Infusion device for continuous glucose monitoring

Abstract

The present disclosure discloses devices and systems that use a combined sensor and cannula mounted to a body. The combination provides electrical coupling of the sensor to a signal processing device and fluidic coupling of the cannula to a drug delivery source for combined subcutaneous liquid drug delivery and amperometric analyte sensing without the need for multiple skin-piercing elements.SOLUTION: The present disclosure provides systems and devices for combining analyte monitoring with fluid delivery, including devices having a sensor and a cannula in a single component and adapted for use with a combined sensor and cannula. These systems and devices may be used for a variety of applications involving simultaneous in vivo monitoring of analyte concentration and drug delivery.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] cross reference

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 861,940, filed June 14, 2019, the entire contents of which are incorporated herein by reference. [Background technology]

[0002]

[0002] Amperometric analyte sensors can be used to detect a variety of analytes, including oxygen, pH, glucose, lactate, drug metabolites, and pathogens in vivo. Additionally, sensors for continuous glucose monitoring (CGM) may be widely adopted clinically. These CGM sensors may be placed in subcutaneous tissue and generate a small, glucose-dependent current, which is detected by associated electronics. In many cases, it is desirable to both track analyte concentrations and deliver medications responsive to analyte levels. For example, this may be implemented in the case of glucose analyte monitoring and insulin medication delivery, as insulin pumps may feature automatic insulin dosing based on readings from CGM sensors. Summary of the Invention [Problem to be solved by the invention]

[0003] The present disclosure discloses devices and systems that use a body-mounted sensor and cannula combination that provides electrical coupling of the sensor to a signal processing device and fluid coupling of the cannula to a drug delivery source for combined subcutaneous liquid drug delivery and amperometric analyte sensing without the need for multiple skin-piercing elements. [Means for solving the problem]

[0004] In one aspect, the disclosure provides a device configured for simultaneously sensing an analyte concentration and administering a therapeutic fluid, the device comprising: a body having an upper housing, a lower housing, and a bottom skin-contacting base, the upper housing having an upper surface including a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via insertion of a needle, the port having a visible opening including a self-sealing septum in contact with the lower housing, thereby forming an internal cavity; and a sensing cannula having a proximal end, a distal end, an outer surface, an internal lumen, at least one hollow channel in the internal lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula and configured to administer a therapeutic fluid, at least one indicator electrode on the outer surface configured to sense the analyte concentration, and a conductor on the outer surface extending from the proximal end of the sensing cannula to the at least one indicator electrode, a sensing cannula, the proximal end of which is held within the body and the distal end of the sensing cannula extends from the skin-contacting base; a channel within the body that is in fluid communication with an internal cavity formed by the self-sealing septum and the proximal end of the combined sensing cannula; a signal processing module having a second body including an upper surface, a lower surface, and a vertical surface between the upper and lower surfaces, the vertical surface providing an electrical potential to the sensing cannula and receiving current from the sensing cannula via a set of electrical contacts on the vertical surface, the second body having a set of arms that contact the upper housing and the lower surface that contacts the skin-contacting base; and an interface circuit having a proximal end and a distal end, the interface circuit including one or more conductors configured to conduct a current signal from the sensing cannula to the signal processing module, the proximal end of the interface circuit in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit in electrical contact with the signal processing module.

[0005] 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, at least one indicator electrode comprises an enzyme layer covering a conductive surface. In some embodiments, the enzyme layer is coated 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 dimethylbipyridine. 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 of less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel comprises a stainless steel needle connecting from the cavity to the proximal end of the sensing cannula. 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 is sufficiently rigid for insertion into the skin surface of a mammal without the use of an inserter needle. In some embodiments, the skin-contacting base comprises an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, 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 additive comprising phenol or cresol.

[0006]

[0006] In another aspect, the disclosure provides a device configured for simultaneously sensing an analyte concentration and administering a therapeutic fluid, comprising: a body having an upper housing, a lower housing, a bottom skin-contacting base, and an injection tube extending outwardly from the body and configured to connect to a source of therapeutic fluid; a sensing cannula having a proximal end, a distal end, an outer surface, an inner lumen, at least one hollow channel in the inner lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula and configured to administer therapeutic fluid, at least one indicator electrode on the outer surface configured to sense the analyte concentration, 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 proximal end of the sensing cannula is retained within the body and the distal end of the sensing cannula extends from the skin-contacting base; and a self-sealing septum. and a channel in the body in fluid communication with an internal cavity formed by the proximal end of the combined sensing cannula; a signal processing module having a second body including an upper surface, a lower surface, and a vertical surface between the upper and lower surfaces, the vertical surface providing an electrical potential to the sensing cannula and receiving current from the sensing cannula via a set of electrical contacts on the vertical surface, the second body having a set of arms in contact with the upper housing and the lower surface in contact with the skin-contacting base; and an interface circuit having a proximal end and a distal end, the interface circuit including one or more conductors configured to conduct a current signal from the sensing cannula to the signal processing module, the proximal end of the interface circuit in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit in electrical contact with the signal processing module.

[0007] In some embodiments, the injection tube is reversibly attached to the body, and the connector comprises one or more cantilever snap joints configured to allow reversible attachment of the injection tube. In some embodiments, the at least one indicator electrode comprises a conductive surface In some embodiments, the sensing cannula comprises an enzyme layer covering the sensing cannula. In some embodiments, the enzyme layer is coated 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 dimethylbipyridine. 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 of less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel comprises a stainless steel needle connecting from the cavity to the proximal end of the sensing cannula. 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 is sufficiently rigid to be inserted into the skin surface of a mammal without the use of an inserter needle. In some embodiments, the skin-contacting base comprises an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, 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 additive comprising phenol or cresol.

[0008] In another aspect, the disclosure provides a device configured for simultaneously sensing an analyte concentration and administering a therapeutic fluid, the device comprising: a body having an upper housing, a lower housing, and a bottom skin-contacting base, the upper housing including a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via insertion of a needle, the port including a self-sealing septum in contact with the lower housing, thereby forming an internal cavity; and a sensing cannula having a proximal end, a distal end, an outer surface, an internal lumen, and a distal end extending from the proximal end of the sensing cannula. a sensing cannula comprising at least one hollow channel within the internal lumen extending from the proximal end of the cannula to the distal end of the sensing cannula and configured to administer a therapeutic fluid, at least one indicator electrode on the outer surface configured to sense an analyte concentration, and a conductor on the outer surface extending from the proximal end of the cannula to the at least one indicator electrode, the proximal end of the sensing cannula being held within the body and the distal end of the sensing cannula extending from the skin-contacting base; and a channel within the body in fluid communication with an internal cavity formed by the self-sealing septum and the proximal end of the combined sensing cannula.

[0009]

[0009] In some embodiments, the upper housing comprises an upper surface including a port. In some embodiments, the port comprises a visible opening including a self-sealing septum. In some embodiments, the device further comprises a signal processing module configured to receive an electrical current from the sensing cannula. In some embodiments, the signal processing module is configured to provide an electrical potential to the sensing cannula. In some embodiments, the signal processing module comprises 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 an electrical potential to the sensing cannula and receives an electrical current from the sensing cannula via a set of electrical contacts on the vertical surface. In some embodiments, the second body comprises a set of arms that contact the upper housing, and a lower surface that contacts the skin-contacting base. In some embodiments, the device conveys an electrical current signal from the sensing cannula to the signal processing module. The fluid delivery device further comprises an interface circuit configured to: transmit a current signal from the sensing cannula to the signal processing module; in some embodiments, the interface circuit comprises a proximal end and a distal end; in some embodiments, the interface circuit comprises one or more conductors configured to conduct a current signal from the sensing cannula to the signal processing module; in some embodiments, the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing cannula, and the distal end of the interface circuit is in electrical contact with the signal processing module; 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 the conductor surface; in some embodiments, the enzyme layer is coated 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 dimethylbipyridine; in some embodiments, the enzyme layer comprises polyvinylimidazole. In some embodiments, the sensing cannula includes 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 includes a stainless steel needle that connects from a cavity to the proximal end of the sensing cannula. 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 is sufficiently rigid to be inserted into the skin surface of a mammal without the use of an inserter needle. In some embodiments, the skin-contacting 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 the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, 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 additive comprising phenol or cresol.

[0010] In another aspect, the present disclosure provides a device configured to simultaneously sense an analyte concentration and administer a therapeutic fluid, the device comprising: a body having an upper housing, a lower housing, a bottom skin-contacting base, and an injection tube extending outwardly from the body and configured to connect to a source of therapeutic fluid; and a sensing cannula having a proximal end, a distal end, an outer surface, an internal lumen, and an internal lumen extending from the proximal end of the sensing cannula to the distal end of the sensing cannula and configured to administer the therapeutic fluid. a sensing cannula having at least one hollow channel, at least one indicator electrode on an outer surface configured to sense an analyte concentration, and a conductor on the outer surface extending from a proximal end of the sensing cannula to the at least one indicator electrode, the proximal end of the sensing cannula being held within the body and the distal end of the sensing cannula extending from a skin-contacting base; and a channel within the body in fluid communication with an internal cavity formed by the self-sealing septum and the proximal end of the combined sensing cannula.

[0011] In some embodiments, the device further comprises a signal processing module configured to receive the electrical current from the sensing cannula. In some embodiments, the signal processing module is configured to provide an electrical potential to the sensing cannula. In some embodiments, the signal processing module is configured to provide an electrical potential to the sensing cannula. In some embodiments, the signal processing module is configured to provide an electrical potential to the sensing cannula. The device further comprises a second body including a first end and a second end. In some embodiments, the vertical surface provides an electrical potential to the sensing cannula and receives an electrical current from the sensing cannula via a set of electrical contacts on the vertical surface. In some embodiments, the second body comprises a set of arms that contact the upper housing, and a lower surface that contacts the skin-contacting base. In some embodiments, the device further comprises an interface circuit configured to conduct an electrical current signal from the sensing cannula to the signal processing module. In some embodiments, the interface circuit comprises a proximal end and a distal end. In some embodiments, the interface circuit comprises one or more conductors configured to conduct an electrical current signal from the sensing cannula to the signal processing module. In some embodiments, the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing cannula, and the distal end of the interface circuit is in electrical contact with the signal processing module. In some embodiments, the injection tube is reversibly attached to the body, and the connector comprises one or more cantilever snap joints configured to enable reversible attachment of the injection tube. In some embodiments, at least one indicator electrode comprises an enzyme layer covering a conductor surface. In some embodiments, the enzyme layer is coated with a semipermeable membrane. In some embodiments, the enzyme layer comprises glucose oxidase or glucose dehydrogenase. In some embodiments, the enzyme layer includes an osmium-based redox mediator. In some embodiments, the osmium-based redox mediator comprises osmium dimethylbipyridine. 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 of less than 250 millivolts (mV) relative to a reference potential. In some embodiments, the channel comprises a stainless steel needle connecting from the cavity to the proximal end of the sensing cannula.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 is sufficiently rigid for insertion into the skin surface of a mammal without the use of an inserter needle. In some embodiments, the skin-contacting base comprises an adhesive surface configured to attach the device to the skin surface of a subject. In some embodiments, the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens. In some embodiments, the analyte is glucose. In some embodiments, the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, 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 additive comprising phenol or cresol.

[0012]

[0012] In some embodiments, the body is circular or substantially circular and has an accessible surface on one side having a self-sealing inlet port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery channel connecting the inlet port to the cannula; a cavity for receiving an electronic signal processing device; a retaining mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0013]

[0013] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, and includes an accessible surface on one side having a self-sealing inlet port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery channel connecting the inlet port to the cannula; an electronic signal processing device with a set of arms that attach the electronic signal processing device to the housing of the liquid delivery channel; a holding mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0014]

[0014] In some embodiments, the body is oval or substantially oval and includes an accessible surface on one side having a self-sealing inlet port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery channel connecting the inlet port to the cannula; an electronic signal processing device mounted on a vertical surface of the body; a retention mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0015]

[0015] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, and includes an accessible surface on one side having a segment of an injection tube protruding therefrom; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery tube connecting the injection tube to the cannula; a set of holding arms designed to align and hold an electronic signal processing device; features designed to receive the mounting arms of the electronic signal processing device; and an electrical contact interface between the signal processing device and the sensor.

[0016]

[0016] In some embodiments, the body is essentially circular or elliptical and includes an accessible surface on one side having a segment of an injection tube protruding therefrom; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outward therefrom; a liquid delivery tube connecting the injection tube to the cannula; a self-sealing port connected to the liquid delivery channel; a holding arm designed to align and hold an electronic signal processing device; a feature designed to receive the mounting arm of the electronic signal processing device; and an electrical contact interface between the signal processing device and the sensor.

[0017] In some embodiments, the cannula projects outward from the skin-contacting surface at an angle of 40-60°. In some embodiments, the cannula projects outward perpendicularly or substantially perpendicularly from the skin-contacting surface.

[0018] In some embodiments, the device is configured to be inserted or driven into the skin using an insertion device. The insertion device may be in temporary contact with the accessible surface of the body. In some embodiments, the cannula is constructed essentially of a flexible polymer and has a fluid pathway placed into the tissue using a rigid inserter element or trocar that is immediately removed after insertion. In some embodiments, the insertion device includes an insertion needle that pierces a self-sealing entry port, penetrates the fluid delivery channel, and extends slightly beyond the distal end of the cannula. In some embodiments, the cannula includes a fluid pathway formed by a permanently fixed needle that may be placed into the tissue and remains there for the duration of use.

[0019]

[0019] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which merely illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

[0020] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent that any publications and patents or patent applications incorporated by reference conflict with the disclosure contained herein, this specification is not intended to supersede and / or supersede any such conflicting material. will be done.

[0021] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (herein referred to as "Figures"), in which:

[0022]

[0022] Embodiments will be readily understood from the following detailed description, taken in conjunction with the accompanying drawings and claims. The embodiments are illustrated by way of example and not by way of limitation in the accompanying drawings. [Brief explanation of the drawings]

[0023] [Figure 1A]

[0023] FIG. 1 is a perspective view of an example of a combined CGM infusion port with a removable internal electronic module. [Figure 1B]

[0024] 1B is another perspective view of the combined CGM infusion port of FIG. 1A with the removable internal electronic module removed. [Figure 2]

[0025] FIG. 1B is an exploded view of the combined CGM injection port of FIG. 1A. [Figure 3A]

[0026] 1 is a cross-sectional view of an example of a combined CGM infusion port with a removable internal electronic module and insertion device. [Figure 3B]

[0026] FIG. 1 is a cross-sectional view of an example of a combined CGM infusion port with a removable internal electronic module and insertion device. [Figure 3C]

[0026] FIG. 1 is a cross-sectional view of an example of a combined CGM infusion port with a removable internal electronic module and insertion device. [Figure 4]

[0027] FIG. 10 is a cross-sectional view of an example combined CGM infusion port with a removable internal electronic module. [Figure 5]

[0028] FIG. 1 is a cross-sectional view of an example of a combined CGM infusion port with a removable internal electronic module, with a fluid delivery device inserted into the skin of a subject (e.g., a patient), and with a syringe positioned within the device to provide fluid delivery (e.g., drug delivery) to the subject. [Figure 6A]

[0029] FIG. 1 is a perspective view of an example of a combined CGM infusion port with a removable external electronic module. [Figure 6B]

[0029] FIG. 1 is a perspective view of an example of a combined CGM infusion port with a removable external electronic module. [Figure 7A]

[0030] FIG. 6C is an exploded view of the combined CGM injection port of FIGS. 6A and 6B. [Figure 7B] FIG. 6C is an exploded view of the combined CGM injection port of FIGS. 6A and 6B, including a view of the inserter needle. [Figure 8A]

[0031] FIG. 1 is a cross-sectional view of an example of a composite CGM infusion port, including a detailed view of the interconnections, showing a side cross section. [Figure 8B]

[0031] FIG. 1 is a cross-sectional view of an example composite CGM injection port, showing a front cross section, including a detailed view of the interconnections. [Figure 8C]

[0031] FIG. 1 is a cross-sectional view of an example composite CGM injection port, including a detailed view of the interconnections, and a side cross-sectional view showing details of the fluid pathways and electrical contacts. [Figure 8D]

[0031] FIG. 1 is a cross-sectional view of an example composite CGM injection port, including a view of the interconnect details, showing a front cross-section and detailing the fluid pathways and electrical contacts. [Figure 9A]

[0032] FIG. 10 is a cross-sectional view of an example of a combined CGM infusion port contacting the tip of a needleless insulin pen, showing a side cross section. [Figure 9B]

[0032] Figure 1 shows a cross-sectional view and a front cross-section of an example of a combined CGM injection port that contacts the tip of a needleless insulin pen. [Figure 9C]

[0032] Figure 1 shows a cross-sectional view of an example of a combined CGM injection port that contacts the tip of a needleless insulin pen, with a side cross-section showing details of the fluid pathways and electrical contacts. [Figure 9D]

[0032] Figure 1 shows a cross-sectional view of an example of a combined CGM injection port that contacts the tip of a needleless insulin pen, with a front cross-section showing details of the fluid pathways and electrical contacts. [Figure 10A]

[0033] FIG. 1 is a diagram of an example of a disposable CGM infusion port contacting a pen having a needleless insulin pen tip; FIG. 2 is a perspective view of the disposable CGM infusion port with the pen tip attached. [Figure 10B]

[0033] FIG. 1 is a diagram of an example of a disposable CGM infusion port that contacts a pen having a needleless insulin pen tip. FIG. 2 is a perspective view of a disposable CGM infusion port, including internal structures (e.g., electronics). [Figure 10C]

[0033] A diagram of an example of a disposable CGM injection port that contacts a pen having a needle-less insulin pen tip, and a cutaway view of the disposable CGM injection port with the pen tip attached and including a fluid path. [Figure 10D]

[0033] A diagram of an example of a disposable CGM infusion port that contacts a pen having a needleless insulin pen tip, and a cross-sectional view of the disposable CGM infusion port, including details of the electrical interconnections of the sensors. [Figure 10E]

[0033] A diagram of an example of a disposable CGM injection port that contacts a pen having a needle-free insulin pen tip, including a cross-sectional view of the pen tip attached, and a cross-sectional view of a disposable CGM injection port that contacts a pen having a needle-free insulin pen tip. [Figure 10F]

[0033] A diagram of an example of a disposable CGM injection port that contacts a pen having a needleless insulin pen tip, including a detail of the fluid path cross section where the pen tip is disengaged from the fluid path, and a cross section of a disposable CGM injection port that contacts a pen having a needleless insulin pen tip. [Figure 10G]

[0033] A diagram of an example of a disposable CGM injection port that contacts a pen having a needleless insulin pen tip, including a detail of the fluid path cross section where the pen tip engages with the fluid path, and a cross section of a disposable CGM injection port that contacts a pen having a needleless insulin pen tip. [Figure 11A]

[0034] 10A-10C are diagrams of examples of composite CGM infusion ports with rigid sensors, including frontal cross sections. [Figure 11B]

[0034] FIG. 1 is a diagram of an example of a composite CGM injection port with a hard sensor, including a front cross section showing details of the fluid path and electrical contacts. [Figure 12A]

[0035] FIG. 1 is a perspective view of an example of a combined CGM infusion port configured to attach to an insulin pump or gravity-fed source of medication. [Figure 12B]

[0035] FIG. 1 is a perspective view of an example combined CGM infusion port configured to attach to an insulin pump or gravity-fed source of medication. [Figure 12C]

[0035] FIG. 1 is an exploded view of an example combined CGM infusion port configured to attach to an insulin pump or gravity-fed source of medication. [Figure 13A]

[0036] FIG. 1 is a perspective view of an example of a combined CGM infusion port configured to attach to an insulin pump or gravity-fed source of medication with the electronic module detached, showing details of the fluid paths and electrical interconnections. [Figure 13B]

[0036] A top cross-sectional view of an example of a combined CGM infusion port configured to attach to an insulin pump or gravity-fed source of medication with the electronic module detached, showing details of the fluid paths and electrical interconnections. [Figure 14A]

[0037] FIG. 1 is a perspective view of an example of a combined CGM infusion port configured to attach to an insulin pump with a rigid inserter needle or trocar, or to a gravity-fed drug source, showing interconnection to electronics. [Figure 14B]

[0037] A top cross-sectional view of an example of a combined CGM infusion port configured to attach to an insulin pump with a rigid inserter needle or trocar, or a gravity-fed drug source, showing interconnection to electronics. [Figure 14C]

[0037] A front cross-sectional view of an example of a combined CGM infusion port configured to attach to an insulin pump with a rigid inserter needle or trocar, or a gravity-fed drug source, showing a tubular infusion set. [Figure 14D]

[0037] A side cross-sectional view of an example of a combined CGM infusion port configured to attach to an insulin pump with a rigid inserter needle or trocar, or a gravity-fed drug source, showing a tubular infusion set. DETAILED DESCRIPTION OF THE INVENTION

[0024]

[0038] Reference is now made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration exemplary embodiments that may be practiced. Other embodiments may be utilized and structural or logical changes may be made without departing from the scope. Therefore, the following detailed description is not to be construed as limiting.

[0025]

[0039] Various operations may be described in sequence as multiple separate operations to aid in understanding the embodiments; however, the order of description should not be construed to imply that these operations are order dependent.

[0026]

[0040] The description may use viewpoint-based descriptions such as above / below, back / front, and top / bottom, etc. Such descriptions are used for ease of discussion only and are not intended to limit the application of the disclosed embodiments.

[0027]

[0041] As used herein, the term "cannula" generally refers to a hollow tube made using a rigid material, such as a polymer or metal, having an inner (e.g., inner surface) and an outer (e.g., outer surface) surface, and openings at both ends.

[0028]

[0042] As used herein, the term "sensing cannula" generally refers to a cannula having an analyte sensor disposed on an exterior surface and one or more fluid delivery channels contained within the cannula.

[0029]

[0043] As used herein, the term "continuous glucose monitor (CGM)" generally refers to a system comprising electronic devices configured to continuously or nearly continuously measure glucose levels from a subject (e.g., a human, animal, or mammal) and / or report such measurements.

[0030]

[0044] As used herein, the term "CGM injection port" generally refers to a device (e.g., an integrated device) configured for use on the skin of a subject (e.g., a human, animal, or mammal) that has a sensor and cannula combination that includes an electrical interface to signal acquisition electronics, and a port for attaching a fluid source, such as an insulin pen, syringe, or another fluid delivery device.

[0031]

[0045] As used herein, the term "CGM infusion set" generally refers to a device (e.g., an integrated device) configured for use on the skin of a subject (e.g., a human, animal, or mammal) that has a sensor and cannula combination that includes an electrical interface to signal acquisition electronics, and a port for attaching a fluid source, such as a pump or gravity-fed source.

[0032]

[0046] The terms "coupled" and "connected," along with their derivatives, may be used herein. It should be understood that these terms are not intended as synonyms for each other. Rather, in particular embodiments, "connected" may be used to indicate that two or more elements are in direct physical or electrical contact with each other. "Coupled" refers to two elements that are in direct physical or electrical contact with each other. Although "coupled" may be used to indicate that the elements are in direct physical or electrical contact, it may also be used to indicate that two or more elements are not in direct contact with each other, but yet still co-operate or interact with each other.

[0033]

[0047] As used herein, a phrase of the form "A / B" or of the form "A and / or B" means (A), (B), or (A and B). For purposes of description, a phrase of the form "at least one of A, B, and C" means (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C). For purposes of description, a phrase of the form "(A)B" means (B) or (AB), i.e., A is an optional element.

[0034]

[0048] As used herein, the term "embodiment" or "embodiments" may each refer to one or more of the same or different embodiments. Furthermore, when used with respect to embodiments, the terms "comprising," "including," "having," etc. are synonymous and are generally "open" 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.).

[0035]

[0049] With respect to the use of any plural and / or singular terms herein, the plural may be construed as the singular and / or the singular may be construed as the plural, where appropriate by context and / or application. Various singular / plural permutations may be expressly set forth herein for clarity.

[0036]

[0050] An increasing number of pharmaceutical therapies involve subcutaneous infusion of liquid treatments. For example, glatiramer acetate, a treatment for multiple sclerosis, may be prescribed for daily subcutaneous injection. As another example, heparin may be administered via repeated subcutaneous injections as a treatment for certain clotting disorders. As another example, human menopausal urinary gonadotropin is injected subcutaneously daily to women undergoing infertility treatment. As another example, pediatric patients receiving parenteral nutrition may receive repeated subcutaneous doses of multivitamins. Subcutaneous injections are also commonly used in veterinary medicine.

[0037]

[0051] One of the largest populations for daily subcutaneous injections are individuals receiving insulin therapy for type 1 or type 2 diabetes. Many of these subjects may receive more than one injection per day, a regimen known as multiple-injection (MDI) therapy. For example, an injection port for drug delivery may be designed to be attached to the skin surface with a percutaneous cannula extending perpendicularly from the base (e.g., as described in U.S. Pat. No. 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 multiple days, delivering the drug without the need for additional painful injections.

[0038]

[0052] Amperometric analyte sensors can be used to detect a variety of analytes, such as oxygen, pH, glucose, lactate, drug metabolites, and pathogens in vivo. Additionally, sensors for continuous glucose monitoring (CGM) may be widely adopted clinically. These CGM sensors may be placed in subcutaneous tissue to generate a small, glucose-dependent current that is detected by associated electronics.

[0039]

[0053] In many cases, it is desirable to both track the concentration of an analyte and deliver a medication corresponding to the level of the analyte. For example, this may be done in the case of glucose analyte monitoring and insulin medication delivery, as an insulin pump may feature automated insulin dosing based on readings from a CGM sensor. For user convenience, it may be desirable to combine both sensing and infusion into a single device. However, despite the availability of both CGM sensors and infusion ports, achieving a single, integrated device that effectively combines the two functions remains challenging. As such, automated insulin dispensing pumps may use physically separate sensor and infusion locations. These multiple locations require additional time to administer, increase discomfort and risk of infection, and increase costs to the patient.

[0040]

[0054] In the specific case of glucose measurement, integration may be hindered by the assumption that delivery of insulin in close proximity to a glucose sensor, particularly in a patient's diabetes management, will necessarily impair the sensor reading due to local absorption of analytes. Thus, many commercially available CGM devices use a separation distance between the insulin delivery location and the glucose monitoring location. For example, Dexcom's G6 instructions instruct the user to "select a location at least 3 inches from the insulin pump infusion set or injection site" (Dexcom (G6 User Guide, 2017, p. 11). Similarly, Abbott's instructions instruct users to "keep its Libre sensor at least 1 inch away from the insulin injection site" (Libre In-Service Guide, Abbott, 2017, p. 11, which is incorporated herein by reference in its entirety). ADC-05821 v2.0, October 2017, p. 21). Additionally, Medtronic informs users to use the CGM sensor "one inch away from your insulin pump infusion location" and "one inch away from your manual insulin injection location" (My Guardian Connect manual, Medtronic, April 27, 2018, p. 12, which is incorporated herein by reference in its entirety).

[0041]

[0055] With current devices, every insertion site for insulin injection may require puncturing the skin with a separate needle, which can be painful for the patient and can introduce the risk of complications such as scarring and infection at each insertion site. The physical separation and resulting complexity also increase the cost and size of the body-worn device. To provide a less painful, more convenient, and more discreet experience for the patient, as well as being less expensive, the present disclosure provides improved devices, systems, and methods for an integrated analyte-sensing fluid delivery cannula. These improved devices, systems, and methods feature a glucose sensor disposed directly on the surface of the infusion cannula. The physiological effects of insulin around the subcutaneous tissue are negligible in glucose concentration, as it has been found that the larger effect in amperometric glucose sensors is actually interference from the electroactive components of insulin additives, which initially increases the sensor current and subsequently leads to a permanent loss of glucose sensitivity. Thus, through the use of an appropriately designed amperometric glucose sensor (e.g., as described in U.S. Patent Application Publication No. 2016 / 0354542, the entirety of which is incorporated herein by reference), it is possible to measure interstitial fluid glucose levels in the immediate vicinity of insulin delivery.

[0042]

[0056] In view of the problems outlined above, the present disclosure provides an infusion device to meet the requirements of a reliable and viable solution for fitting an integrated sensing cannula with the necessary signal processing electronics and a common fluid infusion device. Such an infusion device may enable simultaneous connection of an amperometric sensor on the surface of the infusion cannula to signal processing electronics and a variety of suitable drug delivery mechanisms, including syringes, pens, and pumps, to the fluid path of the same infusion cannula.

[0043]

[0057] The present disclosure provides a method for analyte monitoring, including devices adapted for use with a sensor and cannula combination, having a sensor and cannula in a single component. Systems and devices for fluid delivery and integration are provided. These systems and devices can be used in applications involving in vivo monitoring of analyte concentrations (e.g., pH, oxygen, lactate, glucose, and insulin concentrations) and for delivery of drugs (e.g., glatiramer acetate, heparin, human menopausal gonadotropin, insulin, and vitamin and nutritional supplements). These systems and devices can be used for a variety of applications in a variety of settings, such as multiple sclerosis, infertility treatment, diabetes, nutritional supplementation, and automated drug administration.

[0044]

[0058] The infusion devices of the present disclosure can be configured to be worn on the skin surface of a subject (e.g., a patient) using a single combined sensing cannula that penetrates the skin surface into a subcutaneous portion of the subject. These devices can be configured for use with an external fluid source, such as an insulin syringe, insulin pen, smart pen, or infusion pump. Once properly inserted into the body, the device can be used to deliver fluid to the patient for an extended period of time (e.g., three days or more), thereby avoiding the pain and inconvenience of several needle pricks during that period.

[0045]

[0059] The disclosed infusion devices may also have the advantage of being smaller in size than other infusion devices that include amperometric sensors. Instead of requiring two separate devices for the body, the disclosed infusion devices may have only a single component that attaches to or penetrates the skin. Compared to other devices for analyte sensing and drug delivery in a common assembly, the physical separation required for this approach may set physical or practical limitations (e.g., a lower limit) on device size, which are mitigated by the disclosed systems and devices. Furthermore, other devices for analyte sensing and drug delivery in a common assembly may not fully integrate the electronic interface, which can add significant additional size and complexity to a functional solution. Significant challenges may be presented or associated with the co-location of electrical and fluidic operating features in a single transdermal device, because both the electrical and fluidic interfaces must be realized within a limited space. Furthermore, the sensor's ability to accurately record signal current may be compromised by reliability issues, such as fluid leakage into the electrical interface. The systems and devices of the present disclosure provide sensors and fluid delivery cannulas that can handle the connection of electrical and fluid pathways to the systems and devices.

[0046]

[0060] Recognizing the need for an improved combined CGM infusion port that avoids the use of multiple insertion needles, the systems and devices of the present disclosure combine sensors and cannulas with an insertion system that allows the integrated sensing cannula to be placed or inserted into a subject (e.g., a patient) without damaging the fluid and electrical connections. Furthermore, the systems and devices of the present disclosure provide a suitable solution for insertion while meeting the limitations of their own fluid and electrical connections.

[0047]

[0061] In various embodiments, the systems and devices of the present disclosure effectively provide a solution for electronic processing of sensor signals via electronic signal processing modules configured to facilitate an electromechanical interface between the sensor contacts and signal processing hardware, allowing for temporary or permanent electrical connections between the sensors and associated processing electronics, permitting reuse of the electronics as needed.

[0048]

[0062] In some embodiments, the body is circular or substantially circular and has an accessible surface on one side with a self-sealing entry port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; and a sensor and cannula-connecting surface on the opposite side with the entry port connected to the cannula. a connecting fluid delivery channel; a cavity for receiving an electronic signal processing device; a retention mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0049]

[0063] In some embodiments, the body is circular or oval, or substantially circular or oval, with an accessible surface on one side having a self-sealing inlet port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery channel connecting the inlet port to the cannula; an electronic signal processing device with a set of arms that attach the electronic signal processing device to the housing of the liquid delivery channel; a holding mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0050]

[0064] In some embodiments, the body is oval or substantially oval, with an accessible surface on one side having a self-sealing inlet port; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outwardly therefrom; a liquid delivery channel connecting the inlet port to the cannula; an electronic signal processing device mounted on the vertical side of the body; a retention mechanism for the signal processing device; and electrical contacts between the signal processing device and the sensor.

[0051]

[0065] In some embodiments, the body is circular or elliptical, or substantially circular or elliptical, with an accessible surface on one side having a segment of an infusion tube protruding therefrom; a skin-contacting surface on the opposite side with the sensor and cannula combination protruding outwardly therefrom; a fluid delivery tube connecting the infusion tube to the cannula; a set of holding arms designed to align and hold an electronic signal processing device; features designed to receive the mounting arms of the electronic signal processing device; and an electrical contact interface between the signal processing device and the sensor.

[0052]

[0066] In some embodiments, the body is essentially circular or oval, with an accessible surface on one side having a segment of an infusion tube protruding therefrom; a skin-contacting surface on the opposite side with a sensor and cannula combination protruding outward therefrom; a liquid delivery tube connecting the infusion tube to the cannula; a self-sealing port connected to the liquid delivery channel; a holding arm designed to align and hold an electronic signal processing device; a feature designed to receive the mounting arm of the electronic signal processing device; and an electrical contact interface between the signal processing device and the sensor.

[0053]

[0067] In some embodiments, the cannula projects outward from the skin-contacting surface at an angle of 40-60°, hi some embodiments, the cannula projects outward perpendicularly or substantially perpendicularly from the skin-contacting surface.

[0054]

[0068] 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 cannula is composed essentially of a flexible polymer and has a fluid pathway placed into the tissue using a rigid inserter element or trocar that is immediately removed after insertion. In some embodiments, the insertion device includes an insertion needle that pierces a self-sealing entry port, penetrates the fluid delivery channel, and extends slightly beyond the distal end of the cannula. In some embodiments, the cannula includes a fluid pathway formed by a permanently fixed needle that can be placed into the tissue and remains there for the duration of use.

[0055]

[0069] 1A-1B provide perspective views of an example of a combined CGM infusion port 100 with a removable internal electronic module. The combined CGM infusion port 100 includes a main body 110, a main body The body includes a sensing cannula 120 protruding downwardly 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 for adhesive attachment to a subject (e.g., a patient). The access port 130 allows a user (e.g., the subject, patient, doctor, nurse, clinician, or the subject's caregiver) to attach a fluid delivery device (e.g., a syringe, pen needle, or insulin pump) to the subject. The fluid may be a medication, diagnostic agent, or other liquid desired for subcutaneous injection. An inserter 160 allows a user to insert the cannula into the subject's skin.

[0056]

[0070] As shown in FIG. 1B, in some embodiments, the electronic signal processing module 140 may be removable and is shown separate from the body 110 of the infusion device. Infusion components, such as the cannula, may be disposable and have a limited useful life of three days or more. By configuring the electronic signal processing module to be removable, the electronic signal processing module can be reused repeatedly, thereby reducing recurring costs of the system. However, in other embodiments, the transmitter is permanently secured inside the body of the infusion device and is disposed of with the infusion device.

[0057]

[0071] FIG. 2 provides an exploded view of the combined CGM infusion port of FIG. 1A. The body 110 is shown separated into an upper housing 112 and a base 114, with the sensing cannula 120 separated from the base 114. These components may comprise a material such as injection-molded plastic and be joined together via adhesive, ultrasonic welding, or other techniques for joining plastics. An adhesive patch 116 provides for attachment to a subject (e.g., a patient) at the bottom and adhesive attachment to the base 114 at its top. The sensing cannula 120 and access port 130 are shown prior to assembly. A self-sealing septum 134 and a fluid pathway housing 135 serve to provide an intermittent connection between a fluid delivery device and the fluid pathway of the cannula 120. The electronic signal processing module 140 is shown detached from the body.

[0058]

[0072] 3A-3C provide cross-sectional views of an example combined CGM infusion port with a removable internal electronics module and an insertion device used to place the cannula into the subcutaneous tissue. In this configuration, the sensing cannula has conductors long enough to directly contact the electronics module. An opening 162 allows the inserter 160 to pass through the upper housing 112. The inserter's cross section is hollow and circular or roughly rectangular (e.g., three sides, with the fourth side open). The opening in the cross section allows the fluid pathway connection formed by the tube 132 extending out of the sensing cannula 120 to pass outside the hollow inserter and make a fluid connection with the needle cavity 136 formed by the fluid pathway body 135. Fluid is delivered into the subcutaneous tissue of a subject by passing the needle through the septum 134 to access the needle cavity 136. The opening in the inserter also allows the sensor conductors 121 and 123 to pass through. Sensor conductors 121 and 123 are in electrical communication with a set of contacts 122 and 124 at the proximal end of sensing cannula 120. Set of contacts 122 and 124 physically and electrically contact a set of sensor electronics module contacts 142 and 144 of electronic signal processing module 140.

[0059]

[0073] 4 provides a cross-sectional view of an example combined CGM infusion port with a removable internal electronics module. The device features co-located electrical connections for analyte sensing and fluid delivery in an integrated analyte sensing cannula and is configured for use with an intermittently connected fluid source (e.g., a syringe or pen). Electronic signal processing module 240 is shown inserted into the cavity formed by body 210. Electrical connections from electronic signal processing module 240 to sensing cannula 220 are made via contacts 242 and 244, which maintains contact with contacts 222 and 224 at the proximal end of the combined analyte sensor and infusion cannula 220. Fluid connection to the proximal end of the combined analyte sensor and infusion cannula 220 is provided through an opening 219 in the base 214, which allows fluid to flow from the adjacent needle cavity 216 into the infusion cannula. The sensing cannula 220 penetrates the base 214 and exits through opening 218. Access to the needle cavity 216 is provided through an opening 250 in the upper housing 212 and through penetration of the self-sealing septum 234 by a fluid delivery device. Fluid flows from the needle cavity 216 to the sensing cannula 220 through channel 217. In this embodiment, the sensing cannula 220 can be placed into the skin of a subject with the aid of an insertion device. Alternatively, the sensing cannula 220 may be capable of piercing the subject's skin without the need for a temporary inserter needle.

[0060]

[0074] FIG. 5 provides a cross-sectional view of an example of a combined CGM infusion port with a removable internal electronics module, in which 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 in an example application. An integrated sensing cannula 320 is implanted in the subcutaneous tissue 370 essentially perpendicular to the plane of the skin surface. A fluid delivery device 354 is shown with a needle 352 inserted into the cavity 316 through the opening 350 and self-sealing septum 332. The fluid delivery device may be selected from a variety of suitable fluid sources, such as a syringe, an insulin pen, a medication infusion pump, and a gravity-fed fluid source. An electronic signal processing module 340 is shown inserted into the cavity 316 formed by the body 310. Electrical connection from the electronic signal processing module to the sensing cannula 320 is provided via a flexible electrical circuit 346 having a set of electrical contacts 342 and 344 that is held in contact with the set of contacts 322 and 324 at the proximal end of the sensing cannula 320. A permanent, waterproof connection is provided from the set of sensor contacts 322 and 324 to the set of flex circuit contacts 342 and 344 with a waterproof, conductive adhesive, which may be further encapsulated in a non-conductive, waterproof barrier, such as an epoxy-based encapsulant. Fluid connection to the proximal end of the analyte sensor and infusion cannula 320 combination is provided via an opening 313 in the base 314, which allows fluid to flow from the adjacent needle cavity 316. The sensing cannula 320 penetrates the base 314 and exits through an opening 319.

[0061]

[0075] 6A-6B provide perspective views of an example of a combined CGM infusion port with a removable external electronics module. FIG. 6A shows an embodiment of an infusion device in which the electronic signal processing module is contained within a body that attaches to the skin-worn device components via two arms extending 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 extending downwardly 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 that couples with the cannula housing. The inserter port 462 allows an inserter needle to be placed through the housing and surround the cannula 420. Access port 430 allows a user (e.g., a subject, patient, doctor, 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 medication, diagnostic agent, or other liquid desired for subcutaneous infusion.

[0062]

[0076] 6B, the electronic signal processing module 440 is removable and is shown separated from the infusion device body 410. The electronic signal processing module 440 is reversibly attached to the base 414 and upper housing 412 by a set of arms 446 that contact the vertical side edges of the upper housing 412. A set of guides 418 are provided to guide the electronic To aid in holding the signal processing module 440, a transmitter may be displayed on either side of the electronic signal processing module 440. In some embodiments, infusion components such as the cannula 420 are disposable and have a limited useful life of three days or more. By configuring the electronic signal processing module 440 to be removable, the electronic signal processing module 440 can be reused repeatedly, thereby reducing recurring costs of the system. However, in other embodiments, the transmitter may be permanently secured to the infusion device body and disposed of with the infusion device.

[0063]

[0077] Figures 7A-7B provide an exploded view of the combined CGM infusion port of Figures 6A-6B, including a view of the inserter needle (Figure 7B). Figure 7A shows an exploded view of an embodiment of the infusion device before assembly, 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 pathway connecting needle 432, a septum 434, an access port 430 at the top surface of the cannula housing, and a sensing cannula 420 that protrudes downward from the body after assembly. The septum 434 may be made of self-sealing silicone or other elastomeric material and serves to allow attachment to a fluid source when pierced. An electronic interconnect circuit 426 is inserted into the sensor housing 413 and, at its proximal end, contacts and electrically connects sets of contacts 422 and 424 on the top and bottom surfaces of the proximal end of the sensing cannula 420. The circuitry 426 also contacts contacts on the electronic signal processing module 440 at its distal end via pogo pins, conductive rubber buttons, or other interconnection devices 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. These are shown as separate arms, but may connect to enclose the transmitter.

[0064]

[0078] FIG. 7B shows an exploded view of an embodiment of an infusion device configured with an insertion device used to place a sensing cannula into a subject's subcutaneous tissue. A base 414 is attached to an adhesive patch 416 used to attach the device to the skin, and a sensor housing 413 is mounted on top of the base 414. A sensing cannula 420 is held by the upper housing 412 and the sensor housing 413 and is held in physical and electrical contact with the flex circuit 426. An insertion device 460 is placed through an insertion device guide channel 462 in the upper housing 412. The upper housing 412 may include a self-sealing septum to seal the opening remaining after removal of the insertion device. The insertion device may include a rigid hollow structure 464 comprising a rigid material such as stainless steel. The hollow structure 464 is coaxial with and surrounds the sensing cannula 420 after assembly. In some embodiments, hollow structure 464 is used to puncture the subject's skin to place sensing cannula 420 subcutaneously. Insertion device 460 is then withdrawn through opening 462, leaving sensing cannula 420 positioned within the subject's tissue. This embodiment is shown essentially vertical. In other embodiments, sensing cannula 420 may be positioned at an angle such that sensing cannula 420 forms an angle of about 30 to about 45 degrees (e.g., about 30°, about 31°, about 32°, about 33°, about 34°, about 35°, about 36°, about 37°, about 38°, about 39°, about 40°, about 41°, about 42°, about 43°, about 44°, about 45°) between the base of device 414 and the plane of the skin surface. The sensing cannula 420 may also be inserted slightly below the skin surface, as in the case of a microneedle, at a fairly shallow angle (e.g., about 1°, about 2°, about 3°, about 4°, about 5°, about 6°, about 7°, about 8°, about 9°, about 10°, about 11°, about 12°, about 13°, about 14°, about 15°, about 16°, about 17°, about 18°, about 19°, about 20°, about 21°, about 22°, about 23°, about 24°, about 25°, about 26°, about 27°, about 28°, about 29°).

[0065]

[0079] 8A-8D are cross-sectional views of an example composite CGM infusion port, including diagrams of interconnections. 8A-8B show cross-sectional views of an embodiment of an infusion device in which an electronic signal processing module is temporarily or permanently attached to a body containing the device's components that are worn on the skin. FIGS. 8C-8D show further details of the electrical and fluid pathway connections to the combined sensing cannula. Electronic signal processing module 540 is shown attached to body 510. Electrical connection from the signal processing module to the sensing cannula is provided through a set of electrical contacts 542 and 544 on the module, which are electrically connected through a set of conductive interface material 543 and 545 to a set of contacts in interconnect circuit 526. This material may include conductive rubber, a zebra connector, or similar selectively conductive compressive material. While two contacts are shown, there may be a single contact, or more than two contacts to carry additional signals. Interconnect circuit 526, which may be a flex circuit, sequentially electrically contacts the sets of sensor contacts 522 and 524 at the proximal end of sensing cannula 520. This contact may be achieved using a variety of suitable electrical connection materials, such as welding or conductive epoxy. This connection may also be coated with a waterproof epoxy adhesive or other encapsulant to prevent moisture ingress. Fluid connection to the proximal end of the analyte sensor and infusion cannula 520 combination is achieved through connecting tubing 532 held in sensor housing 513, allowing fluid to flow from the adjacent needle cavity 536 formed by sensor housing 513 and self-sealing septum 534. Sensing cannula 520 penetrates base 514 and exits through opening 518. Access to needle cavity 536 is provided through opening 530 in housing 512 and through penetration of self-sealing septum 534 by a fluid delivery device.

[0066]

[0080] 9A-9D provide cross-sectional views of an example combined CGM infusion port in contact with the tip of a needle-free insulin pen. FIGS. 9A-9B show cross-sections of an embodiment of an infusion device in which the fluid pathway is configured to couple or mate (e.g., mate) with a drug delivery device. FIGS. 9C-9D show further details of the electrical and fluid pathway connections to the combined sensing cannula. An electronic signal processing module 640 is shown mounted to the body 610. A set of electrical connections from the sensing cannula to a PC board 647 within the signal processing module is established via a set of electrical contacts 642 and 644 in the module, which are electrically connected to a set of contacts in the interconnect circuit 626 via a set of conductive interface material 643 and 645. This material may include conductive rubber, a zebra-type connector, or a similar selectively conductive compressible material. While two contacts are shown, there may be a single contact, or more than two contacts to convey additional signals. An interconnect circuit 626, which may be a flex circuit, is in turn in electrical communication with the set of sensor contacts 622 and 624 at the proximal end of the sensing cannula 620. This contact, shown as a ball on the sensor face in the cross-sectional view of FIG. 9D, may include an electrical connection material such as welding, conductive epoxy, or carbon paste. Contacts may be made on both the top and bottom surfaces when the sets of contacts 622 and 624 face each other (as shown), or when the sensor is configured with both contacts on the same surface, with both contacts on the bottom surface. These connections may also be coated with a waterproof epoxy adhesive or other encapsulant to prevent moisture ingress. Fluid connection to the proximal end of the analyte sensor and infusion cannula 620 combination is achieved through a connecting tube 632 held in the sensor housing 613, allowing fluid to flow from a front chamber 636 formed by the sensor housing 613 and a septum 634. The septum 634 has a preformed central hole. This central hole is normally closed but allows a blunt tube 658 contained within a matching pen tip 656 to be pressed through it. The septum 634 may also have a check valve 635, such as a ball valve, cross valve, or the like.This helps prevent backflow of fluid (e.g., medication or interstitial fluid) when the pen tip is removed. This is advantageous for protecting the attached pen tip tubing 658 from biohazards. The housing 613 also has alignment features 631 that can guide the pen tip 656 into proper alignment while mating. The pen tip 656 can slide over the pen housing 655 via the action of a compression spring 657. The sensing cannula 620 is , through an adhesive patch 616 and through an opening 618, exiting a base 614 which is attached to the subject's skin.

[0067]

[0081] Figures 10A-10G provide illustrations of an example disposable CGM infusion port in contact with a pen having a needle-free insulin pen tip. Figures 10A-10B show perspective views of an embodiment of an infusion device configured with a fluid path to mate with an appropriate drug delivery device. Figure 10C shows a cutaway view revealing details of the fluid path, and Figure 10D includes further details of the electrical connection to the combined sensing cannula. The electronic signal processing module 740 is shown in a disposable configuration, in which the signal processing electronics module 741 and sensing cannula 720 are housed within a single continuous element supported in the housing base 714. The unique pen tip 756 is shown mated with a complementary alignment feature on the housing of 740. The housing 713 also has an alignment feature 731 that can guide the pen tip 756 to align properly during mating. The pen tip 756 can slide over the pen housing 755 via the action of a compression spring 757. Fluid is shown being delivered from the internal cavity of the pen 755 through a hollow tube 758 into the infusion device. The fluid exits through a sensing cannula 720, which extends through the base 714 via an opening 718. A channel 762 allows for temporary placement of an inserter needle. Further details of the fluid pathway are shown in Figures 10E-10G. Figures 10E-10G provide cross-sectional views of a disposable CGM infusion port in contact with a pen having an insulin pen tip that does not include a needle. These include a cross-section with the pen tip attached (Figure 10E), a detail of the fluid pathway cross-section with the pen tip disengaged from the fluid pathway (Figure 10F), and a detail of the fluid pathway cross-section with the pen tip engaged with the fluid pathway (Figure 10G). The set of electrical connections from the signal processing electronics 741 to the sensing cannula 720 is made via sets of electrical contacts 722 and 724 at the sensor surface that contact a socket having sets of contacts 743 and 745. The socket conducts the signal current to a PC board 747 that contains an electronic module that processes the electronic signal. The socket contacts may include metal springs or conductive rubber, or zebra-type connectors, or similar selectively conductive compressive materials.Although two contacts are shown, there may be a single contact, or more than two contacts to carry additional signals. This contact may also include an electrical connection material such as a weld or conductive epoxy. This connection may also be coated with a waterproof epoxy adhesive or other encapsulant to prevent moisture ingress.

[0068]

[0082] FIGS. 10E-10G are sectioned to show various internal features of the device. FIG. 10F shows a pen tip 756 with the fluid pathway tube 758 in contact but withdrawn, and FIG. 10G shows the same pen tip with the fluid pathway tube 758 fully inserted. As shown in these cross-sectional views in FIGS. 10E-10G, fluid connection to the proximal end of the sensing cannula 720 is achieved through a connecting tube 732 held in the sensor housing 713, which allows fluid to flow from a front chamber 736 within the fluid pathway connector 734. The fluid pathway connector 734 may include an elastomeric element created by molding a material such as silicone or a rubber, such as butyl rubber or ethylene propylene diene monomer (EPDM) rubber. It has a preformed central hole 735. This central hole is normally closed but allows a blunt tube 758 contained within the mating pen tip 756 to be pressed through it. The fluid pathway connector may also have a check valve 737, such as a ball valve, cross valve, or the like, in the fluid pathway, which helps prevent backflow of fluid (e.g., medication or interstitial fluid) when the pen tip is removed. This is advantageous for protecting the attached pen tip tubing 758 from biohazards.

[0069]

[0083] 11A-11B provide diagrams of an example of a combined CGM infusion port with a rigid sensor. They include a front cross section (FIG. 11A) and a front cross section (FIG. 11B) showing details of the fluid pathways and electrical contacts. These diagrams are intended to illustrate the concept of a combined CGM infusion port with a rigid sensor, whether temporary or permanent. 8 shows a cross-sectional side view of an embodiment of an infusion device and a sensing cannula configured to be inserted without the aid of an inserter needle, permanently attached to the skin-worn device components. An electronic signal processing module 840 is shown attached to the body 810. An interconnect circuit 826, which may be a flex circuit, makes electrical contact with sets of sensor contacts 822 and 824 at the proximal end of the sensing cannula 820. These sensor contacts may be on the same or opposite sides of the cannula. The contacts include an electrical connection material, such as a weld or conductive epoxy, and may be encapsulated with a waterproof material, such as epoxy or other encapsulant. Fluid connection to the proximal end of the sensing cannula 820 is achieved through a connecting tube 832 carried by the sensor housing 813, allowing fluid to flow from the adjacent needle cavity 836 formed by the sensor housing 813 and a self-sealing septum 834. The sensing cannula 820 exits through the base 814 through an opening 818. The sensing cannula 820 is configured with a sharp tip and is sufficiently rigid to penetrate the skin of a subject 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 penetration of a self-sealing septum 834 by a fluid delivery device.

[0070]

[0084] 12A-12C provide perspective views (FIGS. 12A-12B) and exploded views (FIG. 12C) of an example combined CGM infusion port configured to attach to an insulin pump or gravity-fed medication source. FIGS. 12A-12B show perspective views of an embodiment of an infusion device configured to co-locate electrical and fluid connections with the sensing cannula and further configured for use with an insulin pump or gravity-fed fluid source. FIG. 12C shows an exploded view of an embodiment of an infusion device configured to co-locate electrical and fluid connections with the integrated analyte sensor and fluid delivery cannula 920 and further configured for use with an insulin pump or gravity-fed fluid source. The main body 910 is shown separate from the electronic signal processing module 940. In one embodiment, the infusion tube 970 protrudes from an opening 911 formed by the upper housing 912 and the sensor housing 913. Infusion tube 970 has an in-line connector 972 that allows it to be temporarily attached to a matching fluid pump connector and is connected to a source of therapeutic fluid, such as a drug delivery pump or gravity-fed source. In some embodiments, infusion tube 970 is attached to body 910 via a connector at the end of the body (e.g., having one or more cantilevered snap joints that allow reversible attachment of the tube to the body). Fluid source connection to sensing cannula 920 is established via a fluid path coupler 932 inserted into infusion tube 970. Sensing cannula 920 penetrates base 916 and adhesive patch 916 and exits through opening 918. Flexible circuit 926 establishes electrical contact with sets of contacts 922 and 924 inside cap 912 at the proximal end of sensing cannula 920. Electrical contacts 923 and 925 at the proximal end of flexible circuit 926 are held in contact with a set of contacts 922 and 924 at the proximal end of sensing cannula 920. Electrical connection to sensor electronics module 940 is provided by a set of elastomeric electrical contacts 943 and 945 exposed for contact with sensor electronics module 940. These contacts establish electrical connection with a set of contacts 927 and 928 on flexible circuit 926 via their opposite surfaces.A set of holding arms 918 is provided on the base 914 for temporary mounting of a sensor electronics module 940. Figure 12A shows an inserter needle 960 used to insert the cannula into the tissue of a subject (e.g., a human, animal, or mammal).

[0071]

[0085] 13A-13B provide a perspective view (FIG. 13A) and a top cross-sectional view (FIG. 13B) of an example combined CGM infusion port configured to attach to an insulin pump or gravity-fed drug source, with the electronic module removed and showing details of the fluid pathways and electrical interconnections. These detailed views allow for electrical and fluid connections to be placed in the same location on the sensing cannula. The present invention relates to an embodiment of an infusion device configured to be placed in a cap 912 or cap 914 and further configured for use with an insulin pump or gravity-fed fluid source. In one embodiment, an infusion tube 970 protrudes from an opening 911 in a sensor housing 913. The infusion tube 970 has an in-line connector 972 that allows it to temporarily attach to a matching fluid pump connector 974, providing a fluid connection to a source of therapeutic fluid (e.g., a drug delivery pump or gravity-fed source). The fluid source connection to the sensing cannula 920 is established via a fluid path coupler 932 inserted into the infusion tube 970, which passes through the opening 911 in the cap 912. The sensing cannula 920 penetrates the base 914 and exits through an opening 918. The electrical connection to the sensing cannula 920 is established via a set of electrical contacts 923 and 925 on a flexible circuit 926, which is held in contact with a set of contacts 922 and 924 at the proximal end of the sensing cannula 920. Electrical connection to the sensor electronics module 940 is established by a set of elastomeric electrical contacts on the module, which are electrically connected with a set of contacts 927 and 928 on the flexible circuit 926. A set of retention arms 918 is provided on the base 914 for temporary mounting of the sensor electronics module 940.

[0072]

[0086] 14A-14D provide a perspective view (FIG. 14A), a top cross-sectional view (FIG. 14B), a front cross-sectional view (FIG. 14C), and a side cross-sectional view (FIG. 14D) of an example combined CGM infusion port with a rigid inserter needle or trocar and configured to attach to an insulin pump or gravity-fed medication source. FIGS. 14-14B show the interconnections to electronics. FIGS. 14-14D show a tubular infusion set. FIGS. 14A-14B show a detailed view of an embodiment of an infusion device configured to co-locate electrical and fluid connections with the sensing cannula 920 and further configured for use with an insulin pump or gravity-fed fluid source, along with an insertion needle configured to place the sensing cannula 920 into tissue. In one embodiment, the infusion tube 970 protrudes from an opening 911 in the sensor housing 913. Inserter 960 is a long, needle-like, open metal member with a rectangular cross-section that is used on three sides to surround sensing cannula 920. Inserter 960 is installed through inserter port 962. Electrical connection to sensor electronics module 940 is established by a set of electrical contacts 927 and 928 on flexible circuit 926. Compressible material 948 is installed behind the set of contacts 927 and 928 and is adapted for compression by a set of contact pins 942 and 944 on sensor electronics module 940.

[0073]

[0087] 14C-14D show details of an embodiment of an infusion device configured to co-locate electrical and fluid connections on the sensing cannula 920 and further configured for use with an insulin pump or gravity-fed fluid source, with the sensor fluid path provided by a rigid tube. In one embodiment, the infusion tube 970 protrudes from an opening 911 in the sensor housing 913. An upper housing 912 surrounds and secures these elements below. The sensing cannula 920 has a pre-formed fluid path with tubing 921 that is inserted directly into the infusion tube 970. This connection can be sealed with a biocompatible adhesive or bonded directly to the infusion tube 970 using adhesive or thermal bonding techniques. The electrical connection to the sensor electronics module 940 is established by a set of electrical contacts 927 and 928 on the flexible circuit 926. A compressible material 948 is placed behind the set of contacts 927 and 928 and adapted for compression by the set of contact pins 942 and 944 in the sensor electronics module 940 .

[0074]

[0088] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present invention be limited to the specific examples provided herein. The present invention has been described with reference to the foregoing specification, and it is to be understood that these descriptions and illustrations of the embodiments herein are provided by way of example only. It is not meant to be construed as limiting. Numerous modifications, changes, and substitutions will occur to those skilled in the art without departing from the invention. Moreover, it is to be understood that all aspects of the invention are not limited to the specific expressions, configurations, or related characteristics described herein, but rather depend upon a variety of conditions and variables. It is to be understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the invention. Accordingly, the present invention is intended to cover any such alternatives, modifications, variations, or equivalents. The following claims define the scope of the invention, and methods and structures within the scope of these claims and their equivalents are intended to be covered thereby.

Claims

1. 1. A device configured to simultaneously sense an analyte concentration and administer a therapeutic fluid, comprising: a body having an upper housing, a lower housing, and a bottom, skin-contacting base, the upper housing having a top surface including a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via insertion of a needle, the port having a visible opening including a self-sealing septum in contact with the lower housing, thereby 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 and configured to administer the therapeutic fluid; 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 proximal end of the sensing cannula is retained within the body and the distal end of the sensing cannula extends from the skin-contacting base; a channel within the body in fluid communication with the internal cavity formed by the self-sealing septum and the combined proximal end of the sensing cannula; a signal processing module comprising a second body including an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface, the vertical surface providing an electrical potential to the sensing cannula and receiving an electrical current from the sensing cannula via a set of electrical contacts in the vertical surface, the second body comprising a set of arms contacting the upper housing, and the lower surface contacting the skin contact base; an interface circuit having a proximal end and a distal end, the interface circuit including one or more conductors configured to conduct a current signal from the sensing cannula to the signal processing module, the proximal end of the interface circuit in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit in electrical contact with the signal processing module; A device comprising:

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

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

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

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

6. The device of claim 5 , wherein the enzyme layer is covered with a semipermeable membrane.

7. The device of claim 2 , wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

8. The device of claim 2 , wherein the enzyme layer comprises an osmium-based redox mediator.

9. 9. The device of claim 8, wherein the osmium-based redox mediator comprises osmium dimethylbipyridine.

10. The device of claim 2 , wherein the enzyme layer comprises polyvinylimidazole.

11. 10. The device of claim 1, wherein the sensing cannula comprises a reference electrode comprising silver / silver chloride (Ag / AgCl).

12. 10. The device of claim 1, wherein the signal processing module provides a bias potential to the sensing cannula 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 connecting from the cavity to the proximal end of the sensing cannula.

14. 10. The device of claim 1, wherein the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into a skin surface of a mammal.

15. 10. The device of claim 1, wherein the sensing cannula comprises sufficient rigidity for insertion into the skin surface of a mammal without the use of an inserter needle.

16. The device of claim 1 , wherein the skin-contacting base comprises an adhesive surface configured to attach the device to a skin surface of a subject.

17. The device of claim 1 , wherein the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens.

18. The device of claim 17 , wherein the analyte is glucose.

19. 10. The device of claim 1, wherein the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, vitamins, and minerals.

20. 20. The device of claim 19, wherein the therapeutic fluid is insulin or an insulin analog.

21. 21. The device of claim 20, wherein the insulin or insulin analog comprises an additive comprising phenol or cresol.

22. 1. A device configured to simultaneously sense an analyte concentration and administer a therapeutic fluid, comprising: a main body including an upper housing, a lower housing, a bottom skin-contacting base, and an inlet tube extending outwardly from the main body and configured to connect to a source of the therapeutic fluid; 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 and configured to administer the therapeutic fluid; 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 proximal end of the sensing cannula is retained within the body and the distal end of the sensing cannula extends from the skin-contacting base; a channel within the body in fluid communication with the interior cavity formed by the self-sealing septum and the combined proximal end of the sensing cannula; a signal processing module comprising a second body including an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface, the vertical surface providing an electrical potential to the sensing cannula and receiving an electrical current from the sensing cannula via a set of electrical contacts on the vertical surface, the second body comprising a set of arms contacting the upper housing, and the lower surface contacting the skin contact base; an interface circuit having a proximal end and a distal end, the interface circuit including one or more conductors configured to conduct a current signal from the sensing cannula to the signal processing module, the proximal end of the interface circuit in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit in electrical contact with the signal processing module; 1. A device comprising:

23. 23. The device of claim 22, wherein the infusion tube is reversibly attached to the body, and the connector comprises one or more cantilever snap joints configured to allow reversible attachment of the infusion tube.

24. 23. The device of claim 22, wherein the at least one indicator electrode comprises an enzyme layer overlying a conductive surface.

25. 25. The device of claim 24, wherein the enzyme layer is covered with a semipermeable membrane.

26. 24. The device of claim 23, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

27. 24. The device of claim 23, wherein the enzyme layer comprises an osmium-based redox mediator.

28. 28. The device of claim 27, wherein the osmium-based redox mediator comprises osmium dimethylbipyridine.

29. 25. The device of claim 24, wherein the enzyme layer comprises polyvinylimidazole.

30. 23. The device of claim 22, wherein the sensing cannula includes a reference electrode comprising silver / silver chloride (Ag / AgCl).

31. 23. The device of claim 22, wherein the signal processing module provides a bias potential to the sensing cannula of less than 250 millivolts (mV) relative to a reference potential.

32. 23. The device of claim 22, wherein the channel comprises a stainless steel needle connecting from the cavity to the proximal end of the sensing cannula.

33. 23. The device of claim 22, wherein the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into a skin surface of a mammal.

34. 23. The device of claim 22, wherein the sensing cannula comprises sufficient rigidity for insertion into the skin surface of a mammal without the use of an inserter needle.

35. 23. The device of claim 22, wherein the skin-contacting base comprises an adhesive surface configured to attach the device to a skin surface of a subject.

36. 23. The device of claim 22, wherein the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens.

37. 37. The device of claim 36, wherein the analyte is glucose.

38. 23. The device of claim 22, wherein the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, vitamins, and minerals.

39. 39. The device of claim 38, wherein the therapeutic fluid is insulin or an insulin analog.

40. 40. The device of claim 39, wherein the insulin or insulin analog comprises an additive comprising phenol or cresol.

41. 1. A device configured to simultaneously sense an analyte concentration and administer a therapeutic fluid, comprising: a body having an upper housing, a lower housing, and a bottom, skin-contacting base, the upper housing comprising a port configured to reversibly attach to a fluid delivery device configured to deliver fluid via insertion of a needle, the port comprising a self-sealing septum in contact with the lower housing, thereby 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 and configured to administer the therapeutic fluid; 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 cannula to the at least one indicator electrode, wherein the proximal end of the sensing cannula is retained within the body and the distal end of the sensing cannula extends from the skin-contacting base; a channel within the body in fluid communication with the interior cavity formed by the self-sealing septum and the combined proximal end of the sensing cannula; 1. A device comprising:

42. 42. The device of claim 41, wherein the upper housing comprises a top surface that includes the port.

43. 42. The device of claim 41, wherein the port comprises a visible opening that includes the self-sealing septum.

44. 42. The device of claim 41, further comprising a signal processing module configured to receive electrical current from the sensing cannula.

45. 45. The device of claim 44, wherein the signal processing module is configured to provide an electrical potential to the sensing cannula.

46. 46. ​​The device of claim 45, wherein the signal processing module comprises a second body including an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface.

47. The vertical surface provides the electrical potential to the sensing cannula, and the electrical connection at the vertical surface 47. The device of claim 46, wherein the current is received from the sensing cannula through a set of points.

48. 48. The device of claim 47, wherein the second body comprises a set of arms that contact the upper housing and the lower surface contacts the skin-contacting base.

49. 45. The device of claim 44, further comprising an interface circuit configured to communicate a current signal from the sensing cannula to the signal processing module.

50. 50. The device of claim 49, wherein the interface circuit comprises a proximal end and a distal end.

51. 51. The device of claim 50, wherein the interface circuitry comprises one or more conductors configured to conduct the current signal from the sensing cannula to the signal processing module.

52. 52. The device of claim 51, wherein the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit is in electrical contact with the signal processing module.

53. 42. The device of claim 41, wherein the fluid delivery device comprises a syringe or a pen.

54. 54. The device of claim 53, wherein the fluid delivery device comprises a syringe.

55. 54. The device of claim 53, wherein the fluid delivery device comprises a pen.

56. 42. The device of claim 41, wherein the at least one indicator electrode comprises an enzyme layer overlying a conductive surface.

57. 57. The device of claim 56, wherein the enzyme layer is coated with a semipermeable membrane.

58. 54. The device of claim 53, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

59. 54. The device of claim 53, wherein the enzyme layer comprises an osmium-based redox mediator.

60. 60. The device of claim 59, wherein the osmium-based redox mediator comprises osmium dimethylbipyridine.

61. 54. The device of claim 53, wherein the enzyme layer comprises polyvinylimidazole.

62. 42. The device of claim 41, wherein the sensing cannula comprises a reference electrode comprising silver / silver chloride (Ag / AgCl).

63. 42. The device of claim 41, wherein the signal processing module provides a bias potential to the sensing cannula of less than 250 millivolts (mV) relative to a reference potential.

64. The channel extends from the cavity to the proximal end of the sensing cannula.

42. The device of claim 41, comprising a stainless steel needle.

65. 42. The device of claim 41, wherein the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into a skin surface of a mammal.

66. 42. The device of claim 41, wherein the sensing cannula comprises sufficient rigidity for insertion into the skin surface of a mammal without the use of an inserter needle.

67. 42. The device of claim 41, wherein the skin-contacting base comprises an adhesive surface configured to attach the device to a skin surface of a subject.

68. 42. The device of claim 41, wherein the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens.

69. 69. The device of claim 68, wherein the analyte is glucose.

70. 42. The device of claim 41, wherein the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, vitamins, and minerals.

71. 71. The device of claim 70, wherein the therapeutic fluid is insulin or an insulin analog.

72. 72. The device of claim 71, wherein the insulin or insulin analog comprises an additive comprising phenol or cresol.

73. 1. A device configured to simultaneously sense an analyte concentration and administer a therapeutic fluid, comprising: a main body comprising an upper housing, a lower housing, a bottom skin-contacting base, and an inlet tube extending outwardly from the main body and configured to connect to a source of the therapeutic fluid; 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 and configured to administer the therapeutic fluid; 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 proximal end of the sensing cannula is retained within the body and the distal end of the sensing cannula extends from the skin-contacting base; a channel within the body in fluid communication with the interior cavity formed by the self-sealing septum and the combined proximal end of the sensing cannula; A device comprising:

74. 74. The device of claim 73, further comprising a signal processing module configured to receive electrical current from the sensing cannula.

75. 75. The device of claim 74, wherein the signal processing module is configured to provide an electrical potential to the sensing cannula.

76. The signal processing module has an upper surface, a lower surface, and a vertical surface between the upper surface and the lower surface.

76. The device of claim 75, comprising a second body comprising:

77. 77. The device of claim 76, wherein the vertical surface provides the electrical potential to the sensing cannula and receives the electrical current from the sensing cannula via a set of electrical contacts on the vertical surface.

78. 78. The device of claim 77, wherein the second body comprises a set of arms that contact the upper housing and the lower surface contacts the skin-contacting base.

79. 75. The device of claim 74, further comprising an interface circuit configured to communicate a current signal from the sensing cannula to the signal processing module.

80. 80. The device of claim 79, wherein the interface circuit comprises a proximal end and a distal end.

81. 81. The device of claim 80, wherein the interface circuit comprises one or more conductors configured to conduct the current signal from the sensing cannula to the signal processing module.

82. 82. The device of claim 81, wherein the proximal end of the interface circuit is in electrical contact with the proximal end of the sensing cannula and the distal end of the interface circuit is in electrical contact with the signal processing module.

83. 74. The device of claim 73, wherein the infusion tube is reversibly attached to the body, and the connector comprises one or more cantilever snap joints configured to allow reversible attachment of the infusion tube.

84. 74. The device of claim 73, wherein the at least one indicator electrode comprises an enzyme layer overlying a conductive surface.

85. 85. The device of claim 84, wherein the enzyme layer is coated with a semipermeable membrane.

86. 86. The device of claim 85, wherein the enzyme layer comprises glucose oxidase or glucose dehydrogenase.

87. 86. The device of claim 85, wherein the enzyme layer comprises an osmium-based redox mediator.

88. 88. The device of claim 87, wherein the osmium-based redox mediator comprises osmium dimethylbipyridine.

89. 85. The device of claim 84, wherein the enzyme layer comprises polyvinylimidazole.

90. 74. The device of claim 73, wherein the sensing cannula comprises a reference electrode comprising silver / silver chloride (Ag / AgCl).

91. 74. The device of claim 73, wherein the signal processing module provides a bias potential to the sensing cannula of less than 250 millivolts (mV) relative to a reference potential.

92. The channel is a stainless steel tube that connects the cavity to the proximal end of the sensing cannula.

74. The device of claim 73, comprising a steel needle.

93. 74. The device of claim 73, wherein the upper and lower housings are configured to receive a hollow inserter needle that partially surrounds the sensing cannula for insertion into a skin surface of a mammal.

94. 74. The device of claim 73, wherein the sensing cannula comprises sufficient rigidity for insertion into the skin surface of a mammal without the use of an inserter needle.

95. 74. The device of claim 73, wherein the skin-contacting base comprises an adhesive surface configured to attach the device to a skin surface of a subject.

96. 74. The device of claim 73, wherein the analyte is selected from the group consisting of oxygen, glucose, lactate, drug metabolites, and pathogens.

97. 97. The device of claim 96, wherein the analyte is glucose.

98. 74. The device of claim 73, wherein the therapeutic fluid is selected from the group consisting of insulin or an insulin analog, glatiramer acetate, heparin, human menopausal gonadotropin, vitamins, and minerals.

99. 99. The device of claim 98, wherein the therapeutic fluid is insulin or an insulin analog.

100. 100. The device of claim 99, wherein the insulin or insulin analog comprises an additive comprising phenol or cresol.

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