Implantable glucose monitor

Abstract

To allow for simple and unobtrusive measurements of glucose concentration in a body fluid.SOLUTION: There is provided an implantable device of an implantable glucose monitor for measuring the glucose concentration of a body fluid when implanted, the device comprising a glucose measurement unit, the glucose measurement unit comprising a light source configured to emit light towards a light transmissive part of a housing of the device, the device further comprising an optical sensor configured to detect linearly polarized light returned through the transmissive part from the light source, 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, wherein the wireless communication module is configured to wirelessly transmit a signal based on the electrical signal to the external wireless communication device.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present disclosure relates to an implantable device for measuring the glucose concentration of a body fluid when implanted, a system including the implantable device, and a method for measuring the glucose concentration.

Background Art

[0002] In insulin therapy, it is generally often necessary to repeatedly obtain blood glucose measurement values from diabetic patients. Diabetic patients with type I diabetes may measure their blood glucose 5 to 9 times a day, while patients with gestational diabetes may measure up to 11 times a day.

[0003] Known blood glucose test methods include collecting a blood sample from a patient using a lancet. Blood collection using a lancet can be painful and uncomfortable for diabetic patients, especially when a high test frequency is required. When blood collection from one skin site is repeated, scars or calluses may form, or the nerve density may increase, which in turn makes it difficult to collect blood.

Summary of the Invention

Means for Solving the Problems

[0004] According to one aspect of the present disclosure, there is provided an implantable device for measuring the glucose concentration of a body fluid when implanted, the implantable device comprising: a first light source configured to emit light towards a light transmissive portion of the device housing; and a first optical sensor configured to detect light that has returned through the light transmissive portion from the first light source and output a first electrical signal based on the detected light, the glucose measurement unit including the first optical sensor; and a wireless communication module configured to wirelessly communicate with an external wireless communication device, the wireless communication module being configured to wirelessly transmit a signal based on the first electrical signal to the external wireless communication device. The implantable device enables continuous remote monitoring of the glucose level of a patient in whom the device is implanted and eliminates the need to collect a blood sample using a lancet or similar device.

[0005] The wireless communication module is configured to wirelessly receive power from the 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 repeatedly used to monitor glucose levels over a long period of time and does not need to be replaced due to battery depletion. In some examples, the device can include a rechargeable power source such as a battery, which is recharged by the power received by the wireless communication module.

[0006] The implantable device is dimensioned to be implantable into a human blood vessel or tissue that is sufficiently perfused with a body fluid such as blood. Such an implantable device is advantageous as it enables accurate measurement of a patient's blood glucose.

[0007] The outer surface of the housing can include a recess, which includes at least a portion of the light transmissive portion. This recess is advantageous in that it facilitates the movement of body fluids such as blood or interstitial fluid around the implantable device, ensuring that the body fluid around the device does not stagnate, and thus can provide a more accurate glucose reading. In some examples, the outer surface of the housing can also include one or more protrusions for facilitating the movement of body fluid around the implantable device. In some examples, the recess is formed from one or more protrusions of the housing. The presence of the recess may be described herein in conjunction with other functions of various embodiments, but the presence of this recess is not essential.

[0008] The implantable device can further include at least one lens configured to focus light radiated from a first light source towards a point outside the housing. This lens enables an accurate measurement of the glucose concentration in the body fluid surrounding the housing while reducing interference from external light sources such as ambient light.

[0009] The light radiated from the first light source is linearly polarized and radiated 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 that has returned through the light transmissive portion from the first region outside the housing. 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 the body fluid.

[0010] According to some embodiments, the implantable device further includes a first linear polarizer arranged to linearly polarize the light emitted from the first light source to a first plane, a second linear polarizer arranged to linearly polarize the light from a first region outside the housing to a second plane substantially orthogonal to the first plane, and a third linear polarizer arranged to linearly polarize the light from the first region outside the housing to a third plane parallel to the first plane. The glucose measurement unit may further include a second optical sensor configured to detect the light that has returned through the light transmission portion and 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 radiated from the first light source to 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 radiated from the first light source to the first region outside the housing is incident on the third linear polarizer. The first optical sensor is arranged to detect a first portion of the linearly polarized light passing through the second linear polarizer from the first region outside the housing, and the second optical sensor is arranged to detect a second portion of the linearly polarized light passing through the third linear polarizer from the first region outside the housing. This arrangement provides a simple means for determining the glucose concentration in the body fluid with interference suppressed.

[0011] According to some embodiments, the implantable device further includes a second light source configured to emit light through a light transmission portion to a second region outside the housing, and a second optical sensor configured to detect the light that has returned through the light transmission portion and output a second electrical signal based on the detected light. The implantable device further includes a first linear polarizer arranged to linearly polarize the light emitted from the first light source in a first plane, a second linear polarizer arranged to linearly polarize the light from a first region outside the housing in 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 in a third plane, and a fourth linear polarizer arranged to linearly polarize the light from a second region outside the housing in a fourth plane, where the fourth plane is parallel to the third plane. The second linear polarizer is arranged such that at least a part of the linearly polarized light emitted from the first light source to the first region outside the housing is incident on the second linear polarizer. The fourth linear polarizer is arranged such that at least a part of the linearly polarized light emitted from the second light source to the second region outside the housing is incident on the fourth linear polarizer. The first optical sensor is configured to be able to detect at least a part of the linearly polarized light emitted from the first light source and passing through the second linear polarizer. The second optical sensor is configured to be able to detect at least a part of the linearly polarized light emitted from the second light source and passing through the fourth linear polarizer. This arrangement provides a simple means for determining the glucose concentration in body fluid with interference suppressed.

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

[0013] The refractometer can include a prism, and the first light source and the prism are arranged such that the light emitted from the first light source enters the surface of the prism through the prism, and the first optical sensor is arranged to detect a part of the light emitted from the first light source that is reflected by the surface of the prism through the prism. This arrangement provides a particularly simple means for determining the glucose concentration in body fluid.

[0014] According to some embodiments, the glucose measurement unit is an infrared spectrometer, the light emitted by the first light source is infrared light, is emitted to the area outside the housing through the light transmission part, and the first optical sensor is configured to detect the infrared light that has returned through the light transmission part via the area outside the housing 10 from the first light source and output a first electrical signal based on the detected infrared light. This arrangement provides a simple means for determining the glucose concentration in body fluid with interference suppressed.

[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 an external wireless communication device. This arrangement enables the influence of temperature to be easily taken into account when processing the output of the glucose monitoring unit to determine the glucose concentration, thereby making it possible to obtain a more accurate value of the glucose concentration.

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

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

[0018] The external wireless communication device can be a smartphone. A smartphone is a particularly simple means for wirelessly communicating with the implantable device.

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

[0020] The above and other advantages of various aspects of the present disclosure will become apparent from the embodiments described below.

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

Brief Description of the Drawings

[0022]

Figure 1A

Figure 1B

Figure 1C

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Mode for Carrying Out the Invention

[0023] Next, reference will be made in detail to embodiments of the present disclosure illustrated in the accompanying drawings. The same reference numerals refer to the same elements throughout.

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

[0025] The above-mentioned body fluid is a fluid in a human or animal body containing glucose, and the glucose concentration is measured for insulin treatment. The body fluid is preferably blood, but alternatively or additionally, interstitial fluid may be used. Since blood generally has a higher responsiveness to changes in glucose concentration than interstitial fluid, it is preferable to measure the glucose concentration in the blood rather than in the interstitial fluid of a human or animal.

[0026] Figure 1 shows an implantable device 1 according to some aspects of the present disclosure. The implantable device 1 has a housing 10, and other components of the implantable device 1 are inside the housing 10.

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

[0028] The housing 10 is preferably made of a biocompatible material such as glass, so that the implantable device 1 can be safely implanted in a human or animal. Using glass for the housing 10 is advantageous in that glass allows light to pass through, and thus the housing 10 and the light-transmissive portion 12 can be formed from the same material in a single process.

[0029] The implantable device 1 is intended to be implanted subcutaneously in a human or animal body. Preferably, the implantable device 1 is implanted into a blood vessel of a human or animal so that the glucose concentration in the blood of the human or animal can be measured. In this case, the specific body fluid to be measured is blood.

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

[0031] In some examples, the configured implantable device 1 is implanted within a tissue that is well perfused with a body fluid such as blood. For example, the implantable device 1 is implanted within the interstitial fluid of a human or animal, such as just beneath the skin. In this case, the specific body fluid being measured is interstitial fluid.

[0032] After the implantable device 1 is implanted, the body fluid contacts the light transmissive portion 12 of the housing 10. When the implantable device 1 is implanted in a blood vessel, blood contacts the light transmissive portion 12. When the implantable device 1 is implanted in interstitial fluid, interstitial fluid is in contact with the light transmissive portion 12.

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

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

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

[0036] When the recess 14 is provided in the housing 10, when the device is implanted, the body fluid around the implantable device 1 can be made to move easily. Doing so can be particularly advantageous because when the implantable device 1 is implanted in a blood vessel, the recess may allow blood to flow easily around or through the implantable device 1. Therefore, the blood flowing through the blood vessel is less obstructed by the implant device 1.

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

[0038] The light transmissive portion 12 shown in FIGS. 1B and 1C is included in an individual region of the housing 10, in this case the entire recess 14. However, the light transmissive portion 12 is not limited to this arrangement and can be placed in another part of the housing 10 or can include the entire housing 10 obtained.

[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 housing 10 having a wireless communication module 20, a glucose measurement unit 30, and a light transmissive portion 12.

[0041] The wireless communication module 20 is preferably configured to communicate wirelessly with an external wireless communication device 2 (shown in FIG. 8) using near field communication (NFC), but other forms of wireless communication can also 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 the wireless signals by the antenna is controlled by the control unit 26. The energy storage unit 24 stores the 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 scheduled to be executed by the control unit 26 and / or data related to the measurements performed by the glucose measurement unit 30. The control unit 26 can control one or more operations of the glucose measurement unit 30 described herein, and can also execute any of the method steps described herein with respect to the implantable device 1 described herein.

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

[0045] Optical sensor 34, also known as a photosensor, detects light by converting the received light into an electrical signal. Thus, optical sensor 34 outputs an electrical signal based on the detected light. Optical sensor 34 may include one or more photodetectors such as a photodiode. Optical sensor 34 can detect light having a specific wavelength or a range of wavelengths. Optical sensor 34 can be made variable. That is, the specific wavelength or range of wavelengths detected by optical sensor 34 can be made variable. The wavelength detected by such an optical sensor 34 is selected by changing the voltage applied to optical sensor 34.

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

[0047] The returned light can pass through light transmissive portion 12 from light source 32 and move to the region outside housing 10 and then return inside housing 10 through light transmissive portion 12 where the light is detected by optical sensor 34. In another example, the returned light passes through light transmissive portion 12 from light source 32 and then is internally reflected at the surface of light transmissive portion 12 and returns inside housing 10 through light transmissive portion 12 where the light is detected by optical sensor 34. The surface of light transmissive portion 12 where the light is internally reflected forms a part of the outer surface 11 of housing 10 and is in contact with body fluid 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. Therefore, this 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 the wireless communication module 20 to the external wireless communication device 2 is processed by the external wireless communication device 2 or another device, resulting in an output such as the value of the glucose concentration, which depends on the glucose concentration of the body fluid measured by the implantable device 1. The 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 the temperature sensor 39 shown in FIG. 2. The temperature sensor 39 is preferably installed adjacent to or in the vicinity of the glucose measurement unit 30, but can be installed 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 above-described signal based on the signal output by the optical sensor 34 or another signal.

[0051] The measurements and operations performed by the glucose measurement unit 30 described in this specification are temperature-dependent. By providing the temperature sensor 39 and obtaining the temperature measurement value, the temperature can be taken into account when processing or interpreting the measurement values obtained by the implantable device 1. However, the temperature sensor 39 is optional. The reason is that the temperature can be measured or estimated using a device that does not form part of the implantable device 1 (for example, it can be assumed that the temperature in the human body is 37 °C).

[0052] Some optical properties of fluids such as body fluids change depending on 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 specific 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. By providing an output based on one or more of these properties, the glucose concentration value of the body fluid is determined. The output is provided using a light source 32 configured to emit light towards the light transmissive portion 12 of the housing 10 of the implantable device 1 and an optical sensor 34 configured to detect the light that has passed back through the transmissive portion 12 from the light source 32, and this output is 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 discussed previously, when the implantable device 1 is implanted, the body fluid contacts the light transmissive portion 12 at the outer surface 11 of the housing 10. The light from the light source 32 passes through the light transmissive portion 12 and interacts with the fluid contacting the light transmissive portion 12. This interaction can occur outside the housing 10, within the body fluid itself, or at the interface between the body fluid and the light transmissive portion 12.

[0054] At least a portion of the light that has interacted with the body fluid is directed towards the inside of the housing 10 by the light transmissive portion It returns through 12 and is detected by the optical sensor 34. The interaction between the body fluid and light may include the optical rotation of light by the body fluid, the absorption of at least a part of the light by the body fluid, or the reflection and / or refraction of light at the interface. Therefore, the light emitted from the light source 32 is changed in some way by the glucose in the body fluid. The amount of interaction / change depends on the glucose concentration in the body fluid. The optical sensor 34 outputs an electrical signal based on the detected light, and this electrical signal corresponds to the amount of change in the light by the body fluid, and thus corresponds to the glucose concentration of the body 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 this electrical signal to the external wireless communication device 2. In other words, the signal transmitted wirelessly corresponds to the electrical signal, and the electrical signal 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 body fluid is detected by the optical sensor 34.

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

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

[0060] The specific rotation depends on the temperature of the solution and the wavelength of the polarized light. The concentration of glucose in the solution is determined by measuring the angle α by which the plane of polarization of the linearly polarized light rotates as the linearly polarized light travels through the solution and the path length L of the linearly polarized light passing through the solution. When the temperature T of the container and the wavelength λ of the linearly polarized light are known or estimated, the value of the specific rotation [α] of glucose for that temperature and wavelength is retrieved. Next, the concentration β of glucose in the solution is determined from the angle α, the specific rotation [α], and the path length L by the following formula: T λ is retrieved. Next, the concentration β of glucose in the solution is determined from the angle α, the specific rotation [α] T λ , and the path length L by the following formula:

Equation

[0061] The equivalent amount of the rotation of the linearly polarized light passing through a body fluid such as blood or interstitial fluid is assumed to be caused by glucose rather than other components of the body fluid. Therefore, the optical activity of other components in the body fluid is generally ignored. Therefore, by determining the rotation angle 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 an electrical signal output by the optical sensor 34 or an 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 with a look-up table containing a plurality of measurement values and their corresponding glucose concentration values.

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

[0064] The implantable device 1 of FIG. 3 is shown as including the recess 14, but in some examples, the recess 14 may not be present. As shown in FIG. 3, the first side wall 15 and the second side wall 16 of the recess 14 each include at least a part of the light transmissive portion 12. The light source 32 is arranged in the housing 10 such that the light radiated toward the light transmissive portion 12 passes through the light transmissive first side wall 15 to an area outside the housing and then through the light transmissive second side wall 16 and is detected by the optical sensor 34, as indicated by the arrow in FIG. 3. In some examples, the light source 32 and the optical sensor 34 are arranged in the housing 10 such that the radiated light exits and returns through the same surface of the light transmissive portion 12, for example, the bottom surface 17, as shown in FIGS. 4 and 5.

[0065] As shown in FIG. 3, the light radiated from the light source 32 is linearly polarized by the first linear polarizer 41 and radiated through the light transmissive portion 12 to an area outside the housing 10. This area is in the body fluid when the implantable device is implanted.

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

[0067] FIG. 3 shows the lens 46 installed in the optical path between the light source 32 and the light transmissive portion 12 in the housing 10, but alternatively, the lens 46 can be installed at any suitable position, such as on the surface of the light transmissive portion 12 of the outer surface 11 of the housing 10. FIG. 3 also shows the first linear polarizer 41 installed in the optical path between the light source 32 and the lens 46, but in some examples, the first linear polarizer 41 can also be installed after the lens 46 along the optical path.

[0068] The linearly polarized light passing through the body fluid is rotated by the glucose in the body fluid. As a result, the plane of polarization of the light rotates by an amount depending on the concentration of glucose and the distance the light travels through the glucose. The distance the light travels through the glucose is determined before the device is implanted. The optical sensor 34 is configured to detect the rotation of the linearly polarized light that has passed through the body fluid and returned through the transmission part 12 from the region outside the housing 10. The optical sensor 34 is further configured to output an electrical signal based on the detected, rotated light. This 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 that has returned through the transmission part from the region outside the housing involves using a second linear polarizer 42 installed 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 plane of polarization of the second linear polarizer 42 rotates around the optical path so as to be preferably substantially orthogonal to the plane of polarization of the first linear polarizer 41 with respect to the plane of polarization of the first linear polarizer 41. Therefore, 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 the glucose-containing body fluid. The amount of rotation, and thus the amount of light detected by the optical sensor 34, depends on the glucose concentration in the body fluid. In this way, the electrical signal output by the optical sensor 34 is based on the amount of rotation of the linearly polarized light and is therefore based on the glucose concentration in the body fluid.

[0070] The implantable device 1 shown in FIG. 3 may be susceptible to interference from the optical sensor 34, which detects light such as ambient light that does not come from the light source 32. FIG. 4 is similar to FIG. 3 but shows a partial schematic cross-sectional view of the implantable device 1 configured to greatly suppress interference. Similar to the implantable device 1 shown in FIG. 3, the implantable device 1 shown in FIG. 4 includes a recess 14, but the presence of the recess 14 is optional.

[0071] Similar to FIG. 3, the implantable device 1 shown in FIG. 4 includes a light source 32, a first linear polarizer 41, and a second linear polarizer 42. However, here the glucose measurement 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 the light emitted from the light source 32 through the light transmission portion 12 with a first polarization plane, and this polarization is radiated to the region outside the housing 10. The second linear polarizer 42 is arranged to linearly polarize the light from the region outside the housing 10 into a second polarization plane that is substantially orthogonal to the first plane (i.e., rotated 90° around the optical axis). The third linear polarizer 43 is arranged to linearly polarize the light from the region outside the housing 10 into a third polarization plane, and this third plane is parallel to the first plane (i.e., rotated 0° around the optical axis).

[0073] As described above, FIG. 4 shows three lenses 46 configured to focus light. One or more of the lenses 46 are arranged to focus the light emitted from the light source 32 onto one point or region outside the housing 10 in the body fluid. The first optical sensor 34 and the second optical sensor 36 are arranged to detect the light emitted from the light source 32 that is reflected, for example, in the body fluid near a point or region outside the housing. The detected light is focused by one or more lenses 46 from the point or region outside the housing 10 towards the first optical sensor 34 and the second optical sensor 36. An exemplary optical path is indicated by arrows in FIG. 4.

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

[0075] The third linear polarizer 43 is arranged such that the second part of the linearly polarized light radiated from the light source 32 to the region outside the housing 10 is incident on the third linear polarizer 43. In other words, the third linear polarizer 43 is installed in the optical path between the light source 32 and the second optical sensor 36 and between the region outside the housing 10 and the second optical sensor 36.

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

[0077] The second optical sensor 36 is arranged to detect the second part of the linearly polarized light passing through the third linear polarizer 43 from the region outside the housing 10. This second part of the linearly polarized light emitted from the light source 32 is linearly polarized in the first plane by the first linear polarizer 41, then rotated by 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 by which the plane of linear polarization of the light radiated from the light source 32 is rotated. The composite signals S PD1 and the composite signal S PD2 are used to determine the angle α by which the linearly polarized light is rotated by glucose using the following equation:

Equation

[0079] As discussed previously, 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 PD2 are dependent on factors such as the current passing through the light source 32, the channel gain, the type-specific LED emission intensity, the ambient light, the transmission coefficient of blood or other body fluids (a function of various factors such as the type of food eaten and the time since eating the food), and the transmittance of the linear polarizer. By providing an additional third linear polarizer 43 and a second optical sensor 36, the electrical signals output by the first optical sensor 34 and the second optical sensor 36 are processed, and otherwise the signals S PD1 and S PD2 are reduced or eliminated from the influence of the aforementioned factors on which they depend, for example, the influence of interference caused by ambient light, noise in the electrical components of the implantable device 1, or similar parasitic effects is reduced. Therefore, a more accurate measurement of the glucose concentration that does not depend on these factors is performed.

[0081] FIG. 5 shows another embodiment similar to FIG. 4, where the glucose measurement unit 30 may further include a second light source 35 that may again include one or more LEDs. Similar to that discussed with reference to FIG. 4, the light source 32 in FIG. 5 (referred to hereinafter as the first light source 32 with respect to FIG. 5) is configured to emit light through the light transmission portion 12 to the (first) region outside the housing 10, and the second light source 35 is configured to emit light through the light transmission portion 12 to the (second) region outside the housing 10. The first region and the second region may be the same.

[0082] The first linear polarizer 41 in FIG. 5 is configured to linearly polarize the light emitted from the first light source 32 through the light transmission portion 12 in the first polarization plane, and this light is emitted to the first region outside the housing 10. The second linear polarizer 42 is arranged to linearly polarize the 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° about the optical axis).

[0083] The fourth linear polarizer 44 in FIG. 5 is configured to linearly polarize the light radiated from the second light source 35 through the light transmission portion 12 in the third polarization plane, and this light is radiated to the second region outside the housing 10.

[0084] The third linear polarizer 43 is arranged to linearly polarize the light from the second region outside the housing 10 in the fourth plane, and this fourth plane is parallel to the third plane (i.e., rotated 0° around the optical axis). The fourth plane may be parallel to the third plane.

[0085] The second linear polarizer 42 is arranged such that at least a part of the linearly polarized light radiated 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 installed 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 arranged such that at least a part of the linearly polarized light radiated 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 installed 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 be able to detect at least a part of the linearly polarized light radiated from the first light source 32 (via the first region outside the housing 10) and passing through the second linear polarizer 42. The second optical sensor 36 is configured to be able to detect at least a part of the linearly polarized light radiated from the second light source 35 (via the second region outside the housing 10) and passing through the third linear polarizer 43.

[0088] Preferably, the first optical sensor 34 is arranged in the implantable device 1 so as not to detect the light emitted by the second light source 35, and the second optical sensor 36 is arranged in the implantable device 1 so as not to detect the light emitted by the first light source 32. With this arrangement, the influence of interference on the electrical signals output by the first optical sensor 34 and the second optical sensor 36 is reduced.

[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 thus based on the angle of rotation of the appropriate polarization from the first light source 32 or the second light source 35. The composite signals S PD1 and the composite signal S PD2 are used to determine the angle α by which the linearly polarized light is rotated by glucose using the following equation:

Equation

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

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

[0092] In some embodiments, the glucose measurement unit is a refractometer, and the electrical signal output by the optical sensor 34 is based on the refractive index n2 of the body fluid in contact with the light transmission portion 12.

[0093] The refractive index n2 of a body fluid containing glucose is a function of the glucose concentration in the body fluid (i.e., it depends on the glucose concentration). When 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 of the glucose concentration is thus determined. This determination may include using the look-up table discussed with respect to optical activity.

[0094] FIG. 6 shows a partial schematic cross-sectional view of an implantable device 1 in which the glucose measurement unit 30 is a refractometer. The refractometer includes a prism 60, and the light source 32 and the prism 60 are arranged such that light emitted from the light source 32 enters the prism 60 and is incident on the surface 61 of the prism 60. In other words, as also indicated by the arrows in FIG. 6, the prism 60 and the light source 32 are positioned such that 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 the implantable device 1 is implanted, the body fluid comes into contact with the surface 61. Therefore, the light transmission part 12 includes the prism 60.

[0096] Depending on the angle of incidence θ1 of the light on the surface 61, a part of the light emitted from the light source 32 is reflected (i.e., totally internally reflected) at the body fluid - prism interface at the surface 61 of the prism 60. The optical sensor 34 is arranged to detect a part of this reflected light after the light has passed back through the prism 60 and exited the prism. In particular, the optical sensor 34 is arranged to measure the refractive angle θ2 of the (total internal) reflected light.

[0097] FIG. 6 shows the optical sensor 34 as a CCD sensor 62. The refractive angle θ2 is determined using the position of the reflected light on the CCD sensor 62, and thus the refractive index of the body fluid in contact with the surface 61 is determined. Therefore, the CCD sensor 62 outputs an electrical signal based on the refractive index of the body fluid.

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

Equation

[0099] Therefore, when the incident angle θ1 and the refractive index n1 of the prism 60 are already known, the value of the refractive index n2 of the body fluid can be determined by measuring the refraction angle θ2. Using the value of the refractive index of the body fluid, the value of the glucose concentration in the body fluid can be determined, for example, by comparing the value of the refractive index of the body fluid with a look-up table, or by performing additional calculations on the value of the refractive index of the body fluid.

[0100] Since elements such as the absolute luminance of the light source 32 and the light transmission of the body fluid do not affect the refraction angle and therefore do not affect the determined value of the glucose concentration, the accurate value of the glucose concentration can be determined by measuring the refraction angle using a refractometer.

[0101] In some embodiments, the glucose measurement unit is an infrared spectrometer. The infrared absorption spectrum of the body fluid containing glucose changes depending on 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 measurement unit is an infrared spectrometer.

[0103] The light emitted by the light source 32 is infrared light and is radiated to the area outside the housing 10 through the light transmission part 12. The optical sensor 34 is configured to detect the infrared light that has passed from the light source 32 through the area outside the housing 10 and back through the light transmission part 12, and to output an electrical signal based on the detected infrared light and thus based on the glucose concentration of the body fluid.

[0104] In some cases, the glucose measurement unit 30 includes a first filter 70 configured to filter the light emitted by the light source 32, such that only light of a specific wavelength passes through the first filter 70 and is radiated through the light transmission portion 12 to an area outside the housing 10. In some cases, the glucose measurement unit 30 includes a second filter 72 configured to filter the light that has returned from the light source 32 through the light transmission portion 12, such that only light of a specific wavelength passes through the second filter 72 and is detected by the optical sensor 34. The optical sensor 34 is configured to detect light having a variable band of wavelengths. The band of wavelengths detected by the optical sensor 34 is adjusted by changing the voltage applied to the optical sensor 34.

[0105] The present disclosure also relates to a system including the external wireless communication device 2 and the implantable device 1 according to any of the above-described embodiments. FIG. 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 an animal).

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

[0107] The external wireless communication device 2 wirelessly transmits power to the implantable device 1 by electromagnetic induction between the antenna of the external wireless communication device 2 and the 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 circuit, such as the glucose measurement unit 30 within the device.

[0108] In response to receiving power or in response to receiving an additional wireless signal transmitted to the implantable device 1 by an external communication device, the implantable device 1 proceeds with measuring the glucose concentration of the body 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 transmissive portion 12 of the housing 10 of the implantable device 1. The optical sensor 34 of the implantable device 1 detects the light that has returned through the light transmissive 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 an external wireless communication device 2. The signal wirelessly transmitted from the implantable device 1 to the external wireless communication device 2 is processed (e.g., by the external wireless communication device 2), and the value of the glucose concentration of the body fluid is determined.

[0109] The present disclosure is also related to a method of performing any of the above-described steps related to the implantable device 1 and the external wireless communication device 2.

[0110] FIG. 9 shows a method according to an embodiment of the present disclosure. In step 901, light is emitted by the light source 32 of the implantable device 1 described above toward the light transmissive portion 12 of the housing 10 of the implantable device 1. In step 902, the optical sensor 34 of the implantable device 1 detects the light that has returned from the first light source 32 through the light transmissive portion 12. In step 903, an electrical signal based on the detected light is output by the optical sensor 34. In 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 described above. As discussed previously, the signal wirelessly transmitted from the implantable device 1 to the external wireless communication device 2 is processed (e.g., by the external wireless communication device 2), and the value of the glucose concentration of the body fluid is determined.

[0111] The terms "drug" or "agent" are used interchangeably herein and refer to a pharmaceutical preparation comprising one or more pharmaceutical active ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally, a pharmaceutically acceptable carrier. A pharmaceutical active ingredient ("API") is, in the broadest sense, a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or agent is used in the treatment, cure, prevention, or diagnosis of a disease, or alternatively, to improve physical or mental health. A drug or agent is used for a limited duration, or periodically in the case of chronic diseases.

[0112] As described below, a drug or agent can comprise at least one API of one or more types of formulations, or a combination thereof, for treating one or more diseases. Examples of APIs can include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides, and proteins (such as 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. Nucleic acids are incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0113] The drug or medicament is contained within a primary package or “drug container” that is adapted for use with a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other solid or flexible container configured to provide a chamber suitable for storage of one or more drugs (e.g., short-term or long-term storage). For example, in some cases, the chamber is designed to store 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 from about one month to about two years. Storage can be at room temperature (e.g., about 20° C.) or refrigerated temperature (e.g., from about -4° C. to about 4° C.). In some cases, the drug container can be, or can include, a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation scheduled for administration (e.g., an API and a diluent, or two different types of drugs), one in each chamber. 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 dosing into a 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) and, if desired, allow the two components to be mixed by a user before dosing. Alternatively, or in addition, the two chambers are configured to allow mixing when the components are being dosed into a human or animal body.

[0114] The drugs or agents contained within the drug delivery devices described herein are used for the treatment and / or prevention of numerous 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 thrombosis or pulmonary embolism. Another example of a disorder is acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs include, for example, but not limited to, those described in the Handbook Rote Liste 2014, main group 12 (antidiabetic drugs) or main group 86 (antineoplastic drugs), and the Merck Index, 15th edition, etc.

[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, such as human insulin, or human insulin analogs or derivatives, glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof, dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof, or any mixture thereof. As used herein, the terms “analog” and “derivative” refer to a polypeptide having a molecular structure obtained formally from the structure of a natural peptide, such as the structure of human insulin, by deleting and / or exchanging 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 exchanged amino acid residues can be codable amino acid residues, or other natural residues or fully synthetic amino acid residues. Insulin analogs are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide having a molecular structure obtained formally from the structure of a natural 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 natural peptide may be deleted and / or substituted by other amino acids containing non-codable amino acids, or amino acids containing non-codable amino acids may be added to the natural peptide.

[0116] Examples of insulin analogs 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 proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala and Lys at position B29 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 (registered trademark)), 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; B30-N-palmitoyl-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 (registered trademark)), 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®), r exendin-4, CJC-1134-PC, PB-1023, TTP-054, langlenatide / 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 hormones or hypothalamic hormones or regulatory active peptides and their antagonists such as gonadotropins (folitropin, lutropin, chorionic gonadotropin, menotropin), somatropin (somatropin), desmopressin, terlipressin, gonadorelin, tryptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

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

[0123] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain the ability to bind an antigen. Antibodies can be polyclonal, monoclonal, recombinant, chimeric, non-immune or humanized, fully human, non-human (e.g., murine), or single-chain antibodies. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has low or no ability to bind to an Fc receptor. For example, the antibody can be an isotype or subtype, antibody fragment or variant that does not support binding to an Fc receptor, e.g., having a mutated or deleted Fc receptor binding region. The term antibody also includes antibody-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or cross-over region oriented dual variable domain antibody-like binding proteins (CODVs).

[0124] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy chain and / or light chain polypeptide) that does not include the full-length antibody polypeptide but still includes at least a portion of the full-length antibody polypeptide that is capable of binding to an antigen. An antibody fragment can include a cleaved portion of the full-length antibody polypeptide, but the term is not limited to such cleaved fragments. Antibody fragments 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, tribodies, tetrabodies), monovalent antibody fragments, or multivalent antibody fragments such as divalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelate recombinant antibodies, tribodies or bivalent antibodies, 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. include monospecific antibody fragments, or multispecific antibody fragments such as bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., diabodies, tribodies, tetrabodies), monovalent antibody fragments, or multivalent antibody fragments such as divalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelate recombinant antibodies, tribodies or bivalent antibodies, 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 "complementary determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both the heavy and light chain polypeptides that primarily play a role in mediating specific antigen recognition. The term "framework region" refers to the amino acid sequences within the variable regions of both the heavy and light chain polypeptides that primarily play a role in maintaining the correct positioning of the CDR sequences and enabling antigen binding, rather than being the CDR sequences themselves. The framework region itself is not usually directly involved in antigen binding, as is known in the art, but specific residues within the framework region of a particular antibody can be directly involved in antigen binding or can affect the ability of one or more amino acids within the CDR to interact with the antigen.

[0126] Examples of antibodies include anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0127] Pharmaceutically acceptable salts of any API described herein are also contemplated for use of the drug or agent in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0128] Those skilled in the art will understand that modifications (additions and / or removals) to the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein can be made without departing from the full scope and spirit of the disclosure that encompasses such modifications and any equivalents thereof.

[0129] Although the claims in this application are clearly directed to specific combinations of structures, the scope of the disclosure also includes any novel structure or any novel combination of structures that are disclosed expressly or implicitly herein, or any generalization thereof, whether or not that structure is related to the same disclosure as that which is actually claimed in any claim, and whether or not that structure seeks to alleviate any or all of the same technical problems as those alleviated by the disclosure. The applicant hereby notifies that in this application, new claims may be presented for such structures and / or combinations of structures during the implementation of this application or any further application derived from this application.

[0130] Although some embodiments have been illustrated and described, those skilled in the art will understand that these embodiments can be modified without departing from the principles of the disclosure, the scope of which is defined by the claims.

Claims

1. 1. An implantable device for measuring a glucose concentration of a body fluid when implanted, the implantable device comprising: The device includes a housing having a recess formed in an exterior surface of the housing for receiving a bodily fluid, the housing comprising: a glucose measuring unit, the glucose measuring unit comprising: a first light source configured to emit light into the bodily fluid within the cavity; and a first light sensor configured to detect light returned from the first light source through the bodily fluid in the recess and 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 is configured to wirelessly transmit a signal based on the first electrical signal to an external wireless communication device; The implantable 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 to be implantable within a human blood vessel.

4. The implantable device of any one of claims 1 to 3, further comprising at least one lens positioned to focus light emitted from the first light source towards a point outside the housing.

5. the light emitted from the first light source is linearly polarized and is emitted through the light-transmitting portion of the housing to a first region outside the housing; the first optical sensor is configured to detect the rotated linearly polarized light returned from the first region outside the housing through the light transmissive portion; The first optical sensor is configured to output a first electrical signal based on the detected rotated light. The implantable device of any one of claims 1 to 4, comprising:

6. 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 perpendicular to the first plane; a third linear polarizer positioned to linearly polarize light from the first region outside the housing into a third plane that is parallel to the first plane; 6. The implantable device of claim 5, further comprising: the glucose measuring unit further includes a second optical sensor configured to detect light returned through the light-transmitting 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 the first region outside the housing is incident on the second linear polarizer; the third linear polarizer is positioned such that a second portion of the linearly polarized light emitted from the first light source to 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 through the second linear polarizer from a first region outside the housing; The implantable device, wherein a second optical sensor is positioned to detect a second portion of the linearly polarized light passing through a third linear polarizer from a first region outside the housing.

7. 6. The implantable device of claim 5, comprising: The glucose measuring unit also: a second light source configured to emit light through the light transmissive portion to a second region outside the housing; 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 implantable device may further: 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 perpendicular to the first plane; a third linear polarizer positioned to linearly polarize light emitted from the second light source in a third plane; a fourth linear polarizer positioned to linearly polarize light from the second region outside the housing in a fourth plane, the fourth plane being parallel to the third plane; the second linear polarizer is positioned such that at least a portion of the linearly polarized light emitted from the first light source to 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 the 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 implantable device, wherein 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 a fourth linear polarizer.

8. An implantable device according to any one of claims 1 to 4, wherein the glucose measuring unit is a refractometer.

9. The refractometer includes a prism; The first light source and the prism are configured such that light emitted from the first light source passes through the prism and enters the prism. positioned to be incident on the surface of the 9. The implantable device of claim 8, wherein the first optical sensor is positioned to detect a portion of the light emitted from the first light source that passes through the prism and is reflected off a surface of the prism.

10. 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-transmitting portion of the housing to an area outside the housing; 5. The implantable device of claim 1, wherein the first optical sensor is configured to detect infrared light that has passed from the first light source through an area outside the housing 10 and returned through the light-transmitting portion, and to output a first electrical signal based on the detected infrared light.

11. The implantable device of any one of claims 1 to 10, 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.

12. An implantable device according to any preceding claim, wherein the recess is configured to facilitate the movement of body fluids around the implantable device when the implantable device is implanted.

13. 13. A system comprising an implantable device according to any one of claims 1 to 12 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.

14. The system of claim 13 , wherein the external wireless communication device is a smartphone.

15. 1. A method comprising: emitting light by a first light source of the implantable device of any one of claims 1 to 12 towards the body fluid in the recess of the housing of the implantable device; detecting, by a first optical sensor of the implantable device, light returned from the first light source through the transmissive portion; outputting, by the first optical sensor, a first electrical signal based on the detected light; and The method includes wirelessly transmitting, by a wireless communication module of the implantable device, a signal based on the first electrical signal to an external wireless communication device.

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