Implantable glucose monitor

Abstract

To provide an implantable device for measuring the glucose concentration of a body fluid when implanted.SOLUTION: An implantable device for measuring the glucose concentration of a body fluid when implanted comprises: a glucose measurement unit comprising a first light source configured to emit light towards a light transmissive part of a housing of the device, and a first optical sensor configured to detect light returned through the light transmissive part from the first light source 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, where the wireless communication module is configured to wirelessly transmit a signal based on the first 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 linearly polarized light source configured to emit linearly polarized light to the outside of the housing of the device; and a linearly polarized light sensor configured to detect the linearly polarized light that has returned via the outside of the housing from the linearly polarized light source and to output a first electrical signal based on the detected linearly polarized light; a glucose measurement unit including the same; and a wireless communication module configured to communicate wirelessly 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 linearly polarized light sensor can include a linearly polarized light filter and a first optical sensor, the linearly polarized light filter being configured to linearly polarize the light that has returned from the first linearly polarized light source through the light transmission portion 12, and the first optical sensor being configured to output a first electrical signal based on the detected light linearly polarized by the linearly polarized light filter.

[0006] The polarization plane of the linearly polarized light filter can be adjustable to match the polarization plane of the first linearly polarized light source. This provides an effective means of measuring the angle of rotation of the linearly polarized light when the linearly polarized light passes through the body fluid containing glucose between the first linearly polarized light source and the linearly polarized light filter.

[0007] The linearly polarized light filter can include a cell arranged such that the linearly polarized light that has returned via the outside of the housing from the linearly polarized light source is detected by the first optical sensor after passing through the cell. The cell is a simple means of providing a linearly polarized light filter with an adjustable polarization plane.

[0008] The cartridge can include a first electrode and a second electrode, and the glucose measurement unit is configured to apply a potential difference between the first electrode and the second electrode to generate an electric field therebetween. The linearly polarized light returning from the linearly polarized light source through the outside of the housing passes through the first electrode and the second electrode along a path substantially parallel to the electric field. Thereby a particularly small cartridge is provided.

[0009] The glucose measurement unit can further include a second optical sensor and a linear polarizer. The linear polarizer is configured to linearly polarize the light returning from the linearly polarized light source through the outside of the housing. The second optical sensor is configured to detect the light linearly polarized by the linear polarizer and output a second electrical signal based on the detected light linearly polarized by the linear polarizer. The wireless communication module is configured to wirelessly transmit a signal based on the second electrical signal. This arrangement provides a simple means for determining the glucose concentration in the body fluid with interference suppressed.

[0010] The glucose measurement unit can further include a second linearly polarized light source, a second optical sensor and a linear polarizer. The second linearly polarized light source is configured to emit linearly polarized light to the outside of the housing. The linear polarizer is configured to linearly polarize the light returning from the second linearly polarized light source through the outside of the housing. The second optical sensor is configured to detect the light linearly polarized by the linear polarizer and output a second electrical signal based on the detected light linearly polarized by the linear polarizer. The wireless communication module is configured to wirelessly transmit a signal based on the second electrical signal. This arrangement provides a simple means for determining the glucose concentration in the body fluid with interference suppressed.

[0011] 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 repeatedly used to monitor glucose levels over a long period of time without the need to replace the device 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.

[0012] 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.

[0013] The housing of the implantable device can include a recess, and light radiated from a first linearly polarized light source to the outside of the housing passes through a first sidewall of the recess and the linearly polarized light detected by the linearly polarized light sensor returns through a second sidewall of the recess. This housing is advantageous in that it provides a simple and effective means for determining the glucose concentration of the body fluid within the recess. The recess is formed from one or more protrusions of the housing.

[0014] The implantable device can further include at least one lens configured to focus light radiated from the first linearly polarized light source to a point outside the housing. This lens enables accurate measurement of the glucose concentration in the body fluid surrounding the housing while reducing interference from external light sources such as ambient light.

[0015] 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 enabling a more accurate value of the glucose concentration to be obtained.

[0016] 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.

[0017] The external wireless communication device can be a smartphone. A smartphone is a particularly simple means for wirelessly communicating with the implantable device.

[0018] According to another aspect of the present disclosure: radiating linearly polarized light to the outside of the housing of the implantable device by a first linearly polarized light source of the implantable device; detecting the linearly polarized light that has returned from the outside of the housing via the first linearly polarized light source by a linearly polarized light sensor of the implantable device; outputting a first electrical signal based on the detected linearly polarized light by the linearly polarized light 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: A method including this is provided. This method enables a simple and unobtrusive measurement of the glucose concentration in body fluid.

[0019] The above and other advantages of various aspects of the present disclosure will become apparent from the embodiments described below.

[0020] Exemplary embodiments of the present disclosure will be described with reference to the accompanying drawings.

Brief Description of the Drawings

[0021]

Figure 1A

Figure 1B

Figure 1C

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Figure 12

DETAILED DESCRIPTION OF THE INVENTION

[0022] 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.

[0023] An implantable device is provided that measures the glucose concentration of a body fluid when implanted. 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 are further provided.

[0024] The body fluid described above is a fluid in a human or animal body containing glucose, and the glucose concentration is measured for insulin therapy. The body fluid is preferably blood, but may alternatively or additionally be interstitial fluid. Since blood generally has a higher responsiveness to changes in glucose concentration than interstitial fluid, it is preferred to measure the glucose concentration in blood rather than in the interstitial fluid of a human or animal.

[0025] FIG. 1 shows an implantable device 1 according to some aspects of the present disclosure. The implantable device 1 has a housing 10, and some or all of the other components of the implantable device 1 are inside the housing 10.

[0026] 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 through the light transmissive portion 12 to the inside of the housing 10, 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.

[0027] 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 manufacturing process.

[0028] The implantable device 1 is intended to be implanted subcutaneously in a human or animal body. Preferably, the implantable device 1 can be implanted into a blood vessel of a human or animal to measure the glucose concentration of the blood of the human or animal. In this case, the specific body fluid to be measured is blood.

[0029] In some embodiments, the implantable device 1 is dimensioned to be implantable into a human blood vessel such as an artery or a 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.

[0030] In some examples, the implantable device 1 is configured to be implanted into a tissue that is sufficiently perfused with a body fluid such as blood or interstitial fluid. For example, the implantable device 1 is implanted into the interstitial fluid of a human or animal, for example, just under the skin. In this case, the specific body fluid to be measured is interstitial fluid.

[0031] After the implantable device 1 is implanted, the body fluid surrounds at least a part of the implantable device 1 and contacts the light transmissive portion 12 of the housing 10. When the implantable device 1 is implanted in a blood vessel, the blood contacts the light transmissive portion 12. When the implantable device 1 is implanted in the interstitial fluid, the interstitial fluid is in contact with the light transmissive portion 12.

[0032] FIG. 1B shows an implantable device 1 similar to the implantable device 1 of FIG. 1A, but the housing 10 of the implantable device shown in FIG. 1B further includes a recess 14 formed entirely on the outer surface 11 of the housing 10. FIG. 1C shows a side view of the implantable device of FIG. 1B showing a side view of the recess 14.

[0033] 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 adjacent to the first side wall 15 and the second side wall 16.

[0034] The recess 14 can be a groove in the outer surface 11 of the housing. 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 or tube may extend from one side of the housing 10 to the opposite side of the housing 10. The recess 14 is at least partially filled with body fluid when the implantable device 1 is implanted.

[0035] Providing the recess 14 in the housing 10 can facilitate the movement of the body fluid around the implantable device 1 when the device is implanted. This can be particularly advantageous as the recess may allow blood to flow easily around or through the implantable device 1 when the implantable device 1 is implanted in a blood vessel, so that the blood flowing through the blood vessel is less obstructed by the implant device 1.

[0036] In some examples, the outer surface 11 of 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.

[0037] 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 installed in another part of the housing 10 or can include the entire housing 10.

[0038] FIG. 2 is a schematic cross-sectional view of an implantable device 1 according to an embodiment of the present disclosure.

[0039] 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.

[0040] The wireless communication unit 20 is preferably configured to wirelessly communicate with an external wireless communication device 2 (shown in FIG. 11) using near field communication (NFC), although other wireless protocols and systems can also be used.

[0041] The wireless communication module 20 is preferably configured to wirelessly receive power from the external wireless communication device 2 by electromagnetic induction.

[0042] 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 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 measurements made 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.

[0043] The glucose measurement unit 30 includes a linearly polarized light source 32 and a linearly polarized light sensor 36. The linearly polarized light source 32 can include one or more light sources 33 (not shown) such as one or more light emitting diodes (LEDs), and linearly polarized light is directed outside the housing 10 It is configured to radiate. When the linearly polarized light source 30 is installed inside the housing 10, the linearly polarized light source 30 is configured to radiate linearly polarized light toward and transmit it through the light transmission part 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 33 is preferably powered by the energy storage unit 24 and controlled by the control unit 26.

[0044] The linearly polarized light sensor 36 detects linearly polarized light and converts the received / detected light into an electrical output. The linearly polarized light sensor 36 outputs an electrical signal based on the detected light, particularly based on the amount or intensity of the detected light. The linearly polarized light sensor 36 may include an optical sensor 37 such as one or more photodiodes. The optical sensor 37 can detect only light having a specific wavelength or a range of wavelengths. The optical sensor 37 can be made variable. That is, the specific wavelength or wavelength range detected by the optical sensor 37 can be made variable. The wavelength detected by such an optical sensor 37 is selected by changing the voltage applied to the optical sensor 37.

[0045] The linearly polarized light sensor 36 is configured to detect linearly polarized light that has passed through the light transmission part 12 of the housing 10, etc., and returned via the outside of the housing from the linearly polarized light source, and output an electrical signal based on the detected linearly polarized light. In other words, the linearly polarized light sensor 36 is configured to detect light that has been radiated from the inside of the housing 10 to the outside of the housing 10 by the linearly polarized light source 32 via the light transmission part 12 of the housing 10 and returned to the inside of the housing 10 via the light transmission part 12.

[0046] The returned light can pass through the light transmission part 12 and return to the inside of the housing 10 where the light is detected by the linearly polarized light sensor 36 after moving from the linearly polarized light source 32 through the light transmission part 12 to the area outside the housing 10.

[0047] The wireless communication module 20 is configured to wirelessly transmit a signal based on the electrical signal output by the linear polarization sensor 36 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 linear polarization sensor 36, whether it 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 near the implantable device 1.

[0048] 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 a value of the glucose concentration that depends on the glucose concentration measured by the implantable device 1. The implantable device 1 is calibrated by first performing a standard blood glucose test using a lancet.

[0049] 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 near 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 wireless signal based on the signal output by the linear polarization sensor 36 or another signal.

[0050] 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, when processing or interpreting the measurement value obtained by the implantable device 1, the implantable The temperature in the vicinity of S1 can be taken into account. However, the temperature sensor 39 is optional. The reason is that the temperature can be measured using a device that does not form part of the implantable device 1, or the temperature can be estimated (for example, it can be assumed that the temperature in the human body is 37 °C).

[0051] According to some aspects of the present disclosure, the rotation angle of linearly polarized light passing through a body fluid can be determined directly or indirectly by the implantable device 1. By providing an output based on the rotation angle of linearly polarized light passing through a fluid, the value of the glucose concentration in the body fluid can be determined. This output is brought about using a linearly polarized light source 32 configured to emit linearly polarized light outside the housing 10 of the implantable device 1 and a linearly polarized light sensor 36 configured to detect the light that has returned via the outside of the housing 10 from the linearly polarized light source 32, and this output is an electrical signal based on the detected linearly polarized light, in particular based on the intensity of the detected light.

[0052] Glucose is an optically active material. That is, the plane of polarization of linearly polarized light rotates as the light travels through a glucose solution. 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.

[0053] 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.

[0054] 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 it 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 of glucose for that temperature and wavelength is retrieved. Next, the concentration 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

[0055] The amount of 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. 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.

[0056] Determining the glucose concentration may include processing an electrical signal output by the linearly polarized light sensor 36 or a signal based on an electrical signal wirelessly transmitted to the external wireless communication device 2 to determine a measured value. The glucose concentration value is determined by comparing the measured value with a look-up table containing a plurality of measured values and their corresponding glucose concentration values.

[0057] As discussed previously, when the implantable device 1 is implanted, the body fluid contacts the outer surface 11 of the housing 10, preferably the light transmissive portion 12. The light from the linearly polarized light source 32 passes through the light transmissive portion 12 towards the outside of the housing 10, and the light passes through the body fluid outside the housing 10 It rotates the plane of polarization when passing through. That is, the plane of polarization of light rotates by a certain angle when the light passes through the body fluid.

[0058] At least a part of the light rotated by the body fluid passes through the light transmission part 12 and returns to the inside of the housing 10, and is detected by the linearly polarized light sensor 36. The linearly polarized light sensor 36 detects light of a specific linearly polarized light and outputs an electrical signal based on the amount of the detected linearly polarized light. The plane of polarization of the linearly polarized light emitted by the linearly polarized light source 32 is rotated by glucose in the body fluid. The amount of rotation depends on the glucose concentration in the body fluid. Therefore, the amount of light detected by the linearly polarized light sensor 36 corresponds to the glucose concentration in the body fluid. The linearly polarized light sensor 36 is configured to output an electrical signal based on the detected linearly polarized light. This electrical signal corresponds to the amount of rotation of the plane of polarization of light by the body fluid, and therefore corresponds to the glucose concentration in the body fluid.

[0059] The electrical signal output by the linearly polarized light sensor 36 is processed in the implantable device 1, for example, by the control unit 26. The wireless communication module 20 receives the electrical signal from the linearly polarized light sensor 36 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.

[0060] The signal transmitted to the external wireless communication device 2 by the wireless communication module 20 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.

[0061] 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 in the body fluid.

[0062] The implantable device 1 shown in FIG. 3 is shown to include the groove 14, although in some examples the groove 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 portion of the light transmissive portion 12. The linearly polarized light source 32 is arranged in the housing 10 such that the linearly polarized light radiated to the outside of the housing 10 by the linearly polarized light source 32 passes through the light transmissive portion 12, passes through the first side wall 15 to the area outside the housing 10, then passes through the light transmissive portion 12, passes through the second side wall 16 and returns, and is detected by the linearly polarized light sensor 36, as indicated by the arrow in FIG. 3. In some examples, the linearly polarized light source 32 and the linearly polarized light sensor 36 are arranged in the housing 10 such that the radiated light exits and returns through the same plane of the light transmissive portion 12, as shown, for example, in FIG. 6.

[0063] As shown in FIG. 3, the linearly polarized light source 32 may include a light source 33 and a linear polarizer 34. The light radiated from the light source 33 is first radiated as non-polarized light (i.e., the light is polarized in multiple directions), and then passes through the linear polarizer 34 that linearly polarizes the light in a specific polarization plane. In another example, since the radiated light is already linearly polarized, the linear polarizer 34 is not required. The linear polarizer 34 can be a linear polarization filter, but other means known in the art for linearly polarizing the radiated light can also be used.

[0064] The linearly polarized light is radiated to the area outside the housing 10 through the light transmissive portion 12. This area is in the body fluid when the implantable device is implanted.

[0065] In some embodiments, the linear polarizer 34 is installed in the optical path within the housing 10 between the light source 33 and the light transmissive portion 12 of the housing 10, as shown in FIG. 3. In another embodiment the linear polarizer 34 is installed coupled to the outer surface 11 of the housing 10 in the optical path outside the housing 10 between the light transmissive portion 12 and the linearly polarized light sensor 36. In another embodiment, the linear polarizer 34 is formed integrally with the housing 10.

[0066] Similar to any of the embodiments disclosed in this specification, the implantable device 1 may include at least one lens 35 arranged to focus the light emitted from the linearly polarized light source 32. In particular, the lens 35 can focus the light emitted from the linearly polarized light source 32 towards a point outside the housing 10 and / or towards the linearly polarized light sensor 36.

[0067] FIG. 3 shows the lens 35 installed in the optical path between the linearly polarized light source 32 and the light transmission part 12 in the housing 10. However, alternatively, the lens 35 can also be installed at any suitable position, such as on the outer surface 11 of the housing 10, on the surface of the light transmission part 12. FIG. 3 also shows the linear polarizer 34 installed in the optical path between the light source 33 and the lens 35. However, in some examples, the linear polarizer 34 can also be installed after the lens 35 along the optical path.

[0068] The linearly polarized light radiated from the linearly polarized light source 32 to the outside of the housing 10 and passing through the body fluid outside the housing 10 is rotated by the glucose in the body fluid. As a result, the polarization plane of the radiated light rotates by an amount depending on the concentration of glucose and the distance that the light travels through the glucose. The distance that the light travels through the glucose is determined before implanting the device for use in calculating the value of the glucose concentration.

[0069] The linearly polarized light sensor 36 is arranged to detect the linearly polarized light that is emitted by the linearly polarized light source 32, passes through the body fluid, is rotated by the body fluid, and returns from the region outside the housing 10 through the transmission part 12 of the housing 10. The linearly polarized light sensor 36 is further configured to output an electrical signal based on the detected polarized and rotated light of the linearly polarized light. This output is based on the rotation angle α of the linearly polarized light.

[0070] Figure 3 shows a linearly polarized light sensor 36 including an optical sensor 37 and a linearly polarized light filter 38. The linearly polarized light filter 38 is arranged to linearly polarize the light that has returned from the linearly polarized light source 32 through the light transmission portion 12 of the housing 10. In other words, the linearly polarized light filter 38 allows light with a specific linear polarization to pass through and filters out the remaining light. Preferably, the linearly polarized light filter 38 is a linearly polarized light filter that allows or transmits light with a specific linear polarization. The optical sensor 37 is arranged to detect the linearly polarized light emitted from the linearly polarized light source 32 and passing through the linearly polarized light filter 38 via the outside of the housing 10, and outputs an electrical signal based on the detected light linearly polarized by the linearly polarized light filter 38.

[0071] As shown in FIG. 3, the linearly polarized light filter 38 is installed in the optical path between the linearly polarized light source 32 and the optical sensor 37, and between the optical sensor 37 and the area outside the housing 10.

[0072] Preferably, the polarization plane of the linearly polarized light filter 38 rotates around the optical path of the light with respect to the polarization plane of the linearly polarized light emitted from the linearly polarized light source 32, for example, so that the light is orthogonal to the polarization plane of the linear polarizer 34. Therefore, the amount of linearly polarized light detected by the optical sensor 37 from the light source 33 and the linear polarizer 34 depends on the amount of optical rotation of the light. This optical rotation occurs when the linearly polarized light passes through the glucose-containing body fluid. The amount of optical rotation, and thus the amount of light detected by the optical sensor 37, depends on the glucose concentration in the body fluid. In this way, the electrical signal output by the optical sensor 37 is based on the amount of optical rotation of the linearly polarized light, and therefore on the glucose concentration in the body fluid.

[0073] In some embodiments, the polarization plane of the linearly polarized light filter 38 is the polarization of the linearly polarized light source 32 It can be adjusted according to the surface. That is, the angle of the polarization plane of the linear polarizing filter 38 can be adjustable / variable. In other words, the direction of the linear polarization vector of the light that can pass through the linear polarizing filter 38 can be adjustable. The polarization plane can be adjusted, for example, by applying an appropriate electrical signal to the linear polarizing filter 38 by the control unit 26. By changing / adjusting the polarization plane of the linear polarizing filter 38, the peak value of the light intensity detected by the optical sensor 37 is found. This peak value indicates the dominant rotation angle of the rotation that the light emitted from the linearly polarized light source 32 undergoes due to the optical rotation by the body fluid.

[0074] In some embodiments, the linear polarizing filter 38 includes the cell 40 shown in FIG. 4. The cell 40 includes a first electrode 41 and a second electrode 42. The first electrode 41 and the second electrode 42 are separated from each other at a certain interval. A certain potential difference is applied between the first electrode 41 and the second electrode 42, for example, by the control unit 26 and / or the glucose measurement unit 30. Due to this potential difference, an electric field is generated between the first electrode and the second electrode.

[0075] The Kerr material 43 is between the first electrode 41 and the second electrode 42. The Kerr material 43 is at least partially light-transmissive so that light can pass through the Kerr material 43. The Kerr material 43 is preferably a Kerr liquid or a Kerr crystal that can strongly exhibit the Kerr effect when an electric field penetrates the Kerr material 43. The Kerr material 43 can be a liquid crystal display (LCD) fluid, and this fluid has a large optical rotation degree, so it brings a good signal-to-noise ratio. In some embodiments, the Kerr material 43 is permanently fixed between the first electrode 41 and the second electrode 42. In another embodiment, the Kerr material 43 contains a body fluid, and this body fluid fills the space between the first electrode 41 and the second electrode 42 after the implantable device 1 is implanted, as will be described later with reference to FIGS. 9 and 10.

[0076] Figure 4 shows the first electrode 41 and the second electrode 42 as flat electrodes, but electrodes of other shapes may be used. The first electrode 41 and the second electrode 42 are each directly connected to the car material 43 such that the surface of the first electrode 41 contacts the surface of the car material 43, and the surface of the second electrode 42 contacts the other surface of the car material 43 on the opposite side. Alternatively, one or more of the first electrode 41 and the second electrode 42 are separated at a distance from the car material 43 so as not to be in direct contact with the car material 43.

[0077] The linear polarizing filter 38 in FIG. 4 further includes a first linear polarizer 44 and a second linear polarizer 45 installed on opposite side surfaces of the cell 40. An exemplary path of light passing through the linear polarizing filter 38 is shown by a dotted line in FIG. 4. Light such as linearly polarized light that has returned from outside the housing 10 via the linear polarization light source 32 first passes through the first linear polarizer 44 that linearly polarizes the light. Preferably, the polarization plane of the first linear polarizer 44 is non-parallel to at least a part of the electric field generated between the first electrode 41 and the second electrode 42. The light linearly polarized by the first linear polarizer 44 then passes through the car material 43 and the electric field and then through the second linear polarizer 45 and heads towards the optical sensor 37. Preferably, the polarization plane of the first linear polarizer 44 and the polarization plane of the second linear polarizer 45 are (substantially) orthogonal, that is, rotated by 90° around the path of the light moving through the cell 40.

[0078] The polarization plane of the linearly polarized light that passes through the linear polarizer 44 and enters the cell 40 is rotated by the electric field generated between the first electrode 41 and the second electrode 42. The amount of rotation depends on the magnitude of the electric field. Changing the potential difference between the first electrode 41 and the second electrode 42 changes the magnitude of the electric field, and thus the amount of rotation of the linearly polarized light passing through the cell 40 changes. Since the amount of rotation changes, the amount of light passing through the linear polarizer 45 and heading towards the optical sensor 37 also changes. By changing / varying the potential difference, the amount of light passing through the linear polarizing filter 38 via the cell 40 changes. Therefore, the cell 40 can be used as a shutter. The car Using the cell 40, the amount of optical rotation received by the linearly polarized light radiated to the outside of the housing 10 by the linearly polarized light source 32 can be determined, and the amount of optical rotation is a function of the glucose concentration in the body fluid.

[0079] The change in the rotation angle φ of the polarized light passing through the cell follows a function of the following equation:

Equation

[0080] FIG. 5 shows an exploded assembly view of an alternative construction of the linear polarizing filter 38 including the cell 40 suitable for use in an embodiment of the present disclosure. The linear polarizing filter 38 of FIG. 5 is similar to the linear polarizing filter 38 shown in FIG. 4, but the first electrode 41 is disposed in the optical path between the first linear polarizer 44 and the Kerr material 43, and the second electrode 43 is disposed in the optical path between the second linear polarizer 45 and the Kerr material 43.

[0081] An exemplary optical path of the light beam is indicated by an arrow in FIG. 5. The light returning from the linearly polarized light source 32 via the outside of the housing 10 first passes through the first linear polarizer 44, then the first electrode 41, then the Kerr material 43, then the second electrode 42, and then the second linear polarizer 45. This optical path can be substantially parallel to the electric field generated between the first electrode 41 and the second electrode 42. In some examples, the positions of the first linear polarizer 44 and the first electrode 41 can be interchanged. In some examples, the positions of the second linear polarizer 45 and the second electrode 42 can be interchanged.

[0082] FIG. 6 shows an implantable device 1 according to some embodiments of the present disclosure incorporating the linear polarizing filter 38 and the cell 40 shown in FIG. 5. Other configurations of the cell 40 and / or the linear polarizing filter 38, such as the linear polarizing filter 38 of FIG. 4, may also be used.

[0083] The linearly polarized light source 32, the carousel 40, and the optical sensor 37 are disposed within the housing 10 of the implantable device 1. The linearly polarized light source 32 emits light outward from the housing 10 through the light transmissive portion 12. FIG. 6 shows the linearly polarized light source 32 including the light source 33 and the linear polarizer 34, although the linearly polarized light source 32 may not require the linear polarizer 34 in an alternative method. The linear polarizer 34 and the linear polarizer 44 are shown in the figure as being installed inside the housing 10, although one or more of each may be installed outside the housing 10.

[0084] An exemplary path taken by the linearly polarized light emitted by the linearly polarized light source 32 is shown by the dotted line in FIG. 6. The linearly polarized light is radiated outward from the housing 10. In use, when the implantable device 1 is implanted in the body, the linearly polarized light is radiated into the body fluid that at least partially surrounds the implantable device 1. A portion of the linearly polarized light radiated outward from the housing 10 by the linearly polarized light source 32 is returned through the housing 10. This may be due to a portion of the light being reflected by the body fluid. In some examples, the light returns through the housing 10 with the aid of one or more lenses or due to the shape of the implantable device 1, for example, by providing the recess 14. The various means by which the light is returned will be described throughout.

[0085] The linear polarization filter 38 is disposed within the housing 10 such that light returning from outside the housing 10 from the linearly polarized light source 32 passes through the first linear polarizer 44, then through the carousel 40, and then through the second linear polarizer 45 before being detected by the optical sensor 37. The potential difference applied between the first electrode 41 and the second electrode 42 is changed over time. As a result, the amount of light detected by the optical sensor 37 and the electrical signal output by the optical sensor 37 can change over time. The electrical signal output by the optical sensor 37 corresponds to the amount of rotation experienced by the linearly polarized light emitted by the linearly polarized light source 32 as it passes through the body fluid outside the housing 10. The electrical signal output by the optical sensor 37 is processed to determine the concentration of glucose in the body fluid.

[0086] FIG. 6 shows a lens 46 disposed adjacent to the carousel 40 to focus light passing through the carousel 40 and traveling toward the optical sensor 37. FIG. 6 also shows an implantable device 1 including a wall 18 disposed between the linearly polarized light source 32 and the optical sensor 37 to prevent light emitted from the linearly polarized light source 32 from traveling directly to the optical sensor 37 without first moving outside the housing 10.

[0087] The implantable device 1 shown in FIG. 6 may be susceptible to interference from the optical sensor 37, for example, detecting light such as ambient light that does not exit the linearly polarized light source 32. FIG. 7 shows a partial schematic cross-sectional view of an implantable device 1 that is similar to the implantable device 1 shown in FIG. 6 but is configured to greatly suppress interference.

[0088] FIGS. 7 and 8 show embodiments similar to FIG. 6 but with a reference channel including a second optical sensor 54.

[0089] Similar to the implantable device of FIG. 6, the implantable device 1 shown in FIG. 7 has a linearly polarized light source 32 including a light source 33 and a linear polarizer 34, and a linear polarization filter 38 including a cassette 40. However, here the glucose measurement unit 30 further includes a second optical sensor 54 and an additional linear polarizer 50. The first optical sensor 37 and the second optical sensor 54 may each include one or more photodiodes.

[0090] The linear polarizer 50 is disposed in the housing 10 so as to linearly polarize at least a part of the light that has returned from the linearly polarized light source 32 via the outside of the housing. The second optical sensor 54 is disposed so as to detect the light linearly polarized by the linear polarizer 50 and output a second electrical signal based on the detected linear polarization.

[0091] An optional lens 47 is disposed on the outer surface 11 of the housing 10 so as to focus the linearly polarized light emitted from the linearly polarized light source 32 on one point or region outside the housing 10, and this housing is in the body fluid when the implantable device 1 is implanted. FIG. 7 shows a lens 47 that focuses linearly polarized light in two directions, a first direction toward a lens 48 that focuses light returning to the optical sensor 37 and a second direction toward a lens 49 that focuses light returning toward the optical sensor 54.

[0092] The first optical sensor 37 and the second optical sensor 54 are disposed so as to detect the linearly polarized light emitted from the linearly polarized light source 32 and reflected in the body fluid outside the housing 10, for example, near a point or region outside the housing 10. The detected light is focused by one or more lenses 46, 48, 49 from a point or region outside the housing 10 toward the first optical sensor 37 and the second optical sensor 54. An exemplary optical path is shown by a dotted line in FIG. 7.

[0093] The first optical sensor 37 and the second optical sensor 54 each from the linearly polarized light source 32 An electrical signal S based on the detected intensity of the linearly polarized light output and passing outside the housing 10 PDKerr and S PDRef are each configured to be output. The wireless communication module 20 is configured to wirelessly transmit a signal based on the electrical signal output by the first optical sensor 37 and the electrical signal output by the second optical sensor 54. Each electrical signal corresponds to the angle by which the plane of linear polarization of the light emitted by the linearly polarized light source 32 is rotated, and thus corresponds to the concentration of glucose in the body fluid.

[0094] The linearly polarized light is emitted from the linearly polarized light source 32. The potential difference applied between the first electrode 41 and the second electrode 42 of the cuvette 40 is changed over time until the maximum value maxS PDKerr of S PDKerr is determined, for example, increased over a certain period. S PDRef is also determined and remains constant with respect to the changing potential difference. When maxS PDKerr =S PDRef the potential difference U PDKerr applied between the first electrode 41 and the second electrode 42 to bring about maxS Kerr is proportional to the glucose concentration in the body fluid. Thus, the glucose concentration C is determined using the following equation: C = J·U Kerr The glucose concentration C is determined by obtaining the condition maxS PDKerr =S PDRef and the fixed coefficient J.

[0095] The device is calibrated by in vitro testing under laboratory conditions. Determining the glucose concentration by processing the electrical signal output by the optical sensor 37 and, if applicable, the electrical signal output by the optical sensor 54, as well as the potential difference U Kerr is performed by means and techniques known in the art.

[0096] When a second additional optical sensor 54 and a linear polarizer 50 are provided as reference channels, it becomes possible to process the electrical signals output by the first optical sensor 37 and the second optical sensor 54 (e.g., by the control unit 26 or the external device 2) to reduce or eliminate the influence of interference or background noise. Such interference or background noise is caused, for example, by the ambient light of the implantable device 1 or the electrical noise of the electrical components. As such, a more accurate determination of the glucose concentration is made. That is:

Number

[0097] FIG. 8 shows another embodiment similar to FIG. 7, where the glucose measurement unit 30 further includes a second linear polarization light source 51 that emits linearly polarized light for detection by the second optical sensor 54. FIG. 8 shows the second linear polarization light source 51 including the second light source 53 and the linear polarizer 55, and the first light source 33 and the second light source 53 are optically separated by the wall 18.

[0098] The second linear polarization light source 51 is configured to emit linearly polarized light to the outside of the housing 10. An optional lens 52 focuses the linearly polarized light emitted by the second linear polarization light source 51 to one point or area outside the housing 10. The linear polarizer 50 is arranged to linearly polarize the light that has returned from the outside of the housing 10 from the second linear polarization light source 51. The second optical sensor 54 is arranged to detect the light linearly polarized by the linear polarizer 50 and output an electrical signal based on the detected light linearly polarized by the linear polarizer 50. The wireless communication module 20 is configured to wirelessly transmit a signal based on the second electrical signal output by the second optical sensor 54. signal.

[0099] As described with reference to FIG. 7, in the embodiment shown in FIG. 8, it is possible to process the electrical signals output by the first optical sensor 37 and the second optical sensor 54 to reduce or eliminate the influence of interference or background noise.

[0100] FIG. 9 shows an embodiment in which the housing 10 of the implantable device 1 includes a recess 14 having a first side wall 15 and a second side wall 16. The implantable device 1 of FIG. 9 has a cartridge 40 in which a first electrode 41 is installed adjacent to the first side wall 15 and a second electrode 42 is installed adjacent to the second side wall 16. When the implantable device 1 is implanted, body fluid at least partially fills the recess 14 and acts as a cartridge material 43. A certain potential difference is applied between the first electrode 41 and the second electrode 42 as described above, and an electric field is generated between the first electrode 41 and the second electrode 42 through the recess 14 and thus through a part of the body fluid.

[0101] The light emitted by the light source 33 is focused by the lens 35 toward the outside of the housing 10. The light emitted by the light source 33 is linearly polarized by the linear polarizer 34 and then radiated outside the housing 10 through the first side wall 15. In the embodiment shown in FIG. 9, this outside is located in the recess 14.

[0102] The first portion of linearly polarized light emitted from the light source 33 and the linear polarizer 34 passes through the first electrode 41 and then reaches the outside of the housing 10. This first portion of linearly polarized light returns to the inside of the housing 10 through the second side wall 16, passes through the second electrode 42, where it is linearly polarized by the linear polarizer 58, and then is detected by the first optical sensor 37, which outputs a first electrical signal as described above. In other words, the first electrode 41, the second electrode 42, and the linear polarizer 58 are arranged such that the first portion of the light linearly polarized by the linear polarizer 34 and detected by the first optical sensor 37 passes through the first electrode 41, crosses the recess 14, then passes through the second electrode 42, and then passes through the linear polarizer 58 before being detected by the first optical sensor 37. Therefore, the first portion of linearly polarized light emitted from the light source 33 and the linear polarizer 34 moves through the electric field generated between the first electrode 41 and the second electrode 42 when a potential difference is applied between the first electrode 41 and the second electrode 42.

[0103] The second portion of linearly polarized light emitted from the light source 33 and the linear polarizer 34 passes through the first side wall 15 to the outside of the housing 10, then returns through the second side wall 16 and the linear polarizer 58, and is finally detected by the second optical sensor 54, which outputs a second electrical signal as described above. The second portion of linearly polarized light preferably does not pass through the first electrode 41 and / or the second electrode 42. Therefore, as discussed previously, the second electrical signal detected by the second optical sensor 54 is used as a reference signal for reducing or eliminating the effects of interference or background noise.

[0104] FIG. 10 shows an embodiment similar to that shown in FIG. 9, but the linearly polarized light radiated through the first side wall 15 is reflected by a mirror 60 installed adjacent to the second side wall 16. After the reflected linearly polarized light returns through the first side wall 15, a part of it is detected by the first optical sensor 37, and a part of it is detected by the second optical sensor 54. A part of the returned light detected by the second optical sensor 54 is linearly polarized by a linear polarizer 55 after returning through the first side wall 15. A part of the returned light detected by the first optical sensor 37 is linearly polarized by a linear polarizer 45 after returning through the first side wall 15.

[0105] FIG. 10 shows an optical housing 56 that at least partially surrounds the light source 33. The housing 56 includes a first aperture 57a arranged to direct a first portion of the linearly polarized light emitted by the light source 33 and the linear polarizer 34 towards a first region outside the housing 10, and a second aperture 57b arranged to direct a second portion of the linearly polarized light emitted by the light source 33 and the linear polarizer 34 towards a second region outside the housing 10 that is different from the first region. The first portion of the linearly polarized light is ultimately detected by the second optical sensor 54, and the second portion of the linearly polarized light is ultimately detected by the first optical sensor 37.

[0106] In the embodiments shown in FIGS. 9 and 10, in some examples, a certain potential difference is applied between the first electrode 41 and the second electrode 42, and an electric field is generated through the body fluid in the recess 14. The potential difference is changed over time, and the electrical signals output by the first optical sensor 37 and the second optical sensor 54 are monitored and processed over time to determine the glucose concentration of the body fluid in the recess 14 as discussed with respect to FIG. 7.

[0107] The embodiments shown in FIGS. 9 and 10 may, in some examples, include a second linearly polarized light source 51, similar to that described with reference to FIG. 8.

[0108] 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-described embodiments. FIG. 11 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).

[0109] 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.

[0110] 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, and power is provided to any electrical circuit, such as the glucose measurement unit 30 in the device.

[0111] In response to receiving power or in response to receiving an additional wireless signal transmitted to the implantable device 1 by the external communication device, the implantable device 1 proceeds to measure the glucose concentration of the body fluid in contact with the housing 10 of the implantable device 1. The linearly polarized light source 32 of the implantable device 1 emits linearly polarized light toward the light transmissive portion 12 of the housing 10 of the implantable device 1. The linearly polarized light sensor 36 of the implantable device 1 detects the linearly polarized light returning 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 the external wireless communication device 2. The signal wirelessly transmitted from the implantable device 1 to the external wireless communication device 2 is processed (for example, by the external wireless communication device 2), and a value of the glucose concentration of the body fluid is determined.

[0112] 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.

[0113] FIG. 12 shows a method according to an embodiment of the present disclosure. In step 901, linearly polarized light is radiated outside the housing 10 of the implantable device 1 by the linearly polarized light source 32 of the implantable device 1 described above. In step 902, the linearly polarized light sensor 36 of the implantable device 1 detects the linearly polarized light that has returned via the outside of the housing 10 from the first linearly polarized light source 32. In step 903, an electrical signal based on the detected linearly polarized light is output by the linearly polarized light sensor 36. 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 discussed above, 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 a value of the glucose concentration in the body fluid is determined.

[0114] The terms “drug” or “agent” are used interchangeably herein and refer to a pharmaceutical formulation 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 for the treatment, therapy, prevention, or diagnosis of a disease, or alternatively, for improving physical or mental health. Drugs or agents are used for a limited duration or, in the case of chronic diseases, periodically.

[0115] 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 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.

[0116] 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 up 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 to be administered (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 the 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.

[0117] 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, and thromboembolisms 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 Merck Ind ex, 15th edition, etc.

[0118] 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 amino acid residues added and / or exchanged 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 replaced by other amino acids containing non-codable amino acids, or amino acids containing non-codable amino acids may be added to the natural peptide.

[0119] 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 with Asp, Lys, Leu, Val, or Ala and Lys at position B29 is replaced with Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0120] 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.

[0121] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, liraglutide (Lyxumia (registered trademark)), exenatide (exendin-4, Dyetta (registered trademark), Bydureon (registered trademark), a 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza( registered trademark)), semaglutide, taspoglutide, albiglutide (Syncria (registered trademark)), dulaglutide (Trulicity (registered trademark)), 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.

[0122] Examples of oligonucleotides include, for example: mipomersen sodium (Kynamro (registered trademark)), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0123] Examples of DPP4 inhibitors include vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0124] 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.

[0125] 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.

[0126] 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 a 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).

[0127] 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 can bind 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, tetra-specific, and multispecific antibodies (e.g., diabodies, triabodies, tetra-bodies), monovalent antibody fragments, or multivalent antibody fragments such as divalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelate recombinant antibodies, tribodies or biobodies, 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.

[0128] 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 usually does not directly participate in antigen binding, as is known in the art, but specific residues within the framework region of a particular antibody can directly participate in antigen binding or can affect the ability of one or more amino acids within the CDR to interact with the antigen.

[0129] 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).

[0130] 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.

[0131] Those skilled in the art will understand that modifications (additions and / or removals) of 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.

[0132] Although the claims are clearly directed to specific combinations of structures in this application, the scope of the disclosure also includes any novel structure or any novel combination of structures that are disclosed explicitly 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 that the disclosure alleviates. The applicant hereby notifies that new claims may be presented for such structures and / or combinations of structures during the prosecution of this application or any further application derived therefrom.

[0133] Although several 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

**Claim 1** An implantable device for measuring the glucose concentration of a body fluid when implanted, the implantable device comprising a housing having a recess formed on an outer surface of the housing for containing the body fluid, the housing comprising: a glucose measurement unit; the glucose measurement unit comprising: a first linearly polarized light source configured to emit linearly polarized light into the body fluid within the recess of the housing of the implantable device; a linearly polarized light sensor configured to output a first electrical signal based on the detected linearly polarized light so as to detect the linearly polarized light that has returned via the body fluid within the recess of the housing from the first linearly polarized light source; and a second optical sensor and a linear polarizer configured to linearly polarize the light that has returned via the body fluid within the recess of the housing from the first linearly polarized light source or a second linearly polarized light source, the second optical sensor being configured to detect the light linearly polarized by the linear polarizer and to output a second electrical signal based on the detected light linearly polarized by the linear polarizer; a wireless communication module; the wireless communication module being configured to communicate wirelessly with an external wireless communication device; and being configured to wirelessly transmit a signal based on the first electrical signal and the second electrical signal to the external wireless communication device. The implantable device. **Claim 2** The implantable device according to claim 1, wherein the polarization plane of the linear polarizing filter is adjustable to match the polarization plane of the first linearly polarized light source. **Claim 3** The implantable device according to claim 1, wherein the linearly polarized light sensor comprises a linear polarizing filter and a first optical sensor, the linear polarizing filter being configured to linearly polarize the light that has returned from the first linearly polarized light source through the light transmissive portion of the housing, and the first optical sensor being configured to output a first electrical signal based on the detected light linearly polarized by the linear polarizing filter. **Claim 4** The implantable device according to claim 2, wherein the linear polarizing filter comprises a quarter-wave plate arranged such that the linearly polarized light that has returned via the body fluid within the recess of the housing from the first linearly polarized light source passes through the quarter-wave plate before being detected by the first optical sensor. **Claim 5** The cartridge includes a first electrode and a second electrode, and the glucose measurement unit is configured to apply a potential difference between the first electrode and the second electrode to generate an electric field therebetween. The linearly polarized light returned from the linearly polarized light source through the body fluid in the recess of the housing passes through the first electrode and the second electrode along a path substantially parallel to the electric field. The implantable device according to claim 4.

6. The wireless communication module is configured to wirelessly receive power from an external wireless communication device. The implantable device according to claim 1.

7. The implantable device is dimensioned to be implantable into a human blood vessel. The implantable device according to claim 1.

8. The light emitted by the first linearly polarized light source is emitted through the first side wall of the recess, and the linearly polarized light detected by the linearly polarized light sensor returns through the second side wall of the recess. The implantable device according to claim 1.

9. The recess includes a first side wall and a second side wall facing the first side wall. Here, the light emitted by the first linearly polarized light source is emitted into the body fluid through the first side wall of the recess before being reflected by a mirror installed adjacent to the second side wall toward the linearly polarized light sensor. The implantable device according to claim 1.

10. The implantable device further includes at least one lens configured to focus the light emitted from the first linearly polarized light source toward a point outside the housing. The implantable device according to claim 1.

11. The implantable device further includes a temperature sensor. Here, 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. The implantable device according to claim 1.

12. A system comprising: An implantable device, and The implantable device includes a housing having a recess formed on an outer surface of the housing for containing body fluid, and the housing includes: A glucose measurement unit, and The glucose measurement unit includes: a first linearly polarized light source configured to emit linearly polarized light into the body fluid in the recess of the housing of the implantable device; A linearly polarized light sensor configured to output a first electrical signal based on the detected linearly polarized light so as to detect the linearly polarized light that has returned from the body fluid in the recess of the housing via the first linearly polarized light source; and A second optical sensor and a linear polarizer configured to linearly polarize the light that has returned from the body fluid in the recess of the housing from the first linearly polarized light source or the second linearly polarized light source, wherein the second optical sensor is configured to detect the light linearly polarized by the linear polarizer and output a second electrical signal based on the detected light linearly polarized by the linear polarizer; A wireless communication module configured to communicate wirelessly with an external wireless communication device; Including; The wireless communication module of the implantable device is an external wireless communication device configured to wirelessly transmit a signal based on the first electrical signal and the second electrical signal to the external wireless communication device, Including, said system.

13. The system according to claim 12, wherein the external wireless communication device is a smartphone.

14. The system according to claim 12, wherein the polarization plane of the linear polarizing filter is adjustable in accordance with the polarization plane of the first linearly polarized light source.

15. The system according to claim 12, wherein the wireless communication module is configured to wirelessly receive power from the external wireless communication device.

16. An operating method of the implantable device according to any one of claims 1 to 11, comprising: The first linearly polarized light source of the glucose measurement device of the implantable device emits linearly polarized light into the recess of the housing of the implantable device; The linearly polarized light sensor of the glucose measurement device detects the linearly polarized light that has returned through the recess of the housing from the first linearly polarized light source; The linearly polarized light sensor of the glucose measurement device outputs a first electrical signal based on the detected linearly polarized light; and The wireless communication module of the implantable device wirelessly transmits a signal based on the first electrical signal to the external wireless communication device.

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