Implantable Glucose Monitor

Abstract

An implantable glucose monitor device for measuring a glucose concentration of a bodily fluid when implanted, the implantable device including a glucose measuring unit, the glucose measuring unit including a light source configured to emit light toward a light-transmitting portion of a housing of the device, the device further including an optical sensor configured to detect linearly polarized light returned from the light source through the transmissive portion and to output an electrical signal based on the detected light, and a wireless communication module configured to wirelessly communicate with an external wireless communication device, the wireless communication module configured to wirelessly transmit a signal based on the electrical signal to the external wireless communication device. [Selected figure] Figure 3

Description

[Technical field]

[0001] The present disclosure relates to implantable devices for measuring glucose concentration in bodily fluids when implanted, systems including the implantable devices, and methods of measuring glucose concentration. [Background technology]

[0002] Insulin treatment generally requires that diabetic patients often take repeated blood glucose measurements. Diabetic patients with Type I diabetes may test their blood glucose 5-9 times a day, while those with gestational diabetes may test their blood glucose up to 11 times each day.

[0003] Known blood glucose testing methods involve taking blood samples from a patient using a lancet. Taking blood using a lancet can be painful and uncomfortable for diabetic patients, especially when a high testing frequency is required. Repeated blood sampling from one skin site can lead to scars or calluses or high nerve density, which in turn makes it difficult to draw blood. Summary of the Invention [Means for solving the problem]

[0004] According to one aspect of the present disclosure, there is provided an implantable device for measuring a glucose concentration of a bodily fluid when implanted, the implantable device including: a glucose measuring unit including a first light source configured to emit light toward a light-transmitting portion of a housing of the device, and a first optical sensor configured to detect light returned from the first light source through the light-transmitting portion and to output a first electrical signal based on the detected light; and a wireless communication module configured to wirelessly communicate with an external wireless communication device, the wireless communication module configured to wirelessly transmit a signal based on the first electrical signal to the external wireless communication device. The implantable device allows for continuous remote monitoring of glucose levels of a patient in which the device is implanted, without the need to draw a blood sample using a lancet or similar device.

[0005] The wireless communication module is configured to wirelessly receive power from an external wireless communication device. This configuration is advantageous in that it provides an implantable device that does not require replacement of an internal power source, such as a non-rechargeable battery. Thus, the implantable device can be used repeatedly to monitor glucose levels over an extended period of time without the need to replace the device due to a dead battery. In some examples, the device can include a rechargeable power source, such as a battery, that is recharged by power received by the wireless communication module.

[0006] The implantable device is dimensioned for implantation within a human blood vessel or tissue that is well perfused with bodily fluids such as blood, and is advantageous because such an implantable device allows for accurate measurement of a patient's blood glucose.

[0007] The exterior surface of the housing may include a recess, which includes at least a portion of the light-transmitting portion. The recess is advantageous in that it can facilitate movement of bodily fluids, such as blood or interstitial fluid, around the implantable device to ensure that bodily fluids around the device do not stagnate, thus resulting in a more accurate glucose reading. In some examples, the exterior surface of the housing may include one or more protrusions, also to facilitate movement of bodily fluids around the implantable device. In some examples, the recess is formed from one or more protrusions of the housing. The presence of the recess is sometimes described herein in conjunction with other features of various embodiments, but the presence of the recess is not required.

[0008] The implantable device may further include at least one lens configured to focus light emitted from the first light source toward a point outside the housing, which lens enables accurate measurement of glucose concentration in bodily fluid surrounding the housing while reducing interference from external sources such as ambient light.

[0009] The light emitted from the first light source is linearly polarized and emitted through the light transmissive portion to a first region outside the housing. The first optical sensor is configured to detect the rotated linearly polarized light returning from the first region outside the housing through the light transmissive portion. The first optical sensor is further configured to output a first electrical signal based on the detected rotated light. This configuration provides a simple arrangement for measuring the glucose concentration of a bodily fluid.

[0010] According to some embodiments, the implantable device may further include a first linear polarizer arranged to linearly polarize the light emitted from the first light source into a first plane, a second linear polarizer arranged to linearly polarize the light from the first region outside the housing into a second plane substantially perpendicular to the first plane, and a third linear polarizer arranged to linearly polarize the light from the first region outside the housing into a third plane parallel to the first plane. The glucose measuring unit may further include a second optical sensor configured to detect the light returned through the light transmitting portion and to output a second electrical signal based on the detected light. The second linear polarizer is arranged such that a first portion of the linearly polarized light emitted from the first light source into the first region outside the housing is incident on the second linear polarizer. The third linear polarizer is arranged such that a second portion of the linearly polarized light emitted from the first light source into the first region outside the housing is incident on the third linear polarizer. The first optical sensor is positioned to detect a first portion of the linearly polarized light passing from the first region outside the housing through the second linear polarizer, and the second optical sensor is positioned to detect a second portion of the linearly polarized light passing from the first region outside the housing through the third linear polarizer. This arrangement provides a simple means for interference-free determination of glucose concentration in a body fluid.

[0011] According to some embodiments, the implantable device may further include a second light source configured to emit light through the light transmitting portion to a second region outside the housing, and a second optical sensor configured to detect the light returned through the light transmitting portion and output a second electrical signal based on the detected light. The implantable device may further include a first linear polarizer arranged to linearly polarize the light emitted from the first light source into a first plane, a second linear polarizer arranged to linearly polarize the light from the first region outside the housing into a second plane substantially orthogonal to the first plane, a third linear polarizer arranged to linearly polarize the light emitted from the second light source into a third plane, and a fourth linear polarizer arranged to linearly polarize the light from the second region outside the housing into a fourth plane, the fourth plane being parallel to the third plane. The second linear polarizer is arranged such that at least a portion of the linearly polarized light emitted from the first light source into the first region outside the housing is incident on the second linear polarizer. The fourth linear polarizer is positioned such that at least a portion of the linearly polarized light emitted from the second light source to a second region outside the housing is incident on the fourth linear polarizer. The first optical sensor is configured to detect at least a portion of the linearly polarized light emitted from the first light source and passed through the second linear polarizer. The second optical sensor is configured to detect at least a portion of the linearly polarized light emitted from the second light source and passed through the fourth linear polarizer. This arrangement provides a simple means for interference-suppressed determination of glucose concentration in a body fluid.

[0012] According to some embodiments, the glucose measuring unit is a refractometer. This arrangement provides a simple means for determining the glucose concentration in bodily fluids.

[0013] The refractometer may include a prism, the first light source and the prism arranged such that light emitted from the first light source passes through the prism and is incident on a surface of the prism, and the first optical sensor arranged to detect a portion of the light emitted from the first light source that passes through the prism and is reflected off the surface of the prism. This arrangement provides a particularly simple means for determining the glucose concentration in a body fluid.

[0014] According to some embodiments, the glucose measuring unit is an infrared spectrometer, the light emitted by the first light source is infrared light and is emitted through the light transmissive portion to an area outside the housing, and the first optical sensor is configured to detect infrared light returning from the first light source through the area outside the housing 10 and through the light transmissive portion, and to output a first electrical signal based on the detected infrared light. This arrangement provides a simple means for interference-free determination of glucose concentration in a body fluid.

[0015] According to some embodiments, the implantable device further includes a temperature sensor and the wireless communication module is configured to wirelessly transmit a signal based on the temperature measured by the temperature sensor to the external wireless communication device. This arrangement allows the effect of temperature to be simply taken into account when processing the output of the glucose monitoring unit to determine the glucose concentration, thereby providing a more accurate value of the glucose concentration.

[0016] According to some embodiments, there is provided an implantable device for measuring a glucose concentration of a bodily fluid, the device comprising: a housing including: a light source configured to emit light at least onto an interface between the implantable device and the bodily fluid when the implantable device is surrounded by the bodily fluid; and a glucose measuring unit including an optical sensor configured to detect at least a portion of the light emitted from the light source through the interface when the implantable device is surrounded by the bodily fluid and to output an electrical signal based on the detected light; and a wireless communication module configured to wirelessly communicate with an external wireless communication device; The wireless communication module is configured to wirelessly transmit a signal based on the electrical signal to an external wireless communication device.

[0017] According to another aspect of the present disclosure, there is provided a system including the implantable device described above and an external wireless communication device, wherein the wireless communication module of the implantable device is configured to wirelessly transmit a signal based on the first electrical signal to the external wireless communication device, the system enabling simple and unobtrusive measurement of the glucose concentration of a bodily fluid.

[0018] The external wireless communication device may be a smartphone, which is a particularly simple means for communicating wirelessly with an implantable device.

[0019] According to another aspect of the present disclosure, there is provided a method including: emitting light by a first light source of an implantable device that measures a glucose concentration of a bodily fluid when implanted toward a light-transmitting portion of a housing of the implantable device; detecting light from the first light source returning through the transmissive portion by a first optical sensor of the implantable device; outputting a first electrical signal based on the detected light by the first optical sensor; and wirelessly transmitting a signal based on the first electrical signal to an external wireless communication device by a wireless communication module of the implantable device. The method allows for simple and unobtrusive measurement of the glucose concentration of the bodily fluid.

[0020] These and other advantages of the various aspects of the disclosure will be apparent from the embodiments described hereinafter.

[0021] Exemplary embodiments of the present disclosure will now be described with reference to the accompanying drawings. [Brief description of the drawings]

[0022] [Figure 1A] FIG. 2 is a front view of an implantable device according to an embodiment of the present disclosure. [Figure 1B] FIG. 2 is a front view of an implantable device having a recess according to an embodiment of the present disclosure. [Figure 1C] FIG. 1C is a schematic cross-sectional side view of the implantable device of FIG. [Diagram 2] 1 is a schematic cross-sectional view of an implantable device according to an embodiment of the present disclosure. [Diagram 3] 1 is a schematic cross-sectional view of a portion of an implantable device according to an embodiment of the present disclosure. [Figure 4] 1 is a schematic cross-sectional view of a portion of an implantable device according to an embodiment of the present disclosure. [Diagram 5] 1 is a schematic cross-sectional view of a portion of an implantable device according to an embodiment of the present disclosure. [Figure 6] 1 is a schematic cross-sectional view of a portion of an implantable device including a reflectometer according to an embodiment of the present disclosure. [Figure 7] 1 is a schematic cross-sectional view of a portion of an implantable device including an infrared spectrometer according to an embodiment of the present disclosure. [Figure 8] 1 is a schematic cross-sectional view of a system including an implantable device and an external wireless communication device, where the implantable device is implanted in a blood vessel, according to an embodiment of the present disclosure. [Figure 9] 1 is a flow chart illustrating a method for determining glucose concentration of a bodily fluid, according to an aspect of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Reference will now be made in detail to the embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings, in which like reference numbers refer to like elements throughout.

[0024] An implantable device is provided that, when implanted, measures the glucose concentration of a bodily fluid. Further provided are a system including the implantable device and an external wireless communication device, and a method of measuring the glucose concentration using the implantable device and the external wireless communication device.

[0025] The body fluids mentioned above are fluids in the human or animal body that contain glucose and whose glucose concentration is measured for insulin therapy. The body fluid is preferably blood, but may alternatively or additionally be interstitial fluid. It is preferred to measure the glucose concentration in blood rather than in the interstitial fluid of a human or animal, since blood is generally more responsive to changes in glucose concentration than interstitial fluid.

[0026] 1 illustrates an implantable device 1 according to some embodiments of the present disclosure. The implantable device 1 has a housing 10 inside which other components of the implantable device 1 are located.

[0027] The housing 10 has a light transmitting portion 12 that allows light of one or more wavelengths to pass from one side of the light transmitting portion 12 to another side. Thus, light can travel through the light transmitting portion 12 from outside the housing 10 to the inside of the housing 10, and vice versa. A separate region or window of the housing 10 may include the light transmitting portion 12, as shown in FIG. 1A. Alternatively, the entire housing 10 may be light transmissive. In some examples, the light transmitting portion 12 includes multiple separate regions of the housing 10, which are separated by optically opaque portions of the housing 10.

[0028] Housing 10 is preferably made of a biocompatible material, such as glass, so that implantable device 1 may be safely implanted in a human or animal. The use of glass for housing 10 is advantageous in that glass is transparent to light and therefore housing 10 and light transmitting portion 12 can be formed in a single step from the same material.

[0029] The implantable device 1 is intended to be implanted subcutaneously in a human or animal body. Preferably, the implantable device 1 is implanted in a blood vessel of a human or animal, making it possible to measure the glucose concentration of the blood of said human or animal. In this case, the particular body fluid to be measured is blood.

[0030] In some embodiments, the implantable device 1 is dimensioned to be implantable within a human blood vessel, such as an artery or vein. For example, the device may have a maximum width w along one axis of less than about 5 mm, preferably less than about 3 mm, and more preferably between about 1.35 and 2 mm.

[0031] In some examples, the configured implantable device 1 is implanted in tissue that is well perfused with a bodily fluid, such as blood. For example, the implantable device 1 is implanted in the interstitial fluid of a human or animal, for example just below the skin. In this case, the particular bodily fluid to be measured is the interstitial fluid.

[0032] After implantable device 1 is implanted, bodily fluids come into contact with light-transmitting portion 12 of housing 10. If implantable device 1 is implanted in a blood vessel, blood comes into contact with light-transmitting portion 12. If implantable device 1 is implanted in interstitial fluid, interstitial fluid comes into contact with light-transmitting portion 12.

[0033] Figure 1B shows an implantable device 1 similar to that of Figure 1A, except that the exterior surface 11 of the housing 10 includes a recess 14. Figure 1C shows a side view of the implantable device of Figure 1B showing a side view of the recess 14.

[0034] As shown in FIG. 1C, the recess 14 can include a first sidewall 15, a second sidewall 16, and a bottom surface 17.

[0035] Recess 14 may be a groove in exterior surface 11 of housing 10. In another embodiment, recess 14 may be a conduit or tube through which bodily fluid may flow from one side of implantable device 1 to another side of implantable device 1. For example, the conduit may extend from one side of housing 10 to the opposite side of housing 10. Recess 14 fills with bodily fluid when implantable device 1 is implanted.

[0036] Providing recesses 14 in housing 10 can facilitate the movement of bodily fluids around implantable device 1 when the device is implanted. This can be particularly advantageous when implantable device 1 is implanted in a blood vessel, as the recesses may allow blood to flow more easily around or through implantable device 1, such that blood flow through the vessel is less impeded by implantable device 1.

[0037] In some examples, the housing 10 may include one or more protrusions (not shown) disposed on the exterior surface 11. The one or more protrusions are configured to hold the implantable device 1 in a fixed position within the human or animal body after implantation within the body. When the implantable device 1 is implanted within a blood vessel, the one or more protrusions are configured to hold the implantable device 1 in a fixed position within the blood vessel by exerting pressure against an inner wall of the blood vessel.

[0038] 1B and 1C are depicted as being contained within a discrete region of housing 10, in this case entirely within recess 14. However, light transmitting portion 12 is not limited to this arrangement and may be located in another portion of housing 10 or may comprise the entirety of housing 10.

[0039] FIG. 2 is a schematic cross-sectional view of an implantable device 1 according to an embodiment of the present disclosure.

[0040] The implantable device 1 includes a wireless communication module 20 , a glucose measuring unit 30 , and a housing 10 having a light transmissive portion 12 .

[0041] The wireless communication module 20 is configured to communicate wirelessly with an external wireless communication device 2 (shown in FIG. 8), preferably using near field communication (NFC), although other forms of wireless communication may be used.

[0042] The wireless communication module 20 is preferably configured to wirelessly receive power from the external wireless communication device 2 by electromagnetic induction.

[0043] The wireless communication module 20 includes an antenna 22, an energy storage unit 24, such as a capacitor or a rechargeable battery, and a control unit 26, such as an integrated circuit. The antenna 22 is configured to transmit and receive wireless signals, and the transmission of wireless signals by the antenna is controlled by the control unit 26. The energy storage unit 24 stores electrical energy received from the external wireless communication device 2 via the antenna 22. The control unit 26 may include a memory unit (not shown) for storing instructions to be executed by the control unit 26 and / or data related to measurements made by the glucose measuring unit 30. The control unit 26 may control one or more operations of the glucose measuring unit 30 described herein and may perform any of the method steps described herein with respect to the implantable device 1.

[0044] The glucose measuring unit 30 includes a light source 32 and an optical sensor 34. The light source 32 may include one or more light emitting diodes (LEDs) and is configured to emit light toward the light transmissive portion 12 of the housing 10, i.e., from inside the housing 10 to outside the housing 10. The light source 32 is preferably powered by the energy storage unit 24 and controlled by the control unit 26.

[0045] An optical sensor 34, also known as a light sensor, detects light by converting the light it receives into an electrical signal. Thus, the optical sensor 34 outputs an electrical signal based on the detected light. The optical sensor 34 may include one or more photodetectors, such as photodiodes. The optical sensor 34 may detect light having a particular wavelength or a range of wavelengths. The optical sensor 34 may be variable; that is, the particular wavelength or range of wavelengths detected by the optical sensor 34 may be variable. The wavelength detected by such an optical sensor 34 is selected by varying the voltage applied to the optical sensor 34.

[0046] The optical sensor 34 is configured to detect light that has returned through the light-transmitting portion 12 of the housing 10 and to output an electrical signal based on the detected light. In other words, the optical sensor 34 is configured to detect light that has been emitted by the light source 32 from inside the housing 10 to the light-transmitting portion 12 of the housing 10 and returned through the light-transmitting portion 12 to the inside of the housing 10.

[0047] The returning light can travel from light source 32 through light transmissive portion 12 to an area outside of housing 10 and then return through light transmissive portion 12 to the inside of housing 10 where the light is detected by optical sensor 34. In another example, the returning light can travel from light source 32 through light transmissive portion 12 and then be internally reflected off a surface of light transmissive portion 12 and return through light transmissive portion 12 to the inside of housing 10 where the light is detected by optical sensor 34. The surface of light transmissive portion 12 from which the light is internally reflected forms part of exterior surface 11 of housing 10 and is in contact with bodily fluids when implantable device 1 is implanted.

[0048] The wireless communication module 20 is configured to wirelessly transmit a signal based on the electrical signal output by the optical sensor to the external wireless communication device 2. In other words, the wireless communication module 20 is configured to transmit a signal corresponding to the light detected by the optical sensor 34, whether this corresponds to the intensity of the light, the optical rotation of the light, or the amount of refraction of the light. As such, the signal also corresponds to the glucose concentration of the body fluid in the vicinity of the implantable device 1.

[0049] The wireless signal transmitted by wireless communication module 20 to external wireless communication device 2 is processed by the external wireless communication device 2, or another device, to provide an output, such as a glucose concentration value, which depends on the glucose concentration of the bodily fluid being measured by implantable device 1. Implantable device 1 is calibrated by first performing a standard blood glucose test using a lancet.

[0050] In some embodiments, the implantable device 1 further includes a temperature sensor 39, shown in Figure 2. The temperature sensor 39 is preferably located adjacent or near the glucose measuring unit 30, but may be located anywhere in the implantable device 1 where it is desirable to measure the temperature. The wireless communication module 20 is configured to wirelessly transmit a signal based on the temperature measured by the temperature sensor 39 to the external wireless communication device 2. This signal may be part of the signal described above based on the signal output by the optical sensor 34, or may be a separate signal.

[0051] The measurements and operations performed by the glucose measuring unit 30 described herein are temperature dependent. By providing a temperature sensor 39 and taking temperature measurements, temperature can be taken into account when processing or interpreting measurements obtained by the implantable device 1. However, the temperature sensor 39 is optional, since temperature can be measured or estimated using devices that do not form part of the implantable device 1 (e.g., the temperature inside the human body can be assumed to be 37° C.).

[0052] Some optical properties of a fluid, such as a bodily fluid, change with the glucose concentration in the fluid. These optical properties include the specific rotation of the fluid (the angle of rotation of linearly polarized light passing through the fluid over a particular distance), the refractive index of the fluid, and the infrared absorption spectrum of the fluid. According to some aspects of the present disclosure, one or more of these properties are determined directly or indirectly by the implantable device. A glucose concentration value of the bodily fluid is determined by providing an output based on one or more of these properties. The output is provided using a light source 32 configured to emit light toward the light-transmitting portion 12 of the housing 10 of the implantable device 1 and an optical sensor 34 configured to detect light returned from the light source 32 through the transmitting portion 12, the output being an electrical signal based on the detected light, particularly the intensity of the detected light or the amount of refraction of the detected light.

[0053] As previously discussed, when implantable device 1 is implanted, bodily fluid contacts light-transmitting portion 12 at exterior surface 11 of housing 10. Light from light source 32 passes through light-transmitting portion 12 and interacts with the fluid in contact with light-transmitting portion 12. This interaction can occur outside of housing 10, within the bodily fluid itself, or at the interface between the bodily fluid and light-transmitting portion 12.

[0054] At least a portion of the light that interacts with the bodily fluid returns through the light-transmitting portion 12 toward the inside of the housing 10 and is detected by the optical sensor 34. The interaction between the bodily fluid and the light may include optical rotation of the light by the bodily fluid, absorption of at least a portion of the light by the bodily fluid, or reflection and / or refraction of the light at an interface. Thus, the light emitted from the light source 32 is altered in some way by the glucose in the bodily fluid. The amount of interaction / alteration depends on the glucose concentration in the bodily fluid. The optical sensor 34 outputs an electrical signal based on the detected light that corresponds to the amount of alteration of the light by the bodily fluid and therefore corresponds to the glucose concentration of the bodily fluid.

[0055] The electrical signal is processed within the implantable device 1, for example by the control unit 26. The wireless communication module 20 receives the electrical signal from the optical sensor 34 and wirelessly transmits a signal based on the electrical signal to the external wireless communication device 2. In other words, the wirelessly transmitted signal corresponds to the electrical signal, which corresponds to the glucose concentration in the body fluid.

[0056] The signal transmitted by the wireless communication module 20 to the external wireless communication device 2 is further processed by a processor (not shown) of the external wireless communication device 2 to provide a glucose concentration value of the body fluid.

[0057] According to some embodiments of the present disclosure, the optical rotation of linearly polarized light passing through the bodily fluid is detected by optical sensor 34.

[0058] Glucose is an optically active material, i.e., the plane of polarization of linearly polarized light rotates as it travels through glucose. In a solution of glucose, the angle of rotation α of the plane of polarization of linearly polarized light depends on the glucose concentration in the solution β, the path length L of the light through the solution, λ, and the temperature T of the glucose solution.

[0059] Specific rotation [α] T λ is an intrinsic property of a compound in solution and is the angle of rotation per unit distance × concentration of the plane of polarization of a monochromatic beam passing through a sample of the compound in solution.

[0060] The specific rotation depends on the temperature of the solution and the wavelength of the polarized light. The concentration of glucose in a solution is determined by measuring the angle α through which the plane of polarization of linearly polarized light rotates as it travels through the solution, and the path length L of the linearly polarized light through the solution. If the temperature T of the container and the wavelength λ of the linearly polarized light are known or can be estimated, the specific rotation [α] of glucose for that temperature and wavelength is T λ The value of is then searched for. The concentration of glucose in the solution, β, is then calculated using the angle α and the specific rotation [α] T λ , and the path length L, is determined by:

number

[0061] It is estimated that a significant amount of the optical rotation of linearly polarized light passing through a body fluid, such as blood or interstitial fluid, is caused by glucose, but not by other components of the body fluid. Therefore, the optical activity of other components in the body fluid is generally ignored. Thus, by determining the angle of rotation of the linearly polarized light passing through the body fluid, a good approximation of the glucose concentration in the body fluid is determined. The determination of the glucose concentration in the body fluid is performed by the implantable device 1, for example by the control unit 26, or by an external wireless communication device 2.

[0062] Determining the glucose concentration may include processing a signal based on the electrical signal output by the optical sensor 34 or the electrical signal wirelessly transmitted to the external wireless communication device 2 to determine a measurement value. The glucose concentration value is determined by comparing the measurement value to a look-up table that includes a plurality of measurements and their corresponding glucose concentration values.

[0063] FIG. 3 shows a partial schematic cross-sectional view of an implantable device 1, such as the one shown in FIG. 1B, in which a glucose measuring unit 30 is configured to measure the rotation angle α of linearly polarized light traveling through a body fluid.

[0064] Although the implantable device 1 in FIG. 3 is shown to include a recess 14, in some examples the recess 14 may not be present. As shown in FIG. 3, the first and second side walls 15 and 16 of the recess 14 each include at least a portion of the light-transmitting portion 12. The light source 32 is positioned within the housing 10 such that light emitted toward the light-transmitting portion 12 passes through the light-transmitting first side wall 15 to an area outside the housing, as indicated by the arrows in FIG. 3, and then passes through the light-transmitting second side wall 16 to be detected by the optical sensor 34. In some examples, the light source 32 and the optical sensor 34 are positioned within the housing 10 such that the emitted light exits and returns through the same surface of the light-transmitting portion 12, e.g., the bottom surface 17, as shown in FIGS. 4 and 5.

[0065] 3, light emitted from light source 32 is linearly polarized by first linear polarizer 41 and emitted through light transmissive portion 12 to a region outside housing 10 that will be within the body fluid when the implantable device is implanted.

[0066] As with any of the embodiments disclosed herein, implantable device 1 may include at least one lens 46 positioned to focus light emitted from light source 32. In particular, lens 46 may focus light emitted from first light source 32 toward a point outside of housing 10 or focus light toward optical sensor 34.

[0067] Although Figure 3 shows lens 46 positioned within housing 10 in the light path between light source 32 and light transmissive portion 12, lens 46 could instead be positioned in any suitable location, such as on the exterior surface 11 of housing 10, on the surface of light transmissive portion 12. Figure 3 also shows first linear polarizer 41 positioned in the light path between light source 32 and lens 46, although first linear polarizer 41 could be positioned after lens 46 along the light path in some examples.

[0068] The linearly polarized light passing through the body fluid is rotated by glucose in the body fluid, such that the plane of polarization of the light is rotated by an amount that depends on the concentration of glucose and the distance the light travels through the glucose. The distance the light travels through the glucose is determined prior to implanting the device. The optical sensor 34 is configured to detect the rotation of the linearly polarized light that passes through the body fluid and returns from the area outside the housing 10 through the transmissive portion 12. The optical sensor 34 is further configured to output an electrical signal based on the detected rotated light. The output is based on the rotation angle α of the linearly polarized light.

[0069] As shown in FIG. 3, detecting the rotated linearly polarized light returning from the region outside the housing through the transmission section includes using a second linear polarizer 42 placed in the optical path between the light source 32 and the optical sensor 34, and between the optical sensor 34 and the region outside the housing 10. The polarization plane of the second linear polarizer 42 is rotated about the optical path with respect to the polarization plane of the first linear polarizer 41, preferably substantially orthogonal to the polarization plane of the first linear polarizer 41. Thus, the amount of linearly polarized light detected by the optical sensor 34 from the light source 32 and the first linear polarizer 41 depends on the amount of rotation of the light. This rotation occurs when the linearly polarized light passes through a glucose-containing body fluid. The amount of rotation, and therefore the amount of light detected by the optical sensor 34, depends on the glucose concentration in the body fluid. In that way, the electrical signal output by the optical sensor 34 is based on the amount of rotation of the linearly polarized light, and therefore on the glucose concentration in the body fluid.

[0070] The implantable device 1 shown in Fig. 3 may be susceptible to interference from an optical sensor 34 that detects light, e.g., ambient light that does not originate from light source 32. Fig. 4 shows a partial schematic cross-sectional view of an implantable device 1 similar to Fig. 3, but configured to significantly suppress interference. Like the implantable device 1 shown in Fig. 3, the implantable device 1 shown in Fig. 4 includes a recess 14, although the presence of the recess 14 is optional.

[0071] Similar to Figure 3, the implantable device 1 shown in Figure 4 includes a light source 32, a first linear polarizer 41 and a second linear polarizer 42. However, here the glucose measuring unit 30 further includes a second optical sensor 36. The first optical sensor 34 and the second optical sensor 36 may each include one or more photodiodes.

[0072] Similar to the implantable device 1 of Fig. 3, the first linear polarizer 41 of Fig. 4 is configured to linearly polarize light emitted from the light source 32 through the light-transmitting portion 12 in a first polarization plane, which is emitted to an area outside the housing 10. The second linear polarizer 42 is positioned to linearly polarize the light from the area outside the housing 10 in a second polarization plane that is substantially orthogonal to the first plane (i.e., rotated 90° about the optical axis). The third linear polarizer 43 is positioned to linearly polarize the light from the area outside the housing 10 in a third polarization plane, which is parallel to the first plane (i.e., rotated 0° about the optical axis).

[0073] 4 shows three lenses 46 configured to focus light, as described above. One or more of the lenses 46 are positioned to focus light emitted from the light source 32 to a point or area in the bodily fluid, outside the housing 10. The first optical sensor 34 and the second optical sensor 36 are positioned to detect light emanating from the light source 32, e.g., reflected in the bodily fluid near the point or area outside the housing. The detected light is focused by the one or more lenses 46 from the point or area outside the housing 10 toward the first optical sensor 34 and the second optical sensor 36. Exemplary light paths are indicated by arrows in FIG. 4.

[0074] The second linear polarizer 42 is positioned such that a first portion of the linearly polarized light emitted from the light source 32 to the area outside the housing 10 is incident on the second linear polarizer 42. In other words, the second linear polarizer 42 is disposed in the optical path between the light source 32 and the first optical sensor 34, and between the area outside the housing 10 and the first optical sensor 34.

[0075] The third linear polarizer 43 is disposed such that a second portion of the linearly polarized light emitted from the light source 32 to the area outside the housing 10 is incident on the third linear polarizer 43. In other words, the third linear polarizer 43 is disposed in the optical path between the light source 32 and the second optical sensor 36, and between the area outside the housing 10 and the second optical sensor 36.

[0076] The first optical sensor 34 is positioned to detect a first portion of the linearly polarized light passing through the second linear polarizer 42 from a region outside the housing 10. This first portion of the linearly polarized light from the light source 32 is linearly polarized in a first plane by the first linear polarizer 41 and then rotated by the glucose in the body fluid, passing through the second linear polarizer 42, and detected by the first optical sensor 34.

[0077] The second optical sensor 36 is positioned to detect a second portion of the linearly polarized light passing through the third linear polarizer 43 from an area outside the housing 10. This second portion of the linearly polarized light from the light source 32, after being linearly polarized in the first plane by the first linear polarizer 41, is rotated by the glucose in the body fluid, passes through the third linear polarizer 43, and is detected by the second optical sensor 36.

[0078] The first optical sensor 34 and the second optical sensor 36 are each configured to output an electrical signal based on the detected light intensity, and thus based on the angle through which the linear polarization plane of the light emitted from the light source 32 has been rotated. The composite signal S output by each of the first optical sensor 34 and the second optical sensor 36 is PD1 and composite signal S PD2 can be used to determine the angle α through which linearly polarized light is rotated by glucose using the following formula:

number

[0079] As previously discussed, by determining the value of α, a value corresponding to the concentration of glucose in the body fluid is determined.

[0080] signal S PD1 and S PD2depends on factors such as the current passing through the light source 32, the channel gain, type-specific LED radiant intensity, ambient light, the transmission coefficient of blood or other bodily fluids (which is a function of various factors such as the type of food eaten and the time since the food was eaten), and the transmittance of the linear polarizer. By providing an additional third linear polarizer 43 and second optical sensor 36, the electrical signals output by the first optical sensor 34 and the second optical sensor 36 are processed to reduce the signal S that would otherwise be PD1 and S PD2 The effects of the aforementioned factors on which the measurement depends are reduced or eliminated, reducing the effects of interference, for example caused by ambient light, noise in the electrical components of the implantable device 1, or similar parasitic effects, thus providing a more accurate measurement of the glucose concentration that is not dependent on these factors.

[0081] Figure 5 shows another embodiment similar to Figure 4, but where the glucose measuring unit 30 further includes a second light source 35, which may again include one or more LEDs. In a similar manner as discussed with reference to Figure 4, the light source 32 of Figure 5 (hereinafter referred to as the first light source 32 with respect to Figure 5) is configured to emit light through the light-transmitting portion 12 to a (first) area outside the housing 10, and the second light source 35 is configured to emit light through the light-transmitting portion 12 to a (second) area outside the housing 10. The first area and the second area may be the same.

[0082] 5 is configured to linearly polarize light emitted from the first light source 32 through the light transmitting portion 12 in a first polarization plane, which light is emitted to a first region outside the housing 10. The second linear polarizer 42 is positioned to linearly polarize light from the first region outside the housing 10 in a second plane that is substantially orthogonal to the first plane (i.e., rotated 90° around the optical axis).

[0083] The fourth linear polarizer 44 of FIG. 5 is configured to linearly polarize light emitted from the second light source 35 through the light-transmitting portion 12 with a third polarization plane, and the light is emitted to a second region outside the housing 10.

[0084] A third linear polarizer 43 is positioned to linearly polarize light from the second region outside the housing 10 into a fourth plane, which is parallel to the third plane (i.e., rotated 0° about the optical axis). The fourth plane may be parallel to the third plane.

[0085] The second linear polarizer 42 is disposed such that at least a portion of the linearly polarized light emitted from the first light source 32 to the first region outside the housing 10 is incident on the second linear polarizer 42. In other words, the second linear polarizer 42 is disposed in the optical path between the first light source 32 and the first optical sensor 34, and between the first region outside the housing 10 and the first optical sensor 34.

[0086] The third linear polarizer 43 is disposed such that at least a portion of the linearly polarized light emitted from the second light source 35 to the region outside the housing 10 is incident on the third linear polarizer 43. In other words, the fourth linear polarizer 44 is disposed in the optical path between the second light source 35 and the second optical sensor 36, and between the second region outside the housing 10 and the second optical sensor 36.

[0087] The first optical sensor 34 is configured to detect at least a portion of the linearly polarized light emitted from the first light source 32 (through a first region outside the housing 10) and passed through the second linear polarizer 42. The second optical sensor 36 is configured to detect at least a portion of the linearly polarized light emitted from the second light source 35 (through a second region outside the housing 10) and passed through the third linear polarizer 43.

[0088] Preferably, the first optical sensor 34 is positioned within the implantable device 1 so as not to detect light emitted by the second light source 35, and the second optical sensor 36 is positioned within the implantable device 1 so as not to detect light emitted by the first light source 32. This arrangement reduces the effects of interference on the electrical signals output by the first optical sensor 34 and the second optical sensor 36.

[0089] The first optical sensor 34 and the second optical sensor 36 are each configured to output an electrical signal based on the detected light intensity, and therefore based on the angle of rotation of the appropriate polarization from the first light source 32 or the second light source 35, respectively. The composite signal S output by the first optical sensor 34 and the second optical sensor 36, respectively, is PD1 and composite signal S PD2 can be used to determine the angle α through which linearly polarized light is rotated by glucose using the following formula:

number

[0090] As discussed above, the determined value of α is used to determine a value corresponding to the concentration of glucose in the body fluid.

[0091] By providing the additional third linear polarizer 43, fourth linear polarizer 44 and second optical sensor 36 compared to the implantable device 1 of Figure 3, the electrical signals output by the first optical sensor 34 and the second optical sensor 36 are processed to reduce the effects of interference caused by, for example, ambient light, thus providing a more accurate measurement of the glucose concentration.

[0092] In some embodiments, the glucose measuring unit is a refractometer, and the electrical signal output by the optical sensor 34 is based on the refractive index n 2 of the bodily fluid in contact with the light transmitting portion 12 .

[0093] The refractive index n2 of a body fluid containing glucose is a function of (i.e., dependent on) the glucose concentration in the body fluid. As the glucose concentration of the body fluid changes, the refractive index of the body fluid also changes. The refractive index of the body fluid is determined using a refractometer. By determining the refractive index of the body fluid, a value for the glucose concentration is determined. This determination may include using the look-up table discussed with respect to optical activity.

[0094] 6 shows a partial schematic cross-sectional view of an implantable device 1 in which the glucose measuring unit 30 is a refractometer. The refractometer includes a prism 60, with the light source 32 and the prism 60 positioned such that light emitted from the light source 32 passes through the prism 60 and is incident on a surface 61 of the prism 60. In other words, and as shown by the arrows in FIG. 6, the prism 60 and the light source 32 are positioned such that the light emitted from the light source 32 enters the prism 60 and travels through the prism 60 until it reaches the surface 61 of the prism 60.

[0095] When implantable device 1 is implanted, bodily fluids come into contact with surface 61. Therefore, light transmitting portion 12 includes prisms 60.

[0096] A portion of the light emitted by the light source 32 is reflected (i.e., totally internally reflected) at the surface 61 of the prism 60 at the body fluid-prism interface depending on the angle of incidence θ1 of the light on the surface 61. The optical sensor 34 is positioned to detect this reflected portion of the light after it passes back through the prism 60 and exits the prism. In particular, the optical sensor 34 is positioned to measure the angle of refraction θ2 of the (total internally) reflected light.

[0097] 6 illustrates the optical sensor 34 as a CCD sensor 62. The position of the reflected light on the CCD sensor 62 is used to determine the angle of refraction θ2, and thus the refractive index of the body fluid in contact with the surface 61. The CCD sensor 62 therefore outputs an electrical signal based on the refractive index of the body fluid.

[0098] The relationship between the angle of incidence θ1, the angle of refraction θ2, the refractive index n1 of the prism 60, and the refractive index n2 of the body fluid is given by:

number

[0099] Thus, by measuring the refraction angle θ2, a value for the refractive index n2 of the body fluid can be determined if the angle of incidence θ1 and the refractive index n1 of prism 60 are already known. The value of the refractive index of the body fluid can be used to determine a value for the glucose concentration of the body fluid, for example, by comparing the value of the refractive index of the body fluid to a look-up table or by performing additional calculations on the value of the refractive index of the body fluid.

[0100] By measuring the refraction angle using a refractometer, an accurate value of the glucose concentration can be determined, since factors such as the absolute brightness of the light source 32 and the light transmission of body fluids do not affect the refraction angle and therefore the determined value of the glucose concentration.

[0101] In some embodiments, the glucose measuring unit is an infrared spectrometer. The infrared absorption spectrum of a body fluid containing glucose varies with the glucose concentration. By measuring the infrared absorption of the body fluid, the value of the glucose concentration can be determined. This determination includes using the look-up table discussed with respect to optical activity.

[0102] FIG. 7 shows an embodiment in which the glucose measuring unit is an infrared spectrometer.

[0103] The light emitted by the light source 32 is infrared light and is emitted through the light transmissive portion 12 to an area outside the housing 10. The optical sensor 34 is configured to detect the infrared light that passes from the light source 32 through the area outside the housing 10 and back through the light transmissive portion 12, and to output an electrical signal based on the detected infrared light and, therefore, the glucose concentration of the bodily fluid.

[0104] Optionally, the glucose measuring unit 30 includes a first filter 70 configured to filter the light emitted by the light source 32 such that only light of a particular wavelength passes through the first filter 70 and is emitted through the light transmitting portion 12 to an area outside the housing 10. Optionally, the glucose measuring unit 30 includes a second filter 72 configured to filter the light returning from the light source 32 through the light transmitting portion 12 such that only light of a particular wavelength passes through the second filter 72 and is detected by the optical sensor 34. The optical sensor 34 is configured to detect a variable band of wavelengths of light. The band of wavelengths detected by the optical sensor 34 is adjusted by varying the voltage applied to the optical sensor 34.

[0105] The present disclosure also relates to a system including an external wireless communication device 2 and an implantable device 1 according to any of the above-mentioned embodiments. Figure 8 shows such a system when the implantable device 1 is implanted in a blood vessel 3 of a patient 4 (such as a human or animal).

[0106] Similar to wireless communication module 20 of implantable device 1, external wireless communication device 2 includes an antenna, a power source and a control unit (not shown). During use, external wireless communication device 2 is brought into close proximity to implantable device 1. If implantable device 1 is implanted in a patient 4, this may involve bringing external wireless communication device 2 close to skin 5 of patient 4, for example, within a distance of less than about 2 cm of skin 5.

[0107] The external wireless communication device 2 wirelessly transmits power to the implantable device 1 by electromagnetic induction between an antenna of the external wireless communication device 2 and an antenna 22 of the implantable device 1. A current is induced in the antenna 22 of the implantable device 1 to provide power to any electrical circuitry within the device, such as the glucose measuring unit 30.

[0108] In response to receiving power or in response to receiving an additional wireless signal transmitted by the external communication device to the implantable device 1, the implantable device 1 proceeds to measure the glucose concentration of the bodily fluid in contact with the housing 10 of the implantable device 1. The light source 32 of the implantable device 1 emits light toward the light-transmitting portion 12 of the housing 10 of the implantable device 1. The optical sensor 34 of the implantable device 1 detects the light that returns through the light-transmitting portion 12 and outputs an electrical signal based on the detected light. The wireless communication module 20 of the implantable device 1 is configured to wirelessly transmit a signal based on the electrical signal to the external wireless communication device 2. The signal wirelessly transmitted by the implantable device 1 to the external wireless communication device 2 is processed (e.g., by the external wireless communication device 2) to determine a value of the glucose concentration of the bodily fluid.

[0109] The present disclosure also relates to methods for performing any of the above-described steps involving the implantable device 1 and the external wireless communication device 2.

[0110] 9 illustrates a method according to an embodiment of the present disclosure. At step 901, light is emitted by the light source 32 of the implantable device 1 described above toward the light-transmitting portion 12 of the housing 10 of the implantable device 1. At step 902, the optical sensor 34 of the implantable device 1 detects the light returning from the first light source 32 through the light-transmitting portion 12. At step 903, an electrical signal based on the detected light is output by the optical sensor 34. At step 904, the wireless communication module 20 of the implantable device 1 wirelessly transmits a signal based on the electrical signal to the external wireless communication device 2. As previously discussed, the signal wirelessly transmitted by the implantable device 1 to the external wireless communication device 2 is processed (e.g., by the external wireless communication device 2) to determine a value of the glucose concentration of the bodily fluid.

[0111] The terms "drug" or "medicament" are used synonymously herein to refer to a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharma- ceutically acceptable salts or solvates thereof, and optionally a pharma- ceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest terms, is a chemical structure that exerts a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent, or diagnose disease, or otherwise improve physical or mental health. Drugs or agents are used for a limited duration, or periodically for chronic diseases.

[0112] As described below, the drug or agent may include at least one API, or a combination thereof, in various types of formulations for treating one or more diseases. Examples of APIs may include small molecules with a molecular weight of 500 Da or less; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. The nucleic acid is incorporated into a molecular delivery system such as a vector, a plasmid, or a liposome. Mixtures of one or more drugs are also contemplated.

[0113] The drug or agent is contained within a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, a syringe, a reservoir, or other solid or flexible container configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber is designed to accommodate the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber is designed to store the drug for about one month to about two years. Storage can be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container can be or include a dual-chamber cartridge configured to store two or more components of a pharmaceutical formulation to be administered separately, one in each chamber (e.g., an API and a diluent, or two different types of drugs). In such cases, the two chambers of the dual-chamber cartridge are configured to allow mixing between the two or more components before and / or during administration into the human or animal body. For example, the two chambers are configured such that they are in fluid communication with each other (e.g., by a conduit between the two chambers) to allow mixing of the two components by a user prior to administration, if desired. Alternatively, or in addition, the two chambers are configured to allow mixing of the components as they are being administered into the human or animal body.

[0114] The drugs or agents contained within the drug delivery device described herein are used for the treatment and / or prevention of many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolism, such as deep vein thromboembolism or pulmonary thromboembolism. Other examples of disorders include acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs include, for example, but are not limited to, those listed in the Handbook of Rote Liste 2014, Main Group 12 (antidiabetic drugs) or Main Group 86 (tumor drugs), and Merck Index, 15th Edition.

[0115] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes, or complications associated with type 1 or type 2 diabetes, include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma-ceutically acceptable salt or solvate thereof, or any mixture thereof. The terms "analog" and "derivative" as used herein refer to a polypeptide having a molecular structure that is derived from the structure of a natural peptide, e.g., the structure of human insulin, by deleting and / or replacing at least one amino acid residue found in the natural peptide, and / or by adding at least one amino acid residue. The added and / or replaced amino acid residue can be a codable amino acid residue, or another natural residue, or a completely synthetic amino acid residue. Insulin analogs are also called "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure that is derived formally from that of a naturally occurring peptide, such as the structure of human insulin, in which one or more organic substituents (e.g., fatty acids) are attached to one or more amino acids. Optionally, one or more amino acids found in the naturally occurring peptide may be deleted and / or substituted by other amino acids, including non-codable amino acids, or amino acids, including non-codable amino acids, may be added to the naturally occurring peptide.

[0116] Examples of insulin analogues include Gly(A21),Arg(B31),Arg(B32) human insulin (insulin glargine); Lys(B3),Glu(B29) human insulin (insulin glulisine); Lys(B28),Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala and in position B29, Lys is replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0117] Examples of insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®), B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin. B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin; B29-N-ω-carboxyheptadecanoyl-γ-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®), B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin, and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0118] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists include, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Dyetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rexendin-4, CJC-1134-PC, PB-1023, TTP-054, laxative, cefotaxime ... These include ngrenatide / HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN, and Glucagon-Xten.

[0119] Examples of oligonucleotides include, for example: mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0120] Examples of DPP4 inhibitors include vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0121] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropin (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0122] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, or very low molecular weight heparin, or derivatives thereof, or sulfated forms of the above polysaccharides, such as polysulfated forms, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives include Hylan G-F20 (Synvisc®), sodium hyaluronate.

[0123] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind antigen. Antibodies can be polyclonal, monoclonal, recombinant, chimeric, non-immunoglobulin or humanized, fully human, non-human (e.g., murine), or single chain antibodies. In some embodiments, antibodies have effector functions and can fix complement. In some embodiments, antibodies have reduced ability to bind or cannot bind Fc receptors. For example, antibodies can be isotypes or subtypes, antibody fragments or variants that do not support binding to Fc receptors, e.g., have mutated or deleted Fc receptor binding regions. The term antibody also includes antibody binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins (CODV) with cross-linking region orientation.

[0124] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., antibody heavy and / or light chain polypeptides) that does not include the full-length antibody polypeptide, but still includes at least a portion of the full-length antibody polypeptide that can bind to an antigen. An antibody fragment can include a truncated portion of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific antibody fragments, or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent antibody fragments, or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Further examples of antigen-binding antibody fragments are known in the art.

[0125] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences in the variable regions of both heavy and light chain polypeptides that are not CDR sequences, but are primarily responsible for maintaining the correct positioning of CDR sequences to allow antigen binding. Although framework regions themselves are usually not directly involved in antigen binding, as is known in the art, certain residues in the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDRs to interact with the antigen.

[0126] Exemplary antibodies include anti-PCSK-9 mAb (eg, alirocumab), anti-IL-6 mAb (eg, sarilumab), and anti-IL-4 mAb (eg, dupilumab).

[0127] Pharmaceutically acceptable salts of any of the APIs described herein are also contemplated for use in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0128] It will be understood by those skilled in the art that modifications (additions and / or removals) of the various components of the APIs, formulations, devices, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present disclosure, which encompasses such modifications, and any and all equivalents thereof.

[0129] Although claims are expressly set forth in this application to particular combinations of features, it is to be understood that the scope of this disclosure also includes any novel features or any novel combinations of features explicitly or implicitly disclosed herein, or any generalizations thereof, whether or not such features relate to the same disclosure as is currently claimed in any claim, and whether or not such features alleviate any or all of the same technical problems that this disclosure alleviates. Applicant hereby gives notice that new claims will be expressly set forth to such features and / or combinations of features during the prosecution of this application, or of any further applications derived therefrom.

[0130] While several embodiments have been shown and described, those skilled in the art will understand that changes may be made to these embodiments without departing from the principles of the present disclosure, the scope of which is defined in the claims.

Claims

1. 1. An implantable device for measuring a glucose concentration of a bodily fluid when implanted, comprising: a first light source configured to emit light from inside the housing toward a light-transmitting portion of the housing of the implantable device; and a first optical sensor configured to detect light returned from the first light source through the light transmissive portion of the housing and to output a first electrical signal based on the detected light; A glucose measuring unit comprising: a wireless communication module configured to wirelessly communicate with an external wireless communication device; Includes a housing including: the light emitted from the first light source is linearly polarized and is emitted through the light transmitting portion to a first region outside the housing; The first optical sensor is configured to detect the rotated linearly polarized light returning from the first region outside the housing through the light transmitting portion. the first optical sensor is configured to output a first electrical signal based on the detected rotated light; The implantable device may further comprise: a first linear polarizer positioned to linearly polarize light emitted from the first light source in a first plane; a second linear polarizer positioned to linearly polarize light from the first region outside the housing in a second plane substantially orthogonal to the first plane; a third linear polarizer positioned to linearly polarize light from the first region outside the housing in a third plane that is parallel to the first plane; The glucose measuring unit further includes a second optical sensor configured to detect light returned through the light transmissive portion and to output a second electrical signal based on the detected light; the second linear polarizer is positioned such that a first portion of the linearly polarized light emitted from the first light source to a first region outside the housing is incident on the second linear polarizer; The third linear polarizer polarizes linear light emitted from the first light source toward a first region outside the housing. a second portion of the polarized light is disposed to be incident on a third linear polarizer; the first optical sensor is positioned to detect a first portion of the linearly polarized light passing through the second linear polarizer from a first region outside the housing; a second optical sensor positioned to detect a second portion of the linearly polarized light passing through the third linear polarizer from the first region outside the housing; the implantable device is configured to process the first electrical signal and the second electrical signal to reduce or eliminate the effects of interference; and The implantable device, wherein the wireless communication module is configured to wirelessly transmit a signal based on the first electrical signal and the second electrical signal to an external wireless communication device.

2. The implantable device of claim 1 , wherein the wireless communication module is configured to receive power wirelessly from an external wireless communication device.

3. 3. The implantable device of claim 1 or 2, wherein the implantable device is dimensioned for implantation within a human blood vessel.

4. The implantable device of any one of claims 1 to 3, wherein the outer surface of the housing includes a recess, the recess containing at least a portion of the light transmissive portion.

5. The implantable device of any one of claims 1 to 4, further comprising at least one lens configured to focus light emitted from the first light source towards a point outside the housing.

6. The implantable device of any one of claims 1 to 5, wherein the implantable device further includes a temperature sensor, and the wireless communication module is configured to wirelessly transmit a signal based on the temperature measured by the temperature sensor to an external wireless communication device.

7. 7. A system comprising an implantable device according to any one of claims 1 to 6 and an external wireless communication device, wherein the wireless communication module of the implantable device is configured to wirelessly transmit a signal based on the processed first electrical signal and the processed second electrical signal to the external wireless communication device.

8. The system of claim 7 , wherein the external wireless communication device is a smartphone.

9. 1. A method for measuring and communicating a glucose concentration, comprising: A first light source of the implantable device of any one of claims 1 to 6 emitting light towards a light-transmitting portion of a housing of the implantable device; detecting light from the first light source returned through the transmissive portion with a first optical sensor of the implantable device; detecting light from the first light source returned through the transmissive portion with a second optical sensor of the implantable device; the first optical sensor outputting a first electrical signal based on the light detected by the first optical sensor; the second optical sensor outputting a second electrical signal based on the light detected by the second optical sensor; the implantable device processes the first electrical signal and the second electrical signal to reduce or eliminate the effect of the interference; and The method includes a wireless communication module of the implantable device wirelessly transmitting a signal based on the first electrical signal and the second electrical signal to an external wireless communication device.

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