Opto-electronic hardware configuration for implantable chemical sensors

Abstract

Embodiments herein relate to implantable chemical sensors. In embodiments, an implantable optical chemical sensor includes a circuit board, at least one optical emitter, and at least one optical detector. The optical emitter can be disposed on the circuit board with the optical detector. The optical chemical sensor can also include a base plate and an aperture plate defining at least one aperture, and the aperture plate disposed above the base plate. The aperture plate can include a vertical face and a beveled face disposed on a peripheral edge of the aperture plate. A feedthrough flange can define a window, wherein the vertical face of the aperture plate fits into the window. The optical emitter can emit light through the base plate and into the aperture plate, which is then redirected by the beveled face into the aperture. Other embodiments are included herein.

Description

[0001] This application was filed as a PCT international patent application on September 13, 2024, in the name of Cardiac Pacemakers, Inc. (a U.S. national company, designating applicants in all countries) and Michael J. Kane (a U.S. citizen), Yingbo Li (a U.S. citizen), and James Michael English (an Irish citizen) (designating inventors in all countries). This application claims priority to U.S. Provisional Application No. 63 / 538,366, filed September 14, 2023, and U.S. Application No. 18 / 882,966, filed September 12, 2024, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] The embodiments described herein relate to implantable chemical sensors. Background Technology

[0003] Data on physiological analytes are highly relevant to the diagnosis and treatment of many conditions and disease states. As an example, potassium ion concentration can affect a patient's heart rhythm. Therefore, healthcare professionals frequently assess physiological potassium ion concentrations when diagnosing heart rhythm problems. However, measuring the physiological concentration of analytes such as potassium usually requires drawing blood from the patient. Blood draws are typically performed in medical clinics or hospitals, and therefore often require the patient to travel to the facility in person. Thus, although physiological analyte concentrations are important, they may only be measured occasionally. Summary of the Invention

[0004] Embodiments herein relate to implantable chemical sensors. In a first aspect, an implantable photochemical sensor may be included, having a circuit board, at least one optical emitter, and at least one optical detector. The at least one optical emitter may be disposed on the circuit board together with the at least one optical detector. The photochemical sensor may further include a base plate and a well plate defining at least one well. The well plate may include a vertical surface and a bevel, wherein the bevel and the vertical surface may be disposed on at least one peripheral edge of the well plate. The well plate may be disposed on the base plate. A feedthrough flange may be included, defining a window. The vertical surface of the well plate may fit into the window. The at least one optical emitter may be configured to emit light through the base plate and into the well plate, and then the light may be redirected by the bevel of the well plate into the at least one well.

[0005] In a second aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one hole may have a polished inner surface.

[0006] In a third aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing or subsequent aspects, the inclined plane may be set at an angle of 20 to 70 degrees relative to the surface of the vertical plane.

[0007] In the fourth aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing or subsequent aspects, the orifice plate may define at least two orifices.

[0008] In a fifth aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the aspects, the implantable chemical sensor may also include a sensor element, wherein the sensor element may be configured to fit into at least one pore.

[0009] In the sixth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable chemical sensor may also include a coating, wherein the coating may be disposed on an inclined surface and configured to reflect light from the interior of the inclined surface.

[0010] In the seventh aspect, in addition to one or more of the foregoing or subsequent aspects, or as an alternative to some aspects, the base plate comprises low-refractive-index glass.

[0011] In the eighth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one optical detector may be a photodiode.

[0012] In the ninth aspect, in addition to one or more of the foregoing or subsequent aspects, or as an alternative to some of the aspects, the implantable photochemical sensor may also include a top housing that may define a sensor window. A feedthrough flange may fit into the sensor window.

[0013] In the tenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing aspects, the top surface of the feedthrough flange is flush with the top surface of the top housing.

[0014] In the eleventh aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable photochemical sensor may also include a bottom housing, wherein the bottom housing engages with the top housing along its lateral edge.

[0015] In a twelfth aspect, an implantable photochemical sensor may be included, comprising a circuit board, at least one optical emitter, at least one optical detector, a base plate, and an orifice plate. The at least one optical emitter may be disposed on the circuit board. The orifice plate may define at least one aperture. The orifice plate may be disposed on the base plate. The photochemical sensor may include at least one prism, wherein the at least one prism may be arranged to receive light from the at least one optical emitter and guide it into the orifice plate. The photochemical sensor may include at least one optical detector, wherein the at least one optical detector may be disposed on the circuit board. The photochemical sensor may also include a feedthrough flange defining a window.

[0016] In the thirteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one hole may have a polished inner surface.

[0017] In the fourteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the orifice plate may define at least two orifices.

[0018] In the fifteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the photochemical sensor may also include a prism holder, wherein the prism holder may be configured to hold the prism and engage it over at least one optical emitter, thereby aligning the optical emitter.

[0019] In the sixteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the photochemical sensor may also include a sensor element, wherein the sensor element may be configured to fit into at least one aperture.

[0020] In the seventeenth aspect, in addition to one or more of the foregoing or subsequent aspects, or as an alternative to some aspects, the substrate comprises low-refractive-index glass.

[0021] In the eighteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one optical detector may be a photodiode.

[0022] In the nineteenth aspect, in addition to one or more of the foregoing or subsequent aspects, or as an alternative to some aspects, the implantable photochemical sensor may also include a top housing defining a sensor window, wherein a feedthrough flange engages with the sensor window.

[0023] In the twentieth aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing aspects, the top surface of the feedthrough flange is flush with the top surface of the top housing.

[0024] In the twenty-first aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the photochemical sensor may also include a bottom housing, wherein the bottom housing is engaged with the top housing along its lateral edge.

[0025] In a twenty-second aspect, an implantable photochemical sensor may be included, comprising a circuit board, at least one optical emitter, at least one optical detector, and an orifice plate. The at least one optical emitter and at least one optical detector may be disposed on the circuit board. The implantable photochemical sensor may include at least one prism. The orifice plate may define at least one aperture. The orifice plate may also define at least one prism alignment notch, wherein the at least one prism alignment notch may be configured to receive at least a portion of or connected to the at least one prism, thereby aligning the prism with the orifice plate. The implantable photochemical sensor may also include a feedthrough flange defining a window. The at least one prism may be arranged to receive light from the at least one optical emitter and guide it into the orifice plate.

[0026] In aspect twenty-three, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one hole may have a polished inner surface.

[0027] In aspect 24, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the orifice plate may define at least two orifices.

[0028] In the twenty-fifth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable photochemical sensor may also include a prism holder, wherein the prism holder may be configured to hold the prism and engage it over at least one optical emitter to align the optical emitter.

[0029] In the twenty-sixth aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable photochemical sensor may also include a sensor element, wherein the sensor element may be configured to fit into at least one pore.

[0030] In the twenty-seventh aspect, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable photochemical sensor may also include a substrate, wherein a perforated plate may be disposed above the substrate.

[0031] In aspect 28, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing or subsequent aspects, the substrate comprises low-refractive-index glass.

[0032] In aspect 29, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, at least one optical detector may be a photodiode.

[0033] In the thirtieth aspect, in addition to one or more of the foregoing or subsequent aspects, or as an alternative to some of the aspects, the implantable photochemical sensor may also include a top housing defining a sensor window. A feedthrough flange may fit within the sensor window.

[0034] In the thirty-first aspect, in addition to one or more of the foregoing or subsequent aspects, or in some alternatives to the foregoing or subsequent aspects, the top surface of the feedthrough flange is flush with the top surface of the top housing.

[0035] In aspect thirty-two, in addition to one or more of the foregoing or subsequent aspects, or in an alternative to some aspects, the implantable photochemical sensor may also include a bottom housing, wherein the bottom housing engages with the top housing along its lateral edge.

[0036] This invention provides an overview of some of the teachings of this application and is not intended to be exclusive or exhaustive. Further details can be found in the detailed description and the appended claims. Other aspects will be apparent to those skilled in the art upon reading and understanding the following detailed description and viewing the accompanying drawings, which form a part thereof, and none of these should be considered limiting. The scope of this document is defined by the appended claims and their legal equivalents. Attached Figure Description

[0037] A more comprehensive understanding can be achieved by referring to the following attached diagrams (Figures), in which:

[0038] Figure 1 This is a schematic diagram of an implantable medical device with a photochemical sensor according to various embodiments of the present document.

[0039] Figure 2 This is an exploded view of a portion of an implantable medical device according to various embodiments herein.

[0040] Figure 3 This is a schematic front view of a portion of an implantable medical device according to various embodiments herein.

[0041] Figure 4 This is a schematic front view of a portion of an implantable medical device according to various embodiments herein.

[0042] Figure 5 This is a schematic diagram of the substrate and orifice plate of a photochemical sensor according to various embodiments herein.

[0043] Figure 6This is a schematic cross-sectional view of the substrate and orifice plate of a photochemical sensor according to various embodiments herein.

[0044] Figure 7 This is a schematic plan view of an implantable photochemical sensor according to various embodiments herein.

[0045] Figure 8 This is a schematic side view of an implantable photochemical sensor according to various embodiments herein.

[0046] Figure 9 This is a schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein.

[0047] Figure 10 This is a schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein.

[0048] Figure 11 This is a schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein.

[0049] Figure 12 This is a schematic plan view of an implantable photochemical sensor according to various embodiments herein.

[0050] Figure 13 This is a schematic perspective view of a portion of an implantable photochemical sensor according to various embodiments herein.

[0051] Figure 14 This is a schematic front view of a portion of an implantable photochemical sensor element according to various embodiments herein.

[0052] Figure 15 This is a perspective view of a portion of an implantable chemical sensor element according to various embodiments herein.

[0053] While the embodiments are readily adaptable to various modifications and alternatives, their details have been shown by way of example and accompanying drawings and will be described in detail. However, it should be understood that the scope of this document is not limited to the specific aspects described. Rather, it is intended to cover modifications, equivalents, and alternatives that fall within the spirit and scope of this document. Detailed Implementation

[0054] Data on analytes are highly relevant to the diagnosis, treatment, and / or monitoring of many conditions and disease states. However, in vitro assays used to determine analyte values ​​have significant limitations. In contrast, implantable chemosensors can be used to collect analyte data while patients are away from healthcare facilities, without drawing blood or other fluids from the patient.

[0055] However, implantable chemical sensors present various challenges. For example, space within implantable devices is extremely limited. Therefore, one design challenge for implantable chemical sensors is to keep them as compact as possible. Additionally, there is a need to be able to mass-produce implantable chemical sensors while ensuring proper alignment of components.

[0056] The embodiments described herein relate to implantable medical devices and chemical sensors featuring a highly compact, space-efficient design and characteristics that facilitate precise alignment of components during assembly, allowing for the efficient manufacture of high-precision chemical sensor devices. The embodiments described herein can utilize planar construction designs, including circuit boards and surface-mount components thereon, which can easily and precisely mate with the various optical components described herein. As an example, the implantable photochemical sensor described herein may include a circuit board, at least two optical emitters disposed on the circuit board, at least one optical detector disposed on the circuit board, a base plate, and an orifice plate defining at least one sensor aperture. The base plate may be disposed below the orifice plate and may form the bottom of the sensor aperture. The orifice plate may also include a vertical surface and a bevel disposed on at least one peripheral edge of the orifice plate. A feedthrough flange may define a window, and the vertical surface of the orifice plate may mate into the window. At least two optical emitters may be configured to emit light into the orifice plate (directly or via the base plate), and the light may then be redirected by the bevel of the orifice plate into at least one sensor aperture.

[0057] Now for reference Figure 1 This diagram illustrates an implantable medical device 100 with a photochemical sensor 106 according to various embodiments herein. In this example, the implantable medical device 100 includes a battery module 102. The battery module 102 may include an electrochemical battery disposed therein for providing power to the implantable medical device 100. In various embodiments herein, the electrochemical battery may be a lithium-manganese dioxide (Li anode / MnO2 cathode) primary cell. However, other primary lithium battery chemistry is also contemplated herein. Other primary battery chemistry may include, but is not limited to, CFx, SVO, mixed CFx / MnO2, mixed CFx / SVO, and similar substances. However, in some embodiments, a rechargeable battery may be used. Charging techniques herein may include RF charging, inductive charging, and similar techniques. The implantable medical device 100 also includes a sensor module 104. The sensor module 104 may include the photochemical sensor 106, and optionally, other sensors and electronics.

[0058] Now for reference Figure 2This image shows an exploded view of portions of an implantable medical device 100 according to various embodiments herein. As previously described, the implantable medical device 100 includes a battery module 102 and a sensor module 104. The sensor module 104 includes a top housing 214 and a bottom housing 216. The top housing 214 and the bottom housing 216 may be formed of a biocompatible conductive material, such as titanium or a titanium alloy. The bottom housing 216 may be joined to the top housing 214 along its lateral edges. In various embodiments, the top housing 214 and the bottom housing 216 may be attached together along their intersecting edges (such as their lateral edges) (e.g., by welding or using another technique). The top housing 214 and the bottom housing 216 may define a space between them to accommodate various components, including the chemical sensor component described herein.

[0059] The chemical sensor component of the implantable medical device 100 may include a circuit board 202, one or more optical detectors 204, one or more first optical emitters 206, and one or more second optical emitters 207.

[0060] The implantable medical device 100 also includes a base plate 208, a perforated plate 210, and a feedthrough flange 212. In various embodiments, the base plate 208 and / or the perforated plate 210 may be formed of glass, crystal, ceramic, polymer, and similar materials. In various embodiments, the base plate 208 and / or the perforated plate 210 may be formed of low-refractive-index glass, crystal, ceramic, or polymer, such as materials with a refractive index of 1.5 or lower. In some embodiments, the refractive index of the base plate 208 may be different from that of the perforated plate 210 in order to retain light within the perforated plate 210 after it enters the perforated plate 210. The base plate 208 and / or the perforated plate 210 may be formed using various techniques, including machining, molding, or similar techniques.

[0061] Components such as one or more optical detectors 204, one or more first optical emitters 206, and one or more second optical emitters 207 can be mounted on the circuit board 202 as surface-mount hardware components to facilitate a compact configuration. Various options for optical emitters and detectors are described below, but in some embodiments, the first optical detector 204 may be a photodiode, and the one or more optical emitters 206, 207 may be light-emitting diodes.

[0062] In various embodiments, one or more optical emitters 206, 207 may be configured to emit light through the base plate 208 and into the aperture plate 210. In embodiments where the base plate 208 is omitted or does not extend above the optical emitters, the optical emitters may emit light directly into the aperture plate without passing through the base plate 208. In some embodiments, the base plate 208 and the aperture plate 210 may be physically integrated, but in other embodiments they are discrete components.

[0063] The aperture plate 210 may include a vertical surface (described further below) and an inclined surface (described further below). Light can be redirected by the inclined surface of the aperture plate 210 into at least one sensor element aperture defined by the aperture plate 210. Sensor element ( Figure 2 (Not shown, but will be described further below) can be configured to fit into at least one sensor element hole.

[0064] The feedthrough flange 212 can be fitted into the sensor window 218 defined by the top housing 214. In various embodiments, the top surface of the feedthrough flange 212 is flush with the top surface of the top housing 214. In various embodiments, the feedthrough flange 212 can be formed of metal, ceramic, polymer, or similar materials. In some embodiments, the feedthrough flange 212 can be specifically formed of a metal (such as titanium or a titanium alloy) to allow the feedthrough flange 212 to be welded to a suitable location within the sensor window 218 defined by the top housing 214. In various embodiments, the feedthrough flange 212 can have rounded corners to facilitate attachment to the sensor window 218 while minimizing areas of stress concentration.

[0065] Now for reference Figure 3 This diagram illustrates a schematic cross-sectional view of portions of an implantable medical device 100 according to various embodiments herein. As previously described, the implantable medical device 100 includes a top housing 214 and a bottom housing 216. The implantable medical device 100 also includes a circuit board 202. A first optical detector 204 and one or more optical emitters 206, 207 are disposed on the circuit board 202. The implantable photochemical sensor also includes a base plate 208 and an orifice plate 210. The orifice plate 210 includes a first sensor hole 302. The implantable photochemical sensor also includes a feedthrough flange 212. The feedthrough flange 212 fits into the top housing 214.

[0066] Now for reference Figure 4This diagram shows a schematic front view of a portion of an implantable medical device 100 according to various embodiments herein. As previously described, the implantable medical device 100 includes a top housing 214, a circuit board 202, an optical detector 204, and one or more optical emitters 206, 207 disposed on the circuit board 202. The implantable photochemical sensor also includes a base plate 208, an orifice plate 210, and a feedthrough flange 212 that mates with a sensor window of the top housing 214. In various embodiments, the top surface of the feedthrough flange 212 is flush with the top surface of the top housing 214. In some embodiments, the feedthrough flange 212 may include a recessed edge 402 on which an edge of the top housing 214 surrounding the sensor window 218 may be placed. The feedthrough flange 212 may also define an inner cavity 404 into which a portion of the orifice plate 210 (such as a vertical surface) may mate.

[0067] Although Figure 4 Not shown, but in some embodiments, a protective capping layer that is also permeable to the analyte of interest may be disposed on the exterior of the chemical sensor, such as on the feedthrough flange 212, on the sensor element within the sensor aperture, and / or on the exterior of the top housing 214. In some embodiments, the protective capping layer may be formed of a polymer such as polyHEMA (a polymer of hydroxyethyl 2-methacrylate) or another polymer.

[0068] Now for reference Figure 5 This diagram illustrates a substrate 208 and a well plate 210 of a photochemical sensor according to various embodiments herein. The well plate 210 includes a first sensor well 302. In this embodiment, the well plate 210 also includes a second sensor well 502. However, it should be understood that the well plate 210 may have any specific number of sensor wells (1, 2, 3, 4, 5, 6, 8, 10, etc.). As further described below, sensor elements may be placed in the wells, and components of the sensor elements may interact with the analyte of interest to produce a response detectable by the optical means described herein. In some embodiments, a particular well and the sensor element therein may be specific to a particular analyte of interest. In some embodiments, a particular well and the sensor element therein may be specific to more than one analyte of interest (e.g., in the case of a multimodal sensor element). Analytes detected herein may include, but are not limited to, potassium, sodium, calcium, blood urea nitrogen (BUN), creatinine, and the like. In some embodiments, a pH sensor may also be included in an implantable device.

[0069] In various embodiments, the sensor aperture may have a polished inner surface, such as to facilitate the efficient passage of light from within the aperture plate 210 and into the sensor aperture. In some embodiments, the circular edge of the sensor aperture may have a lens effect to focus light onto a sensor element disposed within the sensor aperture. In many embodiments, the sensor aperture may be circular in shape, although other shapes such as elliptical, square, rectangular, polygonal, or polygonal with rounded corners are also considered herein. In some embodiments, the sensor aperture may be semi-circular, having flat sides (straight portions) on those sides adjacent to the optical emitter, such as two opposing flat sides. The sensor aperture may have various sizes, but may be large enough to accommodate a sensing element therein. In some embodiments, the diameter of the sensor aperture may be 0.2 to 3 mm. In some cases, the diameter of the sensor aperture is about 1.5 or 2 mm.

[0070] The orifice plate 210 includes a bevel 504 and a vertical surface 506. In various embodiments, the bevel 504 and the vertical surface 506 are disposed on at least one peripheral edge of the orifice plate 210. In some embodiments, the bevel 504 and the vertical surface 506 are disposed on two opposite peripheral edges of the orifice plate 210. In some embodiments, the bevel 504 is not on either of the two peripheral edges of the orifice plate 210.

[0071] Now for reference Figure 6 This diagram illustrates a schematic cross-sectional view of a base plate 208 and an orifice plate 210 of a photochemical sensor according to various embodiments herein. As previously described, the orifice plate 210 includes a first sensor aperture 302, an inclined surface 504, and a vertical surface 506. The inclined surface 504 may be angled to guide light from the bottom of the orifice plate 210 through the orifice plate 210 and toward the sensor apertures 302 and 502. In various embodiments, the inclined surface 504 may be positioned at an angle θ of 20 to 70 degrees relative to the surface of the vertical surface 506. In various embodiments, the inclined surface 504 may be positioned at an angle θ of 40 to 50 degrees relative to the surface of the vertical surface 506. However, in some embodiments, the vertical surface 506 may be omitted. In some embodiments, the inclined surface 504 may be omitted.

[0072] In various embodiments, a coating (not shown in this view) may be applied to the ramp 504 and configured to facilitate light reflection from the interior of the ramp 504. For example, the coating may be a reflective coating. This coating may be a metallized or silver-plated coating (such as a sputtered coating). In some embodiments, an adhesive (such as an optically clear adhesive) may be used to secure the perforated plate 210 to the base plate 208.

[0073] Now for reference Figure 7This diagram illustrates a schematic plan view of components of an implantable photochemical sensor according to various embodiments herein. As previously described, the chemical sensor includes a circuit board 202, a first optical detector 204, a first optical emitter 206, and a second optical emitter 207. The implantable photochemical sensor also includes a second optical detector 706. The implantable photochemical sensor also includes an orifice plate 210. The orifice plate 210 defines a first sensor aperture 302 and a second sensor aperture 502. The orifice plate 210 also includes a first bevel 504 and a second bevel 704 disposed on a side of the orifice plate 210 opposite to the first bevel 504. Referring now to... Figure 8 This diagram illustrates a schematic side view of components of an implantable photochemical sensor according to various embodiments herein. The implantable photochemical sensor includes a circuit board 202, a second optical emitter 207, a base plate 208, and a perforated plate 210. The perforated plate 210 includes a first sensor aperture 302 and a second sensor aperture 502. The perforated plate 210 also includes a first bevel 504. In some cases, the edge of the perforated plate 210 may not be in contact with the edge of the base plate 208.

[0074] The device described herein can be configured to operate in scattering and / or transmission modes, using either a dual-ended or single-ended light source configuration. Now refer to... Figure 9 A schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein is shown. Figure 9 An example of an optical sensor used in scattering mode. The implantable photochemical sensor includes a circuit board 202, a first optical detector 204, a first optical emitter 206, and a second optical emitter 207. The implantable photochemical sensor also includes a substrate 208 and an orifice plate 210. The orifice plate 210 includes a first bevel 504 and a second bevel 704.

[0075] In this example, the implantable photochemical sensor also includes a mask coating 904. This mask coating 904 can be disposed on the surface of the orifice plate 210, the base plate 208, and / or other components herein. The mask coating 904 can be an opaque material and prevents ambient light from entering such components, and can be formed from a variety of materials. The mask coating 904 can be used to eliminate or reduce unwanted light leakage paths. In some embodiments, the mask coating 904 can include carbon black and / or various pigments or ingredients to make the coating opaque. In some embodiments, the mask coating 904 can be disposed on the top surface of the orifice plate 210, such as adjacent to the sensor aperture 302. In some embodiments, the mask coating can be disposed on a ramp 504. In some embodiments, a reflective material can later be disposed on the ramp 504, such as a metallized or silver-plated reflective coating (such as a sputtered coating).

[0076] The implantable photochemical sensor may also include an optically clear adhesive 906. The optically clear adhesive 906 can be used between various components of the implantable photochemical sensor and can be used to adhere the components together while substantially not attenuating light passing through them. In some embodiments, the optically clear adhesive 906 may be an adhesive whose refractive index is approximately matched to that of the components being joined, such as the perforated plate 210 and / or the base plate 208. The optically clear adhesives described herein may include various acrylic resins, silicones, and similar materials.

[0077] The implantable photochemical sensor also includes a sensor element 902. In various embodiments, the sensor element 902 may be configured to fit into at least one pore. In some embodiments, the sensor element 902 may include an external permeable layer (such as a polyHEMA layer) and sensor chemicals disposed therein, such as on beads serving as a carrier and / or dispersed in a polymer matrix. Details of exemplary sensor elements are provided below in more detail.

[0078] In operation, light emitted from the first optical emitter 206 and the second optical emitter 207 is directed toward the sensor element 902 within the sensor aperture 302. For example, the light may be emitted directly or, in some embodiments, upwards into the aperture plate 210 after passing through the base plate 208 (in some embodiments, such as...). Figures 3 to 4 As shown, the base plate 208 is disposed between the transmitter and the perforated plate 210, while in other embodiments, such as Figure 9 As shown, the base plate 208 is not located between the emitter and the aperture plate 210. Light originating from the optical emitters 206 and 207 can be guided toward the sensor aperture 302 via inclined planes 504 and 704. This light can interact with and scatter the sensor element 902, including passing downwards through the base plate 208 and reaching the optical detector 204 for detection by the photochemical sensor.

[0079] It should be understood that in some embodiments, the positions of the transmitter and detector, as shown herein, can be interchanged. For example, the transmitter (such as a multicolor light source) can be located at... Figure 9 The position of the optical detector 204 is shown, and detectors (such as detectors with different wavelength sensitivities—using filters and the like) can be located as follows: Figure 9 The positions of optical emitters 206 and 207 are shown. In some embodiments, light of different wavelengths may be emitted sequentially by one or more emitters herein, and the amplitudes of the light detected by an optical detector may be compared relative to each other.

[0080] In some embodiments, the chemical sensor can operate in transmission mode. In such embodiments, light can interact with the sensor element and pass through before being received by an optical detector. For example, now referring to... Figure 10 This document illustrates a schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein, showing operation in transmission mode. As previously described, the implantable photochemical sensor includes a circuit board 202, an optical detector 204, an optical emitter 207, and an aperture plate 210 having a first bevel 504 and a second bevel 704. The implantable photochemical sensor also includes a sensor element 902 disposed within a sensor aperture 302 in the aperture plate 210. The implantable photochemical sensor may also optionally include a mask coating 904 and an optically clear adhesive 906. In operation, light is emitted by the optical emitter 207 and enters the aperture plate 210, and then enters the sensor element 902. The light then passes through the sensor element 902 and is subsequently redirected by the second opposing bevel 704 to reach the optical detector 204.

[0081] In some embodiments, light may be reflected from a wall on one side of the aperture plate before returning to the sensor element and / or being received by the photodetector. For example, now referring to Figure 11 This diagram illustrates a schematic cross-sectional view of components of a photochemical sensor according to various embodiments herein. The implantable photochemical sensor includes a circuit board 202, a first optical detector 204, and an optical emitter 207. The implantable photochemical sensor also includes a base plate 208 and an orifice plate 210. The orifice plate 210 includes a bevel 504. The implantable photochemical sensor also includes a sensor element 902. Optionally, the implantable photochemical sensor may also include a mask coating 904 and an optically clear adhesive 906.

[0082] Figure 11 The implantable photochemical sensor also includes a reflective surface 1102, which may have a metallized or silver-plated coating to promote reflection. In operation, light is emitted by optical emitter 207 and enters aperture plate 210, and then enters sensor element 902. The light then passes through sensor element 902 and reaches reflective surface 1102, where it is reflected back to sensor element 902. This reflection can provide additional interaction between the light and sensor element 902. After interacting with sensor element 902, the light can also be scattered and travel downwards to optical detector 204.

[0083] In some embodiments, one or more prisms may be used to redirect light from the emitter (using refraction) into an aperture plate, and then redirect it into a sensor aperture and the sensor element disposed therein. Now refer to Figure 12 This diagram illustrates a schematic plan view of an implantable photochemical sensor 106 according to various embodiments herein. As previously described, the implantable photochemical sensor may include a circuit board 202, a first optical detector 204, a second optical detector 706, and an orifice plate 210 having a first sensor aperture 302 and a second sensor aperture 502.

[0084] The implantable photochemical sensor 106 may also include a prism 1202 and a prism holder 1204. The prism 1202 can be aligned to receive light from an optical emitter and guide the light into an aperture plate. For example, the prism 1202 may be configured to change the direction of light by approximately 90 degrees (such as using a right-angle prism), but other angles, such as between 45 and 120 degrees, are also considered herein. The prism 1202 may have a silver-plated surface to function like a mirror and facilitate the guidance of light into the aperture plate. The prism 1202 can be formed from a variety of materials, including glass, crystals, ceramics, polymers, and similar materials. The prism can have various sizes. In some embodiments, one side of the prism may be approximately 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 micrometers, or the size may fall within any range of the foregoing. In some embodiments herein, a mirror or waveguide may be used instead of the prism 1202.

[0085] In some embodiments, a prism retainer may be configured to both hold the prism and engage with a light emitter (such as an LED), thereby providing a means of coordinating the prism with the optical emitter. In some embodiments, the prism retainer may be formed of a plastic material, but other materials are also considered herein. The prism retainer may utilize snap-fit ​​mechanisms and / or other securing means (such as adhesive bonding and similar means) to hold the prism.

[0086] Now for reference Figure 13 A schematic perspective view of a portion of an implantable photochemical sensor 106 according to various embodiments herein is shown. As previously described, the implantable photochemical sensor may include a circuit board 202, an optical emitter 207, a first optical detector 204, a second optical detector 706, and an orifice plate 210 having a first sensor aperture 302 and a second sensor aperture 502. The implantable photochemical sensor also includes a prism 1202 and a prism holder 1204.

[0087] Now for reference Figure 14 This diagram illustrates a schematic front view of a portion of an implantable photochemical sensor element according to various embodiments herein. As previously described, the implantable photochemical sensor may include a circuit board 202, an optical emitter 207, a first optical detector 204, a second optical detector 706, and an orifice plate 210 having a first sensor aperture 302 and a second sensor aperture 502. The implantable photochemical sensor also includes the orifice plate 210, which includes the first sensor aperture 302 and the second sensor aperture 502. The implantable photochemical sensor also includes a prism 1202 and a prism holder 1204. In this example, the implantable photochemical sensor may also optionally include a waveguide 1402, which can be used to facilitate the transmission of light from the optical emitter to the corresponding prism.

[0088] In some embodiments, the orifice plate and / or another component of the implantable photochemical sensor (such as a base plate) may include notches to help the components be properly and consistently aligned. Reference now. Figure 15 This image shows a perspective view of portions of an implantable photochemical sensor element according to various embodiments herein. The implantable photochemical sensor includes an optical emitter 207, a base plate 208, and an aperture plate 210 including a first sensor aperture 302. The implantable photochemical sensor also includes a second optical detector 706. The implantable photochemical sensor further includes a prism 1202.

[0089] In this embodiment, the orifice plate 210 also includes a prism alignment notch 1502. In various embodiments, the prism alignment notch 1502 may be configured to receive at least a portion of the prism 1202 or a structure connected thereto (such as a prism retainer structure) to align the prism 1202 with the orifice plate 210. This can improve the consistency and accuracy of the engagement between the prism 1202 and the orifice plate 210.

[0090] In some embodiments, the implantable photochemical sensor further includes a mask layer 1506 (or a light-blocking layer or shielding layer). The mask layer 1506 may be disposed beneath the aperture plate 210 and block light from passing through the bottom of the aperture plate 210. However, the mask layer 1506 may include pores to allow light to pass through the bottom of the sensor aperture and reach the optical detector. The mask layer 1506 may include components such as carbon black or various pigments or dyes to be opaque to light transmission. In some embodiments, the mask layer 1506 may be formed of a material such as black polyester.

[0091] Chemical sensing chemical substances

[0092] Various embodiments described herein include chemical sensing elements that may include chemical sensing compositions. The chemical sensing composition may be part of the chemical sensing element described herein. In some embodiments, the chemical sensing composition may be part of a discrete physical element, such as beads within the chemical sensing element. Further details regarding the chemical sensing composition are provided below. However, it should be understood that this is provided merely by way of example, and further variations are contemplated herein.

[0093] In some embodiments, the chemical sensing composition of the chemical sensor element may be formed from a lipophilic indicator dye. In some embodiments, the chemical sensing composition may be formed from a lipophilic fluorescent indicator dye. In other embodiments, the chemical composition may be formed from a lipophilic colorimetric indicator dye. Suitable lipophilic indicator dyes may include, but are not limited to, ion-selective sensors, such as ion supports or fluorophores.

[0094] In some embodiments, the ion carriers described herein may include, but are not limited to, sodium-specific ion carriers, potassium-specific ion carriers, calcium-specific ion carriers, magnesium-specific ion carriers, and lithium-specific ion carriers. In some embodiments, the fluorophores may include, but are not limited to, lithium-specific fluorophores, sodium-specific fluorophores, and potassium-specific fluorophores.

[0095] The chemical sensing compositions described herein may include components (or response elements) configured to respond to an analyte of interest, such as colorimetric response, photoluminescence response, or another optical sensing mode.

[0096] The colorimetric response elements described herein may be specific to a particular chemical analyte of interest (such as potassium or another electrolyte, or various other compounds of medical / physiological interest). A colorimetric response element may include an element that changes color based on binding to or otherwise complexing with a particular chemical analyte. In some embodiments, a colorimetric response element may include a complexing portion and a colorimetric portion. The colorimetric portion may exhibit different absorbances when the complexing portion binds to the analyte.

[0097] The photoluminescent response elements described herein can be specific to a particular chemical analyte. These elements may include components that absorb and emit light through a photoluminescence process, wherein the intensity and / or wavelength of the emission are influenced by binding to or otherwise complexing with a particular chemical analyte. In some embodiments, the photoluminescent response element may include a complexing portion and a fluorescent portion. These portions may be part of a single chemical compound or distributed across two or more different chemical compounds. In some embodiments, the fluorescent portion may exhibit different fluorescence intensities and / or emission wavelengths based on the binding of the complexing portion to the analyte.

[0098] Some chemicals may not require a separate compound to complex the analyte of interest and generate an optical response. For example, in some embodiments, the response element may include an optical portion or material in which selective complexation with the analyte of interest directly produces a colorimetric or fluorescence response. As an example, a fluorescent ionophore can be used, and it is a compound that simultaneously contains a fluorescent portion and an ion-complexing portion. As just one example, (6,7-[2.2.2]-cryptoether-3-[2”-(5”-ethoxycarbonyl)thiophene]coumarin, a potassium ion-selective fluorescent ionophore (and in some cases covalently attached to a polymer matrix or membrane), can be used to generate fluorescence-based K+. + Response element.

[0099] One exemplary class of fluorescent ionizers is coumarocryptands. Coumarocryptands can include lithium-specific, sodium-specific, and potassium-specific fluorescent ionizers. For example, a lithium-specific fluorescent ionizer can include (6,7-[2.1.1]-cryptoether-3-[2”-(5”-ethoxycarbonyl)furanyl]coumarin. A sodium-specific fluorescent ionizer can include (6,7-[2.2.1]-cryptoether-3-[2”-(5”-ethoxycarbonyl)furanyl]coumarin. A potassium-specific fluorescent ionizer can include (6,7-[2.2.2]-cryptoether-3-[2”-(5”-ethoxycarbonyl)furanyl]coumarin and (6,7-[2.2.2]-cryptoether-3-[2”-(5”-ethoxycarbonyl)thiophenyl]coumarin.

[0100] Suitable fluorescent ionizers include coumarin cryptyl ethers taught in U.S. Patent No. 5,958,782, the entire disclosure of which is incorporated herein by reference. Such fluorescent ionizer compounds can be excited using GaN blue light-emitting diodes (LEDs) that emit light at 400 nm or about 400 nm. These fluorescent ionizer compounds exhibit ion concentration-dependent emission and can be detected in the wavelength range of about 450 nm to about 470 nm.

[0101] These responsive elements may include complexing moieties. Suitable complexing moieties may include cryptanes, crown ethers, double crown ethers, calixarnes, noncyclic amides, and hemispherical moieties, as well as ion-selective antibiotics such as monensin, valacyclomycin, and nigericin derivatives.

[0102] Those skilled in the art will recognize which cryptether and crown ether moieties can be used to complex specific cations, although for further information on this subject, reference may be made to, for example, Lehn and Sauvage, “[2]-Cryptates: Stability and Selectivity of Alkali and Alkaline-Earth Macrocyclic Complexes,” *Journal of the American Chemical Society*, 97, 6700-07 (1975). Those skilled in the art will also recognize which bicrown ethers, calixarenes, acyclic amides, hemispherical and antibiotic moieties can be used to complex specific cations.

[0103] As an example, cryptethers can include structures called cryptether cages. For a cryptether cage, the size of the cage is determined by oxygen and nitrogen atoms, and this size makes the cryptether cage highly selective for cations of similar diameter. For example, [2.2.2] a cryptether cage is selective for cations such as K... + Pb +2 、Sr+2 and Ba +2 The isocations exhibit strong selectivity. [2.2.1] Cavitation cages are effective against substances such as Na+. + and Ca +2 The isocations exhibit strong selectivity. Finally, [2.1.1] cryptane cages are effective against substances such as Li + and Mg +2 Isocations exhibit strong selectivity. The size selectivity of cryptane cages helps improve the sensitivity of chemisensing. When these cryptane cages are incorporated into physiological sensing systems, such as Pb... +2 and Ba +2 The concentration of heavier metals is unlikely to be sufficient to interfere with substances such as Na. + and K + Analysis of ions with broader physiological significance.

[0104] Optical transmitters and detectors

[0105] In some embodiments, the optical emitter herein may include a solid-state light source, such as a GaAs, GaAlAs, GaAlAsP, GaAIP, GaAsp, GaP, GaN, InGaAIP, InGaN, ZnSe, or SiC light-emitting diode or laser diode, which can excite the chemical sensor element at or near the maximum absorption wavelength for a sufficient time to emit a return signal. However, it should be understood that in some embodiments, the wavelength of maximum absorption reflection varies with the concentration in the chemical sensor.

[0106] In some embodiments, the optical emitter may include other light-emitting components, including incandescent components. In some embodiments, the optical emitter may include a waveguide. The optical emitter may also include one or more bandpass filters, high-pass filters, low-pass filters, anti-reflective elements, and / or focusing optics.

[0107] In some embodiments, the optical excitation assembly may include a plurality of LEDs with bandpass filters, each LED filter combination emitting at a different center frequency. According to various embodiments, the LEDs may operate at different center frequencies, sequentially turning on and off during measurement to illuminate the chemical sensor element. Since multiple different center frequency measurements are performed sequentially, a single unfiltered detector may be used in some embodiments. However, in some embodiments, a multicolor source may be used with multiple detectors, each bandpass-filtered to a specific center frequency.

[0108] Chemical sensor elements can include various types of ion-selective sensor chemicals. Physiological analytes of interest can diffuse into or out of the chemical sensor element and combine with the ion-selective sensor component to produce a fluorescence or colorimetric response. Reference analytes can similarly diffuse into or out of the chemical sensor element and serve as a control sample. Exemplary ion-selective sensors are described more fully below.

[0109] An optical detector can be configured to receive light from a chemical sensor element. In one embodiment, the optical detector may include components for receiving light. For example, in some embodiments, the optical detector may include a charge-coupled device (CCD). In other embodiments, the optical detector may include a photodiode, a junction field-effect transistor (JFET) type optical sensor, or a complementary metal-oxide-semiconductor (CMOS) type optical sensor. In some embodiments, the optical detector may include an array of optical sensing components. In some embodiments, the optical detector may include a waveguide.

[0110] The optical detector may also include one or more bandpass filters and / or focusing optics. In some embodiments, the optical detector may include one or more photodiode detectors, each having an optical bandpass filter tuned to a specific wavelength range. The signal from the optical detector may be transmitted to a processor for analysis, such as a microprocessor, which may perform various operations on the signal, including detecting the magnitude of the signal strength, filtering, averaging the signal, converting the signal to the concentration of the analyte of interest using a predetermined correlation, or similar operations.

[0111] method

[0112] This document envisions many different methods, including but not limited to manufacturing methods, usage methods, and similar methods. Aspects of system / device operation described elsewhere in this document may be performed as operations of one or more methods according to the various embodiments described herein.

[0113] For example, this document may include a method for optically sensing a chemical analyte using an implanted device. The method may include: emitting light into a well plate, redirecting the light into a sensor aperture, such as using a bevel to allow the light to interact with a sensor element in the sensor aperture, and receiving the light with an optical detector (in scattering and / or transmission modes), and then processing the signal from the optical detector to determine the amount of the selected analyte.

[0114] It should be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly specifies otherwise. It should also be noted that, unless the context clearly specifies otherwise, the word “or” is generally used to mean “and / or.”

[0115] It should also be noted that, as used in this specification and the appended claims, the phrase “configuration” describes a system, apparatus, or other structure being constructed or configured to perform a particular task or to employ a particular configuration. The phrase “configuration” may be used interchangeably with other similar phrases, such as arrangement and configuration, construction and arrangement, construction, manufacture and arrangement, and similar phrases.

[0116] All publications and patent applications in this specification demonstrate the skill of a person of ordinary skill in the art to which this invention pertains. All publications and patent applications are incorporated herein by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

[0117] As used herein, the representation of a numerical range by endpoints should include all numbers contained within that range (e.g., 2 to 8 includes 2.1, 2.8, 5.3, 7, etc.).

[0118] The headings used herein are for the purpose of aligning with the recommendations under 37 CFR 1.77 or otherwise providing organizational clues. These headings should not be construed as limiting or characterizing one or more inventions set forth in any of the claims that may be derived from this disclosure. As an example, although the headings refer to the “technical field,” such claims should not be limited to the language chosen under this heading to describe the alleged technical field. Furthermore, the description of the technology in the “Background Art” section does not imply an admission that the technology is prior art to any invention in this disclosure. Nor should the “Summary of the Invention” be construed as a characterizing description of one or more inventions set forth in the published claims.

[0119] The embodiments described herein are not intended to be exhaustive or to limit the invention to the precise forms disclosed in the following detailed description. Rather, these embodiments were chosen and described to enable those skilled in the art to appreciate and understand their principles and practice. Therefore, various aspects have been described with reference to specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications can be made while remaining within the spirit and scope of this document.

Claims

1. An implantable photochemical sensor, comprising: Circuit board; At least one optical transmitter, wherein the at least one optical transmitter is disposed on the circuit board; At least one optical detector, wherein the at least one optical detector is disposed on the circuit board; Base plate; and Orifice plate; The perforated plate defines at least one hole; The orifice plate includes: Vertical plane; An inclined surface, wherein the inclined surface and the vertical surface are disposed on at least one peripheral edge of the perforated plate; The perforated plate is disposed above the base plate; A feed-through flange defining a window, wherein the vertical surface of the orifice plate mates with the window; and The at least one optical emitter is configured to emit light through the base plate and into the perforated plate, and then the light is redirected by the slope of the perforated plate into the at least one hole.

2. The implantable photochemical sensor according to any one of claims 1 to 8, wherein, The inclined plane is set at an angle of 20 to 70 degrees relative to the surface of the vertical plane.

3. The implantable photochemical sensor according to any one of claims 1 to 2 and 4 to 8, further comprising a sensor element, wherein, The sensor element is configured to fit into the at least one hole.

4. The implantable photochemical sensor according to any one of claims 1 to 3 and 5 to 8, further comprising a coating, wherein, The coating is applied above the slope and configured such that light is reflected from the interior of the slope.

5. The implantable photochemical sensor according to any one of claims 1 to 4 and 6 to 8, wherein, The base plate comprises low-refractive-index glass.

6. The implantable photochemical sensor according to any one of claims 1 to 5 and 7 to 8, wherein, The at least one optical detector includes a photodiode.

7. The implantable photochemical sensor according to any one of claims 1 to 6 and 8, wherein the implantable electrochemical sensor further comprises a top housing including a sensor window, wherein, The feedthrough flange fits into the sensor window.

8. The implantable photochemical sensor according to any one of claims 1 to 7, wherein, The top surface of the feed-through flange is flush with the top surface of the top housing.

9. An implantable photochemical sensor, comprising: Circuit board; At least one optical transmitter, wherein the at least one optical transmitter is disposed on the circuit board; Base plate; and An orifice plate, the orifice plate defining at least one hole; The perforated plate is disposed above the base plate; At least one prism, wherein the at least one prism is arranged to receive light from the at least one optical emitter and guide the light into the aperture plate; At least one optical detector, wherein the at least one optical detector is disposed on the circuit board; and Feedthrough flange, wherein the feedthrough flange defines a window.

10. The implantable photochemical sensor according to any one of claims 9 and 11 to 12, further comprising a prism retainer, wherein, The prism holder is configured to hold the prism and engage above the at least one optical emitter, thereby aligning the optical emitter.

11. The implantable photochemical sensor according to any one of claims 9 to 10 and 12, further comprising: Top housing, which defines the sensor window; and The feedthrough flange is fitted into the sensor window.

12. The implantable photochemical sensor according to any one of claims 9 to 11, wherein, The top surface of the feed-through flange is flush with the top surface of the top housing.

13. An implantable photochemical sensor, comprising: Circuit board; At least one optical transmitter, wherein the at least one optical transmitter is disposed on the circuit board; At least one optical detector, wherein the at least one optical detector is disposed on the circuit board; At least one prism; and Orifice plate, the orifice plate comprising: At least one hole; and At least one prism alignment notch is provided, wherein the at least one prism alignment notch is configured to receive at least a portion of the at least one prism or a structure connected thereto, thereby aligning the prism with the perforated plate; Feedthrough flange, the feedthrough flange defining a window; and The at least one prism is arranged to receive light from the at least one optical emitter and guide the light into the aperture plate.

14. The implantable photochemical sensor according to any one of claims 13 to 15, further comprising a prism retainer, wherein, The prism holder is configured to hold the prism and engage above at least one optical emitter, thereby aligning the optical emitter.

15. The implantable photochemical sensor according to any one of claims 13 to 14, further comprising a substrate, wherein, The perforated plate is positioned above the base plate.

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