Devices and related methods for light-based modulation of xenobiotic reactions in biological tissues

Abstract

Disclosed are devices and related methods for modulating foreign body responses in biological tissues, more specifically, light-based modulation of foreign body responses in biological tissues. Disclosed are light sources that provide light with foreign body response modulation properties that can be elicited by transcutaneous and / or subcutaneous devices, including medical devices and other consumer electronics. Disclosed are light delivery structures that propagate light from the light source to irradiate associated subcutaneous tissue. Modulation of foreign body responses can include inhibiting collagen and fibrous tissue production, modulating inflammation and healing, and / or increasing nitric oxide production and / or release. Modulating foreign body responses associated with transcutaneous and / or subcutaneous devices can improve the performance characteristics and longevity of such devices.

Description

[Technical Field]

[0001] Related applications

[0001] This application claims the interests of Provisional Patent Application No. 63 / 031,970 and Provisional Patent Application No. 63 / 032,022, filed on 29 May 2020, the disclosures thereof incorporated herein by whole reference.

[0002]

[0002] This disclosure generally relates to the modulation of xenobiotic reactions in biological tissues, and more specifically to devices and related methods for photo-based modulation of xenobiotic reactions in biological tissues. [Background technology]

[0003]

[0003] The foreign body reaction (FBR) generally begins when a foreign body is inserted into the subcutaneous tissue, starting with wound formation and the initiation of the body's innate wound healing cascade. Proteins can adhere to the surface of the foreign body, and associated protein adsorption can provide an interface that facilitates the adhesion of inflammatory cells in the early stages of FBR. As FBR progresses, monocytes, macrophages, mast cells, and fibroblasts are signaled to the site of the foreign body, initiating clearance of the foreign body by releasing chemokines and cytokines. The concentration and type of mediators released induce further cell recruitment, as the body may attempt phagocytosis to digest the foreign body. If digestion of the foreign body is unsuccessful, frustrated phagocytosis from activated macrophages may lead to the fusion of macrophages into foreign body giant cells (FBGCs) that attempt to further break down the foreign body. After a certain period, FBR can proceed to fibroblast infiltration and the formation of a collagen matrix, encapsulating and isolating the foreign body from the native tissue.

[0004]

[0004] There is a wide variety of medical devices that are designed to be inserted percutaneously to extend through at least the epidermis and dermis of the host, thereby having at least one region present in the subcutaneous tissue. Furthermore, there are other medical devices that are designed to be implanted subcutaneously so as to be fully present beneath the dermis of the host. Exemplary devices and applications include biometric sensors, catheters, pacemakers, prostheses, breast implants, biomaterials, etc., and new devices and applications are constantly being developed. While the body's natural FBR can be beneficial in certain cases, the characteristic consequences of collagen encapsulation can adversely affect the performance of inserted or implanted medical devices. Continuous glucose monitors (CGMs) are an example of a device in which FBR can adversely affect performance characteristics.

[0005]

[0005] Diabetes mellitus is a global epidemic characterized by chronic hyperglycemia resulting from either insulin deficiency or resistance. Blood glucose levels in diabetic patients fluctuate significantly throughout the day and can lead to serious complications such as heart attack, stroke, hypertension, renal failure, blindness, and limb amputation. Portable blood glucose sensors allow patients to monitor their blood glucose levels, manage their insulin levels, and reduce the morbidity and mortality of diabetes mellitus. Conventional blood glucose monitoring technologies are based primarily on electrochemical amperometric blood glucose sensors. There are numerous approved biometric sensors for use as blood glucose monitors. One example uses a test strip containing glucose dehydrogenase (GDH) or glucose oxidase (GOx) immobilized on a screen-printed electrode. Analysis is based on obtaining a small amount of blood sample, such as less than 1 microliter (μL), by pricking a finger, which is then introduced into the test strip via capillary action. While these monitorings have improved the health status of diabetic patients by improving blood glucose control, such devices cannot warn in advance of hyperglycemic or hypoglycemic events because such monitoring only provides instantaneous blood glucose concentrations. Furthermore, sample collection methods (i.e., finger pricks) are inconvenient, potentially painful, and can lead to decreased patient compliance. Therefore, there has been a need for analytical methods that enable continuous monitoring of blood glucose.

[0006]

[0006] Continuous glucose monitoring (CGM) has been developed to provide blood glucose levels at appropriate time intervals, allowing for real-time information on trends (e.g., whether blood glucose levels are increasing or decreasing), magnitude, duration, and frequency of diurnal blood glucose fluctuations. The CGM system periodically measures blood glucose levels 24 hours a day and converts the measurements into dynamic data to generate blood glucose direction and rate of change. With this context, CGM users can proactively manage their blood glucose levels and gain further insight into the impact of diet, exercise, and illness on their individual blood glucose levels. CGM can also contribute to improved diabetes management by reducing or minimizing guesswork when making treatment decisions based solely on blood glucose meter readings.

[0007]

[0007] Subcutaneous CGMs require surgery to insert them and later remove them, as they eventually need to be replaced. To overcome these limitations, transcutaneous CGMs have been developed that include transcutaneous needle-type microsensors that can monitor oxygen consumption or corresponding hydrogen peroxide production amperometrically as a measure of blood glucose concentration.

[0008]

[0008] When using CGM devices, design, manufacturing, and usage standards are important, but the inherent FBR can significantly affect bioanalysis and clinical utility. Once the FBR is resolved and the device is encapsulated by a collagen layer, long-term medical implants can be considered biocompatible or inactive. However, in the case of CGM, FBR can limit the accuracy and lifespan of the sensor. The effect of FBR on the performance of a blood glucose sensor may relate to angiogenesis, cellular glucose consumption, capsule thickness, capsule diffusion coefficient, and capsule porosity. In some cases, FBR can lower local pH (e.g., down to 3.6), and since GOx activity may be pH-dependent, the performance of the biosensor may be further reduced. Reduced mass transport increases delay time and can potentially reduce the magnitude and difference when fluctuating between hyperglycemia and hypoglycemia sensor signals. Reduced mass transport of important samples such as blood glucose and oxygen may be due to collagen capsule thickness, vascular density, or other unforeseen factors related to FBR. In this respect, the accuracy and lifespan of the biosensor may be limited.

[0009]

[0009] Because the FBR sequence of events can directly affect the usefulness of medical devices such as CGMs, key research has focused on improving the biocompatibility of device elements as a strategy to improve the relevant sensor performance. These strategies range from chemical changes at the tissue-sensor interface, changes in the physical properties of the device, to the release of biologically active molecules that affect tissue responses.

[0010]

[0010] In the case of devices inserted or implanted subcutaneously, the FBR sequence may result in an initial inflammatory response or gradual loss of function over time. As the FBR sequence progresses, inflammatory cells may lead to the formation of a collagen matrix, which may attempt to isolate the device from the native tissue. If the subcutaneous implant migrates within a fully formed capsule, the cells of the bio-interface may be re-damaged, thereby restarting the FBR sequence. This collagen encapsulation lacks the microvascular system of the native tissue and can persist for the lifetime of the inserted or implanted device.

[0011]

[0011] In the field of this technology, there is a continuous search for improved devices and methods to mitigate FBR while overcoming the challenges associated with conventional devices. [Overview of the Initiative]

[0012]

[0012] This disclosure generally relates to the modulation of xenobiotic reactions in biological tissues, and more specifically to devices and related methods for light-based modulation of xenobiotic reactions in biological tissues. A light source is disclosed that provides light having modulating properties for xenobiotic reactions that can be induced by transcutaneous and / or subcutaneous devices, including medical devices and other consumer electronic devices. A light delivery structure is disclosed that propagates light from such a light source to irradiate the subcutaneous tissue in question. Modulation of xenobiotic reactions may include inhibition of collagen and fibrous tissue production, modulation of inflammation and healing, and / or increased production and / or release of nitric oxide. By modulating xenobiotic reactions associated with transcutaneous and / or subcutaneous devices, the performance characteristics and lifespan of such devices can be improved.

[0013]

[0013] In one embodiment, a method for modulating a foreign body reaction includes providing a foreign body within a region of the host's subcutaneous tissue, providing a light source capable of emitting light of one or more peak wavelengths, and irradiating one or more portions of the subcutaneous tissue region with the light to modulate the foreign body reaction within the subcutaneous tissue region. In a particular embodiment, the light is irradiated onto one or more portions of the subcutaneous tissue region at a tissue depth ranging from 1 millimeter (mm) to 15 mm. In a particular embodiment, the light is irradiated onto one or more portions of the subcutaneous tissue region at a tissue depth ranging from 4 mm to 15 mm. In a particular embodiment, one or more peak wavelengths of the light include a first wavelength in the range of 315 nanometers (nm) to 600 nm, or in the range of 400 nm to 600 nm, or in the range of 600 nm to 1600 nm. In a particular embodiment, one or more peak wavelengths of the light include a first wavelength in the range of 315 nm to 600 nm and a second wavelength different from the first wavelength, the second wavelength being in the range of 600 nm to 1600 nm. In certain embodiments, a first wavelength is irradiated onto a region of subcutaneous tissue during a first time interval, and a second wavelength is irradiated onto a region of subcutaneous tissue during a second time interval different from the first time interval. The first time interval may overlap with the second time interval, or the first time interval may not overlap with the second time interval. In certain embodiments, the first time interval ranges from 3 to 30 days, and the second time interval ranges from 0 to 4 days. In certain embodiments, the second time interval is provided during the hemostatic and inflammatory phases of the foreign body reaction, and the first time interval is provided during the proliferation and remodeling phases of the foreign body reaction. The method may further include providing a light source located outside the host, providing a light delivery structure optically coupled to the light source, and inserting the light delivery structure through the host's skin to reach one or more portions of a region of subcutaneous tissue. In certain embodiments, the light delivery structure includes an optical waveguide. In certain embodiments, the light delivery structure includes an optical fiber with a diameter ranging from 8 microns (μm) to 250 μm. In certain embodiments, this method may further include irradiating the skin above a subcutaneous tissue area with additional light.

[0014]

[0014] In another embodiment, the device includes a foreign body configured to be at least partially inserted into a region of subcutaneous tissue of a host, and a light source capable of emitting light of one or more peak wavelengths to irradiate one or more portions of the region of subcutaneous tissue to modulate a foreign body reaction within the region of subcutaneous tissue. In certain embodiments, the light source is provided outside the region of subcutaneous tissue to irradiate light through a portion of the host skin aligned with the region of subcutaneous tissue. In certain embodiments, the device further comprises a light-delivering structure optically coupled to the light source, at least a portion of which is located within the region of subcutaneous tissue and capable of irradiating one or more portions of the region of subcutaneous tissue. In certain embodiments, the device further comprises an additional light source provided to irradiate light through a portion of the host skin aligned with the region of subcutaneous tissue. In certain embodiments, the one or more peak wavelengths of the light include a first wavelength in the range of 315 nm to 600 nm, or in the range of 400 nm to 600 nm, or in the range of 600 nm to 1600 nm. In certain embodiments, one or more peak wavelengths of light include a first wavelength in the range of 315 nm to 600 nm and a second wavelength different from the first wavelength, the second wavelength being in the range of 600 nm to 1600 nm. In certain embodiments, the device includes a continuous glucose monitor, and the foreign body includes a sensor probe for the continuous glucose monitor. In further embodiments, the device comprises a light delivery structure optically coupled to a light source, at least a portion of which is located within a region of subcutaneous tissue and capable of irradiating one or more portions of the region of subcutaneous tissue.

[0015]

[0015] In another embodiment, the device includes a foreign body configured to be at least partially inserted into a region of subcutaneous tissue of a host, a light source capable of emitting light of one or more peak wavelengths, and a light delivery structure optically coupled to the light source, wherein at least a portion of the light delivery structure is present in a region of subcutaneous tissue and can irradiate one or more portions of the region of subcutaneous tissue. In a particular embodiment, the device is a continuous glucose monitor, and the foreign body includes a sensor probe of the continuous glucose monitor. In a particular embodiment, the light delivery structure is arranged to surround one or more portions of the sensor probe. In a particular embodiment, the light delivery structure is arranged parallel to the sensor probe. In a particular embodiment, the light delivery structure is arranged non-parallel to the sensor probe. In a particular embodiment, at least a portion of the light delivery structure is located within 0.5 mm of the active sensing region of the sensor probe. In a particular embodiment, the one or more peak wavelengths of the light include a first wavelength in the range of 315 nm to 600 nm, or in the range of 400 nm to 600 nm, or in the range of 600 nm to 1600 nm. In certain embodiments, one or more peak wavelengths of light include a first wavelength in the range of 315 nm to 600 nm and a second wavelength different from the first wavelength, the second wavelength in the range of 600 nm to 1600 nm. In certain embodiments, the device is one of a pacemaker, an implantable cardiac defibrillator, an implantable cardiac monitor, a cochlear implant, a joint replacement implant, a cosmetic implant, a drug delivery device, or an intrauterine device. In certain embodiments, the device may further include a power supply configured to power the light source and a control module configured to control the dosing parameters of the light source. In certain embodiments, the power supply includes at least one of a battery and a rechargeable battery. In certain embodiments, the power supply includes an inductively coupled power supply. In certain embodiments, the control module includes a microprocessor that actively controls the dosing parameters of the light source. In other embodiments, the control module may include a microcontroller. In certain embodiments, the dosing parameters of the light source are determined by external electronic equipment.In certain embodiments, the power supply is also configured to provide power to operate one or more functions of the foreign body. In certain embodiments, the power supply and control modules are located outside the area of ​​subcutaneous tissue.

[0016]

[0016] In another embodiment, a continuous blood glucose monitor includes a sensor probe configured to monitor blood glucose concentration in a host, a sensor holder for mechanically supporting the sensor probe for transdermal insertion into the host, a light source capable of emitting light of one or more peak wavelengths, and an optical delivery structure optically coupled to the light source, the optical delivery structure being configured for transdermal insertion into the host. In certain embodiments, the optical delivery structure includes an optical waveguide. In certain embodiments, the optical delivery structure includes an optical fiber with a diameter ranging from 8 μm to 250 μm. In certain embodiments, the optical delivery structure is positioned parallel to the sensor probe. In certain embodiments, the optical delivery structure is positioned non-parallel to the sensor probe. In certain embodiments, the optical delivery structure is mechanically supported by the sensor holder. In certain embodiments, the optical delivery structure includes a length shorter than the length of the sensor probe. In certain embodiments, at least a portion of the optical delivery structure is positioned within 0.5 mm of the active sensing area of ​​the sensor probe. In certain embodiments, the optical delivery structure is mechanically supported by a separate structure positioned between the sensor holder and the host. In certain embodiments, the light delivery structure is mechanically supported by a separate structure positioned along the lateral periphery of the sensor holder. In certain embodiments, one or more peak wavelengths of light include a first wavelength in the range of 315 nm to 600 nm, or in the range of 400 nm to 600 nm, or in the range of 600 nm to 1600 nm. In certain embodiments, one or more peak wavelengths of light include a first wavelength in the range of 315 nm to 600 nm and a second wavelength different from the first wavelength, the second wavelength being in the range of 600 nm to 1600 nm.

[0017] In another aspect, additional advantages can be obtained by individually or together any of the foregoing aspects and / or by combining various distinct aspects and features described herein. Any of the various features and elements disclosed herein can be combined with one or more other disclosed features and elements, unless the contrary is indicated herein.

[0018] Those skilled in the art will understand the scope of the present disclosure and its additional aspects after reading the following detailed description of the preferred embodiments in connection with the accompanying drawings.

[0019]

[0019] The accompanying drawings incorporated herein and forming a part thereof illustrate some aspects of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.

Brief Description of the Drawings

[0020] [Figure 1A]

[0020] A chart showing overall cell growth during the wound healing stages that may be associated with a foreign body reaction (FBR). [Figure 1B]

[0021] A chart of the sensor signals of the first continuous glucose monitor (CGM) over two weeks for non - diabetic male volunteers to observe the effects of FBR. [Figure 1C]

[0022] A chart of the sensor signals of the second CGM of the same volunteers over the same two - week period as in Figure 1B. [Figure 1D]

[0023] A combined chart of the sensor signals from the first and second CGMs over the first two days from the charts of Figures 1B and 1C. [Figure 1E]

[0024] A combined chart of the sensor signals from the first and second CGMs over the 6th and 7th days from the charts of Figures 1B and 1C. [Figure 1F]

[0025] Figures 1B and 1C show combined charts of sensor signals from the first and second CGMs over days 13 and 14, respectively. [Figure 2]

[0026] This is a schematic diagram of the chemical reaction used to measure blood glucose concentration based on enzyme-modified electrodes and electrochemical detection. [Figure 3]

[0027] This figure shows a portion of a device that includes a foreign body for percutaneous placement through the host's skin and further includes FBR modulating capability according to the principles of this disclosure. [Figure 4]

[0028] This figure shows a portion of the device, including light delivery at deeper depths beneath the skin, in order to provide FBR adjustment capability according to the principles of this disclosure. [Figure 5]

[0029] Figures 3 and 4 show some of the devices, including the FBR adjustment capability combinations described for the devices. [Figure 6]

[0030] This is a partial diagram of a device having a sensor probe for transdermal insertion into a host and a corresponding light delivery structure to provide FBR adjustment capability. [Figure 7]

[0031] This is a partial diagram of a device similar to the device in Figure 6, but the optical delivery structure embodies a hollow sheath configured to allow light to propagate between the optical delivery structure and the sensor probe. [Figure 8]

[0032] This is a partial diagram of a device in which a light-delivery structure for transdermal insertion into the host is positioned adjacent to the corresponding sensor probe to provide FBR adjustment capability. [Figure 9]

[0033] Figure 8 is a partial diagram of the device, and this arrangement further includes an optical filter associated with the optical delivery structure. [Figure 10A]

[0034] This is a diagram of a device having a light delivery structure and a corresponding cannula support for transcutaneously delivering light to provide FBR adjustment capability. [Figure 10B]

[0035] This is a diagram of an alternative configuration of the device in Figure 10A for an embodiment in which the light source can be incorporated into the housing. [Figure 11]

[0036] This figure represents a continuous glucose monitor (CGM) with an integrated light source capable of delivering FBR-modulating light to the host's skin during monitoring. [Figure 12]

[0037] This figure represents a CGM similar to that in Figure 11, and further includes a corresponding light delivery structure that can deliver FBR-modulating light under the host's skin during monitoring. [Figure 13]

[0038] This figure represents a CGM similar to that in Figure 12, and includes an alternative arrangement of the light delivery structure for delivering FBR-modulating light under the host skin during monitoring. [Figure 14]

[0039] This figure represents a CGM similar to that in Figure 12, and includes an optical delivery structure and a tilted arrangement of sensor probes for delivering FBR-modulating light under the host skin during monitoring. [Figure 15]

[0040] This is a partial perspective view of a CGM that can be positioned similarly to the CGM in Figure 14 for simultaneous insertion of the light delivery structure with the sensor probe. [Figure 16A]

[0041] This figure shows a continuous glucose monitor (CGM) with a CGM accessory positioned between the sensor holder and the host's skin to deliver FBR-adjusting light during monitoring. [Figure 16B]

[0042] This figure represents a CGM similar to the one in Figure 16A, and shows an alternative configuration of CGM accessories for delivering FBR adjustment light during monitoring. [Figure 16C]

[0043] Figure 16A or Figure 16B is a top view of the CGM accessory. [Figure 16D]

[0044] Figure 16C is a cross-sectional view of the CGM accessory along the cutting line 16D-16D. [Figure 17A]

[0045] This is a disassembled top perspective view of an assembly that provides the ability to retrofit a conventional CGM with FBR-adjustable optical capability. [Figure 17B]

[0046] Figure 17A is a bottom perspective view of the assembly after insertion of the light delivery structure and removal of the corresponding insertion guide. [Figure 18]

[0047] This is an exploded perspective view of a sensing device having a microneedle array for sensing and one or more light sources for providing FBR-adjustable light capability. [Figure 19]

[0048] This is a diagram of a luminescent bandage having FBR adjustment capability according to the principle of this disclosure. [Figure 20A]

[0049] This figure schematically illustrates a pacemaker that may include the optical-based FBR adjustment capability described herein. [Figure 20B]

[0050] Figure 20A is a schematic diagram of a portion of the housing, showing the arrangement of light sources to provide FBR adjustment capability. [Figure 20C]

[0051] Figure 20A is a schematic diagram of a portion of the housing surface, showing an alternative arrangement of the light source. [Figure 21]

[0052] This is a schematic diagram of an implantable cardioverter-defibrillator (ICD) implanted in a patient, showing the ICD including the FBR adjustment capability as disclosed herein. [Figure 22]

[0053] This is a schematic diagram of an implantable cardiac monitor (ICM) implanted in a patient, showing the ICM including the FBR adjustment capability as disclosed herein. [Figure 23]

[0054] This is a schematic diagram of a cochlear implant in a patient, showing the cochlear implant including the FBR adjustment capability according to this disclosure. [Figure 24]

[0055] This is a schematic diagram of a prosthesis including the FBR adjustment capability as disclosed herein. [Figure 25]

[0056] This is a schematic diagram of the control scheme for the device, including the FBR adjustment capability, as disclosed herein. [Figure 26]

[0057] This is a schematic diagram of the control scheme for a device similar to the device in Figure 25, but the operation of the light source is provided separately from the other functions of the device. [Figure 27]

[0058] This is a schematic diagram of a control scheme for a device similar to the device in Figure 26, but in which at least a portion of the power supply is provided separately from the device. [Figure 28]

[0059] This is a schematic diagram of the control scheme for a device similar to the device in Figure 26, but the operation of the light source is provided separately from the other functions of the device. [Modes for carrying out the invention]

[0021]

[0060] The embodiments described below provide the information necessary to enable those skilled in the art to carry out the embodiments and indicate the best mode of carrying out the embodiments. By reading the following description in reference to the accompanying drawings, those skilled in the art will understand the concepts of this disclosure and recognize the applications of these concepts not specifically mentioned herein. It should be understood that these concepts and applications are within the scope of this disclosure and the accompanying claims.

[0022]

[0061] Terms such as "first," "second," etc., may be used herein to describe various elements, but it will be understood that these elements should not be limited by these terms. These terms are used solely to distinguish one element from another. For example, without departing from the scope of this disclosure, the first element may be called the second element, and similarly, the second element may be called the first element. The term "and / or" as used herein includes any and all combinations of one or more of the relevant list items.

[0023]

[0062] When an element such as a layer, region, or substrate is described as being "on" or "onto" another element, it will be understood that it may be directly on top of the other element, or may have an intervening element. In contrast, when an element is described as being "directly on" or "directly onto" another element, there is no intervening element. Similarly, when an element such as a layer, region, or substrate is described as being "over" or "over" another element, it will be understood that it may be directly on top of the other element, or may have an intervening element. In contrast, when an element is described as being "directly over" or "directly over" another element, there is no intervening element. When an element is described as being "connected" or "joined" to another element, it will be understood that it can be directly connected or joined to the other element, or that there may be an intermediary element. In contrast, when an element is described as being "directly connected" or "directly joined" to another element, there is no intermediary element.

[0024]

[0063] Relative terms such as "downward" or "upward" or "up" or "down" or "horizontal" or "vertical" may be used herein to describe the relationship between one element, layer, or region and another, as shown in the figure. It will be understood that these terms and the terms discussed above are intended to encompass various orientations of the device, in addition to the orientation shown in the figure.

[0025]

[0064] The terms used herein are intended solely to describe specific embodiments and are not intended to limit the disclosure. Where used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context explicitly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes,” and / or “including,” where used herein, specify the presence of the described features, integers, steps, actions, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, actions, elements, components, and / or groups thereof.

[0026]

[0065] Unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. Terms used herein should be construed to have meanings consistent with their meanings in the context of this specification and related art, and it should be further understood that they should not be construed in an idealized or overly formal sense unless expressly defined herein.

[0027]

[0066] Embodiments are described herein with reference to schematic drawings of embodiments of the present disclosure. Therefore, the actual dimensions of layers and elements may differ, and are expected to differ from the shapes shown, for example, as a result of manufacturing techniques and / or tolerances. For example, areas shown or described as squares or rectangles may have rounded or curved features, and areas shown as straight lines may have some irregularities. Therefore, the areas shown in the drawings are schematic, and their shapes are not intended to represent the exact shapes of areas in the device, nor are they intended to limit the scope of the disclosure. Furthermore, the size of structures or areas may be exaggerated relative to other structures or areas for illustrative purposes, and are therefore provided to illustrate the general structure of the subject matter, and may or may not be drawn to a certain scale. Elements common to both drawings may be shown herein with a common element number and may not be described again thereafter.

[0028]

[0067] This disclosure generally relates to the modulation of xenobody reactions (FBRs) in biological tissues, and more specifically, to devices and related methods for light-based modulation of FBRs in biological tissues. Disclosed are light sources that provide light having properties for modulating FBRs that can be induced by transcutaneous and / or subcutaneous devices, including medical devices and other consumer electronic devices. Disclosed are light-delivering structures that propagate light from such light sources to irradiate relevant subcutaneous tissue. Modulation of FBRs may include inhibition of collagen and fibrous tissue production, modulation of inflammation and healing, and / or increased production and / or release of nitric oxide. By modulating FBRs associated with transcutaneous and / or subcutaneous devices, the performance characteristics and lifespan of such devices can be improved.

[0029]

[0068] When a foreign body is inserted into living tissue, FBR can initiate a cascade of various stages of wound healing over time. Hemostasis is the initial stage that occurs immediately after insertion of the foreign body, thereby initiating coagulation to reduce blood loss. The inflammatory phase follows hemostasis, where local inflammation can further control bleeding, reduce infection, and prepare the wound for new tissue formation. During proliferation, new tissue is formed along the wound site, followed by a remodeling or maturation phase in which collagen is remodeled to facilitate wound closure. In this regard, Figure 1A is Chart 10, which provides an overall view of the ongoing cell proliferation of the wound healing stages that may be associated with FBR. In Chart 10, the relative amounts of various cell types and oxygen availability in the associated tissue are plotted against the number of days after the start of FBR. Chart 10 further provides exemplary timing of the hemostasis, inflammation, proliferation, and remodeling stages, although the exact timing is expected to vary from patient to patient. As illustrated, the hemostasis and inflammation stages are characterized by a rapid increase in neutrophils consuming available oxygen. As neutrophils decrease, monocytes, and then macrophages, increase, consuming more oxygen as the tissue transitions to proliferation. The increased activity of neutrophils and monocytes triggers signaling between fibroblasts and endothelial cells, which can ultimately close the wound during remodeling over a long period. If foreign body remains, the acquired tissue attempts to encapsulate it, thereby surrounding it with a wall from the surrounding tissue.

[0030]

[0069] For transcutaneous and / or subcutaneous objects such as various medical and consumer electronic devices, the associated fast-burning factor (FBR) can affect the accuracy and / or lifespan of the device. To investigate the effect of FBR on continuous glucose monitors (CGMs), two CGM sensors were implanted in a 52-year-old non-diabetic male volunteer for 14 days. The two CGM sensors were identical sensors inserted above the belt line, with one sensor positioned to the left of the midline and the other to the right of the midline. The sensors were connected to an amperometric potentiostat and biased to 0.55V relative to the corresponding reference electrode. The signals generated by the sensors were recorded every two minutes over two weeks. The volunteer also collected blood glucose levels at least twice a day during the study using conventional meters and common blood glucose strips, with blood glucose levels ranging between 75 mg / dL and 125 mg / dL. Figures 1B to 1F show data plots for the two sensors (represented as Sensor 1 and Sensor 2) over two weeks.

[0031]

[0070] Figure 1B is a chart of the sensor 1 signal in nanoamperes (nA) over two weeks. Figure 1C is a chart of the sensor 2 signal in nA over the same two weeks in a volunteer. As shown in the figures, the sensitivity and signal strength of the sensor signals tend to be low during the first two days, followed by a period where both sensor signals tend to track each other more accurately. Beyond about 10 days, the noise in the sensor signals increases and the signal strength decreases. Such variability in signal strength and sensitivity can be attributed to various FBR stages, as will be explained below for Figures 1D through 1F.

[0032]

[0071] Figure 1D is a combined chart of sensor signals from Sensor 1 and Sensor 2 over the first two days, taken from the charts in Figures 1B and 1C. For the first two hours after powering on Sensors 1 and 2, electrochemical break-in may take approximately 1–2 hours for the signals to settle in the 1–3 nA range. While the signals from Sensors 1 and 2 begin to track more closely by day 2, both sensors still exhibit low sensitivity to the volunteer's actual blood glucose changes. This may correspond to one or more parts of the hemostatic and inflammatory phases of FBR, as shown in Figure 1A. This indicates decreased oxygen availability to Sensors 1 and 2.

[0033]

[0072] Figure 1E is a combined chart of sensor signals from Sensor 1 and Sensor 2 over days 6 and 7 from the charts in Figures 1B and 1C. As shown in the figure, both sensors acquire signal strengths in the range of 2 to 5 nA and track each other with improved accuracy and sensitivity and reduced noise. This indicates improved accuracy of the volunteer's actual blood glucose levels. Returning to Figure 1A, this period may correspond to a specific portion of proliferation and the early part of the remodeling phase, suggesting that the FBR response may have reduced the impact on sensor operation during this period.

[0034]

[0073] Figure 1F is a combined chart of sensor signals from Sensor 1 and Sensor 2 over days 13 and 14 from the charts in Figures 1B and 1C. As shown in the figure, the signal intensity of both sensors shows a decrease, with values ​​currently ranging from 0.5 to 4 nA, and Sensor 2 shows a significantly greater decrease in signal intensity than Sensor 1. This decrease in raw signal intensity may be due to diffusion limitation provided by FBR capsule formation during the remodeling phase. In this regard, both sensors show greater noise with respect to the charts in Figures 1D and 1E.

[0035]

[0074] Embodiments of this disclosure are provided for optically modulating FBR for transcutaneous and / or subcutaneous objects such as various medical and consumer electronic devices. By modulating the relevant FBR, the performance characteristics and operating life of such devices can be improved. In the example of a transcutaneous and / or subcutaneous sensor, modulating the relevant FBR can improve the accuracy and / or lifespan of the sensor by altering the mechanism by which the FBR may attempt to encapsulate the sensor. In the example of a CGM provided in Figures 1B to 1E, the FBR modulating light is delivered to slow the later stages of FBR progression, thereby extending the operating period as shown in Figure 1E. It is also possible to provide FBR modulating light to accelerate progression through the initial FBR stages to reach the operating period as shown in Figure 1E more quickly. Compared to the actual blood glucose concentration of a blood glucose monitoring embodiment, FBR modification according to this disclosure can improve the measurement of interstitial blood glucose by reducing time lag, increasing accuracy, and extending the duration of clinically relevant sensor performance. In the example of a subcutaneous implant, other metrics may be useful in determining the improvements associated with FBR modification. In the case of artificial joint replacement, pain associated with range of motion within the joint can be reduced by modifying the FBR in accordance with this disclosure. Certain aspects of this disclosure concern the application of light to inhibit the production of collagen and fibrous tissue (e.g., inhibition of collagen biosynthesis, inhibition of procollagen production, inhibition of collagen proliferation, and / or inhibition of the relative migration rate of collagen), modulate inflammation and healing, and / or increase the production and / or release of endogenous nitric oxide (NO). In certain aspects, the increased production and / or release of endogenous NO according to the present invention may provide one or more desirable effects, thereby the angiogenic behavior indicated by NO may help avoid avascular encapsulation, localized NO may help downregulate the expression of pro-inflammatory cytokines, and / or NO may reduce leukocyte adhesion due to increased NO concentration, thus reducing the localization of inflammatory cells at and near device-tissue interfaces.

[0036]

[0075] Aspects of this disclosure relate to the administration of light to modulate FBR in living tissues. The mechanism by which a particular wavelength of light exerts its effect may vary depending on the wavelength administered and the specific stage of FBR associated with it. Light of various wavelengths may further induce one or more biological effects in or near the irradiated tissue, including inactivating microorganisms in a cell-free environment and / or inhibiting the replication of microorganisms in a cell-associated environment, upregulating local immune responses, stimulating the enzymatic production of NO to increase endogenous NO storage, releasing NO from endogenous NO storage, and antimicrobial effects that induce anti-inflammatory effects. According to aspects of this disclosure, light can be provided across a wide range of wavelengths, including the ultraviolet (UV) range, the visible light range, and the infrared (IR) range, as well as combinations thereof, to modulate various FBR stages and induce other biological effects.

[0037]

[0076] In certain embodiments, shorter wavelengths of light ranging from near-ultraviolet to various wavelengths of blue-green light may induce FBR regulatory responses with reduced impact on tissue viability. Thus, the application of light having peak wavelengths in the range of 300 nanometers (nm) to 600 nm, or 315 nm to 600 nm, or 400 nm to 600 nm, or 400 nm to 450 nm may downregulate collagen biosynthesis and result in an antiproliferative effect on fibroblasts, thereby helping to reduce collagen formation and scarring along foreign bodies. Such wavelengths of light may further provide the expression of macrophage inhibitory cytokine-1 (MIC-1), which can limit the FBR step of macrophage activation, thereby interfering with the progression of the later FBR step associated with fibroblast increase. In further embodiments, light of such wavelengths may induce increased production and / or release of endogenous NO, as described above.

[0038]

[0077] In certain embodiments, ultraviolet light may be administered as part of FBR adjustment and / or antimicrobial photoapplication. The ultraviolet wavelength range of the light may include ultraviolet-A light with peak wavelengths in the range of 315 nm to 400 nm, ultraviolet-B light with peak wavelengths in the range of 280 nm to 315 nm, and ultraviolet-C light with peak wavelengths in the range of 200 nm to 280 nm. However, excessive exposure to ultraviolet light can lead to concerns about cytotoxicity of the relevant tissues. Therefore, it may be preferable to use ultraviolet light with shorter cycles and / or lower doses than the corresponding treatment with visible light alone.

[0039]

[0078] In certain embodiments, longer wavelength ranges, including red and / or near-infrared light, such as having peak wavelengths in the range of 600 nm to 1600 nm, may also help induce different FBR-modulating responses than those induced by the shorter wavelengths mentioned above. While the shorter wavelengths mentioned above may help suppress the activation of collagen and / or macrophages during FBR, longer wavelengths may induce different responses, such as promoting the progression to collagen and / or fibrous tissue formation along various stages of healing.

[0040]

[0079] Returning to Figure 1A, aspects of the present disclosure may relate to irradiating tissue affected by a foreign body to modulate the relevant FBR. Irradiation with one or more combinations of light from one or more wavelength ranges can induce various combinations of FBR modulating responses along different stages of wound healing. For example, light having peak wavelengths in the range of 400 nm to 600 nm, or in the range of 400 nm to 450 nm, may be applied during one or more time intervals associated with different FBR stages. The light may be applied to reduce the formation of collagen and / or fibrous tissue, otherwise it may interfere with the intended function of the foreign body, such as sensing by a medical device sensor. The light may be applied throughout the entire FBR stage, or at selected time intervals such as proliferation or remodeling. In other embodiments, devices and related methods may include irradiating with light from different wavelength ranges to modulate FBR differently at different time intervals. For example, the relevant tissue may be irradiated with longer wavelength light (e.g., near-infrared light, such as in the range of 600 nm to 1600 nm) during one or more parts of the hemostatic and / or inflammatory phase to induce initial local healing, followed by irradiation with near-ultraviolet and / or blue wavelength light (e.g., in the range of 315 nm to 600 nm) to disrupt the later stages of FBR progression. Referring again to Figures 1A-1F, a particular protocol may include the application of long-wavelength light during time intervals of 0 to 4 days and the application of short-wavelength light during time intervals of 3 to 30 days. In this regard, initial local healing may promote the fixation of the foreign body in place, while disrupting the later stages of FBR progression may suppress the formation of collagen and / or fibrous tissue, which could affect the intended function of the foreign body. In yet another embodiment, the device and associated method may provide different doses of FBR-modulating light at various stages of wound healing. Different administrations of FBR-modulating light may refer to different dosing intervals (i.e., time between dosing), dosing duration (i.e., duration of a particular dosing), dosing site, and / or different wavelengths.For example, near-ultraviolet and / or blue wavelength light can be applied throughout the various stages of wound healing, extending the initial dosing interval and / or shortening the initial dosing period (e.g., 0 to 3 or 4 days) during the time interval associated with the hemostatic and inflammatory phases, and then shortening the dosing interval and extending the dosing period during the time interval associated with the proliferative and remodeling phases (e.g., 3 to 30 days). In further examples, near-ultraviolet and / or blue wavelengths may be applied first during the proliferative and remodeling phases, and no wavelength of light may be applied during the hemostatic and inflammatory phases. In other words, the dose of light can be increased after the initial period following foreign body insertion, and the initial time interval may embody no light irradiation or a lower dose of light than in subsequent time intervals. In various embodiments, the above time intervals for different wavelengths may include overlapping or non-overlapping time intervals, depending on the intended use.

[0041]

[0080] Devices disclosed herein may include a light source capable of emitting a suitable optical spectrum for inducing one or more FBR modulating reactions. The optical spectrum can be represented as a graph of emission intensity against wavelength of light from a particular light source. In certain embodiments, the light source may have optical properties of the visible spectrum, for example, emission having peak wavelengths mainly in the range of 400 nm to 700 nm. Depending on the application, the optical properties may also include infrared or near-infrared peak wavelengths above 700 nm, or ultraviolet peak wavelengths below 400 nm. As used herein, the light may include visible and invisible electromagnetic radiation having one or more peak wavelengths in the range of 180 nm to 4000 nm. In certain embodiments, the emission may be in the range of 200 nm to 1,000 nm, or 400 nm to 490 nm, or 400 nm to 435 nm, or 400 nm to 420 nm, or 400 nm to 440 nm, or 400 nm to 450 nm, or 420 nm to 440 nm, or 450 nm to 490 nm, or 600 nm to 1,600 nm, or 490 nm to 570 nm, or 510 nm to 550 nm, or 520 nm to 540 nm, and Alternatively, it may have a single peak wavelength in the range of 525 nm to 535 nm, or 528 nm to 532 nm, or 630 nm to 670 nm, or 320 nm to 400 nm, or 385 nm to 450 nm, or 350 nm to 395 nm, or 280 nm to 320 nm, or 320 nm to 350 nm, or 200 nm to 280 nm, or 260 nm to 270 nm, or 240 nm to 250 nm, or 200 nm to 225 nm. In further embodiments, the emission may include multiple peak wavelengths selected from any of the above ranges, depending on the intended application and the desired biological effect.

[0042]

[0081] The term “peak wavelength” is used herein to generally refer to the wavelength at which the light emitted by a light source has the highest radiant output. The term “dominant wavelength” may refer to the perceived color of the spectrum, i.e., a single wavelength of light (i.e., roughly equivalent to “hue”) that produces the color perception most similar to the color perception perceived by viewing light emitted from a light source, in contrast to the “peak wavelength,” and this refers to the spectral line with the highest output in the spectral output distribution of the light source. The human eye does not perceive all wavelengths equally (for example, it perceives yellow and green light better than red and blue light), and since the light emitted from many solid-state light sources (e.g., LEDs) is actually a range of wavelengths, the perceived color (i.e., dominant wavelength) is not necessarily the same as (and often different from) the wavelength of highest output (peak wavelength). True monochromatic light, such as lasers, may have the same dominant and peak wavelengths. For the purposes of this disclosure, unless otherwise specified herein, wavelength values ​​are described as peak wavelength values.

[0043]

[0082] Depending on the application, the full width at half maximum (FWHM) value for any of the above peak wavelength ranges may be 100 nm or less, or 90 nm or less, or 40 nm or less, or 20 nm or less. In certain embodiments, lower FWHM values ​​are typically associated with light-emitting diodes (LEDs) of a single emission color in any of the above wavelength bands. Larger FWHM values ​​(e.g., from 40 nm to 100 nm) may be associated with phosphor-converted LEDs where the spectral bandwidth is a combination of LED emission and phosphor-converted emission. Exemplary phosphor-converted LEDs that may be applicable to this disclosure are phosphor-converted amber LEDs having peak wavelengths in the range of 585 nm to 600 nm and FWHM values ​​in the range of 70 nm to 100 nm, and phosphor-converted mint and / or lime LEDs having peak wavelengths in the range of 520 nm to 560 nm. Additional embodiments of this disclosure may also be applicable to broad-spectrum white LEDs which may include an LED having peak wavelengths in the range of 400 nm to 470 nm and one or more phosphors to provide a broad emission spectrum. In such embodiments, a broad-spectrum LED can provide specific wavelengths that induce one or more biological effects, while simultaneously providing broad-spectrum emission to a target area for illumination. In this regard, the collision of light with tissue for one and / or more biological effects can be provided with light of a single peak wavelength or a combination of light having multiple peak wavelengths.

[0044]

[0083] The dose of light to induce one or more FBR modulations and / or other biological effects may be administered along with one or more optical properties, including peak wavelength, radiant flux, and irradiance to the target tissue. The irradiance to the target tissue is 0.1 milliwatts / cm² (mW / cm²). 2 ) from 200mW / cm 2 Up to or within the range of 5 mW / cm² 2 From 200 mW / cm² 2 Up to or within the range of 5 mW / cm² 2 From 100mW / cm 2 Up to or within the range of 5 mW / cm² 2 From 60 mW / cm² 2up to a range of, or 60 mW / cm 2 from 100 mW / cm 2 up to, or 100 mW / cm 2 from 200 mW / cm 2 can be provided in the range up to. Such irradiance ranges can be administered in one or more of continuous wave and pulsed configurations, including LED-based photonic devices configured with an output (radiant flux) suitable for irradiating a target tissue within any of the ranges described above. A light source for providing such irradiance ranges can be at least 5 mW, or at least 10 mW, or at least 15 mW, or at least 20 mW, or at least 30 mW, or at least 40 mW, or at least 50 mW, or at least 100 mW, or at least 200 mW, or in the range from 5 mW to 200 mW, or in the range from 5 mW to 100 mW, or in the range from 5 mW to 60 mW, or in the range from 5 mW to 30 mW, or in the range from 5 mW to 20 mW, or in the range from 5 mW to 10 mW, or in the range from 10 mW to 60 mW, or in the range from 20 mW to 60 mW, or in the range from 30 mW to 60 mW, or in the range from 40 mW to 60 mW, or in the range from 60 mW to 100 mW, or in the range from 100 mW to 200 mW, or in the range from 200 mW to 590 mW, or can be configured to provide a radiant flux value from a light source in another range specified herein. Depending on one or more configurations of the light source, the corresponding illumination device, and the distance from the target tissue, the radiant flux value of the light source can be higher than the irradiance value at the tissue.

[0045]

[0084] A specific peak wavelength for a specific target tissue type can be up to 200 mW / cm without causing significant tissue damage. 2While it can be administered at irradiances of 0.1 W / cm², safety considerations for other peak wavelengths and corresponding tissue types may require lower irradiances, particularly in continuous wave applications. In certain embodiments, pulsed irradiance of light can be administered, thereby enabling the safe application of significantly higher irradiances. Pulsed irradiance can be characterized as an average irradiance that falls within a safe range, thereby causing no or minimal damage to the applied tissue. In certain embodiments, 0.1 W / cm² is used. 2 From 10W / cm 2 Irradiance in this range can be safely pulsed onto the target tissue.

[0046]

[0085] The light source may include one or more of the LEDs, organic LEDs (OLEDs), lasers, and other lamps according to embodiments of this disclosure. Lasers can be used for irradiation in combination with optical fibers or other delivery mechanisms. An LED is a solid-state electronic device that can emit light when electrically activated. LEDs are highly efficient, relatively inexpensive, and can be configured across many different target emission spectral bands. Therefore, LEDs can be used as a light source for photonic devices in phototherapy applications. Light from the LED is administered using a device that can deliver the required power to the target therapeutic area or tissue. High-power LED-based devices can be used to meet the diverse spectral and power needs of various different medical applications. The LED-based photonic devices described herein can deliver 100 mW / cm² over a desired wavelength range. 2 or 200mW / cm² 2 It can be configured with a power level suitable for providing high irradiance. The LED array of this device can be integrated into the irradiation head, handpiece, and / or as an external unit.

[0047]

[0086] In addition to various light sources, the principles of this disclosure may also include one or more other types of directed energy sources. As used herein, the directed energy source may include any of the aforementioned various light sources, as well as any energy source capable of providing one or more of the following: heat, infrared heating, resistive heating, radio waves, microwaves, sound waves, ultrasound, electromagnetic interference, and electromagnetic radiation that may be directed towards a target body tissue. The combination of visible and non-visible electromagnetic radiation may include peak wavelengths ranging from 180 nm to 4000 nm. The illumination devices disclosed herein may include a light source and another directed energy source capable of providing directed energy beyond visible and ultraviolet light. In other embodiments, other directed energy sources capable of providing directed energy beyond visible and ultraviolet light may be provided separately from the illumination devices of this disclosure.

[0048]

[0087] Certain aspects of this disclosure relate to devices and corresponding methods for favorably adjusting the fast blood glucose rate (FBR) for continuous glucose monitoring (CGM). By providing a CGM that is less susceptible to FBR-related adverse effects, the associated sensors can maintain accuracy for a relatively longer period than conventional CGMs. For example, the measurement of interstitial glucose compared to actual blood glucose concentration can be improved by reducing the time lag, increasing accuracy, and extending the duration of clinically relevant sensor performance when the FBR is adjusted according to this disclosure. Before further exploring aspects of this disclosure, a general description of CGM is provided. Enzymatic oxidation of blood glucose to gluconolactone (hydrolysis to gluconic acid) can occur in the presence of catalytic glucose oxidase (GOx), and the subsequent electrochemical detection of oxygen depletion and / or hydrogen peroxide formation can be performed by a CGM sensor. Enzymatic oxidation of blood glucose to gluconolactone (hydrolysis to gluconic acid) in the presence of catalytic GOx and the subsequent electrochemical detection of oxygen depletion and / or hydrogen peroxide formation are shown schematicly in Figure 12 of Figure 2. Some sensors can detect blood glucose by monitoring oxygen consumption using two oxygen electrodes (one enzyme-coated and the other for reference). Background fluctuations in oxygen can be compensated for by comparing the differential current between these electrodes. Alternatively, hydrogen peroxide enzymatically produced by GOx can be quantified by amperometry. Amperometric enzyme electrodes vary considerably in electrode design, electrode material, enzyme immobilization method, and polymer membrane composition. Various devices and materials have been employed to perform blood glucose concentration measurements with transcutaneous CGM devices. CGM devices typically include needle-type sensors or sensor probes designed so that the distal end of the sensor is present transcutaneously.

[0049]

[0088] Figure 3 shows a portion of a device 14 that includes a foreign body 16 for percutaneous placement through the host skin 18 and further includes FBR adjustment capability according to the principles of this disclosure. In certain embodiments, the device 14 may include a CGM in which the foreign body 16 represents a sensor probe of the CGM. As shown, a light source 20 may be positioned outside the skin 18 in an arrangement that irradiates and passes light 22 through a portion of the host skin 18 aligned with the area of ​​subcutaneous tissue in which the foreign body 16 is inserted. The light source 20 may embody a single light source or multiple light sources that can independently provide different wavelengths at different times. Depending on the wavelength, some of the light 22 can penetrate the skin 18 and irradiate the underlying tissue at various depths. However, not all wavelengths of light 22 are suitable for passing through the skin 18 and the underlying tissue. For example, red and near-infrared wavelengths can penetrate to certain tissue depths below the skin 18 (e.g., up to about 2.5 millimeters (mm)), while shorter wavelengths such as blue may have little light that penetrates to tissue depths greater than about 0.5 mm. In a typical CGM application, the sensor probe may extend to depths ranging from approximately 3 mm to 15 mm below the skin 18, or from approximately 4 mm to 8 mm, or from approximately 5 mm to 7 mm, depending on the application and insertion angle. In this regard, the sensor probe (e.g., foreign body 16) can pass through the epidermis and dermis so that the distal end 16' of the sensor probe may be present in the subcutaneous tissue layer for interstitial fluid glucose monitoring. Thus, the configuration shown in Figure 3 may be suitable for delivering longer wavelength light 22 to the skin 18 and specific depths below the skin 18 when it is desired to modulate FBR by promoting increased healing along the foreign body 16, such as during hemostasis and / or part of the inflammatory phase.

[0050]

[0089] Even with longer wavelengths, light 22 may not yet penetrate deep enough to reach the distal end 16' of the foreign object 16. However, this can be advantageous in certain applications such as CGM. The active sensing region for a sensor probe in blood glucose monitoring may be located at or near the distal end 16', as shown in Figure 3. The absorbance of blood glucose and glucose oxidase is higher in the range of 560 nm to 760 nm, with a peak absorbance around 660 nm. Furthermore, absorbance may begin to increase below 420 nm. In this regard, it may be desirable to avoid wavelengths with higher absorbance interacting with the active sensing region. To the extent that some light reaches the active sensing region, such effects can be compensated based on the spectrum of light used, the irradiance flux density of the delivered light, and the duration of such light delivery.

[0051]

[0090] Figure 4 shows a portion of the device 24, including the delivery of light 22 at increased tissue depth beneath the skin 18 to provide FBR adjustment capability according to the principles of the present disclosure. In certain embodiments, the light source 20 may be positioned to irradiate light 22 beneath the host skin 18 to reach subcutaneous tissue portions along or near a foreign body or sensor probe 16. For example, an optical delivery structure 26, such as an optical waveguide, may be inserted percutaneously beneath the skin 18, allowing light 22 to propagate from the light source 20 to irradiate tissue at a depth close to the target region of the foreign body 16. In certain embodiments, the optical delivery structure 26 includes an optical waveguide in the form of an optical fiber. For CGM applications, the arrangement of the optical delivery structure 26 may provide suitable delivery of shorter wavelength light, including blue, blue-green, and / or near-ultraviolet, to a target region of the sensor probe corresponding to the location where activity sensing occurs. In yet another embodiment, the optical delivery structure 26 may suitably deliver longer wavelength light, such as the red and / or near-infrared wavelengths described above, alone or in combination with shorter wavelength light. The corresponding tissue depth may range from 1 mm to 15 mm, or from 4 mm to 15 mm, depending on the location of the activity sensing region. For example, in a particular embodiment, an exemplary sensor probe 16 for CGM may have a sensing region located at or near the distal end 16' of the sensor probe 16, provided at a tissue depth ranging from 4 mm to 8 mm. In this way, the light delivery structure 26 can be inserted percutaneously to a depth such that light 22 is delivered in close proximity to the sensing region, for example, within about 0.5 mm of the activity sensing region. In a particular probe tip design, the sensing region may be provided at the distal end 16', or at a distance of about 1 mm from the probe tip of the sensor probe 16.

[0052]

[0091] Figure 5 shows a portion of device 28, including the combination of FBR adjustment capabilities described for device 14 in Figure 3 and device 24 in Figure 4. In this way, the principles described above for Figures 3 and 4 can be incorporated together for device 28. As shown in the figure, a first light source 20-1 may be configured to deliver light 22-1 through a light delivery structure 26 to irradiate a foreign body 16 or nearby tissue at various tissue depths beneath the skin 18. A second light source 20-2 may be configured to irradiate light 22-2 to the surface of the skin 18 and to shallower tissue depths beneath the skin 18, depending on the specific wavelength of light 22-2. For CGM applications, the first light source 20-1 may provide the relevant light 22-1 having shorter wavelengths, including blue, blue-green, and / or near-ultraviolet, while the second light source 20-2 may provide the relevant light 22-2 with longer wavelengths, such as red and / or near-infrared. While the specific wavelengths described above may be suitable for certain embodiments, the configuration of device 28 allows for tuned applications that provide different combinations of wavelengths based on different intended FBR modulation responses. For example, the first and second light sources 20-1, 20-2 may be configured to provide light of the same wavelength to the above and below the skin 18, respectively.

[0053]

[0092] The devices in Figures 3-5 may be capable of delivering different doses of FBR-modulating light at various stages of wound healing shown in Figure 1A. As described above, different doses of FBR-modulating light may refer to different dosing intervals, dosing durations, dosing locations, and / or different wavelengths. In a particular dosing protocol, the device and associated method for delivering FBR-modulating light may include providing light having a first wavelength in the range of 600 nm to 1600 nm during the hemostatic and inflammatory phases, from insertion of the foreign body 16 until day 3. In a subsequent step, light with a second wavelength different from the first wavelength, such as in the range of 400 nm to 600 nm, may be provided from day 3 until the end of the foreign body 16's operation. In a further dosing protocol, the application times of the first and second wavelengths may overlap. In yet another dosing protocol, a single wavelength in the range of 400 nm to 600 nm may be applied from insertion of the foreign body 16 until the end of the foreign body 16's operation. In such protocols, the single-wavelength dose may be constant throughout the entire FBR phase, or, as mentioned above, the single-wavelength dose may be varied based on a specific FBR phase.

[0054]

[0093] In certain embodiments, the arrangement for delivering FBR-modulating light can be incorporated as an element within the entire device, including a transcutaneous foreign body such as a sensor probe for a CGM. The light delivery structure may be positioned to deliver light to a specific depth beneath the skin, outside a specific surface of the skin, and a combination thereof. To deliver light beneath the skin, the corresponding light delivery structure may be positioned to be inserted into the skin simultaneously with or separately from the foreign body. For simultaneous insertion, the light delivery structure may be positioned to surround one or more portions of the foreign body, and / or the light delivery structure may be provided adjacent to the corresponding foreign body, such as within the area of ​​subcutaneous tissue where the foreign body resides. Integrating the light delivery structure together with the foreign body can improve the alignment of the light delivery structure, allowing for more consistent delivery of light to the target area of ​​the foreign body.

[0055]

[0094] Figure 6 is a partial diagram of a device 30 having a sensor probe 32 and a corresponding optical delivery structure 34 for percutaneous insertion into a host to provide FBR adjustment capability. In certain embodiments, the device 30 can embody a medical sensing device such as a CGM, or various other consumer electronic monitoring devices. As shown, the optical delivery structure 34 embodies a hollow structure arranged to surround a portion of the sensor probe 32. For example, the optical delivery structure 34 may include at least one of a sleeve, a film, and a coating provided around the portion of the sensor probe 32. A portion of the sensor probe 32, including an active sensing region 36, is positioned to protrude from the end of the optical delivery structure 34. The active sensing region 36 may correspond to a portion of the sensor probe 32 where the electrode is not covered by an insulator. When inserted percutaneously, the accuracy of the active sensing region 36 may be impaired as the associated FBR advances through various stages. To adjust the FBR, the optical delivery structure 34 is positioned to deliver light 22 percutaneously to or near the active sensing region 36. In certain embodiments, the optical delivery structure 34 includes a hollow optical waveguide to accommodate a portion of the sensor probe passing through it. The optical delivery structure 34 may further include a light scattering region 38 located at an end adjacent to the active sensing region 36. The light scattering region 38 helps to scatter the light 22 leaving the optical delivery structure 34 and may include light scattering particles or light diffusing material having improved uniformity across the active sensing region 36. The light scattering region 38 can be materialized as a coating or film on the optical delivery structure 34, or the light scattering region 38 can be formed inside the optical delivery structure 34.

[0056]

[0095] Figure 7 is a partial diagram of device 40, which is similar to device 30 in Figure 6. However, the optical delivery structure 42 of device 40 is otherwise characterized by embodying a hollow sheath configured to allow light 22 to propagate between the optical delivery structure 42 and the sensor probe 32. As shown, the sensor probe 32 extends through the space defined by the optical delivery structure 42. The light 22 may be directed into a gap formed between the sensor probe 32 and the optical delivery structure 42, and the light 22 may exit into a tissue region containing an active sensing region 36 for regulating the associated FBR. In certain embodiments, the optical delivery structure 42 may embody a hollow reflecting tube or a hollow optical guide for the propagation of light 22. In certain embodiments, the optical delivery structure 42 may further include the light scattering region described above for Figure 6.

[0057]

[0096] Figure 8 is a partial diagram of a device 44 in which an optical delivery structure 46 for percutaneous insertion into a host is positioned adjacent to a corresponding sensor probe 32 to provide FBR adjustment capability. As shown, the optical delivery structure 46 may be positioned adjacent to the sensor probe 32, and the distal end 46' of the optical delivery structure 46 may be offset from the distal end 32' of the sensor probe 32. In this way, light 22 emanating from the optical delivery structure 46 may be delivered to a region of tissue, including an active sensing region 36 for the adjustment of the relevant FBR. The optical delivery structure 46 may include an optical waveguide such as an optical fiber. In certain embodiments, the optical delivery structure 46 may be attached to the sensor probe 32 for simultaneous percutaneous insertion. In other embodiments, the optical delivery structure 46 may be spaced apart from the sensor probe 32. In such arrangements, the optical delivery structure 46 and the sensor probe 32 may be fixed to a common part of the device 44 for simultaneous percutaneous insertion. In yet another embodiment, the light delivery structure 46 and the sensor probe 32 may be fixed to different elements of the device 44 for either simultaneous transdermal insertion or transdermal insertion at different times. Furthermore, the light delivery structure 46 and the sensor probe 32 may be aligned parallel to each other or at an angle to deliver light 22 to the active sensing region 36. The light delivery structure 46 may further include a light scattering region as described above with respect to Figure 6.

[0058]

[0097] Figure 9 is a partial diagram of the device 44 of Figure 8, further comprising an arrangement that includes an optical filter 48 associated with the optical delivery structure 46. In certain embodiments, the optical filter 48 may be positioned between a light source that delivers light 22 and the distal end 46' of the optical delivery structure 46 to attenuate specific wavelengths of light 22. The optical filter 48 may be incorporated into the optical delivery structure 46, or the optical filter 48 may embody a separate structure positioned at the light-receiving end of the optical delivery structure 46. The optical filter 48 may be configured to filter specific wavelengths of light 22 while allowing other wavelengths of light 22 to propagate through it toward the distal end 46'. For example, the optical filter 48 may embody a low-pass filter that filters wavelengths above a certain value, a high-pass filter that filters wavelengths below a certain value, a band-pass filter that allows wavelengths within a certain wavelength band to pass through, or a notch filter that blocks wavelengths within a certain wavelength band. Thus, the light delivery structure 46 may be configured to further tune the received light 22 so that only a desired wavelength or a desired wavelength range passes through the rest of the light delivery structure 46. For example, for applications where it is desirable to deliver light of shorter wavelengths to the active sensing region 36, the light filter 48 may be configured to filter at least 50 percent, or at least 80 percent, of the light 22, which may be in the wavelength range of 590 nm to 1,000 nm, or in the range of 590 nm to 600 nm. In yet another example, one or more light filters 48 may be provided to filter shorter wavelengths of the light 22, such as one or more wavelengths in the ultraviolet spectrum. In this regard, by using one or more light filters 48, a user can tune light of specific wavelengths for a particular application without necessarily having to change the corresponding light source.

[0059]

[0098] On the other hand, while Figures 6-9 describe sensor probes 32 such as sensor probes for CGM, the disclosed principles are applicable to any foreign body that can be inserted percutaneously (e.g., 16 in Figures 3-5). As disclosed herein, foreign bodies may include enzymatic electrochemical blood glucose sensors, non-enzymatic electrochemical sensors, microsensors or microsensor rays that amperometrically monitor hydrogen peroxide production as a measure of blood glucose concentration, implantable microdialysis probes, catheters, intravenous lines, chemotherapy ports, lactate biosensors, cancer biosensors, glycated hemoglobin or A1C biosensors, NO concentration detectors, percutaneous electroneurostimulation (PENS) devices, and percutaneous devices that need to access body tissues or fluids to perform their intended function.

[0060]

[0099] In cases where the foreign substance is a lactose biosensor, lactose biosensing can be based on lactate oxidase and palladium benzoporphyrin immobilized on a hydrogel. L-Lactate is a very interesting specimen due to its role in sports medicine, clinical chemistry, and overall normal metabolic function. Lactate is a normal byproduct of cellular metabolism. However, intracellular lactate concentrations rise during anaerobic respiration, and interstitial lactate levels rise as lactate is excreted from cells, accumulating in muscles and other tissues, which can cause pain, discomfort, and dysfunction. Lactate concentration can be used to assess a variety of acute deoxygenation events, such as hypovolemia (shock), heart disease, and renal failure. High lactate levels are also common in trauma where the patient has experienced significant blood loss. The ability to monitor blood lactate levels can improve the identification of patients requiring resuscitation compared to standard blood pressure monitoring. In certain embodiments, continuous lactate monitoring is used for dynamic health assessment of active military personnel and other high-risk personnel, or to estimate the "oxygen debt" of endurance athletes. In certain embodiments, a lactate biosensor uses an enzyme to generate hydrogen peroxide (H2O2) on the surface of a transcutaneously inserted electrode, and the resulting change in potential can be correlated with the interstitial lactate concentration. As with any foreign body, the challenges associated with transcutaneous monitoring of lactate levels are related to the foreign body reaction induced by the implantation of the lactate sensor. In this regard, the principle of the present disclosure advantageously provides the ability to adjust the fast break-rate (FBR) to mitigate the foreign body reaction to the lactate sensor function, thereby improving accuracy and extending the effective life of such a device.

[0061]

[0100] In certain embodiments, the foreign bodies disclosed herein may include cancer biosensors. Significant efforts have been made to detect biomarkers of cancers such as breast and lung cancer. In this regard, cancer biosensors may provide a relatively non-invasive method for detecting cancer progression. Cancer biosensors may include specific biorecognition molecules, such as antibodies, complementary nucleic acid probes, or other immobilized biomolecules, on the transducer surface. The biorecognition molecules specifically interact with the biomarker (target), and the resulting biological reaction is converted into a measurable analytical signal by the transducer. Depending on the type of biological reaction, cancer biosensors can be manufactured using a variety of transducers, including electrochemical, optical, and mass-based transducers. As with other foreign bodies, challenges associated with percutaneous monitoring by cancer biosensors may include induced foreign body reactions. In this regard, the principles of this disclosure can advantageously provide FBR modulating capability to mitigate foreign body reactions to cancer sensor function, thereby improving accuracy and extending the effective life of such devices.

[0062]

[0101] Figure 10A is a diagram of a device 50 having an optical delivery structure 52 and a corresponding cannula support 54 for transcutaneously delivering light to provide FBR adjustment capability. The optical delivery structure 52 may comprise an optical waveguide in the form of an optical fiber or optical fiber cannula. The cannula support 54 may include one or more projections 54' configured for insertion below the surface of the skin 18 and into the dermis in order to improve the mechanical support of the optical delivery structure 52. Furthermore, other parts of the cannula support 54 may be fixed to the surface of the host skin 18 by adhesive. The optical delivery structure 52 may include a flange or housing 56 that engages with the cannula support 54 and is dimensioned to form a stopper for the optical delivery structure 52 during insertion. For example, after the cannula support 54 is fixed to the host skin 18, the optical delivery structure 52 may be guided into the skin 18 through an opening in the cannula support 54. The housing 56 can then engage with a portion of the cannula support 54 to set the depth of the optical delivery structure 52 below the skin 18. In this way, the housing 56 and cannula support 54 can collectively provide the distal end 52' of the light delivery structure 52 at a desired depth, such as intracutaneously as shown in the figure. The light source 20 may be located externally to provide light to the light delivery structure 52. In certain embodiments, such arrangement may be used for testing and / or delivery of FBR-modulated light in a clinician's office. Figure 10B is a diagram of an alternative configuration of the device 50 of Figure 10A for an embodiment in which the light source 20 can be incorporated into the housing 56. In this regard, once the light delivery structure 52 is inserted under the skin 18, the housing 56 and the incorporated light source 20 can enhance the mobility of the host user.

[0063]

[0102] As shown in Figures 10A and 10B, the optical delivery structure 52 may include a light scattering region 38 positioned at the distal end 52' to facilitate light extraction. In certain embodiments, the light scattering region 38 has a smaller surface area compared to the rest of the optical delivery structure 52 and concentrates the light emanating at the distal end 52'. As an example, the portion of the optical delivery structure 52 inserted under the skin 18 (e.g., an optical guide or optical fiber) may have a length ranging from about 5 mm to about 15 mm under the skin 18 and a diameter ranging from 8 microns (μm) to 250 μm, and the length of the light scattering region 38 measured from the distal end 52' may be shorter than the diameter. In this regard, substantially the majority of the light that can propagate within the optical delivery structure 52 can emanate at the distal end 52', thereby enabling a high dose of delivered light relative to the amount of light provided by the light source 20. Such an arrangement may be advantageous in improving the lifespan of the power supply in portable applications where the power supply may include a battery or a rechargeable power supply.

[0064]

[0103] The devices shown in Figures 10A and 10B may be provided as part of a CGM or other monitoring device to deliver FBR-modulating light to or near a sensor probe under the skin. In another application, the devices shown in Figures 10A and 10B may be well suited to delivering therapeutic doses of light to subcutaneous tissue or subcutaneous tissue for purposes other than FBR modulation. In this regard, the principle of this disclosure may also be applicable to subcutaneous light delivery even in the absence of foreign bodies. In another application, the devices shown in Figures 10A and 10B may also be useful as test structures for evaluating FBR-modulating light in experimental studies. In certain applications, pigs may be used (as hosts) as a human model in in vivo studies in protocols for evaluating FBR-modulating light. While rats, mice, and rabbits have been used in skin studies, pig skin has been shown to be similar to human skin in many respects, including epidermal thickness and dermal-to-epidermal thickness ratio. Furthermore, pigs and humans have similar patterns of hair follicles and blood vessels in their skin.

[0065]

[0104] The principles of this disclosure may be applicable to various CGM applications for providing FBR-tuned light during monitoring. Figures 11–17B illustrate various arrangements of a CGM or CGM component having FBR-tuned capability. Exemplary arrangements include one or more light sources and light delivery structures that may be contained within a CGM and / or in accessories that can be used in combination with a CGM. In certain examples, such accessories may provide the ability to retrofit a conventional CGM with FBR-tuned capability.

[0066]

[0105] Figure 11 is a diagram representing a CGM 58 having an integrated light source 20 capable of delivering FBR-modulating light to the host's skin 18 during monitoring. The CGM 58 may generally include a sensor holder 60 containing a sensor probe 32. The sensor holder 60 can mechanically support the sensor probe 32 during transdermal insertion. In certain configurations, the sensor probe 32 may be provided perpendicular to the CGM 58. However, in other configurations, the sensor probe 32 may be provided at a certain angle to the CGM 58. The sensor holder 60 is typically fixed to the skin 18 by adhesive as described above. The CGM 58 may further include a transmitter 62 capable of relaying blood glucose sensing information to an external device such as a portable monitor, a mobile phone, a wearable device (e.g., a watch or other graphic display device), a computer, and one or more of the networks. The transmitter 62 may include one or more of the following: a power source (e.g., a battery or rechargeable battery), a microprocessor and / or microcontroller, a communication module for facilitating wireless and / or wired communication, and other related electronic equipment. In certain embodiments, the sensor holder 60 may be initially attached to the skin 18 to position the sensor probe 32 beneath the surface of the skin 18. Thus, the transmitter 62 may embody a separate component that can later be attached to the sensor holder 60. In other embodiments, the sensor holder 60 and the transmitter 62 may be elements of a single CGM that are not detachably removable from each other. In further embodiments, the CGM 58 may further include an optional insulin infusion catheter 64. In other embodiments, the associated insulin infusion catheter may be provided separately from the CGM 58. As shown in Figure 11, one or more light sources 20 may be provided within the sensor holder 60 or the CGM 58 in an arrangement that provides light to the injection site of the sensor probe 32 or to an area of ​​skin 18 near the site. Such an arrangement may be suitable for providing light to adjust the FBR at the injection site and, depending on the wavelength, to a depth beneath the skin 18 corresponding to the tissue area containing the sensor probe 32.

[0067]

[0106] Figure 12 is a diagram representing a CGM 66 similar to the CGM in Figure 11, further including a corresponding optical delivery structure 26 that can deliver FBR-adjusting light under the host skin 18 during monitoring. In Figure 12, the optical delivery structure 26 can embody an optical waveguide, such as an optical fiber, that receives light from at least one of the light sources 20-1, 20-2 in the CGM 66. In a particular embodiment, the light source 20-1 may be located within a sensor holder 60, and the optical delivery structure 26 may be mechanically supported by the sensor holder 60. Thus, the sensor probe 32 and the optical delivery structure 26 can now be inserted under the skin 18. As shown, the optical delivery structure 26 may have a length shorter than the length of the sensor probe 32 in order to deliver light to or near the distal end 32' where the aforementioned activity-sensing region may be located. In this regard, the optical delivery structure 26 may be suitable for delivering light at or near the distal end 32' in order to adjust the FBR and improve the accuracy of the sensor probe 32 over time. In further embodiments, the CGM66 may also include a light source 20-2 positioned to provide light to an area of ​​skin 18 at or near the injection site of the sensor probe 32. For example, the light source 20-1 may be configured to emit blue or near-ultraviolet light that would otherwise not penetrate the skin 18 to its distal end 32', and the light source 20-2 may be configured to emit longer wavelengths, such as red and / or near-infrared light, along the surface of the skin 18.

[0068]

[0107] Figure 13 is a diagram representing a CGM 68 similar to the CGM in Figure 12. This includes an alternative arrangement of an optical delivery structure 26 for delivering FBR-modulating light under the host skin 18 during monitoring. As shown, the optical delivery structure 26 is arranged as a hollow structure surrounding a portion of the sensor probe 32. In this regard, the optical delivery structure 26 in Figure 13 may be similar to the optical delivery structure 34 in Figure 6 or the optical delivery structure 42 in Figure 7. For example, the optical delivery structure 26 in Figure 13 may embody a sleeve, film, coating, or sheath configured to define an optical propagation path for delivering FBR-modulating light along a portion of the sensor probe 32 and at or near the distal end 32'.

[0069]

[0108] Figure 14 is a diagram representing a CGM 70 similar to the CGM in Figure 12. This includes a tilted arrangement of an optical delivery structure 26 and a sensor probe 32 for delivering FBR-modulating light beneath the host skin 18 during monitoring. Depending on the type of CGM 70, the sensor probe 32 may be designed to be present in the host skin 18 at a certain angle. As shown, the optical delivery structure 26 may be positioned within the skin 18 at a corresponding angle, either parallel to the sensor probe 32 or within approximately 10 degrees from parallel to the sensor probe 32, providing light to or near the distal end 32'. For example, the sensor probe 32 may be positioned within the skin 18 at a 45-degree angle, and the optical delivery structure 26 may be positioned at an angle ranging from 35 to 55 degrees from the sensor probe 32. In certain embodiments, the light source 20-1 and the corresponding optical delivery structure 26 may be incorporated within a sensor holder 60. As shown, the CGM 70 may further include a light source 20-2, as described above for Figure 12.

[0070]

[0109] Figure 15 is a partial perspective view of the CGM72, which can be positioned in a similar manner to the CGM70 in Figure 14 for simultaneous insertion of the optical delivery structure 26 with the sensor probe 32. For illustrative purposes, the transmitter 62 is omitted in Figure 15 to better show the sensor holder 60, the corresponding sensor probe 32, and the optical delivery structure 26. As shown, the sensor probe 32 is positioned on the bottom surface 60 of the sensor holder 60. BIt is positioned to extend at a certain angle from the sensor probe 32. The activity sensing region 36 is visible near the distal end 32' of the sensor probe 32. The light delivery structure 26 may also be incorporated into the sensor holder 60 at a position offset from and parallel to (or within 10 degrees of parallel to) the sensor holder 60. In this regard, the light delivery structure 26 may be inserted at the same time as the insertion of the sensor probe 32. As shown in the figure, the light delivery structure 26 may be configured such that at least a portion of the light delivery structure 26, for example, the distal end 26' in Figure 15, is positioned close to the activity sensing region 36 of the sensor probe 32. In this regard, at least a portion of the light delivery structure 26 may be positioned in a region of tissue that also includes one or more portions of the sensor probe 32. For example, the distal end 26' of the light delivery structure 26 may be positioned at a distance of 1 mm or less, or 0.75 mm or less, or 0.5 mm or less from the activity sensing region 36. Such distances may be well suited to providing shorter wavelength light exhibiting relatively shallow penetration depths, such as less than 600 nm to the activity sensing region 36, or in the range of 400 nm to 600 nm, or in the range of 400 nm to 500 nm, or in the range of 400 nm to 450 nm. In certain embodiments, the diameter of the light delivery structure 26 may be smaller than the diameter of the sensor probe 32. For example, the diameter of the sensor probe 32 may be about 400 μm, while the diameter of the light delivery structure 26 may be in the range of 8 μm to 250 μm. In other embodiments, the light delivery structure 26 and the sensor probe 32 may have the same diameter.

[0071]

[0110] Figure 16A is a diagram representing a CGM 74 having a CGM accessory 76 positioned between a sensor holder 60 and the host skin 18 to deliver FBR-adjusting light during monitoring. In certain embodiments, the CGM accessory 76 comprises a separate structure from the CGM 74, such as a flexible printed circuit board, including a light source 20-2 and associated circuitry for driving the light source 20-2. As shown, the CGM accessory 76 may be positioned between the sensor holder 60 and the skin 18. In certain embodiments, the CGM accessory 76 may be attached to the skin 18 by adhesion, or the CGM accessory 76 may embody an adhesive bandage material incorporated into the light source 20-2 and the corresponding electronic equipment. In certain embodiments, the CGM accessory 76 forms an opening 78 that can be aligned with a sensor probe 32. In this regard, the CGM accessory 76 may first be attached to the skin 18, and the sensor probe 32 may then enter the skin 18 by passing through the opening 78 during insertion. As further illustrated, the light delivery structure 26 can also enter the skin 18 through the opening 78 simultaneously with the sensor probe 32. Thus, the CGM accessory 76 can provide the ability to retrofit one or more FBR adjustment capabilities to the CGM 74.

[0072]

[0111] Figure 16B is a diagram representing a CGM 80 similar to the CGM 74 in Figure 16A, having an alternative configuration of the CGM accessory 76 for delivering FBR-modulating light during monitoring. In Figure 16B, the CGM accessory 76 includes both light sources 20-1 and 20-2. As shown, the light delivery structure 26 associated with light source 20-1 can also be incorporated into the CGM accessory 76. In this regard, the light delivery structure 26 may be first inserted under the skin 18 when the CGM accessory 76 is attached to the skin. The sensor probe 32 can then enter the skin 18 through the opening 78 once the sensor holder 60 is attached to the CGM accessory 76 and / or the skin 18. In this way, the lateral spacing of the opening 78 relative to the light delivery structure 26 may be configured to guide the sensor probe 32 into the skin 18 at a suitable position to receive FBR-modulating light from the light delivery structure 26. Although shown at an angle in Figure 16B, both the sensor probe 32 and the light delivery structure 26 may be positioned vertically without deviating from the disclosed principle.

[0073]

[0112] Figure 16C is a top view of the CGM accessory 76 of Figure 16A or Figure 16B. The CGM accessory 76 may include one or more alignment marks 84 for positioning the sensor holder 60 of Figures 16A and 16B relative to the opening 78 during installation. The CGM accessory 76 may include adhesive material for adhering it to the host's skin. The CGM accessory 76 may further include optional wing portions 76' that extend beyond the footprint occupied by the sensor holder to allow for additional forms of securing the CGM accessory 76 to the underlying skin. For example, the wing portions 76' may include their own adhesive material, and / or the wing portions 76' may form tabs that can be secured with adhesive tape. In certain embodiments, the CGM accessory 76 may include a connector 85 for providing external power to the light source 20 and / or for signal transmission. As an example, Figure 16C is depicted with four light sources 20. However, any number of light sources 20 can exist in various configurations and combinations thereof of light sources 20-1 and 20-2 in Figures 16A and 16B.

[0074]

[0113] Figure 16D is a cross-sectional view of the CGM accessory 76 along the cutting line 16D-16D in Figure 16C. In certain embodiments, the CGM accessory 76 can embody a double-sided flexible component such as a double-sided flexible printed circuit board. Thus, the connector 85 is located on the upper surface 76 of the CGM accessory 76. T The light source 20 may be provided above or accessible from there, on the bottom 76 opposite the CGM accessory 76. B It may be provided on or inside. Thus, the connector 85 is accessible from the outside, while the light source 20 may be positioned to provide FBR-adjusted light to the skin below. In certain embodiments, the top surface 76 T and bottom 76 B One or both of these may include a thermally conductive coating or film, such as copper, which can act as a thermal spreader, dissipating heat from the light source towards the surrounding air or the skin below.

[0075]

[0114] Figure 17A is an exploded top perspective view of assembly 86, which provides the ability to retrofit a conventional CGM with FBR-adjustable optical capability. As shown, a light delivery structure holder 88, which is a separate structure from the CGM, may be positioned along the lateral periphery of the sensor holder 60. In certain embodiments, the light delivery structure holder 88 can be attached to the sensor holder 60 after the sensor holder 60 has been positioned on the host's skin by mechanical connections. The mechanical connections may include snap fasteners, press fasteners, spring clips, or other suitable mechanical connections for securing the light delivery structure holder 88 in place. A removable insertion guide 90 may be provided on a portion of the light delivery structure holder 88. The insertion guide 90 may include channels 92 that function as guides for inserting the light delivery structure as described above (e.g., 26 in Figure 4 or 52 in Figures 10A-10B). The insertion path 94 defined by the channels 92 is indicated by dashed arrows superimposed in Figure 17A. As shown in the figure, the insertion path 94 extends through the opening 96 of the insertion guide 90 and through the corresponding opening 98 of the optical delivery structure holder 88. In certain embodiments, the relative sizes of the openings 98 can form stoppers to control the depth of insertion of the exemplary optical delivery structure along the insertion path 94. After insertion of the optical delivery structure, the insertion guide 90 can be removed from the rest of the assembly 86.

[0076]

[0115] Figure 17B is a bottom perspective view of the assembly 86 of Figure 17A after insertion of the optical delivery structure 26 and removal of the insertion guide 90. As shown, the sensor probe 32 can be incorporated into the sensor holder 60. In this regard, the sensor probe 32 can first be inserted into the host skin. Then, the optical delivery structure holder 88 can be attached to the sensor holder 60, and the optical delivery structure 26 can be inserted by the insertion guide 90 of Figure 17A. Thus, as shown, the optical delivery structure 26 can be provided at a different angle from the sensor probe 32. In certain embodiments, such arrangement may allow the distal end 26' of the optical delivery structure 26 to be precisely positioned near or adjacent to the activity sensing region 36 of the sensor probe 32. For example, the distal end 26' of the optical delivery structure 26 may be positioned to point toward the activity sensing region 36 at a distance of 1 mm or less, or 0.75 mm or less, or 0.5 mm or less from the activity sensing region 36.

[0077]

[0116] Figure 18 is an exploded perspective view of a sensing device 100 having a microneedle array 102 for sensing and one or more light sources 20 for providing FBR-modulating light capability. In certain embodiments, the sensing device 100 is a continuous glucose monitor (CGM) having a microneedle array 102 that forms a probe for monitoring blood glucose levels in the skin 18. The sensing device 100 may include electrodes 104, such as silver / silver chloride electrodes provided within a silicon frame 106. A hydrogel material 108 may be provided between the electrodes 104 and the frame 106 and the microneedle array 102. The microneedle array 102 may form part of a microneedle tip 110. In certain embodiments, one or more light sources 20 may be provided within the sensing device, such as being incorporated into the microneedle tip 110, to provide FBR-modulating light on or near the portion of skin 18 into which the microneedle array 102 is inserted.

[0078]

[0117] Figure 19 shows a luminescent bandage 112 having FBR adjustment capability according to the principles of the present disclosure. The luminescent bandage 112 may include a body or housing 114 to which one or more strap hooks 116 are attached for receiving a strap 118 for supporting the bandage 112. One or more types of light sources 20-1, 20-2 may be dispersed around a region of the surface 114' of the housing 114 and may be interconnected by an electrical connector 120. The light sources 20-1, 20-2 may include LEDs, lasers, or other types of light sources described above. In certain embodiments, one or more light sources 20-1 may be configured to emit light of different wavelengths than one or more light sources 20-2. For example, light source 20-1 may be configured to emit blue or near-ultraviolet light, while light source 20-2 may be configured to emit red or near-infrared light. In yet another example, one or more light sources 20-1, 20-2 may be light sources of the same type configured to emit light of the same or similar wavelengths. In yet another embodiment, the light sources 20-1 and 20-2 may be different types of light sources, such as an LED for light source 20-1 and a laser for light source 20-2. As a particular example, the laser may include a vertical-cavity surface-emitting laser (VCSEL) that emits light in the wavelength range of 600 to 800 nm with a nominal output between about 2 milliwatts and about 100 milliwatts. The electrical connector 120 may include a flexible flat wire connector or trace formed on the housing 114. In a particular embodiment, the electrical connector 120 may connect to a control module 121 incorporated within the housing 114. The control module 121 may also include a central power supply along with other control circuit elements. The housing 114 may include molded silicon material bonded to a flexible printed circuit board, and if present, the power supply may include a flexible lithium polymer battery.

[0079]

[0118] The luminescent bandage 112 in Figure 19 can be used to provide FBR-modulating light to the tissue surrounding an inserted biosensor on the surface of the host skin and / or beneath the skin. In this way, the luminescent bandage 112 can embody a light delivery device or a plurality of devices capable of delivering light having desired FBR-modulating properties as described above (e.g., wavelength characteristics, irradiance flux density, duration, pulsed or unpulsed, coherence, etc.). In certain embodiments, the luminescent bandage 112 may further include an integrated biosensor, but in other applications, the luminescent bandage 112 is a separate structure from a conventional biosensor. In embodiments with a biosensor, the control module 121 may further include a communication module with a telemetry / transmission portal for transmitting sensed information (e.g., blood glucose concentration) to a display. Such a display may further be integrated into the housing, or the display may be provided by an external device. The luminescent bandage 112 may also include an adhesive layer to facilitate adhesion to the underlying skin. Although the term "bandage" is used in the context of the luminescent bandage 112, the principle described above for Figure 19 may also be applicable to other types of wearable luminescent devices such as sleeves, cuffs, or bands, and luminescent covers such as blankets or pads.

[0080]

[0119] In various embodiments, the principles described above for percutaneous foreign bodies can also be applied to subcutaneous or implanted devices to provide FBR regulating capabilities. Such devices may include cardiac implants (such as pacemakers, implantable cardiac monitors, and implantable cardioverter-defibrillators), intraocular implants, cochlear implants, artificial joints (such as knee, hip, shoulder, and elbow), cosmetic implants (such as breast implants, calf implants, and buttock implants), drug delivery devices, contraceptive implants, and vascular stents. Implantable devices perform a variety of functions in the medical field, from vascular stents to electrical stimulation devices that regulate heart rhythm or block spurious signals in the brain, and orthopedic devices that mechanically reinforce the spine or restore range of motion in the hip, shoulder, elbow, and knee. Implantable devices are also used as controlled drug delivery systems. By applying the principles of this disclosure to implantable devices, FBR can be regulated with light to reduce infection and / or mitigate the effects of collagen matrix formation on device function. Embodiments of implantable devices disclosed herein may include an energy storage device and various electronic devices for powering and controlling the operation of one or more associated light sources.

[0081]

[0120] Cardiac implants may include, for example, pacemakers and implantable cardiac defibrillators. Fasting bone regeneration (FBR) can degrade the long-term performance of cardiac implants due to years of surgery, and infection during implantation can increase not only costs but also the risk of mortality and morbidity. In this regard, aspects of the present disclosure provide cardiac implant devices that include light-based FBR adjustment capability.

[0082]

[0121] Figure 20A schematically shows a pacemaker 122 which may include light-based FBR adjustment capability according to this disclosure. The pacemaker 122 may comprise a pulse generator 124 and pulse leads 126 arranged to deliver electrical pulses from the pulse generator 124 to various locations 126a-c in the patient's heart 128. The pulse generator 124 typically comprises a housing 130 having a cardiac sensor 132 located within the housing 130. The pacemaker 122 is typically a small device placed under the skin of the chest to help control the user's heart rate. It is often used in patients with irregular heartbeats (arrhythmias), particularly slow heartbeats. The pacemaker 122 can be surgically implanted in the user's chest. Exemplary embodiments of the pacemaker 122 include a single-chamber pacemaker that delivers electrical impulses to the right ventricle of the heart 128, a double-chamber pacemaker that delivers electrical impulses to the right ventricle and right atrium of the heart 128 to help control the timing of contractions between the two chambers, and a biventricular pacemaker that stimulates the inferior ventricles (i.e., the right and left ventricles) of the heart 128 to make the heart 128 beat more efficiently. During use, the fibrous capsule associated with FBR can surround one or more portions of the pulse lead 126, raising the excitation threshold, thereby requiring more energy from the energy storage device or even preventing the treatment from fully reaching the target tissue. Therefore, prevention, minimization, and / or regulation of FBR can extend the service life of the pacemaker 122 and / or reduce complications associated with initial infection and / or inflammation. In this regard, the housing 130 may further include one or more pulse leads 126 and one or more light sources 134 that can be optically coupled to deliver light along the outside of the housing 130. For example, the pulse leads 126 may be at least partially wrapped in a light guide material for propagating FBR tuning light from the light sources 134 along the portion of the pulse lead 126. Furthermore, the housing 130 may be wrapped in a light guide material for delivering FBR tuning light to the outside of the housing 130.As in other embodiments, the light source 134 can provide multiple wavelength capabilities, including longer wavelengths such as red and / or near-infrared, as well as shorter wavelengths such as blue and / or near-ultraviolet, to promote healing in the early stages of the FBR array and reduce rejection, thereby mitigating the formation of fibrous tissue that might otherwise encapsulate part of the pacemaker 122. The light source 134 may be electrically driven by the same power supply as the rest of the pacemaker 122, or the light source 134 may include a separate power supply within the housing 130.

[0083]

[0122] Figure 20B is a schematic diagram of a portion of the housing 130 shown in Figure 20A. Figure 20A shows the arrangement of the light source 134. As shown, the light source 134 (e.g., an LED) may be provided on the support structure 136 of the housing 130. A light delivery structure 138, such as a light guide material layer or coating, may provide a encapsulation layer along the outside of the housing 130. As shown, the light source 134 can emit light into the light delivery structure 138, where the light propagates along the outer surface of the housing 130 and can adjust the FBR. In certain embodiments, the light delivery structure 138 may include a wavelength conversion material to convert at least a portion of the light from the light source 134 to different wavelengths.

[0084]

[0123] Figure 20C is a schematic diagram of a portion of the surface of the housing 130 in Figure 20A. Figure 20A shows another configuration of the light source 134. In certain embodiments, the light source 134 may be located in a recess within the surface 130' of the housing 130, and the light delivery structure 140 (e.g., a light pipe, fiber, diffuser, one or more lenses, a digital light processor, an index matching function, etc.) may be located where light emitted from the light source 134 can enter the light delivery structure 140 and deliver FBR regulating light to other parts of the pacemaker 122, such as along the pulse lead 126. The light delivery structure 140 in Figure 20C can be used in combination with the light delivery structure 138 in Figure 20B. In certain embodiments, the light delivery structure 140 may include a structure similar to those previously described for the light delivery structures 26, 34, 42, and 46 in the previous figures.

[0085]

[0124] Figure 21 is a schematic diagram 142 of an implantable cardioverter-defibrillator (ICD) 144 implanted in patient 146, the ICD 144 including FBR adjustment capability according to this disclosure. The ICD 144 may include a housing 148 and electrodes 150. The ICD 144 may include a light source 152 similar to the light source 134 in Figures 20A–20C. The light source 152 may be located on or within the housing 148. Alternatively, the light source 152 may be located on the electrodes 150, or on both the housing 148 and the electrodes 150. The light source 152 may be located with one or more of the light delivery structures 138, 140, as shown in Figure 20B or 20C. The ICD 144 is typically a small (usually battery-powered) device placed in the patient's chest to monitor heart rhythm and detect irregular heartbeats (arrhythmias). An ICD-144 can alleviate abnormal heart rhythms by delivering electrical pulses or shocks through one or more wires connected to the user's heart. Patients use the ICD to control dangerously fast heartbeats (ventricular tachycardia) or uncontrolled heartbeats (ventricular fibrillation) that prevent the heart from supplying enough blood to the rest of the body. The ICD-144 is surgically placed under the skin of the patient, usually below the left clavicle, and one or more flexible insulated wires (leads) may extend from the ICD-144 through a vein to the heart. The ICD-144 constantly monitors for abnormal heart rhythms and attempts to correct them immediately. This is especially useful in cases of cardiac arrest where the heart has stopped beating. The ICD-144 delivers electrical pulses to regulate the heart rate. The ICD can be programmed to address mild irregularities in the heart rate with low-energy pacing and more serious heart rhythm problems with high-energy shocks. Mechanical tissue damage during surgical insertion (acute trauma), as well as prolonged contact between the microelectrode and electrically excited tissue, and micro-movements associated with electrode fixation (chronic injury), induce activation of cells involved in FBR. Therefore, it is advantageous to regulate FBR with a light source 152 using the techniques described herein. The light source 152 may be electrically driven by the same power supply as the rest of the ICD 144, or the light source 152 may contain a separate power supply within the housing 148.

[0086]

[0125] Figure 22 is a schematic diagram 154 of an implantable cardiac monitor (ICM) 156 implanted in patient 158, the ICM 156 including FBR adjustment capability according to this disclosure. The ICM 156 may include a light source 160 similar to the light source 134 in Figures 20A–20C. The light source 160 may be electrically driven by the same power supply as the rest of the ICM 156, or the light source 160 may include a separate power supply within the ICM 156. An ICM is typically a small electrophysiological (EP) device used to monitor the electrical activity of a patient's heart over extended periods to detect arrhythmias. An ICM can eliminate the need for bulky external Holter monitors that use wire leads attached to the patient. The ICM 156 is inserted under the skin of patient 158 ​​and can continuously monitor the patient's electrocardiogram and perform real-time analysis of heart rhythm over extended periods, such as up to 36 months. However, a typical ICM may eventually fail, and often at least part of the cause of its failure can be the body's innate FBR. By including the light source 160 and various corresponding light delivery structures according to this disclosure, the FBR-modulating light can extend the operating life of the ICM.

[0087]

[0126] Figure 23 is a schematic diagram of a cochlear implant 162 in a patient 164, the cochlear implant 162 including FBR adjustment capability according to this disclosure. The cochlear implant 162 may comprise an electrode array 166 positioned along the cochlea, a receiver / stimulator 168, a transmitter 170, a speech processor 172, and a microphone 174. The cochlear implant 162 may further comprise a light source 176 similar to the light source 134 in Figures 20A-20C. The cochlear implant 162 is typically a small electronic device that electrically stimulates the cochlear nerve for hearing. Those skilled in the art are familiar with a wide variety of cochlear implants, and the devices and methods according to the present invention may use any of such cochlear implants. The cochlear implant 162 may have external components including a microphone 174 for receiving sound. In response, the cochlear implant 162 processes the sound and transmits it to internal components via implanted wires 177 to an implanted electrode array 166. Active fast-burning radiofrequency (FBR) to the implanted portion of the cochlear implant 162 (e.g., wires 177 and electrode array 166) can be expected to lead to device degradation and / or failure. The severity of the FBR may be negatively correlated with post-implantation performance and maintenance of hearing. Since the cochlear implant 162 is intended to be a long-term implant, even slowly progressing FBR can cause performance degradation or other problems. Therefore, it is advantageous to minimize or prevent the onset of FBR using the techniques described herein. In certain embodiments, the light source 176 can be incorporated into one or more external components, such as a receiver / stimulator 168, and may be provided with an optical delivery structure, such as optical fiber light with an optional diffuser at the end, to propagate light along the injected portion and modulate the FBR. In certain embodiments, the energy storage device of the cochlear implant 162 can also be used to power the light source 176. Because replacing cochlear implants carries inherent risks, adjusting FBR to improve long-term function has merits.

[0088]

[0127] The principles of this disclosure may also be applicable to providing FBR-modulating light for complete and / or partial joint replacement implants, as well as cosmetic implants, drug delivery systems, and intrauterine devices. Total junction replacement (TJR) and partial joint replacement may be used to treat end-stage arthritis that would otherwise be impractical. Those skilled in the art are familiar with a wide variety of artificial joints, and the devices and methods according to the present invention can be used with any such artificial joint. TJRs can be used in large joints such as the hip, knee, shoulder, and / or elbow. Various bearing surfaces can be used, but the most common are metal-on-polyethylene (MOP), ceramic-on-ceramic (COC), or metal-on-metal (MOM). The biomaterial used must be sufficiently resistant to support the weight-bearing load of the joint while minimizing adverse effects on surrounding tissues and avoiding infection. Most modern materials are well acceptable as long as they maintain their bulk state, achieve mechanical stability in the bone, and do not allow microorganisms to colonize and cause chronic infection, although excessive wear can generate wear particles or ionic complexes. This can cause acute and chronic inflammation, potentially leading to osteolysis around the prosthesis, loss of bone support, subsequent loosening, and implant failure. Furthermore, the initial local inflammatory response after surgery can lead to further complications. Thus, while orthopedic implants used in joint replacement surgery are effective in relieving pain and restoring function, their life expectancy is limited due to the possibility of wear and foreign body reactions to wear byproducts (including particles). In this regard, aspects of this disclosure may be applicable to various joint replacement structures implanted in the hip, knee, shoulder, and / or elbow, as well as other implantable devices that may induce FBR, such as cosmetic implants, drug delivery systems, and intrauterine devices. Such structures may include a light source and corresponding power source integrated within the joint replacement structure.

[0089]

[0128] Figure 24 is a schematic diagram of a prosthesis 178 including FBR adjustment capability according to the present disclosure. The prosthesis 178 may comprise a first prosthesis 180 (attached to the femur) and a second prosthesis 182 (attached to the tibia). The prosthesis 178, comprising one or more of the first prosthesis 180 and the second prosthesis 182, may further comprise one or more light sources 184 similar to the light source 134 in Figures 20A-20C for providing FBR adjustment light. Although Figure 24 is provided in the context of a prosthesis, the disclosed principle may be applicable to other implants, including cosmetic implants, drug delivery systems, and intrauterine devices, which may include one or more FBR adjustment light sources in a similar manner.

[0090]

[0129] According to the principles of this disclosure, one or more light sources can be provided to modulate the FBR associated with transcutaneous and / or subcutaneous devices. One or more FBR modulating light sources can be incorporated as a separate structure from the device or as a structure integrated with the device. Power supplies and / or control circuits for electrically activating and controlling such light sources can be integrated with the device's existing power supplies and control circuits. In other embodiments, power supplies and / or control circuits for electrically activating and controlling the light sources may be separate from those that power and control other functions of the device. In yet another embodiment where the device does not require power supplies and / or control circuits (e.g., joint replacement, cosmetic implants), various elements of electronic equipment can be incorporated integrally and / or remotely to operate the light sources. In certain embodiments, the power supply for the implant may include a rechargeable battery that can be recharged inductively, optically using a photocell, ultrasonically, and / or electromagnetically. Additional power supplies for FBR modulating light sources in implantable devices may include energy generated and collected from potential sources surrounding the implant, for example, using a biofuel cell that utilizes blood glucose and oxygen abundant in the blood to generate energy. Electricity may also be collected from body heat and / or bodily movements such as breathing and exercise, using thermoelectric and / or piezoelectric generators.

[0091]

[0130] Figure 25 is a schematic diagram of a control scheme for device 186, including FBR adjustment capability according to the present disclosure. Device 186 can represent a transcutaneous device such as a CGM or other biosensor, a subcutaneous device fully implanted under the host's skin, or a topical device such as a bandage, blanket, or other cover. As shown, device 186 may include a power supply 188 and a control module 190 configured to provide power and control to both the medical device 192 and the light source 194. The power supply 188 may include a battery and / or rechargeable battery, among other integrated power supplies. The control module 190 may include active electronics such as a microprocessor and / or microcontroller, which actively control and / or determine dosing parameters such as duration, interval, and wavelength provided by the light source 194, and provide power and other operating functions to the medical device 192. In other embodiments, the control module 190 may embody passive electronics that power only the light source 194. In such embodiments, dosing parameters may be controlled by external electronics, including those operating by radio frequency communication. As an example, device 186 can embody a CGM, and therefore medical device 192 can represent a sensor probe for blood glucose monitoring. In such an embodiment, the light source 194 can also be operated using the same control module 190 and power supply 188 used to operate the blood glucose monitoring function of device 186. In another example, device 186 can embody a pacemaker, in which medical device 192 represents a cardiac sensor and pulse lead. Therefore, the light source 194 can also be operated using the same control module 190 and power supply 188 that operate the sensing and pacing functions of the pacemaker. In yet another example, where device 186 represents a structure that does not require an integrated power supply and control module, such as an orthopedic implant, catheter, and / or chemotherapy port, the power supply 188 and control module 190 may be incorporated solely to control the operation of the light source 194.

[0092]

[0131] Figure 26 is a schematic diagram of the control scheme for device 196, similar to device 186 in Figure 25, except that the operation of the light source 194 is provided separately from the other functions of device 196. In this regard, medical device 192 may be powered and controlled by a first power supply 188-1 and a first control module 190-1, while light source 194 may be powered and controlled by a second power supply 188-2 and a second control module 190-2. In this regard, FBR-adjusted light may be delivered by dedicated electronic equipment separate from the other functions of device 196.

[0093]

[0132] Figure 27 is a schematic diagram of a control scheme for device 198 similar to that of device 186 in Figure 25, except that at least a portion of the power supply 188 is provided remotely from device 198. In this regard, power supply 188 can embody an inductively coupled power supply for providing wireless power transmission to control module 190, medical device 192, and light source 194. Such a configuration may be useful in applications where device 198 may not be easily accessible, such as one or more of the aforementioned subcutaneous devices.

[0094]

[0133] Figure 28 is a schematic diagram of a control scheme for device 200, similar to device 196 in Figure 26, except that the operation of the light source 194 is provided separately from other functions of device 200. In this regard, a first power supply 188-1 and a first control module 190-1 can be incorporated into device 200 to control functions related to medical device 192, while a second power supply 188-2 is provided remotely, as described with respect to Figure 27. In such embodiments, a second control module 190-2 for controlling the administration parameters of the light source 194 can be incorporated into device 200.

[0095]

[0134] Further advantages can be obtained by combining any of the embodiments described herein, and / or various distinct embodiments and features described herein. Any of the various embodiments disclosed herein can be combined with one or more other disclosed embodiments unless otherwise indicated herein.

[0096]

[0135] Those skilled in the art will recognize improvements and modifications to preferred embodiments of this disclosure. All such improvements and modifications are deemed to fall within the scope of the concepts disclosed herein and the following claims.

Claims

1. A foreign body configured to be at least partially inserted into a region of the host's subcutaneous tissue, the foreign body comprising a sensor probe, the sensor probe having an activity sensing region adjacent to the distal end of the sensor probe, A light source capable of emitting light of one or more peak wavelengths for irradiating one or more portions of the subcutaneous tissue region in order to regulate the foreign body reaction within that region of the subcutaneous tissue, wherein the one or more peak wavelengths include a first wavelength in the range of 400 nm to 450 nm. A light delivery structure optically coupled to the light source, wherein the distal end of the light delivery structure is separated from the activity sensing region by a portion of the subcutaneous tissue region, and the light delivery structure is configured to be inserted through the host skin such that the distal end includes a light scattering region integral with the light delivery structure, and the light scattering region is offset from the activity sensing region, A device that includes this.

2. The device according to claim 1, wherein the light source is provided outside the region of the subcutaneous tissue in order to irradiate the light through the portion of the host's skin that is aligned with the region of the subcutaneous tissue.

3. The device according to claim 1, wherein at least a portion of the light delivery structure is located within the region of the subcutaneous tissue and can irradiate one or more portions of the region of the subcutaneous tissue.

4. The device according to claim 3, further comprising an additional light source provided for irradiating light through the portion of the host's skin aligned with the region of subcutaneous tissue.

5. The device according to claim 1, wherein one or more of the peak wavelengths of the light include a second wavelength in the range of 315 nanometers (nm) to 400 nm.

6. The device according to claim 1, wherein one or more of the peak wavelengths of the light include a second wavelength in the range of 400 nanometers (nm) to 1600 nm.

7. The device according to claim 1, wherein one or more of the peak wavelengths of the light include a second wavelength in the range of 600 nanometers (nm) to 1600 nm.

8. The device according to claim 7, wherein the second wavelength is in the range of 630 nm to 670 nm.

9. The device according to claim 1, wherein the device includes a continuous blood glucose monitor.

10. The device according to claim 9, wherein at least a portion of the light delivery structure is located within the region of the subcutaneous tissue such that the distal end of the light delivery structure is spaced 1 millimeter (mm) or less away from the activity sensing region in the region of the subcutaneous tissue, and can irradiate one or more portions of the region of the subcutaneous tissue.

11. The device according to claim 1, wherein the light scattering region includes a coating on the light delivery structure.

12. The device according to claim 1, wherein the light scattering region is formed inside the light delivery structure.

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