Infusion device for continuous glucose monitoring

Abstract

The present disclosure provides systems and devices for combining analyte monitoring with fluid delivery, including devices adapted for use with a combination sensor and a cannula with a sensor and a cannula on a single assembly. These systems and devices can be used for various applications of simultaneous in vivo monitoring of analyte concentration and drug delivery.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 861,940, filed June 14, 2019, which is incorporated by reference in its entirety. BACKGROUND

[0003] Amperometric analyte sensors can be used to detect a variety of analytes, such as oxygen, pH, glucose, lactate, drug metabolites, and pathogens in the body. In addition, sensors for continuous glucose monitoring (CGM) can have wide clinical adoption. These CGM sensors can reside in subcutaneous tissue and generate a small amount of glucose-related current that is detected by associated electronics. In many cases, it is desirable to both trace the concentration of an analyte and deliver a drug in response to the level of the analyte. This can be done, for example, in the case of glucose analyte monitoring and insulin drug delivery, as an insulin pump can feature automatic insulin dosing based on readings from a CGM sensor. SUMMARY

[0004] The present disclosure provides devices and systems that use a combined sensor and cannula attached to a body that provides electrical coupling of the sensor to a signal processing device and fluidic coupling of the cannula to a drug delivery source in order to combine subcutaneous liquid drug delivery and amperometric analyte sensing without the need for multiple skin-piercing elements.

[0005] In one aspect, the present disclosure provides a device configured to simultaneously sense an analyte concentration and therapeutic fluid administration, comprising: a main body comprising an upper housing, a lower housing, and a bottom skin contact base, wherein the upper housing comprises a top face comprising a port configured to reversibly attach to a fluid delivery device configured for delivering fluid via an insertion needle, wherein the port comprises a visible opening comprising a self-sealing septum in contact with the lower housing forming an internal cavity; a sensing cannula comprising a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel within the inner lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicating electrode on the outer surface configured to sense the concentration of the analyte, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicating electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the proximal end of the sensing cannula remains within the main body, and wherein the distal end of the sensing cannula extends from the skin contact base; a channel within the main body in fluid communication with the internal cavity formed by the self-sealing septum and the proximal end of the combined sensing cannula; a signal processing module comprising a second main body comprising an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface, wherein the vertical surface provides an electrical potential to the sensing cannula and receives current from the sensing cannula via a set of electrical contacts on the vertical surface, wherein the second main body comprises a set of arms in contact with the upper housing, and wherein the lower surface is in contact with the skin contact base; and an interface circuit comprising a proximal end and a distal end, wherein the interface circuit comprises one or more conductors configured to transmit a current signal from the sensing cannula to the signal processing module, wherein the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing cannula, and wherein the distal end of the interface circuit is in electrical contact with the signal processing module.

[0006] In some embodiments, the fluid delivery device comprises a syringe or a pen. In some embodiments, the fluid delivery device comprises a syringe. In some embodiments, the fluid delivery device comprises a pen. In some embodiments, the at least one indicator electrode comprises an enzyme layer covering a conductive surface. In some embodiments, the enzyme layer is covered with a semipermeable membrane. In some embodiments, the enzyme layer comprises glucose oxidase or glucose dehydrogenase. In some embodiments, the enzyme layer comprises an osmium-based redox mediator. In some embodiments, the osmium-based redox mediator comprises osmium dimethyl pyridine. In some embodiments, the enzyme layer comprises polyvinylimidazole. In some embodiments, the sensing cannula comprises a reference electrode comprising silver / silver chloride (Ag / AgCl). In some embodiments, the signal processing module provides a bias potential to the sensing cannula that is less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel comprises a stainless steel needle connecting the lumen to the proximal end of the sensing cannula. In some embodiments, the upper housing and the lower housing are configured to receive a hollow inserter needle that partially encloses the sensing cannula for insertion into a skin surface of a mammal. In some embodiments, the sensing cannula comprises a rigidity sufficient for insertion into a skin surface of a mammal without the use of an inserter needle. In some embodiments, the skin contact base comprises an adhesive surface configured to attach the device to a skin surface of a subject. In some embodiments, the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from insulin or insulin analog preparations, glatiramer acetate, heparin, human menopausal gonadotropin, vitamins, and minerals. In some embodiments, the therapeutic fluid is insulin or insulin analog preparations. In some embodiments, the insulin or the insulin analog preparations comprise an excipient comprising phenol or cresol.

[0007] On the other hand, this disclosure provides an apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: a body including an upper housing, a lower housing, a bottom skin contact base, and an infusion conduit extending outwardly from the body and configured to connect to a source of the therapeutic fluid; a sensing cannula including a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel within the inner lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface configured to sense the concentration of the analyte, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the proximal end of the sensing cannula remains within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; The signal processing module includes a channel within the body that is in fluid communication with the cavity formed by the self-sealing diaphragm and the proximal end of the combined sensing sleeve; a second body comprising an upper surface, a lower surface, and a vertical surface between the upper and lower surfaces, wherein the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface, wherein the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base; and an interface circuit comprising a proximal end and a distal end, wherein the interface circuit includes one or more conductors configured to transmit a current signal from the sensing sleeve to the signal processing module, wherein the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing sleeve, and wherein the distal end of the interface circuit is in electrical contact with the signal processing module.

[0008] In some embodiments, the infusion tubing is reversibly attached to the body via a connector comprising one or more cantilever snap-fit ​​joints configured to allow reversible attachment of the infusion tubing. In some embodiments, the at least one indicating electrode comprises an enzyme layer covering a conductive surface. In some embodiments, the enzyme layer is covered with a semi-permeable membrane. In some embodiments, the enzyme layer comprises glucose oxidase or glucose dehydrogenase. In some embodiments, the enzyme layer comprises an osmium-based redox mediator. In some embodiments, the osmium-based redox mediator comprises osmium dimethyl bipyridine. In some embodiments, the enzyme layer comprises polyvinylimidazole. In some embodiments, the sensing sleeve comprises a reference electrode comprising silver / silver chloride (Ag / AgCl). In some embodiments, the signal processing module provides the sensing sleeve with a bias potential less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel comprises a stainless steel needle connected from the cavity to the proximal end of the sensing sleeve. In some embodiments, the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into the skin surface of a mammal. In some embodiments, the sensing cannula includes stiffness sufficient for insertion into the skin surface of a mammal without the need for the inserter needle. In some embodiments, the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from insulin or insulin analogs, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals. In some embodiments, the therapeutic fluid is insulin or an insulin analog. In some embodiments, the insulin or insulin analog comprises an excipient comprising phenol or cresol.

[0009] On the other hand, this disclosure provides a device configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: a body including an upper housing, a lower housing, and a bottom skin contact base, wherein the upper housing includes a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via an insertion needle, wherein the port includes a visible opening including a self-sealing diaphragm that contacts the lower housing to form an inner lumen; and a sensing cannula including a proximal end, a distal end, an outer surface, an inner lumen, and an inner lumen extending from the proximal end of the sensing cannula to the sensing cannula. The tube includes at least one hollow channel at its distal end, at least one indicator electrode on its outer surface configured to sense the concentration of the analyte, and a conductor on its outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the application of the therapeutic fluid, wherein the proximal end of the sensing cannula remains within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; and a channel within the body that is in fluid communication with the lumen formed by the self-sealing diaphragm and the proximal end of the combined sensing cannula.

[0010] In some embodiments, the upper housing includes a top surface containing the port. In some embodiments, the port includes a visible opening that includes the self-sealing diaphragm. In some embodiments, the device further includes a signal processing module configured to receive current from the sensing sleeve. In some embodiments, the signal processing module is configured to provide a potential to the sensing sleeve. In some embodiments, the signal processing module includes a second body including an upper surface, a lower surface, and a vertical surface between the upper and lower surfaces. In some embodiments, the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface. In some embodiments, the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base. In some embodiments, the device further includes interface circuitry configured to transmit a current signal from the sensing sleeve to the signal processing module. In some embodiments, the interface circuitry includes a proximal end and a distal end. In some embodiments, the interface circuitry includes one or more conductors configured to transmit the current signal from the sensing sleeve to the signal processing module. In some embodiments, the proximal end of the interface circuitry is in electrical contact with the proximal end of the sensing sleeve, and the distal end of the interface circuitry is in electrical contact with the signal processing module. In some embodiments, the fluid delivery device includes a syringe or a pen. In some embodiments, the fluid delivery device includes a syringe. In some embodiments, the fluid delivery device includes a pen. In some embodiments, the at least one indicating electrode includes an enzyme layer covering a conductive surface. In some embodiments, the enzyme layer is covered with a semi-permeable membrane. In some embodiments, the enzyme layer contains glucose oxidase or glucose dehydrogenase. In some embodiments, the enzyme layer contains an osmium-based redox mediator. In some embodiments, the osmium-based redox mediator includes osmium dimethyl bipyridine. In some embodiments, the enzyme layer includes polyvinylimidazole. In some embodiments, the sensing sleeve includes a reference electrode containing silver / silver chloride (Ag / AgCl). In some embodiments, the signal processing module provides the sensing sheath with a bias potential of less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel includes a stainless steel needle connected from the cavity to the proximal end of the sensing sheath. In some embodiments, the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing sheath for insertion into the skin surface of a mammal. In some embodiments, the sensing sheath includes stiffness sufficient for insertion into the skin surface of a mammal without the need for the inserter needle.In some embodiments, the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from insulin or insulin analog preparations, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals. In some embodiments, the therapeutic fluid is insulin or an insulin analog preparation. In some embodiments, the insulin or insulin analog preparation comprises an excipient comprising phenol or cresol.

[0011] In another aspect, this disclosure provides an apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: a body including an upper housing, a lower housing, a bottom skin contact base, and an infusion conduit extending outwardly from the body and configured to connect to a source of the therapeutic fluid; a sensing cannula including a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel within the inner lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface configured to sense the concentration of the analyte, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the proximal end of the sensing cannula is retained within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; and a channel within the body in fluid communication with the lumen formed by the self-sealing diaphragm and the proximal end of the combined sensing cannula.

[0012] In some embodiments, the device further includes a signal processing module configured to receive current from the sensing sleeve. In some embodiments, the signal processing module is configured to provide a potential to the sensing sleeve. In some embodiments, the signal processing module includes a second body comprising an upper surface, a lower surface, and a vertical surface between the upper and lower surfaces. In some embodiments, the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface. In some embodiments, the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base. In some embodiments, the device further includes interface circuitry configured to transmit a current signal from the sensing sleeve to the signal processing module. In some embodiments, the interface circuitry includes a proximal end and a distal end. In some embodiments, the interface circuitry includes one or more conductors configured to transmit the current signal from the sensing sleeve to the signal processing module. In some embodiments, the proximal end of the interface circuit is electrically contacted with the proximal end of the sensing sleeve, and the distal end of the interface circuit is electrically contacted with the signal processing module. In some embodiments, the infusion tubing is reversibly attached to the body via a connector including one or more cantilever snap-fit ​​joints configured to allow reversible attachment of the infusion tubing. In some embodiments, the at least one indicating electrode includes an enzyme layer covering a conductive surface. In some embodiments, the enzyme layer is covered with a semi-permeable membrane. In some embodiments, the enzyme layer comprises glucose oxidase or glucose dehydrogenase. In some embodiments, the enzyme layer comprises an osmium-based redox mediator. In some embodiments, the osmium-based redox mediator comprises osmium dimethyl bipyridine. In some embodiments, the enzyme layer comprises polyvinylimidazole. In some embodiments, the sensing sleeve includes a reference electrode comprising silver / silver chloride (Ag / AgCl). In some embodiments, the signal processing module provides a bias potential of less than 250 millivolts (mV) relative to a reference potential to the sensing sheath. In some embodiments, the channel includes a stainless steel needle connected from the cavity to the proximal end of the sensing sheath. In some embodiments, the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing sheath for insertion into the skin surface of a mammal. In some embodiments, the sensing sheath includes stiffness sufficient for insertion into the skin surface of a mammal without the need for the inserter needle. In some embodiments, the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens.In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from insulin or insulin analog preparations, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals. In some embodiments, the therapeutic fluid is insulin or insulin analog preparations. In some embodiments, the insulin or insulin analog preparation contains excipients, the excipients comprising phenol or cresol.

[0013] In some embodiments, the body is circular or substantially circular, having an accessible surface on one side with a self-sealing inlet; a skin-contact surface on the opposite side having a combined sensor and a sleeve protruding outward therefrom; a liquid delivery channel connecting the inlet to the sleeve; a cavity for receiving an electronic signal processing device; a retention mechanism for the signal processing device; and electrical contact between the signal processing device and the sensor.

[0014] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, having an accessible surface on one side with a self-sealing inlet; a skin-contact surface on the opposite side, having a combined sensor and an outwardly projecting sleeve; a liquid delivery channel connecting the inlet to the sleeve; an electronic signal processing device having a set of arms to which the housing is attached to the liquid delivery channel; a retention mechanism for the signal processing device; and electrical contact between the signal processing device and the sensor.

[0015] In some embodiments, the body is elliptical or substantially elliptical, having an accessible surface on one side with a self-sealing inlet; a skin-contact surface on the opposite side having a combined sensor and a sleeve protruding outward therefrom; a liquid delivery channel connecting the inlet to the sleeve; an electronic signal processing device attached to a vertical surface of the body; a retention mechanism for the signal processing device; and an electrical contact between the signal processing device and the sensor.

[0016] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, having an accessible surface on one side with an infusion conduit section protruding therefrom; a skin-contact surface on the opposite side having a combined sensor and an outwardly protruding sleeve; a liquid delivery tube connecting the infusion conduit to the sleeve; a set of retaining arms designed to align and retain an electronic signal processing device; features designed to receive an attachment arm of the electronic signal processing device; and electrical contact between the signal processing device and the sensor.

[0017] In some embodiments, the body is substantially circular or elliptical, having an accessible surface on one side with an infusion conduit section protruding therefrom; a skin-contact surface on the opposite side having a combined sensor and an outwardly protruding sleeve; a liquid delivery tube connecting the infusion conduit to the sleeve; a self-sealing port connecting to the liquid delivery channel; a retaining arm designed to align and retain an electronic signal processing device; features designed to receive an attachment arm of the electronic signal processing device; and electrical contact between the signal processing device and the sensor.

[0018] In some embodiments, the cannula protrudes outward from the skin contact surface at an angle of 40 to 60 degrees. In some embodiments, the cannula protrudes outward from the skin contact surface vertically or substantially vertically.

[0019] In some embodiments, the device is configured to be inserted or driven into the skin using an insertion device. The insertion device may temporarily contact the accessible surface of the body. In some embodiments, the surgical cannula has a fluid path composed substantially of a flexible polymer and is placed in the tissue using a rigid inserter element or needle that is removed immediately after insertion. In some embodiments, the insertion device includes an insertion needle that pierces the self-sealing inlet, passes through the fluid delivery channel, and extends just beyond the distal end of the retractable cannula. In some embodiments, the cannula includes a fluid path formed by a permanently fixed needle that can be placed in the tissue and remain present for its service life.

[0020] Additional aspects and advantages of this disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only exemplary embodiments of this disclosure are shown and described. It should be understood that this disclosure can have other and different embodiments, and that several details thereof can be modified in various obvious respects without departing from this disclosure. Therefore, the drawings and descriptions should be considered illustrative rather than restrictive.

[0021] INCORPORATION BY REFERENCE

[0022] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application is specifically and individually cited and incorporated herein by reference. In the event of any conflict between a publication, patent, or patent application cited and the disclosure contained herein, this specification is intended to substitute for and / or give precedence to any such conflicting material. Attached Figure Description

[0023] The novel features of the invention are set forth in the appended claims. A better understanding of the features and advantages of the invention will be obtained by referring to the following detailed description and accompanying drawings (also referred to herein as “illustrations” and “figures”) illustrating embodiments in which the principles of the invention are utilized:

[0024] The embodiments will be readily understood through the following detailed description taken in conjunction with the accompanying drawings and claims. The embodiments are shown by way of example rather than by means of limitation of the figures.

[0025] FIG. 1A A perspective view is provided of an example of a combined CGM infusion port with an internally removable electronic module.

[0026] FIG. 1B Provided FIG. 1A Another perspective view of the combined CGM infusion port, in which the internal removable electronic module has been removed.

[0027] FIG. 2 Provided FIG. 1A A breakdown diagram of the combined CGM infusion ports.

[0028] FIG. 3A-3C A cross-sectional view of an example of a combined CGM infusion port with an internally removable electronic module and an insertion device is provided.

[0029] FIG. 4 A cross-sectional view of an example of a combined CGM infusion port with an internally removable electronic module is provided.

[0030] FIG. 5 A cross-sectional view is provided of an example of a combined CGM infusion port with an internally removable electronic module, wherein a fluid delivery device is inserted into the skin of a subject (e.g., a patient), and a syringe is positioned within the device to provide fluid delivery (e.g., drug delivery) to the subject.

[0031] FIG. 6A-6B A perspective view is provided of an example of a combined CGM infusion port with an externally removable electronic module.

[0032] FIG. 7A-7B Provided FIG. 6A-6B An exploded view of the combined CGM infusion port, including a view of the inserter needle. FIG. 7B ).

[0033] FIG. 8A-8D A cross-sectional view of an example of a combined CGM infusion port is provided, including a view of interconnection details. FIG. 8A A side section view is shown. FIG. 8B A front cross-sectional view is shown. FIG. 8C A side cross-sectional view showing details of the fluid path and electrical contact is shown, andFIG. 8D A front cross-sectional view showing details of the fluid path and electrical contact is shown.

[0034] FIG. 9A-9D A cross-sectional view of an example of a combined CGM infusion port that contacts a needle-free insulin pen tip is provided. FIG. 9A A side section view is shown. FIG. 9B A front cross-sectional view is shown. FIG. 9C A side cross-sectional view showing details of the fluid path and electrical contact is shown, and FIG. 9D A front cross-sectional view showing details of the fluid path and electrical contact is shown.

[0035] FIG. 10A-10G A view is provided of an example of a disposable CGM infusion port that contacts a pen with a needle-free insulin pen tip. FIG. 10A A perspective view of the disposable CGM infusion port attached to the pen tip is provided. FIG. 10B A perspective view of a disposable CGM infusion port, including its internal structure (e.g., electronics), is provided. FIG. 10C A cross-sectional view of a disposable CGM infusion port attached to a pen tip, including the fluid path, is provided. FIG. 10D A cross-sectional view of the one-time CGM infusion port, including details of the sensor electrical interconnection, is provided. FIG. 10E-10G Cross-sectional views of a disposable CGM infusion port in contact with a pen tip are provided, including cross-sectional views with the pen tip attached. FIG. 10E ), including details of the fluid path portion where the pen tip detaches from the fluid path ( FIG. 10F ), and details of the fluid path portion where the pen tip joins the fluid path ( FIG. 10G ).

[0036] FIG. 11A-11B A view of an example of a combined CGM infusion port with a rigid sensor is provided, including a front cross-sectional view. FIG. 11A ) and a front cross-sectional view showing details of the fluid path and electrical contact ( FIG. 11B ).

[0037] FIG. 12A-12C A perspective view is provided showing an example of a combined CGM infusion port configured for attachment to an insulin pump or a gravity-fed drug delivery source. FIG. 12A-12B ) and exploded diagram ( FIG. 12C ).

[0038] FIG. 13A-13B A perspective view is provided showing an example of a combined CGM infusion port configured for attachment to an insulin pump or a gravity-fed drug delivery source. FIG. 13A ) and top view section ( FIG. 13B (The electronic modules have been removed, and details of the fluid paths and electrical interconnections are shown.)

[0039] FIG. 14A-14D A perspective view is provided of an example of a combined CGM infusion port with a rigid inserter needle or cannula configured for attachment to an insulin pump or gravity-fed drug source. FIG. 14A ), top view section ( FIG. 14B ), front section diagram ( FIG. 14C ) and side section view ( FIG. 14D Figure 14 to FIG. 14B Interconnections to electronic devices are shown. Figure 14 to FIG. 14D The tubular infusion kit is shown. Detailed Implementation

[0040] This document refers to the accompanying drawings, which form part of and are shown therein through illustrative embodiments that can be implemented. It should be understood that other embodiments may be used, and structural or logical changes may be made without departing from the scope. Therefore, the following detailed description should not be taken in a limiting sense.

[0041] Various operations can be described as a series of discrete operations in a manner that helps to understand the implementation; however, the order of description should not be interpreted as implying that these operations depend on the order.

[0042] The description may use perspective-based descriptions, such as top / bottom, back / front, and top / bottom. Such descriptions are only used to facilitate discussion and are not intended to limit the application of the disclosed embodiments.

[0043] As used herein, the term “casing” generally refers to a hollow tube made of a rigid material such as a polymer or metal, having an internal (e.g., inner) surface and an external (e.g., outer) surface, as well as openings at both ends.

[0044] As used herein, the term "sensing sleeve" generally refers to a sleeve having an analyte sensor mounted on an external surface and one or more fluid delivery channels contained within the sleeve.

[0045] As used herein, the term “continuous glucose monitor (CGM)” generally refers to an electronic device configured to continuously or nearly continuously measure the glucose level of a subject (e.g., a human, animal, or mammal) and / or report such measurements.

[0046] As used herein, the term “CGM injection port” generally refers to a device (e.g., a uniform device) configured for use on the skin of a subject (e.g., a human, animal, or mammal) that has a combination of a sensor and a cannula including an electrical interface to signal acquisition electronics and a port for attaching a fluid source such as an insulin pen, syringe, or other fluid delivery device.

[0047] As used herein, the term “CGM infusion kit” generally refers to a device (e.g., a uniform device) configured for use on the skin of a subject (e.g., a human, animal, or mammal) that has a combination of sensors and a cannula including an electrical interface to signal acquisition electronics and a port for attaching a fluid source such as a pump or gravity supply source.

[0048] The terms “coupling” and “connection” and their derivatives may be used herein. It should be understood that these terms are not intended to be synonyms. Rather, in certain implementations, “connection” may be used to indicate that two or more elements are in direct physical or electrical contact with each other. “Coupling” may be used to indicate that two or more elements are in direct physical or electrical contact with each other. However, “coupling” may also be used to indicate that two or more elements are not in direct contact with each other, but still cooperate or interact with each other.

[0049] As used herein, phrases of the form "A / B" or "A and / or B" represent (A), (B), or (A and B). For descriptive purposes, phrases of the form "at least one of A, B, and C" represent at least one of (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C). For descriptive purposes, phrases of the form "(A)B" represent (B) or (AB), where A is an optional element.

[0050] As used herein, the terms “embodiment” or “implementation” may each refer to one or more of the same or different implementations. Furthermore, the terms “comprising,” “including,” “having,” etc., used with respect to implementations are synonymous and are generally intended as “open-ended” terms (e.g., the term “comprising” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “including” should be interpreted as “including but not limited to,” etc.).

[0051] Regarding the use of any plural and / or singular terms in this document, plural may be interpreted as singular, and / or singular may be interpreted as plural, as appropriate to the context and / or application. For clarity, various singular / plural substitutions may be explicitly stated in this document.

[0052] There is a growing number of medical treatments involving subcutaneous fluid infusion regimens. For example, glatiramer acetate (a treatment for multiple sclerosis) can be prescribed for daily subcutaneous injection. As another example, heparin can be administered via routine subcutaneous injection as a treatment for certain coagulation disorders. As yet another example, human menopausal gonadotropins are administered daily subcutaneously to women undergoing fertility treatment. As yet another example, pediatric patients receiving parenteral nutrition can receive repeated subcutaneous doses of multivitamins. Subcutaneous injections are also commonly used in veterinary applications.

[0053] One of the largest groups receiving daily subcutaneous injections is individuals with type 1 or type 2 diabetes who require insulin therapy. Most such subjects can receive more than one injection per day, a regimen known as multiple daily injection (MDI) therapy. For example, the infusion port for drug delivery can be designed to attach to the skin surface with a percutaneous cannula extending perpendicularly to the base (e.g., as described in U.S. Patent 7,338,465, the entire contents of which are incorporated herein by reference). After insertion with an insertion needle, the cannula remains in the subcutaneous tissue for several days to deliver the drug without requiring additional painful injections.

[0054] Abe-type analyte sensors can be used to detect a variety of analytes, such as oxygen, pH, glucose, lactate, drug metabolites, and pathogens in the body. Furthermore, sensors for continuous glucose monitoring (CGM) may have broad clinical applications. These CGM sensors can reside in subcutaneous tissue and generate a small amount of glucose-related current that is detected by associated electronics.

[0055] In many cases, it is desirable to track the concentration of an analyte and deliver medication in response to the analyte level. This can be achieved, for example, in cases of glucose analyte monitoring and insulin drug delivery, as an insulin pump can feature automated insulin dosing based on readings from a CGM sensor. For user convenience, it may be desirable to combine sensing and infusion into a single device. However, while both a CGM sensor and an infusion port are available, there are challenges in achieving a single, unified device that effectively combines these two functions. Therefore, automated insulin metering pumps may use physically separate sensors and infusion sites. This multi-site management requires additional time, increases the risk of pain and infection, and raises costs for the patient.

[0056] In the specific context of glucose measurement, integration can be prevented by the assumption that insulin delivery close to the glucose sensor in a patient's diabetes management would necessarily disrupt sensor readings due to local analyte uptake. Therefore, many commercially available CGM devices utilize a separation distance between the insulin delivery site and glucose monitoring. For example, Dexcom's G6 instruction instructs users to "select a site at least 3 inches away from the insulin pump infusion kit or injection site" (Dexcom G6 User Guide, p. 11, 2017, which is incorporated herein by reference in its entirety). Similarly, Abbott's instruction instructs users to keep their Libre sensor "at least 1 inch away from the insulin injection site" (Libre In-Service Guide, p. 21, Abbott ADC-05821V2.0, October 2017, which is incorporated herein by reference in its entirety). In addition, Medtronic recommends that users use the CGM sensor “1 inch from the insulin pump infusion site” and “1 inch from any manual insulin injection site.” (My Guardian Contact Handbook, p. 12, Medtronic, April 27, 2018, which is incorporated herein by reference in its entirety).

[0057] Using current-electrode devices, each insertion site for insulin injection may require piercing the skin with a separate needle, which can be painful for the patient, and each insertion site may carry the risk of complications such as scarring and infection. The physical separation and the resulting complexity also increase the cost and size of the device worn on the body. To be less painful, more convenient, and cheaper for the patient, this disclosure provides improved devices, systems, and methods for a unified analyte-sensing fluid delivery cannula. Such improved devices, systems, and methods are characterized by a glucose sensor directly mounted on the surface of the infusion cannula. The physiological effect of insulin on glucose concentration in surrounding subcutaneous tissue has been shown to be negligible, as the greater effect on ambe-type glucose sensors has been found to actually derive from the electroactive components of the insulin excipients, which cause an initial increase in sensor current followed by a permanent loss of glucose sensitivity. Therefore, interstitial blood glucose levels immediately adjacent to insulin delivery can be measured using a properly designed ambe-type glucose sensor (e.g., as described in U.S. Patent Publication No. 2016 / 0354542A1, which is incorporated herein by reference in its entirety).

[0058] In view of the above challenges, this disclosure provides an infusion device to meet the need for a reliable and feasible solution for attaching a uniform sensing cannula to the necessary signal processing electronics and a common fluid infusion device. Such an infusion device enables simultaneous connection of an Ambe-type sensor on the surface of the infusion cannula to signal processing electronics and various suitable drug delivery mechanisms, including syringes, pens, and pumps with fluid paths to the same infusion cannula.

[0059] This disclosure provides systems and devices for combining analyte monitoring with fluid delivery, including devices suitable for use with combined sensors and cannulas with sensors, as well as cannulas on individual components. These systems and devices can be used for in vivo monitoring of analyte concentrations (e.g., pH, oxygen, lactate, glucose, and insulin concentrations) and delivery of drugs (e.g., glatiramer acetate, heparin, human menopausal gonadotropins, insulin, vitamins, and nutritional supplements). These systems and devices can be used in a variety of situations and applications, such as the treatment of multiple sclerosis, fertility therapy, diabetes, nutritional supplements, and automated drug delivery.

[0060] The infusion devices disclosed herein can be configured to attach to the skin surface of a subject (e.g., a patient), wherein a single, combined sensing cannula penetrates the skin surface to enter the subject's subcutaneous compartment. These devices can be configured for use with external fluid sources such as insulin injectors, insulin pens, smart pens, or infusion pumps. Once properly inserted into the body, the device can be used to deliver fluid to the patient over an extended period of time (e.g., 3 days or longer), thereby avoiding some of the pain and inconvenience of needle pricks within that timeframe.

[0061] The infusion device of this disclosure also has the advantage of a smaller size than other infusion devices that include ampoule-type sensors. Instead of requiring two separate devices on the body, the infusion device of this disclosure can have only a single component attached to or penetrating the skin. The physical separation required by this method can set physical or practical limitations (e.g., a lower limit) on the size of the device compared to other devices used for analyte sensing and drug delivery in a common assembly, which is addressed by the systems and devices of this disclosure. Furthermore, other devices used for analyte sensing and drug delivery in a common assembly may not adequately integrate electronic interfaces, which can add a non-negligible and considerable additional size and complexity to the functional solution. Co-location of electrical and fluid handling features on a single transdermal device can present significant challenges, or be associated with them, because the electrical and fluid interfaces may need to be completed in a limited space. Moreover, the ability of the sensor to accurately record signal current can be compromised by reliability issues such as fluid leakage into the electrical interface. The systems and devices of this disclosure provide a sensor and a fluid delivery cannula capable of handling the electrical and fluid path connections to it.

[0062] Recognizing the need for improved combined CGM infusion port devices that avoid the use of multiple insertion needles, the systems and devices of this disclosure combine a sensor with a cannula having an insertion system that allows a uniform sensing cannula to be inserted into the primary or secondary subject (e.g., a patient) without compromising fluid and electrical connections. Furthermore, the systems and devices of this disclosure provide suitable solutions for insertion that simultaneously meet constraints on both fluid and electrical connections themselves.

[0063] In various embodiments, the systems and apparatus of this disclosure effectively provide solutions for electronically processing sensor signals via an electronic signal processing module configured to facilitate an electromechanical interface between sensor contacts and signal processing hardware. These enable temporary or permanent electrical connections between the sensor and associated processing electronics, and allow for the reuse of electronics as desired.

[0064] In some embodiments, the body is circular or substantially circular, having an accessible surface on one side with a self-sealing inlet; a skin-contact surface on the opposite side having a combined sensor and a sleeve protruding outward therefrom; a liquid delivery channel connecting the inlet to the sleeve; a cavity for receiving an electronic signal processing device; a retention mechanism for the signal processing device; and electrical contact between the signal processing device and the sensor.

[0065] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, having an accessible surface on one side having a self-sealing inlet; a skin-contact surface on the opposite side having a combined sensor and a sleeve protruding therefrom; a liquid delivery channel connecting the inlet to the sleeve; an electronic signal processing device having a set of arms for attaching it to a housing of the liquid delivery channel; a retention mechanism for the signal processing device; and electrical contact between the signal processing device and the sensor.

[0066] In some embodiments, the body is elliptical or substantially elliptical, having an accessible surface on one side with a self-sealing inlet; a skin-contact surface on the opposite side having a combined sensor and a sleeve protruding outward therefrom; a liquid delivery channel connecting the inlet to the sleeve; an electronic signal processing device attached to a vertical surface of the body; a retention mechanism for the signal processing device; and electrical contact between the signal processing device and the sensor.

[0067] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, having an accessible surface on one side with an infusion conduit section protruding therefrom; a skin-contact surface on the opposite side having a combined sensor and an outwardly protruding sleeve; a liquid delivery tube connecting the infusion conduit to the sleeve; a set of retaining arms designed to align and retain the electronic signal processing device; features designed to receive the attachment arms of the electronic signal processing device; and electrical contact between the signal processing device and the sensor.

[0068] In some embodiments, the body is substantially circular or elliptical, having an accessible surface on one side with an infusion conduit section protruding therefrom; a skin-contact surface on the opposite side having a combined sensor and an outwardly protruding sleeve; a liquid delivery tube connecting the infusion conduit to the sleeve; a self-sealing port connecting to the liquid delivery channel; a retaining arm designed to align and retain the electronic signal processing device; features designed to receive the attachment arm of the electronic signal processing device; and electrical contact between the signal processing device and the sensor.

[0069] In some embodiments, the cannula protrudes outward from the skin contact surface at an angle of 40 to 60 degrees. In some embodiments, the cannula protrudes outward from the skin contact surface vertically or substantially vertically.

[0070] In some embodiments, the device is configured to be inserted or driven into the skin using an insertion device. The insertion device may temporarily contact an accessible surface of the body. In some embodiments, the surgical cannula has a fluid path composed substantially of a flexible polymer and is placed in the tissue using a rigid inserter element or needle that is removed immediately after insertion. In some embodiments, the insertion device includes an insertion needle that pierces a self-sealing inlet, passes through a fluid delivery channel, and extends just beyond the distal end of the retractable cannula. In some embodiments, the cannula includes a fluid path formed by a permanently fixed needle that can be placed in the tissue and remain present for its service life.

[0071] FIG. 1A-1BA perspective view of an example of a combined CGM infusion port 100 with an internally removable electronic module is provided. The combined CGM infusion port 100 includes a body 110, a sensing cannula 120 projecting downwards from the body, an access port 130 on the top surface of the body, and an electronic signal processing module 140 enclosed within the body. An adhesive patch 116 provides adhesive attachment to a subject (e.g., a patient). The access port 130 allows a user (e.g., a subject, patient, physician, nurse, clinician, or caregiver of the subject) to attach a fluid delivery device (e.g., a syringe, pen, needle, or insulin pump) to the subject. This fluid may be a drug, a diagnostic agent, or other liquid intended for subcutaneous injection. An inserter 160 allows a user to insert the cannula into the subject's skin.

[0072] like FIG. 1B As shown, in some embodiments, the electronic signal processing module 140 may be removable and is shown as separate from the infusion device body 110. Infusion components such as cannulas may be disposable and have a limited lifespan of 3 days or more. By configuring the electronic signal processing module so that it can be removed and reused, the recurring cost of the system is reduced. However, in other embodiments, the transmitter is permanently fixed within the infusion device body and discarded along with the infusion device.

[0073] FIG. 2 Provided FIG. 1A An exploded view of the combined CGM infusion port. The body 110 is shown separated from the upper housing 112 and base 114, and the sensing cannula 120 is separated from the base 114. These components may include materials such as injection-molded plastic and are bonded to each other via adhesives, ultrasonic welding, or other techniques for bonding plastics. An adhesive patch 116 provides attachment to the subject (e.g., a patient) on its bottom surface and adhesively attaches to the base 114 on its top surface. The sensing cannula 120 and inlet port 130 are shown prior to assembly. A self-sealing diaphragm 134 and a fluid path housing 135 provide an intermittent connection between the fluid delivery device and the fluid path of the cannula 120. The electronic signal processing module 140 is shown being removed from the body.

[0074] FIG. 3A-3CA cross-sectional view is provided of an example of a combined CGM infusion port having an internally removable electronic module and an insertion device for placing the cannula into subcutaneous tissue. In this configuration, the sensing cannula has a conductor of sufficient length to directly contact the electronic module. Opening 162 allows the inserter 160 to pass through the upper housing 112. The inserter cross-section is hollow and may be circular or approximately square (e.g., having three sides open with a fourth side opening). The opening in the cross-section allows for fluid connection through a fluid path formed by a tube 132 extending from the sensing cannula 120, to the outside of the hollow inserter and to a needle lumen 136 formed by a fluid path body 135. Fluid is delivered to the subject's subcutaneous tissue by inserting a needle through a diaphragm 134 into the needle lumen 136. The opening in the inserter also allows the passage of sensor conductors 121 and 123, which are electrically connected to a set of contacts 122 and 124 at the proximal end of the sensing cannula 120. The set of contacts 122 and 124 make physical and electrical contact with a set of sensor electronics module contacts 142 and 144 on the electronic signal processing module 140.

[0075] FIG. 4 A cross-sectional view of an example of a combined CGM infusion port with an internally removable electronic module is provided. The device features a co-located electrical connection for unifying analyte sensing and fluid delivery on an analyte sensing sleeve configured for use with an intermittently connected fluid source (e.g., a syringe or pen). An electronic signal processing module 240 is shown inserted into a cavity formed by a body 210. An electrical connection from the electronic signal processing module 240 to the sensing sleeve 220 is provided via a flexible electrical connector 246, which establishes electrical contact with the electronic signal processing module 240 via a set of contacts 242 and 244, and maintains contact with contacts 222 and 224 at the proximal end of the combined analyte sensor and infusion sleeve 220. A fluid connection to the proximal end of the combined analyte sensor and infusion sleeve 220 is provided via an opening 219 in a base 214, which allows fluid to flow from an adjacent needle lumen 216 into the infusion sleeve. The sensing sleeve 220 exits the base 214 through an opening 218. Fluid is supplied into the needle cavity 216 through an opening 250 in the upper housing 212 and through a fluid delivery device permeating the self-sealing diaphragm 234. Fluid flows from the needle cavity 216 to the sensing cannula 220 via a channel 217. In this embodiment, the sensing cannula 220 can be placed in the subject's skin by means of an insertion device, or it can be able to pierce the subject's skin without a temporary inserter needle.

[0076] FIG. 5A cross-sectional view is provided of an example of a combined CGM infusion port with an internally removable electronic module in an example application, wherein a fluid delivery device is inserted into the skin of a subject (e.g., a patient), and a syringe is positioned within the device to provide fluid delivery (e.g., drug delivery) to the subject. A unified sensing cannula 320 is embedded in subcutaneous tissue 370, substantially perpendicular to the plane of the skin surface. A fluid delivery device 354 is shown as having a needle 352 inserted into a cavity 316 through an opening 350 and a self-sealing diaphragm 332. The fluid delivery device can be selected from a variety of suitable fluid sources, such as syringes, insulin pens, drug infusion pumps, and gravity-fed fluid sources. An electronic signal processing module 340 is shown inserted into a cavity 316 formed by a body 310. An electrical connection from the electronic signal processing module to the sensing cannula 320 is provided via a flexible circuit 346 having a set of electrical contacts 342 and 344 that maintain contact with a set of contacts 322 and 324 at the proximal end of the sensing cannula 320. A permanent, waterproof connection is established from the set of sensor contacts 322 and 324 to the set of flexible circuit contacts 342 and 344 via a waterproof conductive adhesive, and may be further encapsulated in a non-conductive waterproof barrier (such as an epoxy sealant). Fluid connection to the proximal end of the combined analyte sensor and infusion cannula 320 is provided via an opening 313 in the base 314, which 219 allows fluid to flow out from the adjacent needle lumen 316. The sensing cannula 320 exits the base 314 through the opening 319.

[0077] FIG. 6A-6B A perspective view is provided of an example of a combined CGM infusion port with an externally removable electronic module. FIG. 6A An embodiment of the infusion device is depicted, wherein an electronic signal processing module is contained within a body attached to a skin-wearing assembly of the device via two arms protruding from the signal processing module. The infusion device 400 includes a body 410 having an upper housing 412 and a base 414 attached to an adhesive patch 416, a cannula 420 projecting downwards from the body, an access port 430 on the top surface of the cannula housing, an inserter port 462, and an electronic signal processing module 440 mating with the cannula housing. The inserter port 462 allows an inserter needle to be placed through the housing to surround the cannula 420. The access port 430 allows a user (e.g., a subject, patient, physician, nurse, clinician, or caregiver of the subject) to reversibly attach a fluid delivery device (e.g., a syringe, pen, needle, or insulin pump) to the subject. This fluid may be a drug, diagnostic agent, or other liquid desired for subcutaneous injection.

[0078] like FIG. 6BAs shown, the electronic signal processing module 440 is removable and shown detached from the infusion device body 410. The electronic signal processing module 440 is reversibly attached to the base 414 and the upper housing 412 via a set of arms 446 that contact the vertical side edges of the upper housing 412. A set of guides 418 may be present on either side of the electronic signal processing module 440 to help hold it in place. In some embodiments, infusion components such as the cannula 420 are disposable and have a limited lifespan of 3 days or more. By configuring the electronic signal processing module 440 so that it can be removed and reused, the recurring cost of the system is reduced. However, in other embodiments, the transmitter is permanently attached to the infusion device body and can be discarded along with the infusion device.

[0079] FIG. 7A-7B Provided FIG. 6A-6B An exploded view of the combined CGM infusion port, including a view of the inserter needle. FIG. 7B ). FIG. 7A An exploded view of an embodiment of the infusion device prior to assembly is depicted, with the electronic signal processing module removed. The infusion device 400 includes a body 410 having an upper housing 412 and a base 414, an adhesive patch 416, a fluid path coupling needle 432, a diaphragm 434, an inlet port 430 on the top surface of the cannula housing, and a sensing cannula 420 projecting downwards from the body after assembly. The diaphragm 434 may be made of self-sealing silicone or other elastomeric material and serves to allow attachment to a fluid source when punctured. An electronic interconnect circuit 426 is inserted into the sensor housing 413 and contacts and is electrically connected at its proximal end to a set of contacts 422 and 424 on the top and bottom surfaces of the proximal end of the sensing cannula 420. The circuit 426 also contacts the contacts of the electronic signal processing module 440 at its distal end via a spring-loaded pin, conductive rubber button, or other interconnection device on the vertical surface of the electronic signal processing module 440. The base 414 also has a set of holding arms 418 for holding the electronic signal processing module 440. Although shown as separate arms, they can be connected to surround the conveyor.

[0080] FIG. 7BAn exploded view of an embodiment of an infusion device is depicted, configured with an insertion device for placing a sensing cannula into the subcutaneous tissue of a subject. A base 414 is adhered to an adhesive patch 416 for adhering the device to the skin, and a sensor housing 413 is attached to the top surface of the base 414. The sensing cannula 420 is held by an upper housing 412 and a sensor housing 413, maintaining physical and electrical contact with a flexible circuit 426. An insertion device 460 is placed in the upper housing 412 via an insertion device guide channel 462, which may include a self-sealing diaphragm to seal any remaining opening after removal of the insertion device. The insertion device may include a rigid hollow structure 464 comprising a rigid material such as stainless steel. When assembled, the hollow structure 464 is coaxial with and surrounds the sensing cannula 420. In some embodiments, the hollow structure 464 is used to puncture the subject's skin to place the sensing cannula 420 into a subcutaneous compartment. The insertion device 460 can then be withdrawn through the opening 462, positioning the sensing sleeve 420 within the subject's tissue. The embodiment shown here is substantially vertical. In other embodiments, the sensing sleeve 420 can be positioned at an angle such that it can be formed at an angle of approximately 30 to approximately 45 degrees (e.g., approximately 30 degrees, approximately 31 degrees, approximately 32 degrees, approximately 33 degrees, approximately 34 degrees, approximately 35 degrees, approximately 36 degrees, approximately 37 degrees, approximately 38 degrees, approximately 39 degrees, approximately 40 degrees, approximately 41 degrees, approximately 42 degrees, approximately 43 degrees, approximately 44 degrees, or approximately 45 degrees) between the base of the device 414 and the plane of the skin surface. The sensing cannula 420 can also be positioned at a very shallow angle (e.g., about 1 degree, about 2 degrees, about 3 degrees, about 4 degrees, about 5 degrees, about 6 degrees, about 7 degrees, about 8 degrees, about 9 degrees, about 10 degrees, about 11 degrees, about 12 degrees, about 13 degrees, about 14 degrees, about 15 degrees, about 16 degrees, about 17 degrees, about 18 degrees, about 19 degrees, about 20 degrees, about 21 degrees, about 22 degrees, about 23 degrees, about 24 degrees, about 25 degrees, about 26 degrees, about 27 degrees, about 28 degrees, or about 29 degrees), slightly below the skin surface, as in the case of microneedling.

[0081] FIG. 8A-8D A cross-sectional view of an example of a combined CGM infusion port is provided, including a view of interconnection details. FIG. 8A-8B A cross-section of an embodiment of the infusion device is depicted, wherein an electronic signal processing module is momentarily or permanently attached to the body of a skin-wearing component containing the device. FIG. 8C-8DMore detailed descriptions of the electrical and fluid path connections to the combined sensing sleeve are provided. An electronic signal processing module 540 is shown attached to the body 510. The electrical connection from the signal processing module to the sensing sleeve is provided via a set of electrical contacts 542 and 544, which are electrically connected to a set of contacts on interconnecting circuitry 526 via a set of conductive interface materials 543 and 545. This material may include conductive rubber, conductive adhesive strips, or similar selectively conductive compressible materials. Although two contacts are shown, there may be only a single contact, or more than two contacts to carry additional signals. The interconnecting circuitry 526, which may be a flexible circuit, is in electrical contact with a set of sensor contacts 522 and 524 at the proximal end of the sensing sleeve 520. This contact can be established using various suitable electrical connection materials such as solder or conductive epoxy. The connection may also be coated with a waterproof epoxy or other sealant to prevent moisture intrusion. A fluid connection is established to the proximal end of the combined analyte sensor and infusion cannula 520 via a connecting tube 532 held within the sensor housing 513, which allows fluid to flow from the adjacent needle cavity 536 formed by the sensor housing 513 and the self-sealing diaphragm 534. The sensing cannula 520 exits the base 514 through an opening 518. Inlet to the needle cavity 536 is provided through an opening 530 in the housing 512 and through the self-sealing diaphragm 534 via a fluid delivery device.

[0082] FIG. 9A-9D A cross-sectional view of an example of a combined CGM infusion port that contacts a needle-free insulin pen tip is provided. FIG. 9A-9B A cross-sectional view depicts an embodiment of an infusion device in which the fluid path is configured to dock with or couple (e.g., cooperate) with a drug delivery device. FIG. 9C-9D More detailed descriptions of the electrical and fluid path connections to the combined sensing sleeve are provided. An electronic signal processing module 640 is shown attached to the body 610. A set of electrical connections from the sensing sleeve to a PC board 647 within the signal processing module is established via a set of electrical contacts 642 and 644 on the module, which are electrically connected to a set of contacts on interconnect circuitry 626 via a set of conductive interface materials 643 and 645. This material may include conductive rubber, conductive strips, or similar selectively conductive compressible materials. Although two contacts are shown, there may be only a single contact, or more than two contacts to carry additional signals. The interconnect circuitry 626, which may be flexible circuitry, is in further electrical communication with a set of sensor contacts 622 and 624 at the proximal end of the sensing sleeve 620. FIG. 9DSuch contacts, depicted as spheres on the sensor surface in a cross-sectional view, may include electrical connection materials such as solder, conductive epoxy, or carbon paste. If the set of contacts 622 and 624 are on opposite sides (as depicted), the contacts may be on top and bottom, or if the sensor is configured with two contacts on the same surface, the two contacts may be on the bottom. The connection may also be coated with a waterproof epoxy or other sealant to prevent moisture intrusion. A fluid connection is established to the proximal end of the combined analyte sensor and infusion sleeve 620 via a connecting tube 632 held in the sensor housing 613, which allows fluid to flow out from a chamber 636 formed by the sensor housing 613 and the diaphragm 634. The diaphragm 634 has a pre-formed central hole that is normally closed but allows a blunt tube 658 contained within a mating tip 656 to be squeezed through the central hole. The diaphragm 634 may also have a check valve 635, such as a ball valve or a cross-slit valve, in the fluid path to prevent backflow of fluid (e.g., medication or interstitial fluid) when the pen tip is removed. This has the advantage of preventing the attached pen tip tube 658 from becoming a biohazard. The housing 613 may also have an alignment feature 631 to guide the pen tip 656 into proper alignment during mating. The pen tip 656 can slide the pen housing 655 by the action of a compressible spring 657. The sensing sleeve 620 exits the base 614 attached to the subject's skin through an opening 618 via an adhesive patch 616.

[0083] FIG. 10A-10G A view is provided of an example of a disposable CGM infusion port that contacts a pen with a needle-free insulin pen tip. FIG. 10A-10B A perspective view depicting an embodiment of the infusion device is shown, wherein the fluid path is configured to cooperate with a proprietary drug delivery device. FIG. 10C A cross-sectional view showing details of the fluid path is shown, while FIG. 10D More detailed information is provided regarding the electrical connections to the combined sensing sleeve. An electronic signal processing module 740 is configured for single-use applications, wherein a signal processing electronics module 741 and a sensing sleeve 720 are housed within a single continuous element supported on a housing base 714. A proprietary pen tip 756 is shown engaging with complementary alignment features in the housing of 740. The housing 713 may also have alignment features 731 to guide the pen tip 756 into proper alignment during engagement. The pen tip 756 can slide the pen housing 755 via the action of a compressible spring 757. Fluid is shown being delivered from the interior of the pen 755 through a hollow tube 758 and into the infusion device. The fluid exits through the sensing sleeve 720, which extends through the base 714 via an opening 718. A channel 762 allows for temporary placement of the inserter needle. Further details of the fluid path are provided in... FIG. 10E-10G Described in the text. FIG. 10E-10GCross-sectional views of a disposable CGM infusion port in contact with a pen tip are provided, including cross-sectional views with the pen tip attached. FIG. 10E ), including details of the fluid path portion where the pen tip detaches from the fluid path ( FIG. 10F ), and details of the fluid path portion where the pen tip joins the fluid path ( FIG. 10G A set of electrical connections from signal processing electronics 741 to sensing sleeve 720 is provided via a set of electrical contacts 722 and 724 on the sensor surface, which contacts a socket with a set of contacts 743 and 745. This socket transmits signal current to a PC board 747 containing the electronic signal processing electronics module. The socket contacts may include metal springs or conductive rubber, or conductive strips or similar selectively conductive compressible materials. Although two contacts are shown, there may be only a single contact, or more than two contacts to carry additional signals. The contacts may also include electrical connection materials such as solder or conductive epoxy. The connection may also be coated with waterproof epoxy or other sealants to prevent moisture intrusion.

[0084] FIG. 10E-10G It is truncated to show the various internal features of the device. FIG. 10F The pen tip 756 is shown in contact, where the fluid path tube 758 has been withdrawn, while FIG. 10G The same pen tip is shown, with the fluid path tube 758 fully inserted. (See diagram) FIG. 10E-10G As shown in these cross-sectional views, a fluid connection to the proximal end of the sensing sleeve 720 is established via a connecting tube 732 held in a sensor housing 713, which allows fluid to flow out from a chamber 736 within a fluid path connector 734. The fluid path connector 734 may comprise an elastomeric assembly produced by casting a material such as silicone or rubber (e.g., butyl rubber or ethylene propylene diene monomer (EPDM) rubber). It has a pre-formed central hole 735 that is normally closed but allows a blunt tube 758 contained within a mating tip 756 to be squeezed through the central hole. The fluid path connector may also have a check valve 737, such as a ball valve or a cross-slit valve, in the fluid path to prevent backflow of fluid (e.g., medication or interstitial fluid) when the tip is removed. This has the advantage of preventing the attached tip tube 758 from becoming a biohazard.

[0085] FIG. 11A-11B A view of an example of a combined CGM infusion port with a rigid sensor is provided, including a front cross-sectional view. FIG. 11A ) and a front cross-sectional view showing the fluid path and electrical contact details ( FIG. 11BThese figures depict side cross-sections of an embodiment of the infusion device, wherein an electronic signal processing module is momentarily or permanently attached to a body comprising a skin-wearing component of the device and a sensing cannula configured for insertion without the aid of an inserter needle. The electronic signal processing module 840 is shown attached to the body 810. An interconnecting circuit 826, which may be a flexible circuit, makes electrical contact with a set of sensor contacts 822 and 824 at the proximal end of the sensing cannula 820. These sensor contacts may be on the same side of the cannula or on opposite sides. The contacts may include electrical connection materials such as solder or conductive epoxy and may be encapsulated by a waterproof material such as epoxy or other sealant. A fluid connection to the proximal end of the sensing cannula 820 is established via a connecting tube 832 held in a sensor housing 813, which allows fluid to flow from an adjacent needle cavity 836 formed by the sensor housing 813 and a self-sealing diaphragm 834. The sensing cannula 820 exits the base 814 through an opening 818 and is configured with a sharp tip and sufficient rigidity to penetrate the subject's skin without the need for a separate inserter needle. Access to the needle cavity 836 is provided through an opening 830 in the upper housing 812 and through a fluid delivery device via a self-sealing diaphragm 834.

[0086] FIG. 12A-12C A perspective view is provided showing an example of a combined CGM infusion port configured for attachment to an insulin pump or a gravity-fed drug delivery source. FIG. 12A-12B ) and exploded diagram ( FIG. 12C ). FIG. 12A-12B A perspective view depicting an embodiment of the infusion device is shown, configured to co-locate to the electrical and fluid connections of the sensing cannula, and also configured for use with an insulin pump or a gravity-fed fluid source. FIG. 12CAn exploded view of an embodiment of the infusion device is depicted, configured to co-locate electrical and fluid connections to a unified analyte sensor and a fluid delivery cannula 920, and also configured for use with an insulin pump or a gravity-fed fluid source. The body 910 is shown separate from the electronic signal processing module 940. In one embodiment, the infusion tubing 970 protrudes from an opening 911 formed by an upper housing 912 and a sensor housing 913. The infusion tubing 970 has a coaxial connector 972 that allows temporary attachment to a mating fluid pump connector connected to a source of therapeutic fluid, such as a drug delivery pump or a gravity-fed source. In some embodiments, the infusion tubing 970 is attached to the body 910 via a connector at the end of the body (e.g., having one or more cantilever snap-fit ​​joints that allow reversible attachment of the tubing to the body). The connection from the fluid source to the sensing cannula 920 is established via a fluid path coupler 932 inserted into the infusion tubing 970. The sensing cannula 920 exits the base 916 and adhesive patch 916 via an opening 918. Flexible circuit 926 establishes electrical contact with a set of contacts 922 and 924 on the proximal end of sensing sleeve 920 inside cap 912. Electrical contacts 923 and 925 on the proximal end of flexible circuit 926 maintain contact with a set of contacts 922 and 924 at the proximal end of sensing sleeve 920. Electrical connection to sensor electronics module 940 is provided through a set of elastomeric contacts 943 and 945 exposed to contact sensor electronics module 940. These contacts establish electrical connection via their opposing surfaces with a set of contacts 927 and 928 on flexible circuit 926. A set of retaining arms 918 is disposed on base 914 for temporary attachment of sensor electronics module 940. FIG. 12A An inserter needle 960 is shown for inserting a cannula into the tissue of a subject (e.g., a human, animal, or mammal).

[0087] FIG. 13A-13B A perspective view is provided showing an example of a combined CGM infusion port configured for attachment to an insulin pump or a gravity-fed drug delivery source. FIG. 13A ) and top view section ( FIG. 13BThe electronic modules have been removed, and details of the fluid path and electrical interconnections are shown. These detailed views design implementations of the infusion device, configured to co-locate electrical and fluid connections to the sensing cannula, and also configured for use with an insulin pump or gravity-fed fluid source. In one implementation, the infusion conduit 970 protrudes from an opening 911 in the sensor housing 913. The infusion conduit 970 includes a coaxial connector 972 that allows temporary attachment to a mating fluid pump connector 974, providing fluid connection to a therapeutic fluid source (e.g., a drug delivery pump or gravity-fed source). The connection from the fluid source to the sensing cannula 920 is established via a fluid path coupler 932 inserted into the infusion conduit 970, which passes through the opening 911 in the cap 912. The sensing cannula 920 exits the base 914 via an opening 918. Electrical connection to the sensing sleeve 920 is provided via a set of electrical contacts 923 and 925 on a flexible circuit 926, which maintains contact with a set of contacts 922 and 924 at the proximal end of the sensing sleeve 920. Electrical connection to the sensor electronics module 940 is established via a set of elastomeric electrical contacts on the module, which are electrically connected to a set of contacts 927 and 928 on the flexible circuit 926. A set of retaining arms 918 is disposed on the base 914 for temporary attachment of the sensor electronics module 940.

[0088] FIG. 14A-14D A perspective view is provided of an example of a combined CGM infusion port with a rigid inserter needle or cannula configured for attachment to an insulin pump or gravity-fed drug source. FIG. 14A ), top view section ( FIG. 14B ), front section diagram ( FIG. 14C ) and side section view ( FIG. 14D Figure 14- FIG. 14B The interconnections to electronic devices are shown. Figure 14- FIG. 14D The tubular infusion kit is shown. FIG. 14A-14B Detailed views of an embodiment of the infusion device are depicted, configured to co-locate electrical and fluid connections to a sensing cannula, and also configured for use with an insulin pump or a gravity-fed fluid source, wherein an insertion needle is configured to place the sensing cannula 920 into tissue. In one embodiment, an infusion tubing 970 protrudes from an opening 911 in a sensor housing 913. An inserter 960 is an elongated, needle-shaped open metal strip with a square cross-section, three sides of which are used to surround the sensing cannula 920. The inserter is positioned through an inserter port 962. An electrical connection to a sensor electronics module 940 is established via a set of electrical contacts 927 and 928 on a flexible circuit 926. A compressible material 948 is placed behind the set of contacts 927 and 928 to accommodate compression via the set of contact pins 942 and 944 on the sensor electronics module 940.

[0089] FIG. 14A-14D Detailed views of an embodiment of the infusion device are depicted, configured to co-locate electrical and fluid connections to a sensing sleeve 920, and also configured for use with an insulin pump or gravity-fed fluid source, wherein the sensor fluid path is provided via a rigid tube. In one embodiment, an infusion conduit 970 protrudes from an opening 911 in a sensor housing 913. An upper housing 912 surrounds and secures the components below it. The sensing sleeve 920 has a fluid path including a pre-formed tube 921 that is directly inserted into the infusion conduit 970. The connection can be sealed with a biocompatible adhesive or directly bonded to the infusion conduit 970 using adhesive or thermal bonding techniques. The electrical connection to the sensor electronics module 940 is established via a set of electrical contacts 927 and 928 on a flexible circuit 926. A compressible material 948 is placed behind the set of contacts 927 and 928 to accommodate compression via the set of contact pins 942 and 944 on the sensor electronics module 940.

[0090] While preferred embodiments of the invention have been shown and described herein, it will be readily understood by those skilled in the art that such embodiments are provided by way of example only. The invention is not intended to be limited by the specific examples provided in the specification. Although the invention has been described with reference to the foregoing description, the description and illustrations of embodiments herein should not be interpreted in a limiting sense. Many modifications, alterations, and alternative embodiments will now occur to those skilled in the art without departing from the invention. Furthermore, it should be understood that all aspects of the invention are not limited to those set forth herein, but depend on the specific depiction, configuration, or relative proportions of various conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention. The following claims are intended to define the scope of the invention and therefore cover the methods and structures within the scope of these claims and their equivalents. Therefore, it is contemplated that the invention should also cover any such alternatives, modifications, alterations, or equivalents. The following claims are intended to define the scope of the invention and therefore cover the methods and structures within the scope of these claims and their equivalents.

Claims

1. An apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: The body includes an upper housing, a lower housing, and a bottom skin contact base, wherein the upper housing includes a top surface including a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via an insertion needle, wherein the port includes a visible opening including a self-sealing diaphragm that contacts the lower housing to form an inner cavity; A sensing cannula includes a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel extending within the inner lumen from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface, and a conductor extending on the outer surface from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the at least one indicator electrode is configured to sense the concentration of the analyte, wherein the proximal end of the sensing cannula is retained within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; The channel within the body is in fluid communication with the cavity formed by the proximal end of the self-sealing diaphragm and the sensing sleeve; A signal processing module includes a second body comprising an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface, wherein the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface, wherein the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base; as well as An interface circuit including a proximal end and a distal end, wherein the interface circuit includes one or more conductors configured to transmit a current signal from the sensing sleeve to the signal processing module, wherein the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing sleeve, and wherein the distal end of the interface circuit is in electrical contact with the signal processing module. The upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into the skin surface of a mammal, wherein the hollow inserter needle is configured to facilitate simultaneous sensing of the analyte concentration and fluid delivery of the therapeutic fluid.

2. The device of claim 1, wherein the fluid delivery device comprises a syringe or a pen.

3. The apparatus of claim 2, wherein the fluid delivery device comprises a syringe.

4. The apparatus of claim 2, wherein the fluid delivery device comprises a pen.

5. The apparatus of claim 1, wherein the at least one indicating electrode comprises an enzyme layer covering a conductive surface.

6. The apparatus of claim 5, wherein the enzyme layer is covered with a semi-permeable membrane.

7. The apparatus according to claim 5, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

8. The apparatus of claim 5, wherein the enzyme layer comprises an osmium-based redox mediator.

9. The apparatus of claim 8, wherein the osmium-based redox mediator comprises osmium dimethyl bipyridine.

10. The apparatus of claim 5, wherein the enzyme layer comprises polyvinylimidazole.

11. The apparatus of claim 1, wherein the sensing sleeve includes a reference electrode comprising one or more of silver (Ag) or silver chloride (AgCl).

12. The apparatus of claim 1, wherein the signal processing module provides the sensing sleeve with a bias potential of less than 250 millivolts (mV) relative to a reference potential.

13. The device of claim 1, wherein the channel comprises a stainless steel needle connected from the inner cavity to the proximal end of the sensing sleeve.

14. The device of claim 1, wherein the sensing cannula has sufficient rigidity to be inserted into the skin surface of a mammal without the need for an inserter needle.

15. The device of claim 1, wherein the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject.

16. The apparatus of claim 1, wherein the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens.

17. The apparatus of claim 16, wherein the analyte is glucose.

18. The device of claim 1, wherein the therapeutic fluid is selected from insulin or insulin analogs, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals.

19. The device of claim 18, wherein the therapeutic fluid is insulin or an insulin analogue formulation.

20. The device of claim 19, wherein the insulin or the insulin analog formulation comprises an excipient comprising phenol or cresol.

21. An apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: The body includes an upper housing, a lower housing, a bottom skin contact base, and an infusion conduit extending outward from the body, the infusion conduit being configured to connect to a source of the therapeutic fluid; A sensing cannula includes a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel extending within the inner lumen from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the at least one indicator electrode is configured to sense the concentration of the analyte, wherein the proximal end of the sensing cannula is retained within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; The channel within the body is in fluid communication with an inner cavity formed by the self-sealing diaphragm and the proximal end of the sensing sleeve; A signal processing module includes a second body comprising an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface, wherein the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface, wherein the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base; as well as An interface circuit including a proximal end and a distal end, wherein the interface circuit includes one or more conductors configured to transmit a current signal from the sensing sheath to the signal processing module, wherein the proximal end of the interface circuit is electrically contacted with the proximal end of the sensing sheath, and wherein the distal end of the interface circuit is electrically contacted with the signal processing module, wherein the upper housing and the lower housing are configured to receive a hollow inserter needle that partially surrounds the sensing sheath for insertion into the skin surface of a mammal, wherein the hollow inserter needle is configured to facilitate simultaneous sensing of the analyte concentration and fluid delivery of the therapeutic fluid.

22. The apparatus of claim 21, wherein the infusion conduit is reversibly attached to the body via a connector comprising one or more cantilever snap-fit ​​joints configured to allow reversible attachment of the infusion conduit.

23. The apparatus of claim 21, wherein the at least one indicating electrode comprises an enzyme layer covering a conductive surface.

24. The apparatus of claim 23, wherein the enzyme layer is covered with a semi-permeable membrane.

25. The apparatus of claim 23, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

26. The apparatus of claim 23, wherein the enzyme layer comprises an osmium-based redox mediator.

27. The apparatus of claim 26, wherein the osmium-based redox mediator comprises osmium dimethyl bipyridine.

28. The apparatus of claim 23, wherein the enzyme layer comprises polyvinylimidazole.

29. The apparatus of claim 21, wherein the sensing sleeve comprises a reference electrode containing one or more of silver (Ag) or silver chloride (AgCl).

30. The apparatus of claim 21, wherein the signal processing module provides the sensing sleeve with a bias potential of less than 250 millivolts (mV) relative to a reference potential.

31. The device of claim 21, wherein the channel comprises a stainless steel needle connected from the inner cavity to the proximal end of the sensing sleeve.

32. The device of claim 21, wherein the sensing cannula has sufficient rigidity to be inserted into the skin surface of a mammal without the need for an inserter needle.

33. The device of claim 21, wherein the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject.

34. The apparatus of claim 21, wherein the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens.

35. The apparatus of claim 34, wherein the analyte is glucose.

36. The device of claim 21, wherein the therapeutic fluid is selected from insulin or insulin analogs, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals.

37. The device of claim 36, wherein the therapeutic fluid is insulin or an insulin analogue formulation.

38. The device of claim 37, wherein the insulin or the insulin analog formulation comprises an excipient comprising phenol or cresol.

39. An apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: The body includes an upper housing, a lower housing, and a bottom skin contact base, wherein the upper housing includes a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via an insertion needle, wherein the port includes a visible opening that includes a self-sealing diaphragm that contacts the lower housing to form an inner cavity; A sensing cannula includes a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel extending within the inner lumen from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the at least one indicator electrode is configured to sense the concentration of the analyte, wherein the proximal end of the sensing cannula is retained within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; as well as A channel within the body, the channel being in fluid communication with the cavity formed by the proximal end of the self-sealing diaphragm and the sensing sleeve, The upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into the skin surface of a mammal, wherein the hollow inserter needle is configured to facilitate simultaneous sensing of the analyte concentration and fluid delivery of the therapeutic fluid.

40. The device of claim 39, wherein the upper housing includes a top surface containing the port.

41. The apparatus of claim 39, wherein the port includes a visible opening, the visible opening including the self-sealing diaphragm.

42. The apparatus of claim 39 further includes a signal processing module configured to receive current from the sensing bushing.

43. The apparatus of claim 42, wherein the signal processing module is configured to provide a potential to the sensing sleeve.

44. The apparatus of claim 43, wherein the signal processing module includes a second body, the second body including an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface.

45. The apparatus of claim 44, wherein the vertical surface provides a potential to the sensing sleeve and receives the current from the sensing sleeve via a set of electrical contacts on the vertical surface.

46. ​​The device of claim 45, wherein the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base.

47. The apparatus of claim 42 further includes an interface circuit configured to transmit a current signal from the sensing sleeve to the signal processing module.

48. The apparatus of claim 47, wherein the interface circuitry comprises a near end and a far end.

49. The apparatus of claim 48, wherein the interface circuitry includes one or more conductors configured to transmit the current signal from the sensing sleeve to the signal processing module.

50. The apparatus of claim 49, wherein the proximal end of the interface circuit is electrically contacted with the proximal end of the sensing sleeve, and wherein the distal end of the interface circuit is electrically contacted with the signal processing module.

51. The apparatus of claim 39, wherein the fluid delivery device comprises a syringe or a pen.

52. The apparatus of claim 51, wherein the fluid delivery device comprises a syringe.

53. The apparatus of claim 51, wherein the fluid delivery device comprises a pen.

54. The apparatus of claim 39, wherein the at least one indicating electrode comprises an enzyme layer covering a conductive surface.

55. The apparatus of claim 54, wherein the enzyme layer is covered with a semi-permeable membrane.

56. The apparatus of claim 54, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

57. The apparatus of claim 54, wherein the enzyme layer comprises an osmium-based redox mediator.

58. The apparatus of claim 57, wherein the osmium-based redox mediator comprises osmium dimethyl bipyridine.

59. The apparatus of claim 54, wherein the enzyme layer comprises polyvinylimidazole.

60. The apparatus of claim 39, wherein the sensing sleeve includes a reference electrode comprising one or more of silver (Ag) or silver chloride (AgCl).

61. The apparatus of claim 42, wherein the signal processing module provides the sensing sleeve with a bias potential of less than 250 millivolts (mV) relative to a reference potential.

62. The device of claim 39, wherein the channel comprises a stainless steel needle connected from the inner cavity to the proximal end of the sensing sleeve.

63. The device of claim 39, wherein the sensing cannula has sufficient rigidity to be inserted into the skin surface of a mammal without the need for an inserter needle.

64. The device of claim 39, wherein the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject.

65. The apparatus of claim 39, wherein the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens.

66. The apparatus of claim 65, wherein the analyte is glucose.

67. The device of claim 39, wherein the therapeutic fluid is selected from insulin or insulin analogs, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals.

68. The device of claim 67, wherein the therapeutic fluid is insulin or an insulin analogue formulation.

69. The device of claim 68, wherein the insulin or the insulin analog formulation comprises an excipient comprising phenol or cresol.

70. An apparatus configured to simultaneously sense analyte concentration and therapeutic fluid administration, comprising: The body includes an upper housing, a lower housing, a bottom skin contact base, and an infusion conduit extending outward from the body, wherein the infusion conduit is configured to be connected to a source of the therapeutic fluid; A sensing cannula includes a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel extending within the inner lumen from the proximal end of the sensing cannula to the distal end of the sensing cannula, at least one indicator electrode on the outer surface, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, wherein the at least one hollow channel is configured for the administration of the therapeutic fluid, wherein the at least one indicator electrode is configured to sense the concentration of the analyte, wherein the proximal end of the sensing cannula is retained within the body, and wherein the distal end of the sensing cannula extends from the skin contact base; as well as The channel within the body is in fluid communication with an inner cavity formed by the self-sealing diaphragm and the proximal end of the sensing sleeve. The upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into the skin surface of a mammal, wherein the hollow inserter needle is configured to facilitate simultaneous sensing of the analyte concentration and fluid delivery of the therapeutic fluid.

71. The apparatus of claim 70, further comprising a signal processing module configured to receive current from the sensing bushing.

72. The apparatus of claim 71, wherein the signal processing module is configured to provide a potential to the sensing sleeve.

73. The apparatus of claim 72, wherein the signal processing module includes a second body, the second body including an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface.

74. The apparatus of claim 73, wherein the vertical surface provides a potential to the sensing sleeve and receives current from the sensing sleeve via a set of electrical contacts on the vertical surface.

75. The device of claim 74, wherein the second body includes a set of arms that contact the upper housing, and wherein the lower surface contacts the skin contact base.

76. The apparatus of claim 71 further includes an interface circuit configured to transmit a current signal from the sensing sleeve to the signal processing module.

77. The apparatus of claim 76, wherein the interface circuitry comprises a near end and a far end.

78. The apparatus of claim 77, wherein the interface circuitry includes one or more conductors configured to transmit the current signal from the sensing sleeve to the signal processing module.

79. The apparatus of claim 78, wherein the proximal end of the interface circuit is electrically contacted with the proximal end of the sensing sleeve, and wherein the distal end of the interface circuit is electrically contacted with the signal processing module.

80. The apparatus of claim 70, wherein the infusion conduit is reversibly attached to the body via a connector comprising one or more cantilever snap-fit ​​joints configured to allow reversible attachment of the infusion conduit.

81. The apparatus of claim 70, wherein the at least one indicating electrode comprises an enzyme layer covering a conductive surface.

82. The apparatus of claim 81, wherein the enzyme layer is covered with a semi-permeable membrane.

83. The apparatus of claim 82, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

84. The apparatus of claim 82, wherein the enzyme layer comprises an osmium-based redox mediator.

85. The apparatus of claim 84, wherein the osmium-based redox mediator comprises osmium dimethyl bipyridine.

86. The apparatus of claim 81, wherein the enzyme layer comprises polyvinylimidazole.

87. The apparatus of claim 70, wherein the sensing sleeve includes a reference electrode comprising one or more of silver (Ag) or silver chloride (AgCl).

88. The apparatus of claim 71, wherein the signal processing module provides the sensing sleeve with a bias potential of less than 250 millivolts (mV) relative to a reference potential.

89. The device of claim 70, wherein the channel comprises a stainless steel needle connected from the inner cavity to the proximal end of the sensing sleeve.

90. The device of claim 70, wherein the sensing cannula has sufficient rigidity to be inserted into the skin surface of a mammal without the need for an inserter needle.

91. The device of claim 70, wherein the skin contact base includes an adhesive surface configured to attach the device to the skin surface of a subject.

92. The apparatus of claim 70, wherein the analyte is selected from oxygen, glucose, lactate, drug metabolites, and pathogens.

93. The apparatus of claim 92, wherein the analyte is glucose.

94. The device of claim 70, wherein the therapeutic fluid is selected from insulin or insulin analogs, glatiramer acetate, heparin, human menopausal gonadotropins, vitamins, and minerals.

95. The device of claim 94, wherein the therapeutic fluid is insulin or an insulin analogue formulation.

96. The device of claim 95, wherein the insulin or the insulin analog formulation comprises an excipient comprising phenol or cresol.

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