HK1176027B - Analyte monitoring and fluid dispensing system - Google Patents

Description

Analyte monitoring and fluid dispensing system

CROSS-REFERENCE TO RELATED APPLICATIONS

Priority of U.S. provisional patent application No.61/264,840, entitled "Analyte monitoring and Fluid Dispensing System," filed on 30/11/2009, the contents of which are incorporated herein by reference in their entirety.

Technical Field

Systems, devices, and methods for continuous monitoring of bodily analytes and continuous dispensing of therapeutic fluids are described herein. More specifically, a system including a continuous glucose monitor and an insulin dispenser is described herein. Even more particularly, a device configured as a miniature portable unit is described herein that can be attached to a patient's skin and connected to a subcutaneous tip to continuously monitor glucose levels and dispense insulin.

These systems, devices and methods are not strictly limited to delivering insulin and monitoring glucose, but are applicable to delivering any other drug and concomitantly monitoring any analyte. As used in the following description, the word "analyte" refers to any solute composed of a particular molecule dissolved in an aqueous medium.

Background

Continuous subcutaneous insulin injection (SCII)

The treatment of several diseases requires continuous infusion of drugs into various body cavities, such as subcutaneous and intravenous injections. Diabetic (DM) patients, for example, require injections of varying amounts of insulin throughout the day to control their glucose levels. Ambulatory portable insulin infusion pumps have emerged in recent years as a good alternative to injecting insulin with multiple daily syringes, initially for type 1 diabetic patients (Diabetes Medicine 2006;23(2): 141-7) and subsequently for type 2 diabetic patients (Diabetes meta 2007, 30/4 and 26/6 and 2007, Diabetes Obes meta 2007, 26). These pumps, which deliver insulin at a continuous basal rate and bolus volume, were developed to release patients from repeated self-controlled injections and allow them to sustain almost normal daily life. Both basal and bolus volumes must be delivered in precise doses according to individual prescriptions, as either an excess or an insufficient amount of insulin can be fatal.

The first generation of ambulatory infusion pumps involved a "pager-like" device having a memory contained within the housing of the device. These devices are provided with an elongated tube for delivering insulin from a pump attached to a belt (belt) of the patient to a remote insertion point. Both basal and bolus delivery in these "caller-like" devices are controlled via a set of buttons provided on the device. User interface means including a screen are provided on the housing of the device for informing the user of fluid delivery status, design fluid delivery, warnings and alarms. Such devices are disclosed, for example, in U.S. Pat. Nos. 3,771,694, 4,657,486, and 4,498,843. These devices represent a significant improvement over Multiple Daily Injections (MDI), but nonetheless they are large in size, heavy, have long delivery/infusion tubing, and lack care, which significantly interferes with daily living.

To avoid the consequences of a long delivery tube, a new concept was proposed, which was implemented in second generation pumps. As described in the prior art, this new concept relates to a remotely controlled skin adherable device having a housing, a bottom surface adapted to be in contact with the skin of a patient, a reservoir disposed within the housing, and an injection needle adapted to communicate with the reservoir. In these second generation pumps, the user interface device is configured as a separate remote control unit that includes operating buttons and screens that provide fluid delivery status, design fluid delivery, warnings, and alarms, for example as described in U.S. Pat. nos. 5,957,895, 6,589,229, 6,740,059, 6,723,072, and 6,485,461. These second generation devices also have several limitations, such as being heavy, bulky, and expensive, as the devices should be discarded every 2-3 days (due to insertion site infection and reduced insulin absorption). Another significant drawback of these second generation devices is associated with remotely controlled drug administration. The user relies entirely on the remote control unit. For example, if the remote control unit is not at hand, if lost or if a malfunction occurs, the user cannot initiate bolus delivery or operate the device.

The third generation of skin-attachable infusion devices were designed to avoid the cost issues associated with the second generation devices and to extend patient customization. One example of such an apparatus is described in U.S. patent application publication No. 2007-and 0106218 and International patent application publication No. WO2007/052277. This third generation device comprises a remote control unit and a skin fastening (e.g. adhesive) device/patch unit, which may comprise two parts: (1) a reusable portion that contains at least a portion of the drive mechanism, electronics, and other relatively expensive components, and (2) a disposable portion that contains a memory and, in some embodiments, at least one power source (e.g., a battery).

This third generation concept provides a cost effective, skin adherable infusion device and may allow for multiple uses, such as various reservoir sizes, various needle and cannula types.

Infusion devices of the fourth generation are designed as dispensing units that can be disconnected and reconnected to a skin-adherable cradle unit, for example as disclosed in U.S. patent application publication No.2008-0215035 and international patent application publication No. wo 2008/078318. Such skin-adherable dispensing units are operable using a remote control and/or a user interface (e.g. a button-based interface) provided on the housing of the dispensing unit, such as disclosed in international patent application publication No. wo2009/013736 (also disclosed as us patent application publication No. 2010-0204657) and international patent application publication No. wo2009/016636 (also disclosed as us patent application publication No. 2010-0145276), which was filed on 31.2008, claiming priority from us provisional application serial nos. 60/963,148 and 61/004,019, and entitled "Portable Infusion Device provided with Means for Monitoring and Controlling Fluid Delivery", the contents of which are hereby incorporated by reference in their entirety.

Continuous Glucose Monitoring (CGM)

Most diabetics measure their glucose levels several times a day by obtaining a finger prick capillary sample and applying the blood to an analytical reagent strip in a portable meter. Although self-monitoring of glucose levels has had a major impact on improving diabetes over the past decades, the drawbacks of this technique are significant and thus lead to non-compliance. Disadvantages of this blood sampling technique are associated with the discomfort of multiple skin pricks, the inability to test blood during sleep or when the subject is busy (e.g., driving, running), and missed periods of hyperglycemia and hypoglycemia due to intermittent testing. The proposed glucose monitoring technique should therefore take substantially automatic and continuous testing.

It is understood that there are three techniques for continuous monitoring of subcutaneous interstitial fluid (ISF). The first technique is based on the use of glucose oxidase-based sensors, such as U.S. patent No.6,360,888 to McIvor et al and U.S. patent No.6,892,085 to McIvor et al (both of which are assigned to Medtronic MiniMed Inc. (CGMS, Guardian)^TMand CGMS Gold) and assigned to Heller et al and assigned to Abbott laboratory (formerly TheraSense Corp.) (Navigator)^TM) As described in U.S. patent No.6,881,551. These sensors consist of subcutaneously implantable needle-type amperometric enzyme electrodes associated with a portable recorder.

A second technique is based on the use of reverse iontophoresis-based sensors, such as those authorized by Chen et al and assigned to Cygnus corporation (GlucoWatch)^TM) As described in U.S. patent No.6,391,643. The small current passing between the two electrodes located at the skin surface brings ions and (by the phenomenon of electro-endosmosis) interstitial fluid containing glucose to the surface and into the hydrogel pad with glucose oxidase biosensor (JAMA 1999;282: 1839-1844).

A third technique currently in clinical use is based on microdialysis (Diab Care2002;25: 347-) -352, as described in U.S. Pat. No.6,091,976 to Pfeiffer et al and assigned to Roche Diagnostics, and a commercially available device (Menarini Diagnostics, GlucoDay)^TM). In this technique, fine hollow dialysis fibers are implanted into the subcutaneous tissue and perfused with an isotonic fluid. Glucose from the tissue diffuses into the fiber and is pumped out of the body for measurement by a glucose oxidase-based electrochemical sensor. Initial reports (Diab Care2002;25: 347-And (4) stability.

Closed and open loop systems

In an "artificial pancreas" (sometimes referred to as a "closed loop" system), an insulin pump delivers an appropriate dose of insulin in accordance with continuous glucose monitor readings. The artificial pancreas avoids human-machine interfaces and is expected to avoid debilitating periods of hypoglycemia, especially nighttime hypoglycemia. One intermediate step in implementing a "closed loop" system is an "open loop" (or "semi-closed loop" system), also known as a "closed loop with a meal notification". In this model, user intervention is required, in a manner similar to the use of current insulin pumps, by ingesting the desired insulin prior to a meal. One closed loop system is discussed in U.S. patent No.6,558,351 to Steil et al and assigned to Medtronic MiniMed. Such a system consists of two separate devices (i.e. a glucose monitor and an insulin pump attachable to two remote body locations) and the loop is closed by a radio frequency communication link.

However, the closed loop system of Steil et al has some disadvantages. For example, a glucose monitor and an insulin pump are two separate components, requiring two insertion sites and two skin pricking sites each time the insulin pump and sensor are replaced (typically once every 3 days). In addition, due to the separation, the two system components should be connected by a radio communication chain or by wires. Moreover, the pump is heavy and bulky, has long tubing, makes the system less compact, and is very expensive because the pump infusion assembly and monitoring sensors need to be disposed of every 3 days.

Accordingly, it is desirable to provide a skin securable device configured for drug (e.g., insulin) dispensing and continuous body analyte (e.g., glucose) level monitoring. It is also desirable that such devices be miniature, compact, economical for the user, and highly cost effective. One embodiment of such a desired device is preferably connected to a single skin-insertable tip that preferably includes a subcutaneous cannula for delivering the drug to the body and a probe for monitoring the analyte via the single insertion site. Such a device is preferably disconnected and reconnected to the skin-attachable cradle unit, so that after the patch is connected to the cradle, the current generated on the probe is delivered to the processor within the device housing.

Disclosure of Invention

Embodiments of the present disclosure generally relate to systems, devices, kits, and methods for continuously dispensing one or more therapeutic fluids and continuously monitoring one or more bodily analytes. Some embodiments relate to an apparatus comprising a monitoring device and a dispensing device (the latter may be referred to as a pump). The pump may be used to infuse fluid into the body and the monitoring device may be used to monitor an analyte in the body. In some embodiments, the monitoring device and pump share a single subcutaneously insertable dispensing and sensing tip (hereinafter "tip"), which may also be referred to as a single subcutaneously insertable dispensing and sensing cannula, designed to allow analyte level monitoring and fluid dispensing, and in some embodiments, concomitantly. The tip preferably includes structure, such as a sensor, for monitoring one or more analytes within the body, for example, within interstitial fluid ("ISF"). In some embodiments, the sensor may comprise one or more sensors, which in some embodiments comprise electrodes, for monitoring one or more analyte levels within the body, and thus, embodiments involving "electrodes" may also be considered to involve sensors. In some embodiments, the electrodes may be disposed on a probe (e.g., a planar probe), and thus, embodiments involving "probes" may also be considered to involve sensors.

In some embodiments, while the tip monitors the analyte level, it also performs as a cannula through which fluid is delivered to the body. In some embodiments, the tip includes structure for multiple sensing (e.g., multiple sensors) for increased accuracy and reliability. In some embodiments, the pump and monitoring device may also operate independently of each other, or may operate together as a closed loop or plate closed loop system. In some embodiments, the dispensed fluid comprises insulin to be used with a diabetic patient and the analyte comprises glucose. The monitoring device and pump may comprise a fluid delivery apparatus, which may be configured as a skin securable apparatus (hereinafter "patch" or "patch unit").

Some embodiments of the systems and devices include at least one of the following units and elements:

the patch unit comprises a monitoring device and a pump. The monitoring device includes a structure (e.g., one or more sensors) for sensing one or more analytes and an electrical communication element (e.g., electrodes, connecting wires, electrical connectors, electrical contacts) connected thereto. The patch unit may comprise at least one of a reservoir, a drive mechanism and a pump. The patch unit may also include a printed circuit board ("PCB") that includes a processor and can include a transceiver. The processor, in some embodiments, controls the operation of the dispensing and monitoring device (hereinafter "processor controller" or "processor/transceiver" or "processor"). For programming and data display, the device can be provided with a remote control unit, a display and/or with one or more operating buttons/switches located on the patch unit. The device can also be provided with a skin-adherable cradle unit (hereinafter "cradle") to which the patch unit can be repeatedly attached or detached. The pump of the patch unit may employ different dispensing mechanisms such as, for example, a syringe (syringe type) structure with an advancing plunger/piston, a peristaltic mechanism, a pressurized reservoir, etc. The patch unit may further comprise a reservoir and an outlet port allowing fluid communication between the reservoir and the tip when the patch unit is connected to the cradle unit.

The patch unit may be constructed as a single part or be composed of two parts, which may include a reusable part (hereinafter, "RP") and a disposable part (hereinafter, "DP"). RP may include relatively expensive components, including one or more of the following: a drive mechanism (or a portion thereof), a PCB, a processor, an electrical connector for connecting with a carrier unit (for example), and other electrical leads. The DP may comprise relatively inexpensive and disposable components including a reservoir and an outlet port. In some embodiments, the patch unit further comprises a power source, which can be included in the reusable part or the disposable part, or shared between the two.

A carrier, which may also be referred to as a carrier unit, may also be provided for the patch unit. The cradle may be provided with a preferably flat bottom (according to only some embodiments) covered by an adhesive for adhering the cradle to the skin, a channel and at least one anchor (or latch) for the tip (the channel and anchor may be referred to as "well" hereinafter). The cradle unit may also include latching or snap-fit means for enabling the patch unit to be repeatedly connected to and disconnected from the cradle unit (hereinafter referred to as "latching" or "snap-fit"). The cradle unit may also include a first set of electrical connectors surrounding the cradle passage, electrical leads, and a second set of electrical connectors for connecting with the RP for enabling electrical communication with the tip.

Systems according to some embodiments of the present disclosure may also include a tip that is insertable into the body for fluid delivery and analyte monitoring. Thus, upon insertion, the tip is preferably rigidly connected to the well.

According to some embodiments, the tip preferably comprises a soft multi-lumen tubing (hereinafter "cannula"). One chamber includes a fluid distribution channel and at least one other chamber provides an analyte sensing structure (e.g., a sensor, a probe, one or more electrodes). The distal ends of the multilumen tubing preferably converge to provide a smooth puncture of the skin. To this end, the proximal end of the multi-lumen tube becomes wider, preferably forming a conical funnel (according to some embodiments) to provide a stable connection with the tip liner (or tip housing).

Longitudinal openings or windows may also be provided in one or more of the cavities. According to some embodiments, such openings (or windows) may provide direct contact of bodily fluids with sensing probes/electrodes positioned in the one or more lumens.

In some embodiments, the electrodes may be disposed within or on a probe positioned within one lumen of a double lumen cannula. Thus, the probe may include a distal end having a sensing electrode disposed thereon, one or more leads for forming electrical communication with the electrode, and a proximal end including an electrical connector in electrical communication with the one or more leads and thus the electrode. The distal end of the probe may be configured to be thin relative to the diameter of the lumen. In some embodiments, the probe may have a width of about 0.6 millimeters, a thickness of about 0.1 millimeters, and a length between about 5 millimeters and 9 millimeters (when inserted vertically, an over-angled insertion may include a longer length) and have a length generally corresponding to the length of the lumen and preferably have a rectangular shape. The proximal end of the probe may be wider and preferably matches the distal end of the cannula housing form/shape, and is preferably arcuate (e.g., circular, semi-circular, or partially circular). According to some embodiments, the probe comprises a "neck" between the narrow distal end and the broad proximal end to allow bending of the proximal end and fixation of the proximal end to the distal end of the cannula housing (see below).

In some embodiments, the tip may further comprise: a cannula cover (hereinafter "cover") -to support a septum, the cannula septum (hereinafter "septum") being capable of maintaining fluid communication between the connection cavity and the cannula; cannula bushing (hereinafter "bushing") -connecting the cannula to the cannula housing and the cannula cover.

Systems according to some embodiments of the present disclosure may also include a cartridge (which may also be referred to as a "cartridge unit") and/or a piercing element, preferably a sharp needle or needle-like feature for piercing the skin during tip insertion, while configured to be removed upon tip insertion. Additionally, a protector element (which may also be referred to as a "protector") may also be included and may be used to protect the tip and piercing element.

In some embodiments, the tip insertion can be performed automatically by means of a spring-loaded inserter as described in international patent application No. pct/IL08/000860 (published as WO 2009/001346) and U.S. patent application No.12/215,255 (published as US 2008/0319414), which disclosures are incorporated herein by reference in their entirety.

In some embodiments, for example, a remote control for controlling the patch unit is provided. The remote controller may at least enable programming and/or control of the operation of the pump and/or the sensor. In some embodiments, the remote controller comprises a blood glucose monitor.

In some embodiments, the system and/or device includes an additional external glucose monitoring unit (e.g., a blood glucose meter) and/or an insulin dispensing unit (e.g., an insulin pen/syringe).

In some embodiments, the system and/or device includes one unit for continuous insulin delivery and continuous blood glucose monitoring using one common insertion site and one tip.

In some embodiments, the system and/or device may be constructed of one or two parts and can be connected and disconnected from the body at the discretion of the user.

In some embodiments, the separate tip is insertable into the body, having a proximal end that remains outside the body and is connectable and reconnectable to the insulin dispenser and the blood glucose monitor.

In some embodiments, the system and/or device includes a blood glucose monitoring and insulin dispensing unit that can be disconnected and reconnected to the end inserted into the body.

In some embodiments, the system and/or device includes a blood glucose monitoring and insulin dispensing unit that is very inexpensive for the patient.

In some embodiments, a skin securable medical device is provided, including one or more of: a tip configured for insertion and delivery of a therapeutic fluid into a patient's body, a pump for delivering the therapeutic fluid into the patient's body via the tip, a sensor disposed at the tip and configured for sensing a level of one or more analytes within the patient's body and configured for providing at least one sensor signal indicative of the level of the one or more sensed analytes, a processor for processing the at least one sensor signal and for controlling the delivery of the therapeutic fluid, at least one first connector disposed on the tip for enabling electrical communication between the sensor and the processor, and an attachable housing portion for securing at least a portion of the device to the skin of the patient, wherein the attachable housing portion comprises an opening and at least one second connector.

In some embodiments, such as those described above, upon insertion of the tip through the opening, the at least one first connector couples to the at least one second connector, forming electrical communication therebetween and enabling transmission of the at least one sensor signal from the sensor to the processor.

In some embodiments, the tip may include a cannula for delivering the therapeutic fluid therethrough.

In some embodiments, the sensor may include a plurality of electrodes for sensing the level of one or more analytes.

In some embodiments, the one or more analytes comprise glucose. In still other embodiments, the therapeutic fluid comprises insulin.

In some embodiments, at least one electrode of the plurality of electrodes includes one or more oxidoreductases for oxidizing glucose and generating an electrical current for transmitting the at least one sensor signal. In some embodiments, at least one of the plurality of electrodes may include at least one glucose binding protein.

In some embodiments, the sensor and/or tip may further comprise a plurality of conductive elements for transmitting the at least one sensor signal from the sensor to the processor via the at least one first and second connectors.

In some embodiments, the plurality of conductive elements comprises wires.

In some embodiments, such as those described above, at least a portion of the sensor is bent (or folded or twisted) for enabling physical contact between the at least one first and second connectors when the tip is inserted through the opening.

In some embodiments, the cannula/tip includes a first lumen for delivering the therapeutic fluid and one or more second lumens for providing at least a portion of the sensor. To this end, the one or more second cavities can comprise any number, including 1, 2, 3, 4, 5, 6, etc.

In some embodiments, the plurality of electrodes includes a working electrode, a counter electrode, and optionally a reference electrode.

In some embodiments, the plurality of electrodes includes three working electrodes, three counter electrodes, and optionally one reference electrode.

In some embodiments, each electrode resides in a separate one or more second lumens of the tip.

In some embodiments, the plurality of electrodes are disposed on a probe that may reside within a lumen of the one or more second lumens of the tip.

In some embodiments, the one or more second cavities may include one or more windows such that at least a portion of the sensor can be exposed to the ambient environment. The ambient environment includes interstitial fluid.

In some embodiments, the one or more windows are configured such that the at least a portion of the sensor can be mechanically supported.

In some embodiments, the one or more second cavities are substantially shorter than the first cavity.

In some embodiments, the one or more second lumens are sealed at a distal end.

In some embodiments, the first cavity has a substantially circular cross-section and the one or more second cavities have a substantially arcuate cross-section.

In some embodiments, the pump delivers the therapeutic fluid in response to the at least one sensing signal.

In some embodiments, the processor automatically operates the pump and the sensor.

In some embodiments, the device operates in a mode selected from the group consisting of a closed-loop mode, a semi-closed-loop mode, and an open-loop mode.

In some embodiments, including those described above, the attachable housing portion includes a cradle that may include a well for receiving the tip and at least one latch for connecting the cradle and the device. In some embodiments, the attachable housing portion includes a latch including at least one second connector for establishing electrical communication with the at least one first connector. In some embodiments, the latch may be used interchangeably with one of "connection device", "connection mechanism", "protrusion", and/or "anchor".

Embodiments of attachable housing portions may include any of the features described in this disclosure in connection with the bracket.

In some embodiments, the well may include at least one second connector for making electrical communication with the at least one first connector.

In some embodiments, the cradle may include at least one third connector configured to transmit the at least one sensor signal received from the sensor to a fourth connector positioned in another unit (e.g., pump, RP, DP, external device).

In some embodiments, the bracket may also include one or more electrical leads that may be embedded within the bracket (e.g., within one or more tunnels). In some embodiments, wires are used to transmit sensor signals received from sensors/probes/electrodes in the cannula/tip.

In some embodiments, the attachable housing portion comprises an adhesive tape, and the adhesive tape comprises at least one second connector, at least one third connector, and at least one wire connected between the at least one second and third connectors for transmitting the at least one sensor signal received from the cannula/tip to the processor.

In some embodiments, the cradle includes an amplifier and/or a power supply.

In some embodiments, the opening (well) is configured such that the tip can be inserted at an angle relative to the attachable housing portion (e.g., cradle).

In some embodiments, the apparatus may further comprise: a cannula cartridge unit having a piercing element for piercing the skin of a patient during tip insertion; and an inserter. The cannula cartridge and the penetrating member may be configured to align the tip such that the at least one first connector contacts the at least one second connector when the tip is inserted through the opening.

Embodiments of the systems and/or apparatus may include any of the features described in this disclosure, including but not limited to any one or more of the methods, systems, and/or apparatus, and any one or more of the above and/or below features.

In some embodiments, a cannula assembly for use with a drug dispensing pump is provided, wherein the cannula assembly comprises a probe comprising at least one electrode and a cannula housing. The proximal end of the probe includes a first wire/connector that conforms to the configuration of the cannula housing and the probe folds (or bends or twists) according to the configuration of the cannula housing. The folded probe may enable a first wire/connector to make contact with a second wire/connector provided on another unit.

In some embodiments, the cannula housing may include a slot configured to receive a wire/connector in intimate contact with a bottom or side of the cannula housing. The slot can be annularly configured in an annular configuration.

According to some embodiments, such a cannula may comprise a dual lumen cannula including a first lumen for providing a passageway for fluid dispensing and a second lumen for providing a stylet.

In some embodiments, a cannula for use with a drug dispensing pump is provided, wherein the cannula comprises a plurality of electrodes and a cannula housing. The proximal ends of the plurality of electrodes include a first lead/connector that conforms to the configuration of the cannula housing. This arrangement may allow a first wire/connector to be brought into contact with a second wire/connector provided on another unit, for example a housing (e.g. a cradle) that may be attached to the skin.

In some embodiments, the cannula may include a plurality of lumens: a first chamber for providing a channel for fluid distribution, and a further chamber for providing respective electrodes such that each electrode corresponds to a separate chamber.

In some embodiments, the further lumens surround the first lumen and the cannula assembly may comprise a connector plate on one side of the cannula housing, such that the electrodes are connected to the connector plate via openings provided on each of the further lumens (e.g. by a lead).

In some embodiments, the connector plate is formed as a circular or annular plate. In some embodiments, the leads and connector plate may be formed as a single unitary conductive element

In some embodiments, the connector board comprises: a first plurality of folding connectors configured to contact the plurality of electrodes provided by the further chamber via openings; and a second plurality of folded connectors that constitute second wires/connectors provided on another unit. In some embodiments, the plurality of electrodes folded according to the configuration of the cannula housing are used to enable the first lead/connector to make contact with the second lead/connector.

Embodiments of the system and/or the apparatus may include any of the features described in this disclosure, including but not limited to any one or more of the methods, systems, and/or apparatuses, and any one or more of the above and/or below features.

In some embodiments, a skin attachable cradle is provided that is coupled to the patch pump and that may include a well for receiving the cannula assembly, a plurality of electrical leads, a plurality of electrical contacts configured as snap-fit connectors, wherein each electrical contact corresponds to one of the plurality of electrical leads.

In some embodiments, the skin adherable cradle may comprise a plurality of first electrical connectors configured to contact the electrical connectors of the cannula assembly, each corresponding to one of the plurality of electrical leads, and a plurality of second electrical connectors configured to contact the electrical connectors of the patch unit, each corresponding to one of the plurality of electrical leads.

The snap connectors may be configured such that they maintain a seal when the patch unit is disconnected from the cradle. To this end, a non-conductive sealing cap may be provided to cover the one or more snap connectors. Such a sealing cap may further comprise electrically conductive contact pads embedded within the cap so as to conduct electrical current when in contact with the connector of the patch unit. In other embodiments, the connector of the patch unit is configured to pierce the non-conductive sealing cap for electrical communication with the plurality of second connectors.

In some embodiments, the connectors may be sealed (e.g., via O-rings provided through the openings) when the plurality of first electrical connectors are connected with the connectors of the ferrule assembly.

Also, in some embodiments, a cannula cartridge is provided for use with a cannula insertion device and may comprise one or more of the following: a housing, a handle, and a cannula, wherein the cannula may include one or more of a plurality of electrodes, a plurality of respective connectors, each for a respective electrode, and a plurality of lumens including a first lumen for delivering a fluid and one or more second lumens for providing electrodes. The cartridge may also include a puncturing element provided initially longitudinally through one of the lumens. In some embodiments, the cartridge unit further comprises a housing, and the housing is configured to be coupled to the housing. Moreover, in some such embodiments, the piercing element can include a needle and a needle cover.

In further embodiments of the cannula cartridge, latches may be provided at the bottom of the needle cover and at corresponding slots provided in the cover of the cannula for aligning and engaging the needle cover with the cannula. In some embodiments, the slot may comprise a plurality of slots and a plurality of latches may then be provided on the cannula cartridge housing for aligning and/or coupling the needle cover with the cartridge housing. The one or more slots may be configured as a track for enabling movement of the needle cover for insertion of the cannula into the patient's body when aligned with the cannula cartridge housing.

In some embodiments, a kit for therapeutic treatment of a patient is provided, which may include one or more of any one or more devices and/or elements/components for any one or more of the described or otherwise described embodiments of the present disclosure.

Other embodiments of the present disclosure include methods of assembly, use, and methods of treatment for any of the device, system, and kit embodiments described in the present disclosure or elements/components thereof.

It is therefore an object of some embodiments to provide a system and/or device comprising means for frequently or continuously measuring analyte levels of a body and means for frequently or continuously delivering a therapeutic fluid into the body.

It is another object of some embodiments to provide a system and/or device comprising means for frequently or continuously measuring glucose levels and means for frequently or continuously delivering insulin.

It is another object of some embodiments to provide a system and/or device comprising means for frequently or continuously measuring glucose levels and means for frequently or continuously delivering insulin in dependence of the monitored glucose levels.

It is another object of some embodiments to provide a system and/or apparatus configured as a skin attachable unit comprising a glucose monitoring device and an insulin pump.

It is another object of some embodiments to provide a single patch unit in which the monitor and pump can concomitantly use a common insertion site and one tip that serves as a probe for monitoring glucose levels and as a cannula for delivering insulin. Glucose levels can be monitored within the ISF in the subcutaneous tissue and insulin can be delivered into the subcutaneous tissue.

It is another object of some embodiments to provide a patch unit that includes a monitor and a pump and has two parts, a reusable part and a disposable part. The reusable portion may include relatively expensive components, e.g., electronics, drive mechanisms, and the disposable portion may include relatively inexpensive components, e.g., a reservoir.

It is another object of some embodiments to provide a system and/or apparatus configured as a patch unit and containing a continuous glucose monitoring device and an insulin pump. The patch unit can be controlled by a remote control unit or by a button provided anywhere on the patch unit.

It is another object of some embodiments to provide a patch unit that enables analyte monitoring and fluid dispensing and is thin and miniature, can be hidden under clothing, can be attached to the patient's body at any desired location, avoids long conduits, and does not affect normal daily activities.

It is another object of some embodiments to provide a patch unit including a monitor and a pump, wherein the patch unit is attachable to a tip insertable into various body tissues including, for example, subcutaneous tissue, blood vessels, peritoneal cavity, muscles, and adipose tissue.

Drawings

Fig. 1a-c illustrate block diagrams of systems including a patch unit, which can be made up of one or two components according to some embodiments of the present disclosure. The system may include a remote control unit.

Fig. 2a-b illustrate a one-part patch (2 a) and a two-part patch (2 b) according to some embodiments of the present disclosure. The patch is removably secured to a skin-attachable cradle, which is attached to the skin with an adhesive. The tip is rigidly connected to the cradle and resides within the body. The tip serves as a conduit for drug delivery and a probe for sensing the analyte.

Fig. 3 shows a schematic view of a sensing device and a pump of a patch unit according to some embodiments of the present disclosure. A single tip is provided for dispensing the drug into the body and sensing the analyte level within the body. The pump can be controlled fully (closed loop system) or partially (open loop system) by the sensing device.

Fig. 4 illustrates a two-piece patch unit pump according to some embodiments of the present disclosure.

Fig. 5 illustrates a perspective view of a system including a patch unit, a remote control unit, a cradle unit, and a tip unit, according to some embodiments of the present disclosure.

Fig. 6a-b illustrate cross-sectional views of a tip and a bracket after tip insertion according to some embodiments of the present disclosure.

Fig. 7 illustrates a perspective view of a patch according to some embodiments of the present disclosure prior to attachment to a bracket.

Fig. 8 illustrates a perspective view of tip components prior to assembly according to some embodiments of the present disclosure.

Figures 9a-b illustrate cross-sectional views of two preferred configurations of a cannula including multiple lumens according to some embodiments of the present disclosure. Fig. 9a shows a cannula with two lumens. Figure 9b shows a cannula with four lumens.

Fig. 10 shows a schematic view of a dual function (sensing and dispensing) patch including a reusable portion and a disposable portion according to some embodiments of the present disclosure.

FIG. 11 illustrates electrical leads and connections of a sensing device according to some embodiments of the present disclosure.

12a-d illustrate longitudinal cross-sectional views of a tip including a cannula and a sensing electrode according to some embodiments of the present disclosure. Figures 12a-b illustrate electrodes positioned on a stylet provided by one lumen of a dual lumen cannula. The word "provided by …" includes any arrangement of electrodes relative to a lumen, including, for example, electrodes inserted into or positioned within a lumen unless specifically stated otherwise. Fig. 12c-d show the electrodes positioned apart from each other such that each electrode is provided by a separate lumen positioned on the outer circumference of the sleeve surrounding the lumen serving as the fluid passageway.

Fig. 13a-b show schematic views of a tip comprising two lumens before (13 a) and after (13 b) inserting the tip into the body, according to some embodiments of the present disclosure.

Fig. 14a-b show schematic views of a tip including two lumens before (14 a) and after (14 b) inserting the tip into a body, according to some embodiments of the present disclosure.

Fig. 15a-b show schematic views of a tip including more than two lumens before (15 a) and after (15 b) inserting the tip into the body, according to some embodiments of the present disclosure.

Fig. 16a-b show schematic views of a tip including more than two lumens before (16 a) and after (16 b) inserting the tip into the body, according to some embodiments of the present disclosure.

17a-b illustrate an insertion process of inserting a tip into a body and connecting the tip to a cradle with an automated inserter according to some embodiments of the present disclosure. Fig. 17a shows the tip before insertion. Fig. 17b shows the process of tip insertion.

Fig. 18a-b illustrate a patch and a bracket according to some embodiments of the present disclosure, before (18 a) and after (18 b) the patch is attached to the bracket.

Fig. 19 illustrates an example of remotely controlling a Graphical User Interface (GUI) and operation buttons according to some embodiments of the present disclosure.

20a-b illustrate a perspective view (20 a) and a cross-sectional view (20 b) of a dual lumen cannula according to some embodiments of the present disclosure.

FIG. 21 illustrates a preferred embodiment of a single sensing probe including three (3) electrodes according to some embodiments of the present disclosure.

Figures 22a-b illustrate a three-dimensional configuration of a folded probe including three (3) electrodes according to some embodiments of the present disclosure.

FIG. 23 illustrates an example of a manufacturing process for a plurality of probes according to some embodiments of the present disclosure.

Fig. 24 illustrates a perspective view of a cannula housing according to some embodiments of the present disclosure.

Fig. 25a illustrates a cross-sectional view of the bottom side of a tip, according to some embodiments of the present disclosure.

Fig. 25b illustrates a perspective view of a tip according to some embodiments of the present disclosure.

Fig. 26 illustrates a perspective view of tip components prior to assembly according to some embodiments of the present disclosure.

27a-b illustrate electrical leads and connectors of a bracket that transmit electrical current from a well connector to a snap connector according to some embodiments of the present disclosure.

28a-b illustrate perspective views of circuitry in a cradle according to some embodiments of the present disclosure.

28c-d illustrate perspective views of the patch and cradle prior to connection and the circuit between the cradle well and the reusable portion of the patch according to some embodiments of the present disclosure.

29a-d illustrate a cradle circuit according to some embodiments of the present disclosure.

Figures 30a-d show views of a probe before and after folding and before insertion of the probe into a cannula lumen according to some embodiments of the present disclosure.

Fig. 31 illustrates a perspective view of tip components prior to assembly according to some embodiments of the present disclosure.

Fig. 32a-c illustrate perspective and bottom views of a tip according to some embodiments of the present disclosure.

33a-b illustrate the tip prior to connection to the carrier and the conduction of current from a probe in the tip to a wire in the carrier according to some embodiments of the present disclosure.

Figures 34a-c illustrate a multi-lumen cannula according to some embodiments of the present disclosure.

Fig. 35a-c show perspective (35 a), top (35 b), and bottom (35 c) views of a connector according to some embodiments of the present disclosure.

Fig. 36 illustrates a perspective view of tip components prior to assembly according to some embodiments of the present disclosure.

Fig. 37a-b illustrate attachment of a connector plate to a tip according to some embodiments of the present disclosure.

Fig. 38 illustrates the tip prior to insertion onto a carrier according to some embodiments of the present disclosure.

39a-b illustrate bottom views of a tip and a bracket after insertion of the tip according to some embodiments of the present disclosure.

Fig. 40 illustrates a folded electrode according to some embodiments of the present disclosure.

Fig. 41 illustrates a tip including a folded electrode according to some embodiments of the present disclosure.

Fig. 42 illustrates an end component including a folded electrode prior to assembly according to some embodiments of the present disclosure.

43a-b illustrate electrical connections between a tip and a bracket according to some embodiments of the present disclosure.

Fig. 44a-b illustrate an electrically conductive adhesive tape being attached to a bracket according to some embodiments of the present disclosure.

Fig. 45 illustrates a bracket including a well opening and one or more connector openings according to some embodiments of the present disclosure.

Fig. 46a-b illustrate a bracket after attachment to a conductive adhesive strip and after insertion of the tip through a well opening according to some embodiments of the present disclosure.

Fig. 47a-b illustrate a bracket before (47 a) and after (47 b) attachment to a conductive adhesive tape according to some embodiments of the present disclosure.

Fig. 48a-b illustrate the connection of the tip, the bracket, and the conductive adhesive tape according to some embodiments of the present disclosure.

Fig. 49a-b illustrate a bottom cross-sectional view (49 a) and a perspective view (49 b) of a cannula cartridge according to some embodiments of the present disclosure.

Fig. 50a-e illustrate assembly of the tip to the needle and cannula according to some embodiments of the present disclosure.

Fig. 51 illustrates an example package of a cannula cartridge and a tray according to some embodiments of the present disclosure.

FIG. 52 illustrates a cannula cartridge mounted to an inserter according to some embodiments of the present disclosure.

Detailed Description

In the following detailed description, like structures/elements referred to in the various embodiments shown in the drawings are designated with the same reference numerals throughout. Thus, in many instances, repeated descriptions of the described elements/features illustrated in the preceding figures are avoided in the later-described figures. Moreover, any one or more elements/features/structures and/or steps of any one or more disclosed embodiments may be substituted and/or provided with any other disclosed embodiment to provide yet another embodiment of the disclosure.

Fig. 1a-c show block diagrams of a system and apparatus that may include a dispensing unit 10 (i.e., a pump) and, in some embodiments, a remote control unit 40. In some embodiments, the dispensing unit 10 may be referred to as a "patch" because its structure resembles a thin patch that can be secured to the patient's body. In some embodiments, the patch unit 10 may include a pump for delivering one or more fluids into the body and a sensing device for monitoring one or more analyte levels within the body. Fluid delivery may be automatically adjusted (via one or more processors or controllers, for example) (e.g., a closed loop system) or partially adjusted (e.g., an open loop system) according to one or more analyte levels. For example, fluid delivery may be adjusted during portions of the day, only during the night, all times except eating, and so forth.

The patch 10 may comprise a single portion (fig. 1 b), or in some embodiments two portions (fig. 1 c). The two-part patch 10 may include a reusable portion 100 and a disposable portion 200. In some embodiments, the sensing device and/or pump may be located within reusable portion 100, disposable portion 200, or both. The reusable portion may contain electronics (e.g., a printed circuit board and/or a processor and/or memory), a drive mechanism (or at least a portion thereof), and other relatively expensive components (e.g., sensors). The disposable portion may contain the reservoir, the outlet port, a portion of the drive mechanism (in some embodiments), and other relatively inexpensive components. In some embodiments, the remote controller ("RC") 40 may be configured as a handheld device for programming fluid infusion rates, controlling at least the dispensing unit/patch, acquiring data, communicating with other electronic devices (e.g., a personal computer), and providing one or more visual, acoustic, and vibratory alerts regarding at least the operation and/or programming of the dispensing unit and/or sensing device. In some embodiments, remote control 40 may include a screen and a keyboard. 40 may also include a blood glucose monitor, wherein the test strip may be inserted into a designated slot and a glucose reading may be presented on the screen. Two-part patches are disclosed, for example, in U.S. patent application publication No.2007-0106218, and International patent application publication No. WO2007/052277, the contents of which are incorporated herein by reference in their entirety.

In some embodiments, the remote controller may be configured as, but is not limited to, a watch, a cellular phone, a personal digital assistant ("PDA"), a smartphone (e.g., an iPhone or Android device), a media player (e.g., an iPod, an mp3 player), an iPad, a laptop, and/or a PC.

In some embodiments, the system may not include the remote controller 40 and the patch unit 10 may be operable using a user interface (e.g., a button/switch-based interface and/or voice commander) provided on a housing of the patch unit 10, such as disclosed, for example, in international patent application publications nos. wo2009/013736 and wo2009/016636, the entire contents of which are incorporated herein by reference in their entirety.

Fig. 2a-b show an embodiment of a patch unit 10, which is similar in structure to the patch unit shown and described in fig. 1b-1 c. Thus, in some embodiments, the disposable portion 200 may include an outlet port having a connecting lumen to enable fluid communication between a reservoir (e.g., positioned in the disposable portion 200) and the patient's body via the subcutaneous insertion tip 300.

As also shown in fig. 2a-b, in some embodiments, a cradle unit 20 may be provided to secure the patch 10 to the body of the patient. Embodiments of the cradle unit ("cradle") 20 may be configured as a substantially flat plate that includes a surface that can be secured (e.g., adhered) to the patient's skin 5, such as via an adhesive layer disposed on the bottom surface of the cradle. Thus, the patch 10 may be disconnected and reconnected to the bracket 20. The cradle may also include a channel (e.g., opening, window) for inserting the tip 300 into a patient's body, for example, to the subcutaneous tissue 6. Examples of devices comprising a cradle are disclosed, for example, in U.S. patent application publication No.2008-0215035 and international patent application publication No. wo 2008/078318.

The tip 300 may pierce the patient's skin 5 and reside (at least partially) within the patient's body 6 (e.g., within subcutaneous tissue). The tip 300 may be used as a catheter (hereinafter "cannula") for delivering therapeutic fluid to the body of a patient and may include a sensor. In some embodiments, the sensor may include a probe and/or electrodes for sensing an analyte within the body (the probe may include one or more electrodes). In some embodiments, the drug comprises insulin and the analyte comprises glucose.

Such a dual function patch 10 may be operated with function buttons/switches located on the patch and/or by means of a remote control 40. For example, in a two-part patch 10, two operating buttons 15 (e.g., small circular buttons) may be located on the reusable portion 100 (one (1) of the two (2) buttons is shown in fig. 2a-2 b) for issuing instructions, for example, regarding fluid delivery.

Fig. 3 shows an embodiment of a patch unit 10, which may comprise a sensing arrangement 1777 for sensing analyte levels and a pump 1888 for delivering a therapeutic fluid. In some embodiments, the therapeutic fluid may comprise insulin, the analyte may comprise glucose, and the sensing device may comprise a continuous glucose monitor ("CGM"). The sensing device 1777 and/or the pump 1888 may be controlled by the processor (which may also include a receiver) 130. The analyte level sensed by the sensing device 1777 may be processed by the processor 130. In some embodiments, the processor 130 may control the delivery of the therapeutic fluid by the pump 1888 (forming a closed-loop system) as a function of (or based on) the analyte level sensed by the sensing device 1777. In some embodiments, the delivery of therapeutic fluid may be controlled (forming an open loop system or a semi-closed system) by processor 130, for example, according to a predetermined programming scheme given, for example, by a medical record card, based on sensed analyte levels, and/or by programming that is manually adjusted by the patient via a user interface (e.g., a manual button or switch) located on a remote controller or patch unit. Combinations thereof may also be implemented, for example, basal insulin delivery during the night may be automatically dispensed according to glucose levels and bolus delivery may be manually programmed by the user.

The processor 130 may be configured to establish bi-directional communication with the RC 40 via the receiver for programming the pump and/or sensing device using the RC interface and/or presenting data related to the pump and/or sensing device on the RC screen. For example, fluid delivery may be programmed using an RC interface and analyte delivery may be presented on an RC screen. In some embodiments, a screen may be provided on the reusable portion housing, also presenting data related to the dispensing device and/or sensing device.

In some embodiments, the tip 300 may be shared between the dispensing device (which may be referred to as a pump) 1888 and the sensing device 1777. The tip 300 may be used as a catheter (hereinafter "cannula") for delivering therapeutic fluid to the body of a patient and may also include probes and/or electrodes for sensing one or more analytes within the body. The tip 300 may be inserted through an opening in the cradle 20 and through the patient's skin 5 into the patient's body 6 (e.g., subcutaneous tissue). According to some embodiments, the probe may be positioned within or on the cannula 6, as described in U.S. patent application publication nos. 2007/0191702 and 2008/0214916 to Yodfat et al, and international patent application publication No. wo2008/078319 to Yodfat et al, the disclosures of which are incorporated herein by reference in their entirety.

Fig. 4 illustrates a longitudinal cross-sectional view of a two-part patch 10 including components of a pump according to some embodiments. As previously described, in some embodiments, patch 10 may include a reusable portion ("RP") 100 and a disposable portion ("DP") 200. The reusable portion may include components of a reusable shell and a reusable insert (e.g., reusable chassis) 105 to support the RP, and the disposable portion may include components of a disposable shell and a disposable insert (e.g., disposable chassis) 205 to support the DP.

Upon connection of the RP-DP, the insert 105 of the RP and the insert 205 of the DP engage and the housings of the RP and DP align and are capable of sealing, such as via a sealing gasket to provide a watertight seal. Reusable portion 100 can include a drive mechanism (e.g., motor and transmission) 188, a rotating sleeve 187, and a Printed Circuit Board (PCB) 189 with electronic components (e.g., an antenna). Disposable portion 200 may include reservoir 230, plunger (piston) 240, plunger rod 234, battery 220, and outlet/exit port 204. When RP is connected to DP, the toothed end of the plunger rod 234 may be inserted inside the toothed inner side of the rotating sleeve 187 so that rotation of the motor and transmission mechanism may rotate the plunger rod 234. A nut (nut) within the insert 205 of the DP may translate the rotational motion into a linear displacement of the plunger rod 234 and the plunger 240 within the reservoir 230 such that the fluid (e.g., insulin) contained within the reservoir 230 is dispensed from the reservoir through the delivery tube (curved dashed line) via the exit port 204.

Fig. 5 illustrates a perspective view of a system according to some embodiments, which may include one or more of the following components:

a patch unit ("patch") 10, wherein according to some embodiments, fluid dispensing instructions may be issued by a button/switch 15 located on the patch 10. In some embodiments, RP 100 may be a durable unit/component that is replaced, for example, every three (3) months, and DP 200 may be a single use unit/component that is disposed of and replaced, for example, every 2-3 days.

A remote control unit ("RC") 40 that may include a screen 41 and a keyboard 42. In some embodiments, RC 40 may also include an integrated blood glucose monitor having a socket 43 that receives a blood test strip 44. The RC 40 may be used for patch programming (e.g., fluid dispensing instructions) and/or data acquisition. Data acquisition may be accomplished in some embodiments through communication of the RC 40 with other electronic devices, such as a PC, for example, to effect data downloads and uploads.

A cradle unit ("cradle") 20, which may comprise a substantially flat plate base with an opening that enables insertion of the tip into the body via the cradle. The bracket 20 may include an adhesive layer at its bottom surface for securing the bracket to the patient's skin. The cradle 20 may also include connection means (e.g., "snap" or latch) 206, 207 for rigidly securing the patch 10 to the cradle 20 and allowing disconnection and reconnection of the patch to the cradle 20 at the discretion of the patient. A tubular protrusion (also referred to as a "well") 25 surrounding the opening can provide support to the tip 300 by maintaining the rigid connection of the tip 300 (and/or tip-related components, as shown in fig. 6 a) to the cradle 20 after the tip is inserted into the body via the well 25.

A tip unit ("tip") 300, which may include a fluid conduit for fluid delivery and probes and/or electrodes for continuous monitoring of body analytes.

One example of such a device is disclosed in U.S. patent application publication No.2008/0215035 to Yodfat et al and international patent application publication No. wo2008/078318 to Yodfat et al, the contents of which are all incorporated herein by reference in their entirety. Such devices are also disclosed in U.S. patent application publication No.2007/0106218 to Yodfat et al, international patent application publication No. wo2007/052277 to Yodfat et al, and international patent application publication No. wo2009/125398 to Yodfat et al, the contents of which are all incorporated herein by reference in their entirety. U.S. patent application publication No.2007/0191702, the contents of which are incorporated herein by reference in its entirety, discloses a device that includes a dispensing patch unit (e.g., an insulin dispensing patch) and an analyte sensor (e.g., a continuous glucose monitor). This type of dual function device has a similar construction to that described above and can also be disconnected from and reconnected to the skin at the discretion of the patient.

Fig. 6a-b show cross-sectional views of the tip 300 and the cradle 20 after the tip 300 has been inserted into the patient's body. The carrier 20 is attachable to the skin 5 and comprises connection means 206 and 207 for fastening the patch unit to the carrier. The well 25 may provide support (e.g., mechanical support) for the tip 300 and maintain a rigid connection of the tip 300 to the cradle 20 after insertion of the tip into the body through the well 25. The tip 300 may include a proximal portion and a distal portion. The proximal portion of the tip 300 has a cap 302 configured to be secured within the well 25 (after tip insertion). The proximal portion may also include a self-sealing septum 301 that provides a seal with at least the cannula 305. The distal portion of the tip 300 is configured to be positioned within subcutaneous tissue beneath the skin 5 after the tip 300 is inserted into the body. The distal portion may include a fluid conduit (hereinafter "cannula") 305 for delivering or dispensing a therapeutic fluid (e.g., insulin) to the body of a patient, as well as a probe 30 and/or electrodes for sensing an analyte (e.g., glucose) within the body. Fig. 6b shows an enlarged view of one example of the probe 30. The probe 30 may include one or more electrodes, such as a working electrode 321, a counter electrode 322, and optionally a reference electrode 323. Working electrode 321 may include a region where electrochemical, optionally enzymatic, reactions occur; counter electrode 322 may complete an electrical circuit with the fluid with which the sensor is in contact; and the reference electrode 323 may optionally be used to determine, by differential or other means, the voltage associated with the electrochemical reaction occurring at the working electrode.

In some embodiments, probe 30 (which may also be referred to as a sensor) may include multiple working electrodes and/or multiple counter electrodes and/or multiple reference electrodes. In one particular embodiment, the probe may include three (3) working electrodes, three (3) counter electrodes, and one (1) reference electrode.

In some embodiments, the one or more electrodes may be positioned on the outer circumference of the cannula. In other embodiments, the one or more electrodes may be positioned within one or more lumens within the cannula 305. In some embodiments, each of the one or more electrodes (which may also be referred to as sensors) may be separately positioned within a lumen within the cannula 305.

Fig. 7 shows a perspective view of the patch 10 and the bracket 20 before the patch is attached to the bracket and includes similar structure to that described above and, as such, includes the same corresponding reference numerals. The patch 10 may comprise recesses (one recess 107 is shown) positioned at both sides of the patch, the recesses being configured to receive corresponding attachment means of the bracket 20, such as snap-fits 206 and 207. Patch 10 may also include exit port 204 and connection lumen 213. After the patch 10 is connected to the bracket 20, the snaps 206 and 207 engage with the depressions and the connection cavity 213 pierces the septum of the tip 300 residing in the well 25.

Fig. 8 illustrates a perspective view of components of the tip 300 prior to assembly, according to some embodiments of the present disclosure. Tip 300 may be comprised of a cap 302, a septum 301, a liner 303, a cannula housing 304, and a cannula 305. Cannula 305 may include a proximal portion and a distal portion. The distal portion may be configured to reside within the patient's body when the tip is inserted into the body. The proximal portion may be configured to reside within the cannula housing 304 and in some embodiments include a conically-widened end aligned with the conically-shaped liner 303. The bushing 303 is preferably rigidly connected to the sleeve 305 and to the inner surface of the housing 304. The diaphragm 301 may be placed over the liner 303 and within the cover 302. The septum 301 may be made of a self-sealing material (e.g., rubber, silicone, etc.) that provides a seal with the cannula 305 and is configured to be pierced by the connection lumen, e.g., when the patch is connected, providing fluid communication between a reservoir, e.g., positioned within the patch, and the cannula 305. The cover 302 may be configured to be received within a well of a cradle (e.g., via a snap-fit arrangement).

Figures 9a-b illustrate transverse cross-sectional views of a multi-lumen cannula 305 according to some embodiments. Cannula 305 may include a lumen (as part of a pump) that provides a pathway for fluid (e.g., insulin) delivery, and one or more additional lumens (as part of a sensing device) for providing one or more electrodes or probes.

In some embodiments, the cannula or tip is characterized by a length of about 6mm, 9mm, or 12 mm. In further embodiments, where the tip is inserted into the body non-perpendicularly, i.e. the cannula or tip is inclined at an angle (α) with respect to the skin surface, the cannula or tip can be even longer. For example, penetration into subcutaneous tissue to a vertical depth of about 6mm with α =45 ° can be implemented with a cannula or tip having a length of a portion within the body of about 8.5mm (i.e., 6/cos (45)). The larger portion of the sleeve or tip within the body may enlarge the contact surface of the one or more electrodes (or probes) with the analyte and improve analyte monitoring.

In some embodiments, the lumen or lumens providing the one or more electrodes (or the one or more electrodes themselves) may be shorter (e.g., about 3 mm) than the lumen or cannula itself providing the channel for fluid delivery. In some embodiments, the one or more additional cavities may include openings/windows (e.g., longitudinal) that provide direct contact between the surroundings (e.g., ISF) and the one or more electrodes. In some embodiments, the one or more lumens including longitudinal openings (for example) may be closed/sealed at their distal ends.

Some embodiments of the present disclosure may enable maintaining a separation distance (e.g., about 3 mm) between a fluid dispensing location (e.g., a distal opening of a cannula) and an analyte sensing location (e.g., a contact region between the one or more electrodes and a body). In some embodiments, the outer surface of the one or more further cavities may be provided with a plurality of holes/openings, for example exposing the active surface (sensing surface) of the one or more electrodes to ISF.

Fig. 9a specifically shows a cannula 305a having two lumens, a first lumen 355 for fluid delivery and a second lumen 356 providing the one or more electrodes (or probes). In this configuration, the one or more electrodes may be printed on a flat probe provided by one lumen, as further illustrated schematically in fig. 12a and 12b and in perspective in fig. 25a-b and 26, for example. In some embodiments, the cannula 305a may be generally circular in shape, the first lumen 355 may be generally circular, and the second lumen 356 may be generally arcuate. In some embodiments, cannula 305a may have a "D" shape, wherein first lumen 355 may be substantially circular and second lumen 356 may be substantially flat or have a substantially rectangular shape. In some embodiments, the one or more electrodes may each be provided by separate lumens, for example as shown schematically in fig. 12c and 12d and stereoscopically in fig. 34 a-c. In some embodiments, the one or more electrodes may be embedded within the material of the wall of the cannula 305b, as shown in fig. 9 b. For example, a cavity (also referred to as a "groove" or "recess") may be formed in the wall of the cannula. These cavities (e.g., identified as 356a, 356b, 356c in fig. 9 b) may be filled with a conductive material. Optionally, the one or more electrodes may be deposited within the cavities by at least one of vapor deposition, sputtering, coloring, printing, replication, electroless deposition, or any other method and technique known in the art, or any combination thereof.

Referring to fig. 9b, cannula 305b is specifically shown having four lumens. A first lumen 355 for fluid transport and three (3) additional lumens 356a, 356b and 356c are provided. The other three (3) chambers may include three (3) electrodes, such as a working electrode, a counter electrode, and a reference electrode. In some embodiments, the cannula may include three (3) lumens, one for fluid delivery and two others each including one electrode-a working electrode and a counter electrode, for example. In some embodiments, more than one electrode each may be provided (e.g., three (3) working electrodes, three (3) counter electrodes, and one (1) reference electrode). In some embodiments, each electrode may be provided in a separate cavity. In some embodiments, the cannula 305b can be generally circular in shape, the first lumen 355 can be generally circular and the one or more additional lumens 356a, 356b, and 356c can be generally arcuate. For example, the first lumen may be positioned centrally in the cannula 305b and the one or more lumens may be positioned on the outer circumference of the cannula surrounding the first lumen. In some embodiments, the one or more electrodes may be embedded in the material of the wall of the sleeve 305 b. Any other combination of shapes of the cannula and/or lumen may also be implemented.

Fig. 10 schematically illustrates a dual function ("sensing and dispensing") patch 10 according to some embodiments. The structure/elements of the patch 10 comprise similar structures/elements as the previously described embodiments in the other figures and, therefore, the same reference numerals are referred to for similar structures. Two-part patch 10 may be removably secured to cradle 20, and cradle 20 may be rigidly connected to tip 300 after the tip is inserted into the patient's body. In some embodiments, the bracket 20 may include one or more electrical leads 23 and/or other conductive elements, and one or more RP connectors and/or contacts (e.g., electrical connectors connected to the reusable portion) 21. The wires 23 and/or other conductive elements may be embedded within (and/or disposed on) the carrier. Connector 21 may be combined with connector 28 included in reusable portion 100. The tip 300 may include a cannula 305 having at least two lumens, including a first lumen (e.g., 355 as shown in fig. 9 a-b) that provides a pathway for fluid delivery and one or more other lumens (e.g., 356 or 356a-c as shown in fig. 9 a-b) that include the one or more electrodes or probes 30. The one or more electrodes preferably continuously sense glucose levels within body 6 (e.g., interstitial fluid (ISF) in subcutaneous tissue in some embodiments, the one or more cavities may include longitudinal openings (as shown by the arrows) that provide, for example, direct contact between the ISF and the one or more electrodes.

In some embodiments, the power source (e.g., battery) 220 may be located within the disposable portion. In some embodiments, the power source may reside in the reusable portion and may be periodically charged and/or replaced. In some embodiments, the power source may reside in the cradle. In some embodiments, the pump and analyte sensing device may be shared between (at least) reusable portion 100 and disposable portion 200. In some embodiments, electrical connectors 221, 222 (RP-DP connectors) may be provided at the disposable portion and the reusable portion (respectively) for maintaining an electrical connection between the power source 220 positioned in the disposable portion 200 and the electronic device 180 or processor 130 positioned in the reusable portion 100. In some embodiments, electrical connectors 221 and 222 can establish electrical communication with the sensing device, e.g., transmit glucose readings from the probe to the reusable portion via the disposable portion.

Once the processor 130 evaluates (or determines) the delivery command/instruction, the drive mechanism 188 may be actuated and fluid may be expelled from the reservoir 230 into the patient's body 6 (e.g., subcutaneous tissue) through the exit port 204 and cannula 305. The one or more electrodes (and/or probe 30, which may include the one or more electrodes) may be positioned within the patient's body 6 when the tip is inserted into the body. In some embodiments, the one or more electrodes may sense analyte levels in the body of the patient via an electrochemical reaction that generates an electrical current. This current may be transmitted to the processor 130 via the wire 23 and the connectors 21, 28 (indicated with arrows). For example, the one or more electrodes may sense glucose levels in subcutaneous tissue through oxidation of glucose, generating an electrical current, as is well known in the art.

The current (e.g., signal) may be converted to a glucose level by a processor. The glucose level may be presented as a glucose reading, for example, on a screen positioned on the remote controller or on the patch unit.

FIG. 11 illustrates electrical connections of a sensing device according to some embodiments of the present disclosure. Thus, upon insertion into the body of the user, the tip may be rigidly connected to the cradle 20, which may be fastened (e.g., adhered) to the patient's skin 5. In some embodiments, the one or more electrodes (e.g., working electrode, counter electrode, and optional reference electrode) of probe 30 may be embedded within a polymer 400 (e.g., a flexible polymer), for example. Each electrode may be connected to one or more leads (and/or conductive elements) positioned on the probe ("probe leads"), such as leads 311, 312, and 313. The probe wires may be connected to one or more probe-carrier connectors, such as connectors 251, 252, and 253, providing electrical communication between the probe wires and one or more wires or other conductive elements ("carrier wires", such as wires 311, 312, and 313) disposed within (and/or on) the carrier. In some embodiments, one or more electrical connectors/contacts, such as connectors 111, 112, and 113, may be provided on the carrier for maintaining electrical communication between the carrier wires and RP wires positioned within reusable portion 100, providing electrical communication with processor 130.

The location of the various wires and the various connectors on the probe 30, carrier 20 and reusable portion 200 are shown in the drawings by way of example only. In other embodiments, only a portion of the wires and connectors may be implemented, such as establishing a direct electrical connection between the probe and the reusable portion, e.g., via the carrier. The one or more connectors 111, 112 and 113 and/or 251, 252 and 253 may be configured to seal (or embed) when the patch unit is disconnected from the carrier, for example as further described in fig. 27. In some embodiments, the carrier may include an amplifier for amplifying the signal transmitted from the electrode to the processor, or other electronic components required for its function. In some embodiments, the cradle may include a power source so that the electrode/probe can be continuously (or periodically) operated even when the patch is disconnected. In such an embodiment, for example, a desired hydrogen peroxide decomposition may be maintained (at least to some extent).

Fig. 12a-d show longitudinal cross-sectional views of a tip 300 having one or more electrodes. The components of the tip 300 are similar to those shown and described in fig. 8.

In some embodiments, as shown in fig. 12a-d, the one or more electrodes may be configured (e.g., printed or otherwise disposed) on a flat probe 30 provided by second lumen 356 of dual lumen cannula 305 a. In this configuration, the first lumen 355 may serve as a fluid pathway and the second lumen 356 serves as a "bag" to contain and/or support the probe 30. In some embodiments, the second lumen 356 may be provided with a longitudinal opening (window) enabling direct contact between, for example, the ISF and the one or more electrodes provided by the second lumen 356. The probe 30 may also include electrical leads, and/or connectors.

Fig. 12a shows a specific example in which the probe is bent over the cannula housing 304 several times to bring the electrical leads and/or connectors 310 into intimate (e.g., mechanical, physical, or press fit) contact with the bottom side of the cannula housing 304. A detailed illustration of this configuration is shown in fig. 30a-32 c. Fig. 12b illustrates a specific example, wherein the cannula housing 304a includes a slot (window), e.g., at its bottom side, as further illustrated in fig. 24-26. In this configuration, the probe is folded once and resides within a slot of the cannula housing 304a such that the electrical leads and/or connectors 310 are in intimate contact with the bottom side of the cannula housing 304 a.

In further embodiments, the wires and/or connectors (e.g., 310 or 320) for the probes may form a ring shape. For example, the groove may be annularly formed to receive an annular wire/connector in intimate contact with the bottom or side of the casing.

In some embodiments, as shown in fig. 12c-d, the one or more electrodes are positioned apart from each other such that each electrode corresponds to (is disposed on or within) a separate cavity (30 a, 30b, see, e.g., fig. 12 c-d).

FIG. 12c shows a specific example in which a multi-lumen cannula 305b includes four (4) lumens: a first chamber for providing a passageway for fluid distribution, and three further (3) chambers (only two chambers shown) for providing three (3) electrodes (only two electrodes 30a and 30b are shown). The electrodes 30a and 30b are preferably connected by wires to a connector plate 330 positioned at the bottom side of the cannula housing 304. The connector board 330 provides electrical communication between the electrodes and connectors positioned on the board, as further shown in fig. 35a-37 b. In some embodiments, the connector plate may be formed as a circular or annular plate ("connector ring"). In some embodiments, the leads and the connector plate may be formed as a single integral conductive element. FIG. 12d shows a specific example in which a multi-lumen cannula 305b includes four (4) lumens: a first chamber for providing a passageway for fluid distribution, and three further (3) chambers (only two chambers shown) for providing three (3) electrodes (only two electrodes 30a and 30b are shown). The electrodes 30a and 30b can be connected by a folded (e.g., bent, twisted, meandering) lead and a connector 340 positioned on the upper side of the cannula housing 304. Once the end components are assembled, the electrical leads 341 connecting the electrodes 30a, 30b and the connector 340 can be provided through the bushing 303 and bent under the cover 302 and diaphragm 301 as further shown in fig. 40-42. In some embodiments, the electrodes (e.g., 30a, 30 b) and/or the leads and/or connectors (340 and/or 341) may be formed as a single integral conductive element. Some (or all) of these conductive elements may be embedded within the tip component (e.g., the connector 341 may be embedded (at least partially) within the ferrule housing 304 and the sleeve 303).

Fig. 13a-b show schematic views of a tip 300 including one or more connectors 310 before (13 a) and after (13 b) insertion of the tip 300 into a body 6 (e.g., subcutaneous tissue). Tip 300 includes a double lumen cannula 305a, as described in one or more of the previous descriptions above.

In some embodiments, the cradle 20 may be used and the cradle 20 may be secured to the patient's skin prior to insertion of the tip 300 into the body, e.g., the cradle may be adhered to the patient/user's skin via an adhesive layer at the bottom side of the cradle. The cradle 20 may include an opening (e.g., a well) 25 to secure the tip 300 to the cradle 20 when the tip is inserted into the user's body. At least one anchoring mechanism may be provided for establishing a secure connection of the tip 300 to the bracket 20 after tip insertion. For example, one or more latches or protrusions 24a and 24b provided at well 25 may engage with one or more recesses/grooves (e.g., annular recesses 309, 309') of tip 300, forming a snap-fit arrangement (e.g., a "snap-fit" arrangement). In some embodiments, as shown in figures 13a-b, the cradle connector 26 may be positioned on the underside of the well 25, and upon insertion of the tip into the patient's body, the tip connector 310, as shown for example in figure 12a, engages the cradle connector 26 to enable the current generated on the electrode or probe 30 to be transmitted to the RP (via the RP connector 21) via the cradle electrical lead 24. The well 25 and/or the tip 300 may be configured such that the connectors 26 and 310 remain sealed once the tip 300 is connected to the well 25. For example, the well may include two O-rings, one (1) at its bottom side and the other at its upper side, both of which substantially seal the connector.

As described above, the RP connector 21 provides electrical communication between the bracket 20 and the reusable portion 100 of the patch after the patch is connected to the bracket and may be positioned, for example, on the base of the bracket, as shown in fig. 13 a-b. In some embodiments, the connector 21 may be positioned on the cradle latch, or may be positioned on a side wall of the cradle, as further shown below. The bracket electrical leads 23 and the RP connector 21 may be embedded within the bracket. The RP-connector 21 may be configured to seal when the patch unit is disconnected from the cradle, as will be further described with reference to fig. 27 a-b.

Fig. 14a-b show a schematic view of a tip 300 comprising one or more connectors 320, for example as shown in fig. 12b, before (fig. 14 a) and after (fig. 14 b) insertion of the tip 300 into a patient's body 6 (e.g., subcutaneous tissue), wherein the one or more connectors 320 may be positioned at the bottom side of the cannula housing 304 a. The one or more connectors 320 are configured to engage the bracket connector 26 positioned on the bottom surface of the well 25.

In some embodiments, as shown in fig. 14a-b, the RP connector 21 may be positioned on the bracket latch and/or on a side wall of the bracket. The RP-connector 21 may be configured to seal when the patch unit is disconnected from the cradle, as will be further described with reference to fig. 27 a-b.

Fig. 15a-b show a schematic view of the tip 300 including the connector plate 330, before (fig. 15 a) and after (fig. 15 b) the tip 300 is inserted into the patient's body 6 (e.g., subcutaneous tissue). The tip 300 may comprise four (4) cavities, for example as shown in fig. 12c, wherein a first cavity serves as a fluid channel and each of the other three (3) cavities comprises one of three (3) electrodes (only two electrodes 30a, 30b are shown), which may be electrically connected to a connector plate 330 positioned at the bottom side of the cradle housing 304. The connector plate 330 is configured to engage the bracket connector 26 positioned at the bottom of the sidewall of the well 25.

Fig. 16a-b show schematic views of a tip 300 including one or more connectors 340, before (fig. 16 a) and after (fig. 16 b) the tip is inserted into a patient's body 6 (e.g., subcutaneous tissue). The tip 300 may comprise four lumens, for example as shown in fig. 12d, a first lumen serving as a fluid channel and three (3) further lumens each of which may provide (within or on) one of three (3) sensing electrodes (e.g. electrodes 30a and 30b shown in fig. 16 a-b). The electrodes may be electrically connected to one or more connectors (e.g., shown as connectors 340a and 340 b), e.g., three (3) electrodes may be connected to three (3) connectors.

In some embodiments, the protrusions 24a and 24b can include electrode connectors ("well connectors") such that the one or more end connectors (e.g., 340a, 340 b) can engage the one or more well connectors after the end 300 is inserted into the patient's body 6.

Fig. 17a-b illustrate insertion of the tip 300 into the body 6 of a patient according to some embodiments of the present disclosure.

In some embodiments, the automatic inserter 700 may be used to insert the tip 300 into the body 6 of a patient and connect the tip 300 to the cradle 20. The inserter may include a slot (or receiving opening/recess) 701 configured to receive a tip cartridge (tip cartridge) having a tip, a tip protector, and a piercing element (i.e., a sharp needle). According to some embodiments, the end cartridge is configured to align the end with the well such that the end connector contacts the well connector when the end is engaged within the well. Examples of end cartridges are shown in figures 50a-e and 51 and an example of an inserter is shown in figure 52. As shown in FIG. 17a, prior to insertion into the body, the end cartridge may be loaded into inserter 700 and positioned in inserter slot 701. The carrier 20 may be secured (e.g., adhered) to the patient's body 6 prior to the insertion process. In some embodiments, the carriage can be provided with different wells that can be tilted (or skewed) at different angles relative to the carriage 20 to allow for various penetration angles. An example for such angled/tilted insertion is described in U.S. patent application publication No.2008/0319414, the disclosure of which is incorporated herein by reference in its entirety.

Fig. 17b shows an example of insertion of the tip 300 via the inserter 700. Inserter 700 may be coupled to carriage 20 after end 300 is loaded onto (or into) slot 701. Upon operation of button 702, the spring-loaded mechanism may fire tip 300 into body 6 through well 25 such that the tip engages the well and electrical connectors 320 and 26 are also engaged. The current generated on the electrodes can be conducted to the RP (also via the RP connector 21) via, for example, the connectors 320, 26 and the wire 23. The arrow indicated at inserter slot 701 shows the direction of movement of tip 300 during insertion.

Fig. 18a-b illustrate the patch 10 and the bracket 20 according to some embodiments of the present disclosure, before (fig. 18 a) and after (fig. 18 b) the patch 10 is connected to the bracket 20.

Fig. 19 illustrates an example of a User Interface (UI) that may be used in various embodiments of the present disclosure. The UI may be disposed on a remote controller 40 in some embodiments and includes a screen 41 and one or more keys, such as navigation keys ("operating buttons") 42. The screen 41 may present data relating to the sensing device (e.g., glucose readings) and/or the pump (e.g., insulin delivery profile). In this example shown in fig. 19, glucose readings are presented via a curve/graph 1001 (named "BG reading") and an insulin delivery profile (e.g., a daily basal profile) is presented via a bar graph 1002. A user may navigate between and/or within screen elements (e.g., displays, menus) using the navigation key 42 and/or soft keys 1003, 1004, 1005. The function of the soft keys may correspond to instructions displayed on the screen (in the soft key bar, e.g., on the bottom of the screen) and may depend on the application environment and the particular function currently activated. In the example shown in fig. 19, key 1003 corresponds to a "select" function, key 1004 corresponds to a "refresh" function, and key 1005 corresponds to a "return" function. The user may use the navigation key 42 and/or soft keys 1003, 1004, 1005 to program and/or actuate the pump and/or sensing device. An on/off button/key 1006 may be provided for turning the remote controller 40 on or off. Other remote controls may be used, such as implementing a touch screen or the like.

Fig. 20a-b illustrate a perspective view (fig. 20 a) and a transverse cross-sectional view (fig. 20 b) of a tip having a dual lumen cannula 305a according to some embodiments of the present disclosure. As shown, cannula 305a includes two lumens, a first lumen 355 providing a channel for insulin delivery and a second lumen 356 providing a sensing probe containing/providing one or more sensing electrodes. The longitudinal window 306 may be disposed at an outer surface of the second lumen 356 such that interstitial fluid (ISF) within the body can contact the one or more sensing electrodes provided by the second lumen 356. The longitudinal window 306 allows the active surface of the one or more electrodes to be exposed while mechanically holding (or supporting) the probe within the second lumen. For example, a distal portion of window 306 may be configured to have a smaller size (e.g., smaller diameter) than a proximal portion of window 306 to enable mechanically supporting a probe (or electrode) within the lumen. In some embodiments, the outer surface of the second cavity may be provided with a plurality of holes or openings exposing the one or more active surfaces to ISF.

In some embodiments, the proximal portion of the cannula 305a may be widened to obtain a conical configuration 307 that is precisely aligned with a corresponding conical bushing (e.g., as shown in fig. 8). In some embodiments, the widening of the proximal portion of the cannula may be achieved via heating (e.g., ultrasonic welding) and/or via any other technique known in the art.

FIG. 21 shows an exemplary embodiment of a flat sensing probe 30, probe 30 comprising three (3) electrodes: working electrode 321, counter electrode 322, and reference electrode 323. In some embodiments, a probe may include more than one electrode each, such as three (3) working electrodes, three (3) counter electrodes, and 1 (1) reference electrode. The electrodes may be connected to electrical connectors 310a, 310b, and 310c via wires 311, 312, and 313. Electrical connectors 310a, 310b, and 310c may be positioned on a wider surface to increase the conductive contact area. The wider surface may be arcuate (e.g., partially circular) to match the shape of the bottom side of the casing housing. In some embodiments, the probe 30 can be folded (e.g., bent, twisted, curved) to fit the configuration of the tip. One or more gaps (or nodes) 314 may be formed in the probe surface to allow flexibility of the probe and to allow the probe to fold (e.g., along the dashed line).

Fig. 22a-b illustrate a probe 30 having three electrodes 321, 322, 323, wires (e.g., 312), and respective connectors 310a, 310b, 310c according to some embodiments of the present disclosure. In some embodiments, the probe is configured to fold at a fold line at one or more gaps 314. As shown in the enlarged view (fig. 22 b), the wire 312 is also folded accordingly.

Fig. 23 shows an example of a manufacturing process of the plurality of probes 30. May be provided in a non-conductive flexible polymer (e.g., polyimide @)) The finished plate or film 3100. Electrodes made of conductive metal (e.g., gold, titanium covered/coated with gold) can be sputtered onto the polymer in the desired shape by using a protective mask (e.g., photolithography) as is known in the art. The probe 30 can be configured in a desired shape to surround the electrode and then can be cut 3102 to the final desired shape by any cutting device 3101 known in the art.

Fig. 24-26 illustrate perspective views of a tip (or portion of a tip) having a probe as schematically illustrated in fig. 12b, according to some embodiments of the present disclosure. Fig. 24 illustrates a perspective view of a cannula housing 304a according to some embodiments of the present disclosure. The cannula housing 304a may include a cannula passage 344 and a cannula slot 345. Cannula passage 344 is configured to receive a multi-lumen cannula, such as, for example, a dual lumen cannula, one lumen for delivering fluid and the other for providing a stylet. The cannula slot 345 is configured to occupy a folded portion of the probe.

Fig. 25a illustrates a cross-sectional view of the bottom side of the tip 300 according to some embodiments of the present disclosure. The cannula 305a may be positioned within a cannula passage of a cannula housing (e.g., indicated at 344 in fig. 24). As illustrated in the earlier disclosed embodiments, the cannula may comprise two or more lumens, with a first lumen 355 providing a channel for insulin delivery and a second lumen 356 providing a probe. The probe may include a proximal portion and a distal portion and the distal portion of the probe may reside within or on the lumen 356 and contain the sensing electrodes. The probe may be folded as shown in fig. 22a and its proximal portion may reside on or within a cannula slot on the bottom side of the cannula housing. Electrical leads 311, 312 and 313 (not shown in fig. 25 a) may connect the electrodes to connectors 320a, 320b and 320c positioned at the proximal side of the probe.

Fig. 25b illustrates a perspective view of the tip 300 according to some embodiments of the present disclosure. Tip 300 may include cannula cover 302, cannula housing 304a with cannula slot 345, and cannula 305a, cannula 305a including two lumens (355 and 356) for fluid delivery and probe provision. The connectors 320a, 320b and 320c positioned at the bottom side of the casing housing 304a are configured to fit into corresponding connectors positioned, for example, within the wells of the carrier. Longitudinal opening (window) 306 may provide direct communication of interstitial fluid with the probe electrode.

Fig. 26 illustrates a perspective view of various components of the tip 300 according to some embodiments of the present disclosure. In some embodiments, tip 300 may be similarly configured as the tip described in fig. 8, for example, still including cannula housing 304a having a slot (e.g., indicated as 345 in fig. 24), probe 30, and cannula 305a having two or more lumens for delivering fluids and providing probe 30.

Fig. 27a-b illustrate an example of a carrier 20 according to some embodiments, which may include one or more electrical leads (or conductive elements) 231, 232, 233 for transmitting electrical current from one or more connectors (e.g., 251, 252, and 253) positioned within a well 25 to one or more connectors 201, 202, 203, such as provided on a connection device (e.g., snap connectors) 206 (e.g., snap connectors). In some embodiments, the carrier may include conductive paths (e.g., microchannels formed in the carrier) for receiving the wires 231, 232, 233 that carry the electrical current. In some embodiments, the carrier may also include other electronic components, such as, for example, an amplifier, to enhance the signal generated on the electrode positioned within the tip, preventing possible signal attenuation. In some embodiments, the cradle may further comprise a power source to enable continuous operation of the electrodes. Connectors 251, 252, and 253 ("well connectors") may be disposed within or on well opening 24 and configured to form electrical communication with one or more end connectors positioned on an end configured to be received within well opening 24. In the example shown in fig. 27b, the connectors 251, 252, 253 are positioned on the lower surface of the well 25. In other embodiments, the connector may be positioned on at least one protrusion within well 25 and configured to receive any of the tip configurations described herein. The well 25 and/or the tip may be configured such that the connectors 251, 252, 253 remain sealed once the tip is connected to the well 25. The snap connectors 201, 202, 203 are configured to enable electrical communication with an RP connector positioned in a recess in the patch configured to connect to the snap means 206 of the bracket 20. In some embodiments, the one or more snap connectors 201, 202, 203 may be disposed on a sidewall of the bracket below the snap 206 and contact an RP connector positioned below the recess.

Fig. 28a-b show perspective views of examples of electrical paths used in the carriage 20. In some embodiments, the carrier may include a well 205, a snap device 206, electrical leads 231, 232, and 233, and electrical contacts/snap connectors 201, 202, 203, as described with reference to fig. 27 a-b. The snap connectors 201, 202, 203 shown in fig. 28a-b, for example, may be configured such that they remain sealed when the patch unit is disconnected from the cradle. For example, a non-conductive sealing cap may be provided to cover the connectors 201, 202, 203. The sealing cap may be made of a sealing material (e.g., rubber, silicone, etc.) that provides a seal for the connectors 201, 202, 203. In some embodiments, the RP connector may be configured to pierce a sealing cap for contacting the snap connector. In other embodiments, the sealing cap may be removed when the patch is connected to the bracket. In other embodiments, the sealing cap may include contact pads embedded within the sealing material to conduct electrical current upon contact with a connector positioned on the reusable portion.

Fig. 28c-d show perspective views of the patch 10 and the carrier 20 before connection and examples of electrical paths between the carrier and the patch 10. After patch 10 is connected to cradle 20, cradle snap fitting 206 engages with depression 106 and the snap connectors contact RP connectors 111, 112 and 113 to cause current to be delivered from the one or more electrodes to the processor.

Fig. 29a-d show another example of an electrical path between the carrier 20 and the patch 10. In some embodiments, the connector to the patch unit may be configured as a conductive protrusion 21. Fig. 29b-c show a transverse cross-sectional view of the carrier 20 showing contact between the wires within the microchannels 22 and the conductive protrusions 21. The conductive protrusions 21 may be constructed of any conductive material (e.g., conductive polymers, composites, graphite, etc.), which may be resilient and provide electrical communication between the wires 235, 236, 237 and the patch 10. A sealing cap may be provided to cover the conductive protrusions 21 when the patch unit is disconnected from the cradle. In other embodiments, the conductive protrusions 21 may be configured to remain sealed when the patch unit is disconnected from the cradle. For example, the contact pads may be embedded within an encapsulant material (e.g., rubber, silicone, etc.) so that the wires 235, 236, 237 may contact the contact pads and deliver current to the RP upon contact with a connector positioned on the reusable portion.

Fig. 29d shows the connection of the patch 10 to the bracket 20. Thus, when the patch 10 is connected to the bracket 20, electrical communication is formed between the conductive protrusions 21 and the connectors 121 in the patch 10. In some embodiments, electrical connector 121 is disposed at the bottom of RP 100. The connector 121 may be constructed of any conductive material (i.e., conductive polymer, composite material, etc.), which may be elastic, and may be configured to contact the conductive protrusions 21. The connector 121 may be configured to remain sealed when the patch is disconnected from the bracket. For example, a sealing cap may be provided to cover the connector 121 when the patch is disconnected from the bracket. When patch 10 is connected to cradle 20, electrical connector 121 may be pressed against conductive protrusion 21 so that wires 235, 236, 237 may contact pads within conductive protrusion 21 for conveying electrical current generated on the one or more electrodes to a processor.

FIGS. 30a-33b show a configuration having a tip of a probe such as described in FIGS. 12a and 13 a-b. According to some embodiments, the tip may comprise a cannula housing such that the proximal end of the probe is folded over the outer curve of the cannula housing.

Thus, FIG. 30a shows the probe 30 prior to insertion into the cannula lumen and folding. The stylet 30 may include a distal end 324 configured for residing within the cannula lumen and a proximal end configured to be positioned below the bottom side of the cannula housing. The distal end 324 may include a sensing probe and connecting leads for transmitting the current generated on the electrodes to connectors 310a, 310b, 310c positioned at the proximal end of the probe. In some embodiments, the proximal end may be widened to match the bottom side of the cannula housing form/shape, and is preferably arcuate (e.g., circular, semi-circular, or partially circular). At the proximal end of the probe, the leads may be folded into one or more surfaces to fit the bottom side of the cannula housing, as shown in fig. 32 a. For example, the wire may be folded into, for example, two fold surfaces 326 and 327 at the pivot point (see dashed lines) as shown in fig. 30 a. Fig. 30b shows a bottom view of the probe 30 shown in fig. 30 a. Fig. 30c shows a perspective view of the probe, the probe 30 comprising folded surfaces 326, 327 to which electrical leads are connected, and connectors 310a, 310b, 310 c. Fig. 30d schematically shows the folded probe 30. Thus, the probe folds at the pivot line according to the fold angles δ, β and α.

Fig. 31 shows a perspective view of various components of tip 300 (as shown in fig. 26), for example, implementing probe 30 shown in fig. 30 a-d. In some embodiments, as shown in fig. 30a-d, the distal end 324 of the probe 30 can be inserted into the second lumen through the opening 306.

Fig. 32a-b illustrate perspective views of the tip 300, such as described in fig. 30a-31, according to some embodiments. The proximal end of the probe may include at least a portion of the connecting wires folded over the cannula housing 304 according to surfaces 326 and 327, and electrical connectors 310a, 310b and 310c positioned at the bottom of the cannula housing 304. In some embodiments, electrical connectors 310a, 310b, and 310c may be spatially arranged around the bottom of the casing housing 304 to mate with corresponding connectors positioned within a well, such as a cradle.

Figure 32b shows an enlarged view of the underside of double lumen cannula 305a shown in figure 32 a.

Fig. 32c shows a bottom view of the tip 300 described above, including a multi-lumen cannula 305a having a lumen 355 for delivering fluid and a second lumen 356 comprising the distal end of the probe. The electrical leads may be folded along the surfaces 326, 327 such that the proximal end can be placed at the bottom side of the cannula housing.

Fig. 33a shows the tip 300 prior to attachment to the bracket 20 according to some embodiments. Once the tip 300 is inserted into the patient's body, the recess 309 engages the well protrusion to provide a rigid connection of the tip 300 to the cradle 20 and stable contact between the tip connector 310 and the cradle connectors 251, 252, 253 so that electrical communication between the probe and cradle leads 231, 232, 233 can be maintained. In some embodiments, the tip connectors 310 may be spatially arranged around the bottom of the casing housing 304 so as to be aligned with corresponding connectors on protrusions positioned at the bottom side of the well 25. In the example shown, once the tip 300 is inserted, the connector 251 is positioned on a first protrusion within the well and the connectors 252, 253 are positioned on a second protrusion.

Figures 34a-c illustrate tip configurations according to some embodiments of the present disclosure having a multi-lumen cannula and sensing electrodes, for example, as previously shown in figures 9b, 12c, and 12 d. According to this configuration, the multi-lumen cannula 305b may include more than two lumens (e.g., 4 lumens), and similar to the previously discussed embodiments, the first lumen 355 provides a channel for fluid (e.g., insulin) delivery and two or more lumens (e.g., 356a, 356b, 356 c) for housing (and/or supporting) sensing electrodes, i.e., each electrode disposed at one of two (2) or more second lumens. In some embodiments, the sensing electrode comprises three (3) electrodes (e.g., working, counter, and reference electrodes) and the two (2) or more second cavities comprise three (3) cavities, respectively, as shown in fig. 34 a-c. In some embodiments, the sensing electrode comprises two (2) electrodes (e.g., a working electrode and a counter electrode) and the two (2) or more second lumens comprise two (2) lumens each providing one (1) electrode. In some embodiments, more than one electrode may be provided per kind, and each electrode may be provided by a separate second lumen. In some embodiments, the multi-lumen cannula 305 can be configured such that the first lumen 355 is in the center of the cannula ("central lumen") and the two (2) or more lumens 356a, 356b, 356c surround the first lumen ("circumferential lumen").

Fig. 34a shows a perspective view of an example of a multi-lumen cannula 305b, fig. 34b is an enlarged view of the distal end of the cannula 305b, and fig. 34c is a transverse cross-sectional view of the cannula 305b showing a central lumen 355 for fluid delivery and circumferential lumens 356a, 356b and 356c providing electrodes. In some embodiments, the second lumens 356a, 356b, and 356c may be closed at the bottom side of the cannula (i.e., at the distal end) so that ISF can be contacted only through the openings 306a, 306b, 306 c. In some embodiments, the electrodes may be configured as "wires" or "ribbons" that pass through the two or more second lumens, and in some embodiments, the one or more electrodes may be embedded within the material of the wall of the cannula 305 b.

Figures 35a-39b show examples of tips of multi-lumen cannulae having configurations such as schematically shown in figure 12 c. In this example, the multi-lumen cannula includes one central lumen for fluid delivery and, for example, three (3) circumferential lumens each providing one electrode. In some embodiments, a connector plate 330 may be provided at the bottom side of the cannula housing for maintaining electrical communication between the electrode provided by the circumferential cavity and the cradle connector.

Fig. 35a-c show perspective (fig. 35 a), top (fig. 35 b) and bottom (fig. 35 c) views of the connector plate 330. The connector board 330 may include, for example, three (3) folded electrode connectors 334, 335, and 336 configured to contact electrodes provided by the circumferential cavity. The connector plate 330 may also include, for example, three (3) cradle connectors 331, 332, and 333 configured to contact the connectors of the cradle. The connector plate 330 may be constructed of an electrically conductive material (e.g., metal) for conducting electrical current from the electrode connectors 334, 335, 336 to the cradle connectors 331, 332, 333. In other embodiments, different combinations of electrodes and connectors may be implemented, i.e., three (3) electrodes and three (3) connectors merely as examples.

Fig. 36 shows an exploded view of the various components of tip 300 prior to assembly, including cannula 305b having four (4) lumens, as previously described, for example, in fig. 26. The connector plate 330 may be pressed and/or attached to the bottom of the cannula housing 304 such that the internal opening of the plate and the folded electrode connector may receive a protruding portion in the bottom of the cannula housing 304. The electrode connectors 334, 335, 336 may also be configured to contact the electrodes provided by the circumferential cavities 356a, 356b, and 356c through the openings (e.g., 306a, 306b, 306 c), respectively.

Fig. 37a-b show an assembled tip 300, which in some embodiments is similar to the tip embodiments described earlier.

Fig. 38 shows the tip 300 prior to attachment to the bracket 20. Connectors (e.g., three connectors) 251, 252, and 253 ("well connectors") may be provided at the bottom of the side walls of the well for contacting the cradle connectors 331, 332, 333 of the connector plate 330. In some embodiments, two well connectors 252, 253 may be disposed on one sidewall of the well and the third connector 251 may be disposed on the opposite wall. Thus, two of the cradle connectors 332, 333 may be positioned on one side of the connector plate and the third cradle connector 331 may be positioned on the other side (e.g., opposite (across)). The carrier connectors 331, 332, 333 may be resilient to ensure contact with the well connectors 251, 252, 253 after tip insertion. Fig. 39a-b show a bottom view of the tip 300 (with sleeve 305 b) and cradle 20 after connection, including a connector plate 330, which for example includes three (3) electrode connectors 334, 335 (336 not shown) and three (3) cradle connectors 331, 332 and 333.

Figures 40-43b show examples of tips with multi-lumen cannulae for example according to the configuration schematically shown in figure 12 d. In this example, the multi-lumen cannula includes one central lumen for fluid delivery and, for example, three (3) circumferential lumens each providing an electrode. According to some embodiments of the present construction, the electrical connection leads are inserted through the bushing and the inside of the casing into a cavity within the casing and they are folded around the outer surface of the casing. An example of such a folded wire 341 is shown in fig. 40. Three (3) connectors 341a, 342a, 343a for three (3) electrodes may be provided by a recess (e.g., an annular recess) formed between the sleeve housing 304 and the cover 302, as shown in fig. 41. In some embodiments, the lead may be integrally formed with the electrode and/or the connector, forming a single continuous element.

Fig. 42 shows an exploded view of a tip 300 implementing a sleeve 305b and three (3) electrodes comprising folded leads connected to connectors 341a, 342a, and 343a, respectively. The electrode lead may be folded from the inside of the sleeve housing toward the outside thereof such that the connectors 341a, 342a, and 343a are positioned on the outside of the sleeve housing 304 and in a recess (e.g., an annular recess) formed between the sleeve housing 304 and the cover 302. A self-sealing septum 301 and cap 302 may be placed on top of the cannula housing 304 such that the septum is received in an aperture on the upper portion of the cap.

Figures 43a-b show the end shown in figure 42 and the bracket before attachment. Fig. 43b shows an enlarged bottom view of the tip 300 and well 25 during the insertion process, before they are connected to each other. In some embodiments, two connectors 252, 253 may be disposed on one protrusion 24b and one connector 251 may be disposed on a second protrusion 24 a. Accordingly, two connectors 342, 342 may be disposed on the opposite side of the recess of the tip 300 from the third connector 341, such that the tip connectors 341, 342, 343 contact the carrier connectors 251, 252, 253 after the tip 300 is inserted through the well 25.

44a-48b illustrate examples of configurations of current transport structures within a cradle according to some embodiments. In this configuration, the electrical leads and connectors are positioned on or within an adhesive layer placed at the bottom of the bracket.

Thus, fig. 44a-b illustrate an adhesive layer 299 which may include an opening 297 aligned with the opening of the carrier providing a passageway for insertion of the tip through the carrier and adhesive layer into the patient's body. In some embodiments, one or more end connectors 29 can be disposed at or near the openings 297 of the adhesive layer 299. For example, the end connector 29 can be positioned on a protruding portion of the adhesive layer 299 that is configured to be received within an opening of the bracket. The one or more connectors 29 may begin to make contact (e.g., mechanically, physically) with one or more connectors disposed on the tip as the tip passes through the bracket and the adhesive layer. The one or more tip connectors 29 may be connected to one or more patch connectors (e.g., 287, 288, and 289) via one or more wires (e.g., 294, 295, and 296). The one or more patch connectors may be configured to form electrical communication with a connector placed on the patch when the patch is connected to the cradle.

Fig. 45 shows a top view of the bracket 20 before the adhesive layer is attached to the bracket 20 and before the tip is inserted. The carrier may include an opening (e.g., well 25) configured to receive any of the end configurations described herein. The bracket 20 may also include one or more openings (e.g., 261, 262, 263) configured to receive the one or more patch connectors positioned on the adhesive layer such that a contact surface with the connectors when connected therebetween is positioned at a bottom side of the patch. In some embodiments, a micro-amplifier may be positioned (at least partially) on the adhesive layer 299 for enhancing the signal generated by the electrode, and the adhesive layer may also include, for example, a power source that enables continuous operation of the electrode.

Fig. 46a-b show the bracket 20 shown in fig. 45 after the adhesive layer 299 is attached to the bracket and after the tip 300 is inserted through the well 25. As shown in fig. 46a, the one or more patch connectors 287, 288 and 289 protrude through the bracket opening, providing contact pads on the surface of the bracket. Connectors 287, 288 and 289 may be configured such that they remain sealed when the patch is disconnected from the bracket. In some embodiments, a sealing cap may be provided to cover connectors 287, 288 and 289 when the patch unit is disconnected from the cradle. FIG. 46b shows an enlarged bottom view of the well 25 and adhesive layer 299 after the end has been inserted through the well opening. The one or more tip connectors 29 may come into contact with probes and/or electrodes and/or connectors positioned within the tip as the tip is inserted through the well opening. The well 25 and/or the tip may be configured such that when the tip is connected to the well 25, the connection remains sealed.

Fig. 47a-b show a specific example of a bracket 20 that includes three (3) end connectors 291, 293 positioned at the opening 297 of the adhesive layer 299. The adhesive layer also includes three (3) electrical leads 294, 295, and 296 and three (3) patch connectors 287, 288, and 289. Fig. 47a shows the adhesive layer and the bracket before they are attached, and fig. 47b shows the bracket with the adhesive layer attached thereto.

Fig. 48a-b show the tip 300, the bracket 20 and the conductive adhesive layer 299. As shown in fig. 48b (magnified view), connectors 320a, 320b, and 320c (also schematically shown in fig. 12a, for example) are configured to come into contact with the one or more end connectors 29 as the ends are inserted through the wells 25 and the adhesive layer openings 297.

Figures 49a-52 show examples of end cartridges (which may also be referred to as "cannula cartridges") and inserters. The cannula cartridge may be configured to receive a tip, as described in various embodiments herein, and to be loaded onto an inserter. The cannula cartridge may include a penetrating member to facilitate tip insertion. The inserter may include a spring-loaded mechanism for launching the penetrating member and tip into the patient. Once the inserter is operated, the penetrating member and tip are launched into the body from the cartridge, and following insertion of the tip into the body, the penetrating member is retracted into the cartridge to avoid self-penetration. In some embodiments, the tip may be connected to a bracket secured to the body during the insertion process. The cannula cartridge (including the puncturing element) may be disconnected from the inserter and disposed of.

Accordingly, fig. 49a-b show a bottom cross-sectional view (fig. 49 a) and a bottom perspective view (fig. 49 b) of the cannula cartridge 900. The cannula cartridge may comprise a body 903 and a handle 901. The tip 300 may be positioned within a cartridge body 903 (which may also be referred to as a housing) and includes a cannula 305 (or any other cannula such as 305a, 305b described above, for example). Cannula 305 includes electrodes and connectors, such as connectors 310a, 310b, and 310 c. The cannula 305 may include a first lumen for delivering fluid and one or more second lumens providing electrodes. The needle 902 of the puncturing element is passed longitudinally through a lumen within the cannula 305 for insertion of the cannula 305 into the body. Providing the electrodes from a cavity within cannula 305 eliminates the necessity of an external piercing element to protect the electrodes and enables the use of an internal piercing element to reduce the piercing area of the tip. In some embodiments, the circumference of the cannula with the electrodes is comparable to a cannula configuration that delivers only fluid. In some embodiments, the circumference of the cannula 305 may be about 1.8 millimeters.

Fig. 50a-e show the assembly of the tip 300, the penetrating member 902 and the cannula cartridge 900. FIG. 50a shows tip 300 and piercing element 902 prior to attachment. Tip 300 includes a septum 301, a cap 302, a cannula housing 304, and a cannula 305 (e.g., with electrodes and connectors). The piercing element includes a needle 902 and a needle cover 908. In some embodiments, teeth/protrusions/latches 905 may be provided at the bottom of needle cover 908 (as shown in fig. 50 c) and corresponding slots 906 may be provided in the tip cover 302 (as shown in fig. 50 b) for aligning and coupling the needle cover 908 with the tip. In some embodiments, one or more grooves 904 may be provided in the needle cover 908 (as shown in fig. 50 a) and one or more protrusions 907 may be provided on the cannula cartridge body 903 (as shown in fig. 50 d) for aligning (and coupling) the needle cover 908 with the cartridge (as shown in fig. 50 e). The one or more slots 904 may be configured as a track such that the needle cover 908 can be moved for insertion of the tip into the patient's body when aligned with the cannula cartridge. Alignment between the tip 300, piercing element 902, and cartridge 900 achieves accurate positioning of the tip within the well of the cradle and serves to ensure proper contact of the electrode connector and the well connector.

Fig. 51 shows an example of a packaging of the sleeve cartridge and carriage of the sensing and dispensing device 90 and the dispensing device 91 only. In the sensing/dispensing device, cannula cartridge 900a includes a tip that includes electrodes, leads and connectors and cradle 20a includes connectors and leads. In a dispensing-only apparatus, the cartridge 900b includes a tip and a cradle 20b, the tip including only fluid dispensing cannulas and the cradle being devoid of leads and connectors. In some embodiments, cartridges 900a and 900b may have similar physical dimensions (e.g., height, length). In some embodiments, the brackets 20a and 20b may also have similar physical dimensions.

FIG. 52 shows the cannula cartridge 900 loaded onto the inserter 700. The inserter includes a slot 701 to receive the cannula cartridge, a winding arrangement 704 and operating/trigger buttons 702 and 703. After firing the tip, the cartridge (needle including the piercing element) can be disconnected from the insert and disposed of.

Any and all references to publications or other documents in this application, including but not limited to patents, patent applications, articles, web pages, books, etc., are incorporated herein by reference in their entirety.

Although a few variations have been described in detail above, other variations are possible. For example, the logic flows illustrated in the figures and described herein do not require the particular order shown, or sequential order, to achieve desirable results.

Although specific embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to limit the scope of the appended claims which follow. In particular, it is contemplated that various substitutions, alterations, and modifications may be made without departing from the spirit and scope of the invention as defined by the exemplary claims. Other aspects, advantages, and variations are considered to be within the scope of the following exemplary claims. The exemplary claims set forth below are merely representative of some of the embodiments and features disclosed herein. Other non-claimed embodiments, inventions, and features are also contemplated.

Claims (26)

1. A skin securable medical device comprising:

a tip configured for insertion and delivery of a therapeutic fluid into a patient's body;

a pump for delivering therapeutic fluid into the body of the patient via the tip;

a sensor disposed at the tip and configured to sense a level of one or more analytes within the body of the patient and configured to provide at least one sensor signal indicative of the level of the one or more sensed analytes;

a processor for processing the at least one sensor signal and for controlling therapeutic fluid delivery;

at least one first connector disposed on the tip for enabling electrical communication between the sensor and the processor; and

an attachable housing portion for securing at least a portion of the device to the skin of a patient, the attachable housing portion comprising at least one second connector;

wherein the attachable housing portion comprises a cradle and the cradle comprises an opening, the at least one second connector being positioned on a bottom side of the opening, the at least one first connector being coupled to the at least one second connector when the tip is inserted through the opening into the patient's body, forming electrical communication therebetween and being capable of transmitting the at least one sensor signal from the sensor to the processor.

2. The device of claim 1, wherein the tip comprises a cannula for delivering the therapeutic fluid through the cannula.

3. A device according to any preceding claim, wherein the sensor comprises a plurality of electrodes for sensing the level of one or more analytes.

4. The device according to claim 1 or 2, wherein the sensor and/or tip further comprises a plurality of conductive elements for transmitting the at least one sensor signal from the sensor to a processor via the at least one first and second connector.

5. The apparatus of claim 4, wherein the plurality of conductive elements comprise wires.

6. The device according to claim 1 or 2, wherein at least a portion of the sensor is curved for enabling physical contact between the at least one first and second connectors when the tip is inserted through the opening.

7. The device according to claim 1 or 2, wherein the tip comprises a first lumen for delivering the therapeutic fluid and one or more second lumens for disposing at least a portion of the sensor.

8. The apparatus of claim 7, wherein the one or more second lumens comprise three lumens.

9. The device of claim 3, wherein the tip comprises a first lumen for delivering the therapeutic fluid and one or more second lumens for disposing at least a portion of the sensor.

10. The apparatus of claim 3, wherein the plurality of electrodes comprises a working electrode, a counter electrode, and a reference electrode.

11. The apparatus of claim 3, wherein the plurality of electrodes comprises three working electrodes, three counter electrodes, and one reference electrode.

12. The device of claim 9, wherein each electrode resides in a separate one or more second lumens of the tip.

13. The device of claim 7, wherein the one or more second cavities comprise one or more windows such that at least a portion of the sensor is exposed to an ambient environment.

14. The apparatus of claim 7, wherein the one or more second cavities are substantially shorter than the first cavity.

15. The apparatus of claim 7, wherein the first lumen has a substantially circular cross-section and the one or more second lumens have a substantially arcuate cross-section.

16. The apparatus of claim 1 or 2, wherein the apparatus operates in a mode selected from the group consisting of a closed-loop mode, a semi-closed-loop mode, and an open-loop mode.

17. The device according to claim 1 or 2, wherein the attachable housing part comprises a cradle, and wherein the cradle comprises a well for receiving the tip and at least one latch for connecting the cradle and the device.

18. The device of claim 1 or 2, wherein the attachable housing part comprises a latch comprising the at least one second connector for establishing electrical communication with the at least one first connector.

19. The apparatus of claim 17, wherein the carrier comprises at least one wire.

20. The apparatus of claim 19, wherein the at least one wire is embedded within the carrier.

21. The device of claim 1 or 2, wherein the attachable housing portion comprises an adhesive tape having at least one connector and at least one wire.

22. The device according to claim 1 or 2, wherein the opening is configured such that the tip is insertable at an angle with respect to the attachable housing part.

23. The apparatus of claim 17, wherein the cradle includes an amplifier for amplifying the signal transmitted by the sensor.

24. The apparatus of claim 17, wherein the carrier includes a power source such that the electrodes or probes can be operated continuously or periodically.

25. The device of claim 24, wherein said continuous or periodic operation of an electrode or probe occurs when said pump is disconnected.

26. The apparatus according to claim 1 or 2, further comprising:

a cannula cartridge unit;

a piercing element for piercing the skin of a patient during tip insertion; and

an inserter is arranged in the device body,

wherein the cartridge unit and the piercing element are configured to align the tip such that the at least one first connector contacts the at least one second connector when the tip is inserted through the opening of the attachable housing portion.