ii) suitable for detecting nonspecific VIS / NIR radiation, (iii) suitable for detecting VIS / NIR radiation with a wavelength in which the intensity of the VIS / NIR radiation detected depends on the concentration of a physiological parameter in the subject's body fluids, and / or (iv) is a temperature sensor for measuring the temperature of a body part.

[0246] 29. The system as described in Example 28, wherein both the at least one first sensor and the at least one second sensor are provided with filter elements and optionally lens elements, which are optically transparent in a predetermined wavelength or wavelength range.

[0247] 30. The system as described in Example 28 or 29 includes at least two different first sensors adapted to detect IR radiation having at least two different wavelengths or wavelength ranges.

[0248] 31. The system as described in Examples 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, wherein the second wavelength range includes the first wavelength or wavelength range and also includes another wavelength or wavelength range.

[0249] 32. The system for determining glucose in blood as described in Example 31, 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 between about 9.2 µm and about 9.6 µm.

[0250] 33. The system for determining glucose in blood as described in Example 31, wherein a first sensor is adapted to detect IR radiation having a wavelength of about 9.6 µm, and another first sensor is adapted to detect IR radiation having a wavelength range between about 9.4 µm and about 9.6 µm.

[0251] 34. The system as described in any one of Examples 28-33 includes at least two different second sensors adapted to detect IR radiation having at least two different wavelengths or wavelength ranges.

[0252] 35. The system for determining glucose in blood as described in Example 33, wherein a second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 8.6 µm and 9.0 µm, and another second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 9.8 µm and about 10.2 µm.

[0253] 36. A system for determining glucose in blood as described in any of Examples 28-33, wherein a second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 7.8 µm and about 8.2 µm, and optionally at least one other second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 8.6 µm and about 9.0 µm and / or is adapted to detect IR radiation having a wavelength or wavelength range between about 9.8 µm and about 10.2 µm.

[0254] 37. A system for determining glucose in blood as described in any of Examples 28-36, comprising at least one third sensor adapted to detect VIS / NIR radiation, specifically having VIS / NIR radiation with a wavelength of about 940 nm.

[0255] 38. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) comprises at least one sensor adapted to detect IR radiation having different wavelengths or wavelength ranges in a time-dependent and individual manner, wherein during at least one first time interval, the sensor is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids, and

[0256] During at least one second time interval, the sensor 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 physiological parameters in the subject's body fluids.

[0257] 39. The system as described in Example 38, wherein the sensing unit (b) includes at least one sensor, the at least one sensor being provided with a plurality of filters adapted to transmit IR radiation with different wavelengths or wavelength ranges.

[0258] 40. The system as described in Example 38 or 39, wherein the sensor is provided with a light-shielding wheel and / or a light-filtering wheel.

[0259] 41. The system of embodiment 40, wherein the light-shielding wheel includes a plurality of openings, wherein at least some of the openings are provided with filter elements and optionally lens elements, the elements being optically transparent in a predetermined wavelength or wavelength range.

[0260] 42. The system as described in Example 38, wherein the sensing unit (b) includes at least one sensor, the at least one sensor being a Fabry-Perot interferometer.

[0261] 43. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) comprises at least one spectral sensor or line sensor or array of spectral or line sensors.

[0262] 44. The system as described in any of Examples 38-42, wherein the sensing unit (b) comprises a single sensor.

[0263] 45. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) includes at least one sensor, said at least one sensor being an optical detector, specifically an optical photovoltaic detector, and more specifically an InAsSb-based detector.

[0264] 46. ​​The system as described in any of the foregoing embodiments, wherein the sensing unit (b) includes at least one sensor, the at least one sensor being a thermopile or a radiative heat meter.

[0265] 47. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein the body part is irradiated with VIS / NIR radiation during at least a portion of the time period.

[0266] 48. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein during at least a portion of the time period, the temperature of the irradiated body part, specifically the absorbing region of the irradiated body part, is higher than that of the surrounding tissue.

[0267] 49. The system of claim 48, wherein the temperature of the irradiated body part, specifically the absorbing region of the irradiated body part, is at least 1°C, at least 2°C, at least 5°C, and up to 10°C higher than that of the surrounding tissue.

[0268] 50. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein during at least a portion of the time period, the temperature of a specific absorption area of ​​the irradiated body part increases.

[0269] 51. The system as described in any of the foregoing embodiments, wherein the temperature increases in the range of about 2°C to about 10°C, specifically in the range of about 3°C ​​to about 5°C.

[0270] 52. The system as described in any of Examples 47-51, wherein the time period is at least about 0.5 s, specifically at least about 1 s to about 120 s, and more specifically at least about 2 s to about 20 s.

[0271] 53. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is also adapted for temperature measurement, for example, having an accuracy of at least about 1°C, at least about 0.1°C, or even at least about 0.01°C.

[0272] 54. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) is adapted to measure and optionally monitor the skin temperature of the irradiated body part and optionally at least one other temperature, such as ambient temperature, the temperature of the respective sensors in the sensing unit (b) and / or the temperature of the electronic components of the sensing unit (b).

[0273] 55. The system as described in any of the foregoing embodiments, wherein the sensing unit (b) includes at least one temperature sensor, specifically multiple temperature sensors, such as two, three, or four temperature sensors for measuring skin temperature, and optionally includes at least one other temperature sensor, such as a sensor for measuring ambient temperature, at least one sensor for measuring the temperature of each sensor in the sensing unit, and / or a sensor for measuring the temperature of the electronic components of the sensing unit (b).

[0274] 56. The system as described in any of the foregoing embodiments, wherein the analysis unit (c) includes a microcontroller adapted to quantitatively determine the concentration of a physiological parameter and / or to non-quantitatively determine the rate of change of a physiological parameter.

[0275] 57. The system as described in any of the foregoing embodiments, wherein the analysis unit (c) is adapted to perform time-dependent analysis of detected IR radiation, wherein the measurement signal is recorded over a time period.

[0276] 58. The system as described in Example 57, wherein the time period is at least about 0.5 s, specifically at least about 1 s to about 120 s, and more specifically at least about 2 s to about 20 s.

[0277] 59. The system as described in any of the foregoing embodiments, wherein the analysis unit (c) is adapted to perform temperature-compensated analysis of detected IR radiation.

[0278] 60. The system as described in Example 59, wherein the temperature compensation analysis includes temperature compensation, in which the measurement signal is temperature corrected.

[0279] 61. The system as described in Embodiment 59 or 60, wherein the temperature compensation is based on the skin temperature of the irradiated body part and optionally at least one other temperature such as ambient temperature, the temperature of the components of the sensing unit, such as the temperature of the various sensors in the sensing unit and / or the temperature of the electronic components of the sensing unit.

[0280] 62. The system as described in any of Examples 57-61, wherein the analysis unit (c) is adapted for time-dependent analysis and temperature-compensated analysis of detected IR radiation.

[0281] 63. The system as described in any of the foregoing embodiments, the system being adapted to detect IR radiation from a body part selected from fingertips, earlobes, forearms, palms, and upper arms.

[0282] 64. The system as described in any of the foregoing embodiments, wherein the radiation source (a) and the sensing unit (b) are arranged on the same side of the body part.

[0283] 65. The system as described in any of the foregoing embodiments, wherein the radiation source (a) and the sensing unit (b) are arranged on different sides, specifically on opposite sides of the body parts.

[0284] 66. The system as described in any of the foregoing embodiments, wherein a first radiation source (a) is arranged on the same side of the body part as the sensing unit (b), and another radiation source (a) is arranged on a different side, specifically on the side of the body part opposite to the sensing unit.

[0285] 67. The system as described in any of the foregoing embodiments further includes a cover, wherein the cover is made at least in part of a material that is optically transparent to VIS / NIR radiation emitted by the radiation source (a) and / or to IR radiation detected by the sensing unit (b).

[0286] 68. The system as described in Example 67, wherein the cover is at least partially made of CaF2 and / or BaF2 or a plastic material that is transparent to IR radiation and optionally to VIS / NIR radiation.

[0287] 69. The system as described in Example 67 or 68, wherein the optically transparent material of the cover has a thickness of about 0.2 mm to about 2 mm, specifically about 0.5 mm to about 1.5 mm, more specifically about 1 mm.

[0288] 70. The system as described in any of the foregoing embodiments further includes a cover, wherein the cover is made at least in part of a material that is optically transparent to the IR radiation to be detected by the sensing unit, specifically in the IR wavelength range or subrange of about 5 µm to about 12 µm, and wherein the material is optionally substantially optically impermeable to VIS / NIR radiation emitted by the radiation source (a).

[0289] 71. The system as described in any of the foregoing embodiments further includes a cover that focuses IR radiation from the body part onto the sensing unit (b), specifically onto at least one sensor of the sensing unit (b).

[0290] 72. The system as described in Example 71, wherein the cover includes an IR Fresnel lens or an array including a plurality of IR Fresnel lenses.

[0291] 73. The use of the system as described in any of the foregoing embodiments for non-invasively determining physiological parameters in the body fluids of a subject.

[0292] 74. The use as described in Example 73, wherein the physiological parameter is glucose and the body fluid is blood.

[0293] 75. Use as described in Examples 73 or 74, wherein the physiological parameter is quantitatively determined.

[0294] 76. The use as described in Examples 73, 74 or 75, wherein the rate of change of the physiological parameter is determined non-quantitatively.

[0295] 77. A method for non-invasively determining physiological parameters in the body fluids of a subject, comprising the following steps:

[0296] (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0297] (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm.

[0298] This includes, respectively, (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 the subject's body fluids.

[0299] 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

[0300] (ii) Detecting IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within said at least one wavelength or wavelength range is substantially independent of the concentration of physiological parameters in the subject's body fluids, and

[0301] (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of the physiological parameters.

[0302] 78. The method as described in Example 77, wherein the body part is not irradiated by an IR radiation source in the wavelength range of about 5 µm to about 12 µm.

[0303] 79. The method as described in Example 77 or 78, wherein the physiological parameter is glucose and the body fluid is blood.

[0304] 80. The method as described in Examples 77, 78 or 79, wherein the physiological parameter is quantitatively determined.

[0305] 81. The method as described in any of Examples 77-80, wherein the rate of change of the physiological parameter is determined non-quantitatively.

[0306] 82. A device comprising a non-invasive system for determining physiological parameters in a subject's bodily fluids, wherein the device includes a housing, and wherein the device comprises:

[0307] (a) A radiation source adapted to emit visible (VIS) / near-infrared (NIR) radiation in the range of about 400 nm to about 1500 nm onto a body part of the subject, wherein the body part is specifically selected from fingertips, multiple fingertips, and the palm, and wherein the radiation source is also adapted to allow the irradiated body part to absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0308] (b) A sensing unit for detecting IR radiation emitted from a previously irradiated body part of the subject in the range of about 5 µm to about 12 µm.

[0309] 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 within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids.

[0310] 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.

[0311] The sensing unit is adapted to (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 physiological parameters in the subject's body fluids, and

[0312] (c) An analysis unit adapted to qualitatively and / or quantitatively determine physiological parameters based on IR radiation detected in the sensing unit (b), and

[0313] The shell includes a first surface, the first surface including a screen, wherein the screen is at least partially made of a material that is optically transparent to VIS / NIR radiation emitted by the radiation source (a) and / or to IR radiation detected by the sensing unit (b).

[0314] The radiation source (a), the sensing unit (b), and the analysis unit (c) are integrated within the housing.

[0315] 83. The device as described in Example 82,

[0316] The radiation source (a) mentioned therein is suitable for emitting radiation through a screen.

[0317] 84. The device as described in Example 82 or 83,

[0318] The sensing unit (b) is adapted to detect radiation entering the housing through the screen.

[0319] 85. The device as described in any one of Examples 82-84,

[0320] The screen described therein is approximately 1 cm 2 Approximately 500 cm 2 The size is approximately 2 cm. 2 Approximately 200 cm 2 The size.

[0321] 86. The device as described in any one of Examples 82-85,

[0322] The screen described therein is essentially flat.

[0323] 87. The device as described in any one of Examples 82-86,

[0324] The device is suitable for displaying the contact position of body parts on a screen.

[0325] 88. The device as described in any one of Examples 82-87,

[0326] The device in question is a mobile device.

[0327] 89. The device as described in any one of Examples 82-88,

[0328] The device is selected from smartphones, smartwatches, tablets, or health trackers.

[0329] 90. The device as described in any one of Examples 82-89,

[0330] The optically transparent material is selected from inorganic materials such as CaF2 and / or BaF2 and organic materials such as plastics.

[0331] 91. The device as described in any one of Examples 82-90,

[0332] The optically transparent material has a thickness of about 0.2 mm to about 2 mm, specifically about 0.3 mm to about 1 mm.

[0333] 92. The device as described in any one of Examples 82-91,

[0334] The device does not include a radiation source for emitting IR radiation with wavelengths ranging from about 5 µm to about 12 µm.

[0335] 93. The device as described in any one of Examples 82-92,

[0336] The physiological parameter mentioned therein is glucose, and the body fluid mentioned is glucose.

[0337] 94. The device as described in any one of Examples 82-93,

[0338] The device is suitable for determining glucose in blood, wherein the sensing unit is suitable for detecting 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, 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 including at least two of a wavelength of about 9.2 µm, a wavelength range including a wavelength of about 9.4 µm, a wavelength range including a wavelength of about 9.2 µm, a wavelength of about 9.4 µm, and a wavelength of about 9.6 µm, or any combination thereof.

[0339] 95. The device as described in any one of Examples 82-94,

[0340] The radiation source (a) described therein is suitable for emitting VIS / NIR radiation in the range of about 550 nm to about 1200 nm, specifically in the range of about 800 nm to about 820 nm (e.g., at about 810 nm), and / or in the range of about 590 nm to about 610 nm (e.g., at about 600 nm), and / or in the range of about 920 nm to about 980 nm (e.g., at about 940 nm).

[0341] 96. The device as described in any one of Examples 82-95,

[0342] The radiation source (a) is an LED, a laser diode, a VCSEL (vertical cavity surface-emitting laser), or a laser.

[0343] 97. The device as described in any one of Examples 82-96,

[0344] The radiation source (a) mentioned therein is a multi-wavelength radiation source.

[0345] 98. The device as described in any one of Examples 82-97, wherein the radiation source (a) is adapted to emit VIS / NIR radiation continuously or intermittently for a period of at least about 0.5 s, specifically at least about 1 s to about 120 s and more specifically at least about 2 s to about 20 s.

[0346] 99. The device as described in any one of Examples 82-98,

[0347] At least one of the first sensors 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.

[0348] The second wavelength range includes the first wavelength or wavelength range and also includes another wavelength or wavelength range.

[0349] The system is specifically adapted to determine 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 between about 9.2 µm and about 9.6 µm, including a first wavelength of about 9.2 µm and including at least one wavelength of about 9.4 µm and about 9.6 µm, and particularly including wavelengths of about 9.4 µm and about 9.6 µm.

[0350] 100. The device as described in any one of Examples 82-99,

[0351] The device includes at least two different second sensors, which are adapted to detect IR radiation having at least two different wavelengths or wavelength ranges.

[0352] The system is specifically adapted to determine glucose in blood, wherein a second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 8.6 µm and 9.0 µm, and another second sensor is adapted to detect IR radiation having a wavelength or wavelength range between about 9.8 µm and about 10.2 µm.

[0353] 101. The device as described in any one of Examples 82-100,

[0354] The sensing unit (b) includes at least one sensor adapted to detect IR radiation of different wavelengths or wavelength ranges in a time-dependent and individual manner.

[0355] During at least one first time interval, the sensor is adapted to detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids, and

[0356] During at least one second time interval, the sensor 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 physiological parameters in the subject's body fluids.

[0357] 102. The device as described in any one of Examples 82-101,

[0358] The sensing unit (b) therein comprises a single sensor.

[0359] 103. The device as described in any one of Examples 82-102,

[0360] The sensing unit (b) includes at least one sensor, which is an optical detector, specifically an optical photovoltaic detector, and more specifically an InAsSb-based detector.

[0361] 104. The device as described in any one of Examples 82-103,

[0362] The device also includes a lens element adapted to focus IR radiation from the body part onto the sensing unit (b), specifically onto at least one sensor of the sensing unit (b).

[0363] The lens element is incorporated within the housing, and specifically, the lens element comprises an IR Fresnel lens or an array comprising a plurality of IR Fresnel lenses.

[0364] 105. The device as described in any one of Examples 82-104, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein the body part is irradiated with VIS / NIR radiation during at least a portion of the time period.

[0365] 106. The device as described in any one of Examples 82-105, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein during at least a portion of the time period, the temperature of the irradiated body part, specifically the absorbing region of the irradiated body part, is higher than that of the surrounding tissue.

[0366] 107. The device as described in Example 106, wherein the temperature of the irradiated body part, specifically the absorbing region of the irradiated body part, is at least 1°C, at least 2°C, at least 5°C, and up to 10°C higher than that of the surrounding tissue.

[0367] 108. The device as described in any one of Examples 82-107, wherein the sensing unit (b) is adapted to detect IR radiation emitted from an irradiated body part over a time period, wherein during at least a portion of the time period, the temperature of the irradiated body part, specifically the absorbing region, rises.

[0368] 109. The device as described in Example 108, wherein the temperature increases in the range of about 2°C to about 10°C, specifically in the range of about 3°C ​​to about 5°C.

[0369] 110. The device as described in any of Examples 102-109, wherein the time period is at least about 0.5 s, specifically at least about 1 s to about 120 s, and more specifically at least about 2 s to about 20 s.

[0370] 111. The device as described in any one of Examples 82-110, wherein the sensing unit (b) is also adapted for temperature measurement, for example, having an accuracy of at least about 1°C, at least about 0.1°C, or even at least about 0.01°C.

[0371] 112. The device as described in any one of Examples 82-111, wherein the sensing unit (b) is adapted to measure and optionally monitor the skin temperature of the irradiated body part and optionally at least one other temperature, such as ambient temperature, the temperature of the respective sensors in the sensing unit (b) and / or the temperature of the electronic components of the sensing unit (b).

[0372] 113. The device as described in any one of embodiments 82-112, wherein the sensing unit (b) includes at least one temperature sensor, specifically multiple temperature sensors, such as two, three, or four temperature sensors for measuring skin temperature, and optionally includes at least one other temperature sensor, such as a sensor for measuring ambient temperature, at least one sensor for measuring the temperature of each sensor in the sensing unit, and / or a sensor for measuring the temperature of the electronic components of the sensing unit (b).

[0373] 114. The device as described in any one of Examples 82-113, wherein the analysis unit (c) includes a microcontroller adapted to quantitatively determine the concentration of a physiological parameter and / or to non-quantitatively determine the rate of change of a physiological parameter.

[0374] 115. The apparatus of any one of Examples 81-114, wherein the analysis unit (c) is adapted to perform time-dependent analysis of detected IR radiation, wherein the measurement signal is recorded over a time period.

[0375] 116. The device as described in Example 115, wherein the time period is at least about 0.5 s, specifically at least about 1 s to about 120 s and more specifically at least about 2 s to about 20 s.

[0376] 117. The apparatus of any one of Examples 82-116, wherein the analysis unit (c) is adapted to perform temperature-compensated analysis of detected IR radiation.

[0377] 118. The device as described in Example 117, wherein the temperature compensation analysis includes temperature compensation, in which the measurement signal is temperature corrected.

[0378] 119. The device as described in Embodiments 117 or 118, wherein the temperature compensation is based on the skin temperature of the irradiated body part and optionally at least one other temperature such as ambient temperature, the temperature of the components of the sensing unit, such as the temperature of the various sensors in the sensing unit and / or the temperature of the electronic components of the sensing unit.

[0379] 120. The device as described in any one of Examples 82-119, wherein the analysis unit (c) is adapted for time-dependent analysis and temperature-compensated analysis of detected IR radiation.

[0380] 121. The use of the device as described in any one of Examples 82-120 for non-invasively determining a physiological parameter in a subject's body fluid, wherein the physiological parameter is glucose, and the body fluid is blood, and wherein the rate of change of the amount of glucose in the blood is determined.

[0381] 122. A method for non-invasively determining physiological parameters in the body fluids of a subject, comprising the following steps:

[0382] (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0383] (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm.

[0384] This includes, respectively, (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 the subject's body fluids.

[0385] 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

[0386] (ii) Detecting IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within said at least one wavelength or wavelength range is substantially independent of the concentration of physiological parameters in the subject's body fluids, and

[0387] (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of the physiological parameters.

[0388] The radiation source (a), the sensing unit (b), and the analysis unit (c) are integrated within the housing, and

[0389] The shell includes a first surface, the first surface including a screen, wherein the screen is made at least partially of a material that is optically transparent to VIS / NIR radiation emitted by the radiation source (a) and / or to IR radiation detected by the sensing unit (b).

[0390] 123. The method as described in Example 122,

[0391] The body parts described herein are not exposed to IR radiation sources in the wavelength range of approximately 5 µm to approximately 12 µm.

[0392] 124. The method as described in Examples 122 or 123,

[0393] The physiological parameter mentioned is glucose and the body fluid mentioned is blood.

[0394] 125. The method as described in any of Examples 122-124,

[0395] The concentration of the physiological parameter is quantitatively determined, and / or the rate of change of the amount of the physiological parameter is determined, specifically non-quantitatively.

[0396] 126. The method as described in any of Examples 122-125,

[0397] Step (b) further includes (iii) performing temperature measurement, and step (c) further includes performing temperature compensation analysis on the detected IR radiation.

[0398] 127. The system as described in any one of Examples 1-72 or the device as described in any one of Examples 82-120, wherein the sensing unit (b) includes at least one sensor, the at least one sensor including a plurality of chips, the plurality of chips including different optical filter elements for detecting different wavelengths or wavelength ranges.

[0399] 128. The system as described in any of Examples 1-72 or the device as described in any of Examples 82-120 is a single unit comprising a radiation source (a), a sensing unit (b), and an analysis unit (c) in a single application-specific integrated circuit (ASIC).

[0400] 129. A non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose, comprising:

[0401] - An outer housing surrounding a non-invasive system for determining ethanol in the tissues and / or body fluids of a subject, such as a human subject, or simultaneously determining ethanol and glucose in the tissues and / or body fluids of a subject, such as a human subject, the system comprising:

[0402] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0403] - Sensing unit

[0404] The sensing unit is adapted to (i) detect IR radiation with a first parameter specific having a first wavelength or a first wavelength range and IR radiation with a second parameter specific having a second wavelength or a second wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the body fluids and / or tissues 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.

[0405] The first parameter-specific IR radiation has a wavelength of approximately 9.2 µm, and the second parameter-specific IR radiation includes a wavelength range from approximately 9.2 µm to approximately 9.6 µm.

[0406] The sensing unit is also adapted to (ii) detect 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 glucose and / or ethanol in the subject's body fluids and / or tissues, and

[0407] - A control unit adapted to qualitatively and / or quantitatively determine both glucose and ethanol based on IR radiation detected in the sensing unit.

[0408] 130. The device as described in Example 129,

[0409] The reference IR radiation has a wavelength of about 8.8 µm or a wavelength range including about 8.8 µm, for example, a wavelength range between about 7.5 µm and about 9.0 µm, and / or

[0410] The reference IR radiation has a wavelength of about 10.2 µm or a wavelength range including about 10.2 µm, for example, a wavelength range between about 9.7 µm and about 10.5 µm.

[0411] 131. A method for non-invasively determining ethanol or glucose and ethanol in the body fluids of a subject, comprising the following steps:

[0412] (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0413] (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm.

[0414] Includes (i) detecting IR radiation specific to a first parameter having a first wavelength or a first wavelength range and IR radiation specific to a second parameter having a second wavelength or a second 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;

[0415] The first parameter-specific IR radiation has a wavelength of approximately 9.2 µm, and the second parameter-specific IR radiation includes a wavelength range from approximately 9.2 µm to approximately 9.6 µm.

[0416] (ii) Detecting reference IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within said at least one wavelength or wavelength range is substantially independent of the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues, and

[0417] (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of both glucose and ethanol.

[0418] 132. The method as described in Example 131,

[0419] The reference IR radiation has a wavelength of about 8.8 µm or a wavelength range including about 8.8 µm, for example, a wavelength range between about 7.5 µm and about 9.0 µm, and / or

[0420] The reference IR radiation has a wavelength of about 10.2 µm or a wavelength range including about 10.2 µm, for example, a wavelength range between about 9.7 µm and about 10.5 µm.

[0421] 133. A non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, comprising:

[0422] - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising:

[0423] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0424] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0425] The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues.

[0426] - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameter based on IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of multiple individual measurements.

[0427] 134. The device as described in Example 133,

[0428] The control unit is adapted to monitor the temperature of the irradiated body part during the measurement process, and to perform separate measurements when the temperature of the body part is excluded from the determination.

[0429] 135. A method for non-invasively determining a physiological parameter, such as glucose, comprising the following steps:

[0430] (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0431] (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm.

[0432] This includes (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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; 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 subject's body fluids and / or tissues.

[0433] (c) Detected IR radiation is analyzed by a measurement sequence consisting of multiple individual measurements for qualitative and / or quantitative determination of the physiological parameters.

[0434] 136. The method as described in Example 135,

[0435] The temperature of the irradiated body part is monitored during the measurement process, and separate measurements performed when the temperature of the body part rises are excluded from the determination.

[0436] 137. A non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, comprising:

[0437] - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising:

[0438] - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0439] - A sensing unit for detecting IR radiation emitted from a previously IR-irradiated body part of the subject, in a range of approximately 5 µm to approximately 12 µm.

[0440] The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues.

[0441] - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit.

[0442] The radiation source is adapted to emit visible (VIS) / near-infrared (NIR) radiation into the body during a predetermined irradiation period, and the sensing unit is adapted to perform a measurement of the IR radiation emitted from the body part during a subsequent dissipation period.

[0443] 138. The device as described in Example 137,

[0444] The sensing unit is adapted to perform measurements within a time period of approximately 1 second, approximately 500 ms, or approximately 200 ms after the radiation source is turned off.

[0445] 139. A method for non-invasively determining a physiological parameter, such as glucose, comprising the following steps:

[0446] (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm.

[0447] (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm.

[0448] This includes (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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; 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 subject's body fluids and / or tissues.

[0449] (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of the physiological parameters.

[0450] The radiation source emits visible (VIS) / near-infrared (NIR) radiation into the body during a predetermined irradiation period, and performs measurements of the IR radiation emitted from the body part during a subsequent dissipation period.

[0451] 140. The method as described in Example 139,

[0452] The measurements were performed within time intervals of approximately 2 s, approximately 1.5 s, approximately 1 s, approximately 500 ms, or approximately 200 ms after the radiation source was turned off.

[0453] 141. The device as described in any of the foregoing embodiments,

[0454] The device also includes a monitoring device, such as a photodiode, for detecting fluctuations, such as power fluctuations in radiation emitted by a radiation source.

Claims

1. An implantable device, comprising: - An implantable outer shell that surrounds a system for determining physiological parameters, such as glucose, in tissues and / or body fluids at a body site, the system comprising: - A radiation source suitable for emitting 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 an increase in local 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 the subject, in a range of approximately 5 µm to approximately 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues. - A control unit, adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on IR radiation detected in the sensing unit. - Power supply, and - Optionally, at least one status indicator.

2. The implantable device as claimed in claim 1, wherein the implantable device is a needle-free device.

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

4. A continuous monitoring device, such as a continuous glucose monitoring device, comprising: - An outer housing surrounding a non-invasive system and an attachment device, the non-invasive system for determining physiological parameters such as glucose in tissues and / or fluids of a body site, and the attachment device for permanently retaining the housing to the body site, the system comprising: - A radiation source suitable for emitting 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 an increase in local 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 the subject, in a range of approximately 5 µm to approximately 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 the subject's body fluids, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (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 a physiological parameter in the subject's body fluids and / or tissues. - A control unit, which is adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit. - Power supply, and - Optionally, at least one status indicator.

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

6. A portable smart device, such as a smartphone, comprising: - A housing comprising a front and a back, wherein the front includes a screen and a keyboard and the back includes a recess for accommodating body parts such as fingertips, and the housing includes a non-invasive system integrated into the recess on the back, the non-invasive system being used to determine physiological parameters such as glucose in bodily fluids and / or tissues of a body part, the system comprising: - A radiation source suitable for emitting 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 an increase in local 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 the subject, in a range of approximately 5 µm to approximately 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 within the at least one wavelength or wavelength range depends on the concentration of a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within the at least one wavelength or wavelength range is substantially independent of the concentration of a physiological parameter in the subject's body fluids and / or tissues. - A control unit, adapted to control the measurement process and optionally to qualitatively and / or quantitatively determine the physiological parameters based on IR radiation detected in the sensing unit, and - Optionally, at least one status indicator.

7. A method for determining physiological parameters, such as glucose, in body fluids and / or tissues of a body part using the intelligent device as described in claim 6.

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

9. The system or method as described in any of the preceding claims, wherein the physiological parameter is glucose.

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

11. A non-invasive device for determining ethanol or for simultaneously determining ethanol and glucose, comprising: - An outer housing surrounding a non-invasive system for determining ethanol in the tissues and / or body fluids of a subject, such as a human subject, or simultaneously determining ethanol and glucose in the tissues and / or body fluids of a subject, such as a human subject, the system comprising: - A radiation source suitable for emitting 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 an increase in local temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm. - Sensing unit The sensing unit is adapted to (i) detect IR radiation with a first parameter specific having a first wavelength or a first wavelength range and IR radiation with a second parameter specific having a second wavelength or a second wavelength range, wherein the intensity of the detected IR radiation depends on the concentration of glucose and / or ethanol in the body fluids and / or tissues 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 approximately 9.2 µm, and the second parameter-specific IR radiation includes a wavelength range from approximately 9.2 µm to approximately 9.6 µm. The sensing unit is also adapted to (ii) detect 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 glucose and / or ethanol in the subject's body fluids and / or tissues, and The reference IR radiation specifically has a wavelength of about 8.8 µm or a wavelength range including about 8.8 µm, for example, a wavelength range between about 7.5 µm and about 9.0 µm, and / or The reference IR radiation specifically has a wavelength of about 10.2 µm or a wavelength range including about 10.2 µm, such as a wavelength range between about 9.7 µm and about 10.5 µm. - A control unit adapted to qualitatively and / or quantitatively determine both glucose and ethanol based on IR radiation detected in the sensing unit.

12. A method for non-invasively determining ethanol or glucose and ethanol in a subject's body fluids, comprising the following steps: (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm. (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm. Includes (i) detecting IR radiation specific to a first parameter having a first wavelength or a first wavelength range and IR radiation specific to a second parameter having a second wavelength or a second 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 approximately 9.2 µm, and the second parameter-specific IR radiation includes a wavelength range from approximately 9.2 µm to approximately 9.6 µm. Specifically, the reference IR radiation has a wavelength of about 8.8 µm or a wavelength range including about 8.8 µm, for example, a wavelength range between about 7.5 µm and about 9.0 µm, and / or The reference IR radiation specifically has a wavelength of about 10.2 µm or a wavelength range including about 10.2 µm, such as a wavelength range between about 9.7 µm and about 10.5 µm. (ii) Detecting reference IR radiation having at least one wavelength or wavelength range, wherein the intensity of the detected IR radiation within said at least one wavelength or wavelength range is substantially independent of the concentration of glucose and / or ethanol in the subject's body fluids and / or tissues, and (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of both glucose and ethanol.

13. A non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, comprising: - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising: - A radiation source suitable for emitting 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 an increase in local 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 the subject, in a range of approximately 5 µm to approximately 12 µm. The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues. - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameter based on IR radiation detected in the sensing unit, wherein the control unit is adapted to perform a measurement sequence consisting of multiple individual measurements. The control unit is specifically adapted to monitor the temperature of the irradiated body part during the measurement process, and to exclude separate measurements performed on the temperature of the body part from the determination.

14. A method for non-invasively determining a physiological parameter, such as glucose, comprising the following steps: (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm. (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm. This includes (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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; 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 subject's body fluids and / or tissues. (c) Analyzing the detected IR radiation through a measurement sequence consisting of multiple individual measurements for qualitative and / or quantitative determination of the physiological parameters. Specifically, the temperature of the irradiated body part is monitored during the measurement process, and separate measurements performed when the temperature of the body part rises are excluded from the determination.

15. A non-invasive monitoring device for determining physiological parameters, such as glucose, in the tissues and / or body fluids of a subject, such as a human subject, comprising: - A housing comprising a non-invasive system for determining physiological parameters, such as glucose, in the body fluids and / or tissues of a subject, such as a human subject, the system comprising: - A radiation source suitable for emitting 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 an increase in local 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 the subject, in a range of approximately 5 µm to approximately 12 µm. The sensing unit is adapted to (i) detect 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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; and the sensing unit is adapted to (ii) detect 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 a physiological parameter in the subject's body fluids and / or tissues. - A control unit adapted to qualitatively and / or quantitatively determine the physiological parameters based on the IR radiation detected in the sensing unit. The radiation source is adapted to emit visible (VIS) / near-infrared (NIR) radiation into the body during a predetermined irradiation period, and the sensing unit is adapted to perform a measurement of the IR radiation emitted from the body part during a subsequent dissipation period. The sensing unit is specifically adapted to perform measurements within a time period of approximately 1 second, approximately 500 ms, or approximately 200 ms after the radiation source is turned off.

16. A method for non-invasively determining a physiological parameter, such as glucose, comprising the following steps: (a) Irradiating body parts 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 parts absorb electromagnetic energy, resulting in an increase in local tissue temperature and an increase in the emission of IR radiation in the wavelength range of about 5 µm to about 12 µm. (b) Detecting IR radiation emitted from previously irradiated body parts of the subject in the wavelength range of approximately 5 µm to approximately 12 µm. This includes (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 a physiological parameter in the subject's body fluids and / or tissues, wherein the intensity of the emitted IR radiation decreases as the concentration of the physiological parameter increases and increases as the concentration of the physiological parameter decreases; 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 subject's body fluids and / or tissues. (c) Analyze the detected IR radiation for qualitative and / or quantitative determination of the physiological parameters. The radiation source emits visible (VIS) / near-infrared (NIR) radiation into the body during a predetermined irradiation period, and performs measurements of the IR radiation emitted from the body parts during a subsequent dissipation period. The measurements are specifically performed within time intervals of approximately 2 s, approximately 1.5 s, approximately 1 s, approximately 500 ms, or approximately 200 ms after the radiation source is turned off.

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