Microneedle capsule and applicator assembly for microneedle array-based continuous analyte monitoring devices

Abstract

An applicator for an analyte monitoring device may include an actuatable housing having a body defining a cavity therein and having a distal opening and a side opening. A ferrule and a transfer member are received in the cavity and are independently movable relative to the housing body. A base may be removably engaged with the housing body at the distal opening. The housing body, the ferrule, the transfer member, and / or the base may be engaged with each other using one or more releasable coupling features. The base may be released from engagement with the housing body, thereby causing the ferrule and the transfer member to be aligned and positioned in a configuration in which the analyte monitoring device, held by the transfer member, is ready for insertion into the skin.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 249,399 filed on September 28, 2021, U.S. Provisional Patent Application No. 63 / 291,293 filed on December 17, 2021, and U.S. Provisional Patent Application No. 63 / 355,987 filed on June 27, 2022, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention relates generally to the field of analyte monitoring, such as continuous glucose monitoring. Background Art

[0004] Diabetes is a chronic disease in which the body cannot produce or properly utilize insulin, a hormone that regulates blood sugar. Diabetics can be given insulin to help regulate blood sugar levels, but these levels must still be carefully monitored to ensure that the timing and dosage are appropriate. If their condition is not properly managed, diabetics may suffer from various complications caused by hyperglycemia (high blood sugar levels) or hypoglycemia (low blood sugar levels).

[0005] Glucose monitors help people with diabetes manage their condition by measuring blood glucose levels in a blood sample. For example, a diabetic patient can obtain a blood sample through a fingerstick sampling mechanism, transfer the blood sample to a test strip containing a suitable reagent that reacts with the blood sample, and use a blood glucose monitor to analyze the test strip to measure the glucose level in the blood sample. However, using this process, a patient can typically only measure their glucose level at discrete moments, which may not capture hyperglycemia or hypoglycemia in a timely manner. A newer type of glucose monitor is a continuous glucose monitoring (CGM) device, which includes a transcutaneously implantable electrochemical sensor that continuously detects and quantifies blood glucose levels by surrogate measurement of glucose levels in the subcutaneous interstitial fluid. However, conventional CGM devices also have weaknesses, including tissue damage caused by insertion and signal delays (e.g., due to the time it takes for the glucose analyte to diffuse from the capillary source to the sensor). These weaknesses also lead to a number of disadvantages, such as pain experienced by the patient when inserting the electrochemical sensor and limited accuracy of glucose measurements, especially when blood glucose levels fluctuate rapidly. Therefore, there is a need for new and improved analyte monitoring systems. Summary of the Invention

[0006] According to one embodiment, the present invention relates to analyte monitoring.

[0007] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a housing including a body defining a cavity therein, wherein the housing body includes a distal opening; a cuff received within the cavity and including a lumen extending therethrough; and a transfer member slidably received within the lumen and configured to releasably retain the analyte monitoring device, wherein the applicator is movable between a collapsed configuration, wherein in the collapsed configuration, the analyte monitoring device is retained within the transfer member and a distal edge of the cuff and the transfer member are in a proximal-most position, an expanded configuration, and a released configuration, wherein in the expanded configuration, the distal edge of the cuff is in a distal-most position and the transfer member is in an intermediate position, and in the released configuration, the analyte monitoring device is released from the transfer member, the distal edge of the cuff is in an intermediate position, and the transfer member is in a distal-most position.

[0008] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a housing including a body defining a cavity therein, wherein the housing body includes a distal opening; a cuff received within the cavity and including a lumen extending therethrough; and a transfer member slidably received within the lumen and configured to releasably retain the analyte monitoring device, wherein the applicator is movable between a collapsed configuration, wherein in the collapsed configuration, the analyte monitoring device is retained within the transfer member, a distal edge of the cuff and the transfer member are positioned proximal to the distal opening of the housing body, in the collapsed configuration, the distal edge of the cuff is positioned distal to the distal opening of the housing body, and the transfer member is positioned proximal to the distal opening of the housing body, and in the released configuration, the analyte monitoring device is released from the transfer member, the distal edge of the cuff is distal to the distal opening of the housing body, and the transfer member is distal to the distal opening of the housing body.

[0009] In various embodiments, the present invention also relates to a method of applying an analyte monitoring device to a skin surface of a user, the method comprising: providing an applicator in a retracted configuration, wherein the applicator includes a transmission member that releasably holds the analyte monitoring device, the transmission member being slidably received within a trigger member cavity of a cuff, the cuff being received within a cavity of a shell, the shell including a body defining the cavity, the shell body including a distal opening; transitioning the applicator from the retracted configuration to an extended configuration; and transitioning the applicator from the extended configuration to a released configuration, wherein in the retracted configuration, a distal edge of the cuff and the transmission member are in a proximal-most position, in the extended configuration, the distal edge of the cuff is in a distal-most position, and the transmission member is in an intermediate position, and in the released configuration, the analyte monitoring device is released from the transmission member, the distal edge of the cuff is in an intermediate position, and the transmission member is in a distal-most position.

[0010] In several embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a. a housing including a body defining a cavity therein, wherein the housing body includes a distal opening and a side opening; b. a ferrule received in the cavity; c. a transfer member received in the cavity and configured to releasably retain the analyte monitoring device; d. a locking member at least partially received in the side opening of the housing body, wherein the locking member engages with the ferrule in a first configuration and disengages from the ferrule in a second configuration; and e. a base configured to be removably coupled to the housing body at the distal opening of the housing body, wherein the base includes a proximal surface, and f. wherein movement of the locking member from the first configuration to the second configuration releases the ferrule, thereby disengaging the proximal surface from the housing body.

[0011] In various embodiments, the present invention also relates to a method of using an applicator with an analyte monitoring device, the method comprising: transitioning a locking member of an applicator from a first configuration to a second configuration, wherein the applicator comprises: a housing body defining a cavity therein, a ferrule and a transfer member each received within the cavity, and a base removably coupled to the housing body, wherein the transfer member releasably retains the analyte monitoring device, wherein transitioning the locking member disengages the locking member from the ferrule, thereby allowing the ferrule to move relative to the housing body; and moving the base of the applicator relative to the housing body.

[0012] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising a housing including a body defining a cavity therein, a cuff received in the cavity and including a lumen, and a transfer member received in the lumen, wherein the transfer member comprises: a shaft; and a base portion at a distal end of the shaft, wherein the base portion comprises a plurality of flexible blades extending from the shaft and a plurality of petals extending from the shaft, and wherein the plurality of flexible blades define a receptacle for holding the analyte monitoring device.

[0013] In various embodiments, the present invention is also directed to an applicator for an analyte monitoring device, the applicator comprising: a housing including a housing body and a mounting seat; a ferrule-ring assembly including a ferrule and a friction ring coupled to the ferrule; and a transfer member configured to releasably retain the analyte monitoring device, wherein the transfer member and the ferrule-ring assembly are independently translatable relative to the housing body, wherein the transfer member and the ferrule-ring assembly are each releasably coupled to the mounting seat.

[0014] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a housing including a housing body defining a cavity therein and a mount extending from an inner surface of a proximal end of the housing body into the cavity; a ferrule-ring assembly including a ferrule having a lumen and a proximal opening and a friction ring positioned in the lumen and extending through the proximal opening, wherein the ferrule-ring assembly is seated about the mount; and a transfer member configured to releasably retain the analyte monitoring device, wherein a portion of the transfer member extends through the mount.

[0015] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a housing including a housing body defining a cavity therein and a mount extending into the cavity; a ferrule-ring assembly including a ferrule and a friction ring coupled to the ferrule; a transfer member configured to releasably retain the analyte monitoring device; and a base removably coupled to the housing, wherein the mount is configured to 1) releasably engage the friction ring to prevent axial movement of the transfer member prior to removal of the base from the housing, and 2) releasably engage the transfer member to control axial movement of the transfer member after removal of the base from the housing.

[0016] In various embodiments, the present disclosure further relates to a method of applying an analyte monitoring device to a skin surface using an applicator, the method comprising: providing an applicator comprising a housing defining a cavity, a ferrule, and a transfer member, wherein the ferrule and transfer member are each received within the cavity, wherein the transfer member retains the analyte monitoring device; applying a distal surface of the ferrule of the applicator to the skin surface; advancing the housing toward the skin surface, wherein advancing the housing moves the housing relative to the ferrule and transfer member and disengages one or more retaining features that prevent the transfer member from moving independently of the housing, wherein disengagement of the one or more retaining features releases the transfer member and advances the transfer member with the analyte monitoring device toward the skin surface; and releasing the analyte monitoring device from the transfer member.

[0017] In various embodiments, the present invention also relates to an applicator for an analyte monitoring device, the applicator comprising: a housing including a body defining a cavity therein and defining a distal opening; a cuff slidably received in the cavity and including a lumen extending therethrough; a transfer member slidably received in the lumen and configured to releasably retain the analyte monitoring device; a first biasing element / first biasing element disposed between the housing and the cuff; a second biasing element / second biasing element disposed between the housing and the transfer member; a microneedle capsule releasably engageable with the analyte monitoring device and configured to encapsulate a portion of the analyte monitoring device when engaged, the microneedle capsule including a third biasing element / third biasing element; and a base releasably engageable with the housing and coupled to the microneedle capsule. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic diagram of an analyte monitoring system with a microneedle array is depicted.

[0019] Figure 2A A schematic diagram of an analyte monitoring device is depicted.

[0020] Figure 2B Schematic diagram depicting the microneedle insertion depth in the analyte monitoring device.

[0021] Figures 3A-3D Depicted are an upper perspective view, a side view, a bottom view, and an exploded view of an analyte monitoring device, respectively.

[0022] Figures 4A-4E Depicted are perspective exploded views, side exploded views, bottom perspective views, side views, and top perspective views of a sensor assembly in an analyte monitoring device, respectively.

[0023] Figures 4F-4H Depicted are a perspective exploded view, a side exploded view, and a side view, respectively, of a sensor assembly in an analyte monitoring device.

[0024] Figures 5A-5D Various aspects of the microneedle enclosure are depicted in exploded view, first side and side cross-sectional view, second side and side cross-sectional view, and bottom perspective view, respectively.

[0025] Figures 5E-5G Various aspects of the microneedle enclosure and the substrate of the analyte monitoring device are depicted in perspective exploded view, perspective view, and side cross-sectional view, respectively.

[0026] Figure 6A A schematic diagram of the microneedle array is depicted. Figure 6B Depicts Figure 6A Schematic illustration of the microneedles in the microneedle array depicted in FIG.

[0027] Figure 7 A schematic diagram depicting a microneedle array for detecting multiple analytes.

[0028] Figure 8A Depicted is a side cross-sectional view of a cylindrical microneedle with a tapered distal end. Figure 8B and 8C They are Figure 8A Perspective and detailed views of one embodiment of a microneedle are shown.

[0029] Figure 9 A schematic diagram of a cylindrical microneedle with a tapered distal end is depicted.

[0030] Figure 10A and 10B Schematic diagrams of the microneedle array and microneedles are depicted, respectively. Figures 10C-10F Depicted are detailed fragmentary views of exemplary variations of microneedles.

[0031] Figure 11A and 11B Illustrative variations of microneedles are depicted.

[0032] Figure 12A and 12B Schematic diagram depicting the microneedle array configuration. Figure 12C and 12D Schematic diagram depicting the microneedle array configuration.

[0033] Figure 13A and 13B Depicted are perspective and orthogonal views, respectively, of exemplary variations of carrier sheets including microneedle arrays.

[0034] Figures 14A-14J Schematic diagrams depicting different variations of microneedle array configurations.

[0035] Figures 15A-15D Various aspects of an applicator for an analyte monitoring device are depicted in first side view, second side view, top perspective view, and bottom perspective view, respectively.

[0036] Figure 15E and Figure 15F Various aspects of the analyte monitoring device relative to the applicator delivery member are depicted in exploded and perspective views, respectively.

[0037] Figures 16A-16D Various aspects of a delivery member of an applicator for an analyte monitoring device are depicted in top perspective, bottom view, side view, and side cross-sectional view, respectively.

[0038] Figure 16E and 16F Various aspects of a delivery member of an applicator for an analyte monitoring device are depicted in bottom perspective and bottom plan views, respectively.

[0039] Figure 16G and 16H Various aspects of a delivery member of an applicator for an analyte monitoring device are depicted in side view and side cross-sectional view, respectively.

[0040] Figures 17A-17E Various aspects of a ferrule for an applicator of an analyte monitoring device are depicted in a top perspective view, a bottom view, a top view, a first side and side cross-sectional view, and a second side and side cross-sectional view, respectively.

[0041] Figure 17F and Figure 17G Aspects of a ferrule for an applicator of an analyte monitoring device are shown in bottom and side views, respectively.

[0042] Figures 18A-18D Aspects of a locking friction ring for an applicator of an analyte monitoring device are depicted in first, second, first, and second bottom perspective views, respectively.

[0043] Figures 19A-19E Various aspects of a ferrule-ring assembly for an applicator of an analyte monitoring device are depicted in top perspective, bottom view, top plan view, side view, and side cross-sectional view with detailed views, respectively.

[0044] Figures 20A-20F Various aspects of a housing for an applicator for an analyte monitoring device are depicted in a first top perspective view, a second top perspective view, a first bottom perspective view, a second bottom perspective view, a first side cross-sectional view, and a second side cross-sectional view, respectively.

[0045] Figures 21A-21B Various aspects of a locking member of an applicator for an analyte monitoring device are depicted in front and rear perspective views, respectively.

[0046] Figures 22A-22G Various aspects of a base for an applicator of an analyte monitoring device are depicted in a top perspective view, a top view, a bottom view, a first side view, a first side cross-sectional view, a second side view, and a second side cross-sectional view, respectively.

[0047] Figures 22H-22J Various aspects of an applicator base of an analyte monitoring device with a microneedle enclosure are depicted in exploded view, top perspective view, and side cross-sectional view, respectively.

[0048] Figure 22K Aspects of a base of an applicator for an analyte monitoring device that engages with a ferrule of the applicator are depicted in a top perspective view.

[0049] Figures 23A-23OViews of various different configurations of applicators for use with an analyte monitoring device are depicted in cross-section and close-up views.

[0050] Figure 24 is a process flow diagram illustrating the progression of the applicator from a collapsed configuration to an expanded configuration.

[0051] Figure 25 is a process flow diagram illustrating the process from the extended configuration to the released configuration of the applicator.

[0052] Figure 26A and Figure 26B Views of various different configurations of applicators for use with an analyte monitoring device are depicted in cross-section and close-up views.

[0053] Figures 27A-27C Depicted are upper perspective, side view, and lower perspective views, respectively, of an analyte monitoring device. Figure 27D Depicts a method comprising an adhesive layer Figure 27A A partially exploded view of the analyte monitoring device shown in FIG. Figure 27E Depicts Figure 27A Exploded view of the analyte monitoring device shown in .

[0054] Figures 27F-27I Depicted are top perspective, bottom perspective, side view, and exploded view, respectively, of a sensor assembly in an analyte monitoring device.

[0055] Figure 27J Depicted is a transparent side view of a sensor assembly in an analyte monitoring device.

[0056] Figures 28A-28E A perspective view, a side view, a bottom view, a side cutaway view, and an upper transparent perspective view of the analyte monitoring device are depicted, respectively.

[0057] Figure 29 Depicted is a side cross-sectional view of a cylindrical microneedle with a tapered distal end.

[0058] Figure 30 A schematic diagram of a cylindrical microneedle with a tapered distal end is depicted.

[0059] Figures 31A-31C An upper perspective view, a side view, and a lower perspective view of the applicator are depicted, respectively. Figure 31D Depicts Figures 31A-31C Exploded view of the applicator shown in .

[0060] Figures 32A-32G An upper perspective view, a lower perspective view, another upper perspective view, another lower perspective view, a top view, a side view, and a bottom view of the applicator conveyor are depicted, respectively.

[0061] Figures 33A-33EDepicted are a top perspective view, a top view, a bottom view, a bottom perspective view, and a side view, respectively, of the applicator trigger. Figure 33F Depicts Figures 33A-33E Another side view of the trigger shown in Figure 33G Depicts the Figure 33F A cross-sectional view of the trigger member taken along line 18G:18G is shown in FIG.

[0062] Figure 34A A top perspective view of the applicator housing is depicted. Figures 34B-34F Depicted separately Figure 34A , top view, bottom view, bottom perspective view and side view of the housing shown in . Figure 34G Depicts the Figure 34F A side cross-sectional view of the housing taken along line 19G:19G is shown in FIG.

[0063] Figure 34H and 34I Example variations of applicator housings are depicted.

[0064] Figure 35A Depicted is a bottom view of the applicator at the beginning of the loading process of loading an analyte monitoring device into the applicator. Figure 35B Depicts the analyte monitoring device after it has been loaded into the applicator. Figure 35A Bottom view of the applicator.

[0065] Figures 36A-36C Depicted is the loading process of loading an analyte monitoring device into an applicator.

[0066] Figure 37A 、 37B and 37D depict a cross-sectional view of the applicator in a loading configuration for deploying an analyte monitoring device from the applicator. Figure 37C Depicted by Figure 37B Detailed cross-sectional view of a portion of the loaded applicator indicated by circle C. Figure 37E Depicted by Figure 37D Detailed cross-sectional view of a portion of the loaded applicator indicated by circle D in FIG.

[0067] Figure 38 Depicted is a cross-sectional view of an applicator in a fired configuration for deploying an analyte monitoring device from the applicator.

[0068] Figures 39A-39C The applicator is depicted in top, side, and bottom perspective views, respectively. Figure 39D Depicts Figures 39A-39C Exploded view of the applicator shown in .

[0069] Figure 40A and 40BDepicted are an upper perspective view and a top view, respectively, of the applicator conveyor.

[0070] Figures 41A-41D Depicted are an upper perspective view, a top view, a lower perspective view, and a side view, respectively, of the applicator trigger. Figure 41E Depicts the Figure 41D 26E: a cross-sectional view of the trigger member taken along line 26E shown in FIG.

[0071] Figures 42A-42C Top perspective, top view, and side view of the applicator housing, respectively. Figure 42D Depicts the Figure 42C A cross-sectional view of the housing taken along line 27D:27D is shown. Figure 42E Depicts Figure 42A and 42B Bottom view of the housing shown in .

[0072] Figure 43 Depicted is a cross-sectional view of an applicator in a loaded configuration for deploying an analyte monitoring device from the applicator.

[0073] Figure 44 Depicted is a cross-sectional view of an applicator in a fired configuration for deploying an analyte monitoring device from the applicator.

[0074] Figures 45A-45C The applicator is depicted in top, side, and bottom perspective views, respectively. Figure 45D Depicts Figures 45A-45C Exploded view of the applicator shown in .

[0075] Figures 46A-46D An upper perspective view, a top view, a lower perspective view, and a side view of the applicator conveyor are depicted, respectively. Figure 46E Depicts the Figure 46D A cross-sectional view of the conveyor taken along line 31E:31E is shown.

[0076] Figures 47A-47C Depicted are top perspective, bottom perspective, and side views, respectively, of an applicator trigger. Figure 47D Depicts the Figure 47C A cross-sectional view of the trigger member taken along line 32D:32D is shown in FIG.

[0077] Figures 48A-48E Depicted are top perspective, bottom perspective, bottom view, and side view of the applicator housing, respectively. Figure 48E Depicts the Figure 48D A cross-sectional view of the housing taken along line 33E:33E is shown.

[0078] Figure 49 Depicted is a cross-sectional view of an applicator in a loaded configuration for deploying an analyte monitoring device from the applicator.

[0079] Figure 50 Depicted is a cross-sectional view of an applicator in a fired configuration for deploying an analyte monitoring device from the applicator.

[0080] Figures 51A-51C A bottom perspective view, a side view, and a bottom view of the applicator delivery member are depicted, respectively.

[0081] Figures 51D-51F A bottom perspective view, a side view, and a bottom view of the applicator delivery member are depicted, respectively.

[0082] Figures 51G-51I Depicted are a top perspective view, a cross-sectional view, and a bottom view, respectively, of an applicator in a loaded configuration for deploying an analyte monitoring device from the applicator.

[0083] Figures 51J-51L Depicted are an upper perspective view, a cross-sectional view, and a bottom view, respectively, of an applicator in a fired configuration for deploying an analyte monitoring device from the applicator.

[0084] Figure 51M and 51N Upper and lower perspective views, respectively, of a delivery member of an applicator with an analyte monitoring device.

[0085] Figure 52A and 52B Depicted are upper and lower perspective views, respectively, of a delivery member of an applicator with an analyte monitoring device.

[0086] Figure 53A An exploded view of the applicator is depicted.

[0087] Figures 53B-53E An upper perspective view, a top view, a lower perspective view, and a cross-sectional view of the applicator delivery member are depicted, respectively.

[0088] Figures 53F-53H Depicted are bottom, bottom, and top perspective views, respectively, of the applicator trigger.

[0089] Figures 53I-53K Depicted are a lower perspective view, a cross-sectional view, and a bottom view, respectively, of the applicator actuator.

[0090] Figure 54A and 54B A perspective view and an exploded view of the applicator delivery member are depicted, respectively. DETAILED DESCRIPTION

[0091] Non-limiting examples of various aspects and variations of the invention are described herein and illustrated in the accompanying drawings.

[0092] Aspects of the present subject matter relate to a microneedle capsule for providing a protective environment in which a microneedle array of an analyte monitoring device can be safely housed. The microneedle capsule can be releasably attached to the analyte monitoring device to protect the microneedle array prior to application of the analyte monitoring device, and the microneedle capsule can be removed from the analyte monitoring device to provide for application of the analyte monitoring device (e.g., insertion of the microneedle array).

[0093] Other aspects of the current subject matter relate to an applicator device (also referred to as an applicator) for applying an analyte monitoring device comprising one or more microneedle arrays to a target area of ​​a user. The applicator devices and variations described herein provide for safe and effective application of an analyte monitoring device to a user such that the microneedle array pierces the user's skin for insertion into the skin, such as the upper dermis region of the skin (e.g., the papillary dermis and the upper reticular dermis).

[0094] Before providing additional details regarding aspects of the microneedle capsules and applicator devices, the following provides a description of some examples of analyte monitoring devices that can be used with the microneedle capsules and / or applicator devices described herein. The following description is exemplary, and aspects related to microneedle capsules and applicator devices consistent with the present subject matter are not limited to the exemplary analyte monitoring devices described herein.

[0095] As generally described herein, an analyte monitoring system may include an analyte monitoring device worn by a user and comprising one or more sensors for monitoring at least one analyte of the user. For example, the sensor may include one or more electrodes configured to electrochemically detect at least one analyte. The analyte monitoring device may transmit sensor data to an external computing device for storage, display, and / or analysis of the sensor data.

[0096] For example, Figure 1As shown, the analyte monitoring system 100 may include an analyte monitoring device 110 worn by a user, and the analyte monitoring device 110 may be a continuous analyte monitoring device (e.g., a continuous glucose monitoring device). The analyte monitoring device 110 may include, for example, a microneedle array including at least one electrochemical sensor for detecting and / or measuring one or more analytes in a user's body fluid. In some variations, a suitable applicator 160 (e.g., any applicator described herein) may be used to apply the analyte monitoring device to the user. The analyte monitoring device 110 may include one or more processors for analyzing sensor data, and / or may be configured to transmit sensor data to a mobile computing device 102 (e.g., a smartphone) or a communication module (e.g., a wireless communication module) of other suitable computing devices. In some variations, the mobile computing device 102 may include one or more processors that execute mobile applications to process sensor data (e.g., display data, analyze data trends, etc.) and / or the mobile computing device 102 may provide suitable alarms or other notifications related to sensor data and / or its analysis. It should be understood that while in some variations the mobile computing device 102 may perform sensor data analysis locally / on-site, other computing devices may alternatively or additionally remotely analyze sensor data and / or communicate information related to such analysis to the mobile computing device 102 (or other suitable user interface) for display to the user. Furthermore, in some variations, the mobile computing device 102 may be configured to transmit sensor data and / or analysis of sensor data to one or more storage devices 106 (e.g., a server) via the network 104 for archiving the data and / or other suitable information related to the user of the analyte monitoring device.

[0097] Analyte monitoring device as described herein has the feature of improving many characteristics, and these characteristics are conducive to continuous analyte monitoring device, such as continuous glucose monitoring (CGM) device.For example, analyte monitoring device as described herein has improved sensitivity (the amount of sensor signal produced by target analyte of each given concentration), improved selectivity (rejecting endogenous and exogenous circulating compounds that may interfere with target analyte detection) and improved stability, to help minimize the change of sensor response over time by the storage and operation of analyte monitoring device.In addition, compared with traditional continuous analyte monitoring device, analyte monitoring device as described herein has shorter warm-up time, so that sensor can quickly provide stable sensor signal after implantation and analyte monitoring device as described herein has short response time, so that sensor can quickly provide stable sensor signal after analyte concentration changes in user's body.In addition, as described in further detail below, analyte monitoring device as described herein can be applied and work at multiple different wearing parts, and provides painless sensor insertion for user.In analyte monitoring device as described herein, other characteristics such as biocompatibility, sterilizability and mechanical integrity are also optimized.

[0098] Although the analyte monitoring systems described herein may be described with reference to glucose monitoring (e.g., in users suffering from type 1 and type 2 diabetes), it will be understood that such systems may additionally or alternatively be configured to sense and monitor other suitable analytes. As described in further detail below, suitable target analytes for detection may, for example, include glucose, ketones, lactate, and cortisol. One target analyte may be monitored, or multiple target analytes may be monitored simultaneously (e.g., in the same analyte monitoring device). For example, monitoring of other target analytes may monitor other indications, such as stress (e.g., by detecting elevated cortisol and glucose) and ketoacidosis (e.g., by detecting elevated ketones).

[0099] like Figure 2AAs shown, in some variations, the analyte monitoring device 110 may generally include a housing 112 and a microneedle array 140 extending outwardly from the housing. The housing 112 may, for example, be a wearable housing configured to be worn on the user's skin so that the microneedle array 140 extends at least partially into the user's skin. For example, the housing 112 may include an adhesive so that the analyte monitoring device 110 is a skin-adhesive patch that is simple and direct to apply to the user. The microneedle array 140 may be configured to puncture the user's skin and include one or more electrochemical sensors (e.g., electrodes) configured to measure one or more target analytes that are accessible after the microneedle array 140 punctures the user's skin. In some variations, the analyte monitoring device 110 may be integrated or self-contained as a single unit, and the unit may be disposable (e.g., for use within a period of time and replaced with another analyte monitoring device 110).

[0100] The electronic system 120 may be at least partially disposed within the housing 112 and include a variety of electronic components, such as sensor circuitry 124 configured to perform signal processing (e.g., biasing and readout of the electrochemical sensor, converting analog signals from the electrochemical sensor to digital signals, etc.). The electronic system 120 may also include at least one microcontroller 122 for controlling the analyte monitoring device 110, at least one communication module 126, at least one power supply 130, and / or various other suitable passive circuits 127. The microcontroller 122 may be configured, for example, to interpret digital signals output from the sensor circuitry 124 (e.g., by executing routines programmed in firmware); perform various suitable algorithms or mathematical transformations (e.g., calibration, etc.); and / or route processed data to and / or from the communication module 124. In some variations, the communication module 126 may include a suitable wireless transceiver (e.g., a Bluetooth transceiver, etc.) for communicating data with the external computing device 102 via one or more antennas 128. For example, the communication module 126 can be configured to provide one-way and / or two-way data communication with an external computing device 102, which is paired with the analyte monitoring device 110. The power supply 130 can be the analyte monitoring device 110, for example, to provide power to the electronic system. The power supply 130 can include a battery or other suitable power source, and can be rechargeable and / or replaceable in some variations. The passive circuit 127 can include various passive / passive circuits (e.g., resistors, capacitors, inductors, etc.) that provide interconnections between other electronic components. For example, the passive circuit 127 can be configured to perform noise reduction, biasing, and / or other purposes. In some variations, the electronic components in the electronic system 120 can be arranged on one or more printed circuit boards (PCBs), for example, the printed circuit board can be rigid, semi-rigid, or flexible. Other details of the electronic system 120 will be further described below.

[0101] In some variations, the analyte monitoring device 110 may further include one or more additional sensors 150 to provide additional information that may be relevant to user monitoring. For example, the analyte monitoring device 110 may further include at least one temperature sensor (e.g., a thermistor) configured to measure skin temperature, thereby enabling temperature compensation of sensor measurements obtained by the microneedle array electrochemical sensor.

[0102] In some variations, the microneedle array 140 in the analyte monitoring device 110 may be configured to puncture the skin of a user. Figure 2BAs shown, when the device 110 is worn by a user, the microneedle array 140 can extend into the user's skin so that the electrodes on the distal region of the microneedles remain in the dermis. Specifically, in some variations, the microneedles can be designed to penetrate the skin and enter the upper dermal region of the skin (e.g., the papillary dermis and the upper reticular dermis) so that the electrodes can access the interstitial fluid surrounding the cells in these layers. For example, in some variations, the microneedles may have a height that is typically in the range of at least 350 μm to about 515 μm. In some variations, one or more microneedles may extend from the housing so that the distal end of the electrode on the microneedle is located less than about 5 mm from the skin interface of the housing, less than about 4 mm from the housing, less than about 3 mm from the housing, less than about 2 mm from the housing, or less than about 1 mm from the housing.

[0103] Compared to conventional continuous analyte monitoring devices (such as CGM devices) that include sensors implanted in the subcutaneous tissue or fat layer of the skin, typically about 8 mm to about 10 mm below the skin surface, the analyte monitoring device 110 has a shallower microneedle insertion depth of about 0.25 mm (so that the electrodes are implanted in the upper dermis region of the skin). These benefits include access to the dermal interstitial fluid containing one or more target analytes for detection, which is advantageous at least because at least some types of analyte measurements of the dermal interstitial fluid have been found to correlate closely with blood measurements. For example, glucose measurements using electrochemical sensors that contact the dermal interstitial fluid have been found to be advantageously highly linearly correlated with blood glucose measurements. Therefore, glucose measurements based on the dermal interstitial fluid are highly representative of blood glucose measurements.

[0104] Furthermore, due to the shallow insertion depth of the microneedles of the analyte monitoring device 110, the time delay of analyte detection is reduced compared to conventional continuous analyte monitoring devices. This shallow insertion depth places the sensor surface in close proximity (e.g., within a few hundred microns or less) to the dense and well-perfused capillary bed of the dermal reticular layer, resulting in negligible diffusion lag from the capillaries to the sensor surface. Diffusion time and diffusion distance are calculated according to t = x 2 / (2D) is related, where t is the diffusion time, x is the diffusion distance, and D is the mass diffusion rate of the analyte of interest. Therefore, positioning the analyte sensing element at a position twice as far away from the analyte source in the capillary will result in four times the diffusion delay time. Therefore, the conventional analyte sensor residing in the very poorly vascularized adipose tissue under the dermis results in a significantly larger diffusion distance from the vascular system in the dermis, thereby resulting in a considerable diffusion delay (e.g., typically 5-20 minutes). In contrast, the shallower microneedle insertion depth of analyte monitoring device 110 benefits from the low diffusion delay from capillaries to the sensor, thereby reducing the time delay in analyte detection, and providing more accurate results in real time or near real time. For example, in some embodiments, the diffusion delay can be less than 10 minutes, less than 5 minutes, or less than 3 minutes.

[0105] Furthermore, when the microneedle array is located in the upper dermis, the lower dermis beneath the microneedle array includes a very high level of vascularization and perfusion to support dermal metabolism, thereby achieving temperature regulation (via vasoconstriction and / or vasodilation) and providing a barrier function to help stabilize the sensing environment around the microneedles. Another advantage of the shallower insertion depth is that the upper dermis lacks pain receptors, thereby reducing pain when the microneedle array punctures the user's skin and providing a more comfortable, minimally invasive user experience.

[0106] Thus, the analyte monitoring devices and methods described herein can improve continuous monitoring of one or more target analytes of a user. For example, as described above, the analyte monitoring device can be applied simply and directly, which improves ease of use and user compliance. In addition, analyte measurement of dermal interstitial fluid can provide highly accurate analyte detection. Furthermore, compared to traditional continuous analyte monitoring devices, the insertion of the microneedle array and its sensor is less invasive and less painful for the user. Other advantages of other aspects of the analyte monitoring device and method will be further described below.

[0107] Figures 3A-3D Various aspects of the analyte monitoring device 110 are depicted. Figures 3A-3D An upper perspective view, a side view, a bottom view, and an exploded view of the analyte monitoring device 110 are depicted, respectively.

[0108] Analyte monitoring device 110 may include a housing that may at least partially surround or encapsulate other components (e.g., electronic components) of analyte monitoring device 110, for example, to protect these components. For example, the housing may be configured to help prevent dust and moisture from entering analyte monitoring device 110. In some variations, an adhesive layer may attach the housing to a surface (e.g., skin) of a user while allowing microneedle array 140 to extend outwardly from the housing and into the user's skin. Furthermore, in some variations, the housing may generally include rounded edges or corners and / or a low profile to reduce interference with clothing, etc., worn by the user.

[0109] For example, Figures 3A-3D As shown, an exemplary variation of the analyte monitoring device 110 may include a housing cover 320 and a base plate 330 configured to at least partially surround the internal components of the analyte monitoring device 110. For example, the housing cover 320 and base plate 330 may provide an enclosure for a sensor assembly 350 including a microneedle array 140 and electronic components. Once assembled, the microneedle array 140 extends outwardly from a portion of the base plate 330 in a skin-facing direction (e.g., an underside) of the analyte monitoring device 110.

[0110] For example, the housing cover 320 and the base plate 330 may comprise one or more rigid or semi-rigid protective shell components that may be coupled together by suitable fasteners (e.g., mechanical fasteners), mechanical interlocking or mating features, and / or engineered fit. The housing cover 320 and the base plate 330 may include rounded edges and corners and / or other damage-resistant features. When coupled together, the housing cover 320 and the base plate 330 may form an interior volume that houses internal components (e.g., the sensor assembly 350). For example, the internal components disposed in the interior volume may be arranged as a compact, low-profile stack as the sensor assembly 350.

[0111] The analyte monitoring device 110 may include one or more adhesive layers to attach the analyte monitoring device 110 (eg, the housing cover 320 and base plate 330 coupled together) to a surface (eg, skin) of a user. Figure 3DAs shown, the one or more adhesive layers can include an internal adhesive layer 342 and an external adhesive layer 344. The internal adhesive layer 342 can adhere to substrate 330, and the external adhesive layer 344 can adhere to the internal adhesive layer 342, and on its side facing outwards, is provided for adhering (for example, temporarily) to the adhesive of the user's skin. The internal adhesive layer 342 and the external adhesive layer 344 together serve as a double-sided adhesive for adhering analyte monitoring device 110 to the user's skin. The external adhesive layer 344 can be protected by a release liner, and before skin is applied, the user removes the release liner to expose adhesive. In some variations, a single adhesive layer is provided. In some variations, the external adhesive layer 344, the internal adhesive layer 342 and / or a single adhesive layer can have a perimeter or a periphery that extends farther than the perimeter of housing cover 320 and substrate 330. This can increase the surface area for attachment, and increases the stability of holding or being attached to the user's skin. The inner adhesive layer 342, the outer adhesive layer 344, and / or the single adhesive layer each have an opening that allows passage of the outwardly extending microneedle array 140, as further described below. The openings of the inner adhesive layer 342 and the outer adhesive layer 344 can be substantially aligned with each other, but in some variations, can be different in size, such that one opening is smaller than the other. In some variations, the openings are substantially the same size.

[0112] The substrate 330 has a first surface (e.g., an outwardly exposed surface) opposite to a second surface, and serves as a support and / or connection structure and a protective cover for the sensor assembly 350. The substrate 330 is sized and shaped to be attached to the housing cover 320. The substrate 330 can be shaped to fit securely within the housing cover 320 so that the outer edge of the substrate 330 is aligned with the corresponding edge of the opening of the housing cover 320. This alignment can be such that there is no gap between the outer edge of the substrate 330 and the corresponding edge of the opening of the housing cover 320.

[0113] Connecting member 332 may be formed in or near the central region of the first surface of substrate 330. Connecting member 332 is a protrusion (e.g., a protruding hub) having sidewalls extending from the first surface of substrate 330 and a first surface substantially parallel to the first surface of substrate 330. The sidewalls extend from the edge of the first surface of connecting member 332 to the first surface of substrate 330. The remaining portion of the first surface of substrate 330 surrounding connecting member 332 may be flat or substantially flat. One or more connector features 336 extend outward from the sidewalls of connecting member 332 to releasably engage with corresponding connectors of the microneedle housing, as described further below. The first surface and sidewalls of connecting member 332 partially define a cavity. This cavity may be further defined by a portion of substrate 330 adjacent to connecting member 332 (e.g., below connecting member 332). This cavity has an opening on the second surface of substrate 330 and is accessible from the second surface of substrate 330. A hole 334 is formed through the first surface of connecting member 332. The size and shape of the aperture 334 can be determined so that the microneedle array 140 fits securely within and extends through the aperture 334. For example, the sidewalls of the microneedle array 140 can be aligned with the corresponding sidewalls of the aperture 334. In some variations, the size and shape of the aperture 334 can be determined to correspond to the area surrounding the microneedle array 140. The openings in the inner adhesive layer 342 and the outer adhesive layer 344 (or a single adhesive layer) are sized so that the connecting member 332 extends through the openings without interfering with the adhesive layers. For example, the diameter of the opening in the inner adhesive layer 342 and the diameter of the opening in the outer adhesive layer 344 are larger than the diameter of the opening in the connecting member 332. In some variations, the opening in the inner adhesive layer 342 and / or the opening in the outer adhesive layer 344 (or the opening in the single adhesive layer) are adjacent to the sidewalls of the connecting member 332 with clearance for accommodating the one or more connector features 336. In some variations, one or more slits or recesses may be formed in inner adhesive layer 342 , outer adhesive layer 344 , and / or a single adhesive layer, extending from an opening to facilitate placement of the corresponding adhesive layer.

[0114] although Figures 3A-3D The housing cover 320 and base plate 330 are shown as being substantially circular, with the housing cover 320 being dome-shaped, but in other variations, the housing cover 320 and base plate 330 may be of any suitable shape. For example, in other variations, the housing cover 320 and base plate 330 may be generally prismatic and have an oval, triangular, rectangular, pentagonal, hexagonal, or other suitable shape. The outer adhesive layer 344 (or a single adhesive layer) may extend outwardly from the housing cover 320 and base plate 330 to extend beyond the perimeter / circumference of the housing cover 320. The outer adhesive layer 344 (or a single adhesive layer) may be circular, such as Figures 3A-3D As shown, or may have an oval, triangular, rectangular, pentagonal, hexagonal, or other suitable shape, and need not be the same shape as the housing cover 320 and / or base plate 330.

[0115] Figures 4A-4E Various aspects of the sensor assembly 350 of the analyte monitoring device 110 are depicted in perspective exploded view, side exploded view, bottom perspective view, side view, and top perspective view, respectively.

[0116] The sensor assembly 350 includes microneedle array components and electronic components to implement the analyte detection and processing aspects of the microneedle array-based continuous analyte monitoring device 110 for detecting and measuring analytes. In some variations, the sensor assembly 350 is a compact, low-profile stack that is at least partially contained within an interior volume defined by the housing cover 320 and the base plate 330.

[0117] In some variations, the sensor assembly 350 includes a microneedle array assembly 360 and an electronics assembly 370 that are interconnected to implement the microneedle array analyte detection and processing aspects described further herein. In some variations, the electronics assembly 370 includes a main printed circuit board (PCB) 450 to which the electronic components are attached, and the microneedle array assembly 360 includes an auxiliary printed circuit board (PCB) 420 to which the microneedle array 140 is attached.

[0118] In some variations, the microneedle array assembly 360 further includes an epoxy skirt 410 and an auxiliary printed circuit board connector / auxiliary PCB connector 430 in addition to the auxiliary PCB 420 and the microneedle array 140. The microneedle array 140 is coupled to the top side (e.g., the side facing outward) of the auxiliary PCB 420 such that the individual microneedles of the microneedle array 140 are exposed, as described with reference to FIG. Figures 3A-3D Auxiliary PCB connector 430 is coupled to the back side of auxiliary PCB 420, opposite the top side. Auxiliary PCB connector 430 may be an electromechanical connector and may be communicatively coupled to main PCB 450 via main PCB connector 470 on the top side (e.g., facing outward) of main PCB 450 to allow signal communication between auxiliary PCB 420 and main PCB 450. For example, signals from microneedle array 140 may be transmitted to main PCB 450 via auxiliary PCB 420, auxiliary PCB connector 430, and main PCB connector 470.

[0119] The auxiliary PCB 420 can partially determine the distance that the microneedle array 140 protrudes from the housing substrate 330. Therefore, the height of the auxiliary PCB 420 can be selected to help ensure that the microneedle array 140 is properly inserted into the user's skin. During microneedle insertion, the first surface (e.g., the outward-facing surface) of the connecting member 332 of the substrate 330 can act as a stop for microneedle insertion. If the auxiliary PCB 420 has a reduced height and its top surface is flush or nearly flush with the first surface of the connecting member 332, the connecting member 332 will prevent the microneedle array 140 from being fully inserted into the skin.

[0120] In some variations, other components (e.g., electronic components such as sensors or other components) may also be connected to the auxiliary PCB 420. For example, the auxiliary PCB 420 may be sized and shaped to accommodate electronic components on the top side or back side of the auxiliary PCB 420.

[0121] In some variations, the epoxy skirt 410 may be deposited along the edge (e.g., perimeter) of the microneedle array 140 to securely fit the microneedle array 140 within the apertures 334 formed in the connecting member 332 of the substrate 330 and / or to mitigate / ease the risk of friction along the microneedle array 140. Figure 3C and Figure 3D For example, the epoxy skirt 410 can occupy the portion of the hole 334 not filled by the microneedle array 140 and / or the portion of the cavity defined in the substrate 330 not filled by the auxiliary PCB 420. The epoxy skirt 410 can also provide a transition from the edge of the microneedle array 140 to the edge of the auxiliary PCB 420. In some variations, the epoxy skirt 410 can be replaced or supplemented by a gasket (e.g., a rubber gasket) or the like.

[0122] Electronic assembly 370 with main PCB 450 includes battery 460 coupled to the back side of main PCB 450 opposite the top side to which main PCB connector 470 is coupled. In some variations, battery 460 may be coupled on the top side of main PCB 450 and / or in other arrangements.

[0123] Figures 4F-4H Aspects of an alternative variation of the sensor assembly 350 of the analyte monitoring device 110 are depicted. Figures 4F-4H A perspective exploded view, a side exploded view, and a side view of the sensor assembly 350 are provided in FIG. 3 , respectively.

[0124] As shown, in the sensor assembly 350, an additional PCB component, namely the intermediate PCB 425, is incorporated. In some variations, the intermediate PCB 425 is part of the microneedle array assembly 360 and is located between and connected to the auxiliary PCB 420 and the microneedle array 140. The intermediate PCB 425 can be added to increase the height of the microneedle array assembly 360 so that the microneedle array 140 extends a greater distance from the substrate 330, which can facilitate insertion of the microneedle array 140 into the user's skin. The microneedle array 140 is coupled to the top side (e.g., the side facing outward) of the intermediate PCB 425 so that the individual microneedles of the microneedle array 140 are exposed, as shown in FIG. Figures 3A-3D Auxiliary PCB 420 is coupled to the back side of intermediate PCB 425, opposite the top side, and auxiliary PCB connector 430 is coupled to the back side of auxiliary PCB 420, opposite the top side. Epoxy skirt 410 (which may be replaced or supplemented by a gasket or the like) provides a transition from the edge of microneedle array 140 to the edge of intermediate PCB 425.

[0125] The intermediate PCB 425 and the auxiliary PCB 420 partially determine the distance that the microneedle array 140 protrudes through the aperture 334 of the base plate 330. The incorporation of the intermediate PCB 425 provides additional height to help ensure that the microneedle array 140 is properly inserted into the user's skin. In some variations, the top side (e.g., facing outward) of the intermediate PCB 425 extends through and protrudes from the aperture 334 so that the first surface (e.g., the top exposed surface) of the connecting member 332 surrounding the aperture 334 does not prevent the microneedle array from being fully inserted into the skin. In some variations, the top side (e.g., the outward facing side) of the intermediate PCB 425 does not protrude from the aperture 334, but the increased height (due to the incorporation of the intermediate PCB 425) ensures that the microneedle array 140 protrudes a sufficient distance from the base plate 330 of the housing.

[0126] In some variations, a microneedle capsule may be provided for releasable attachment to the analyte monitoring device 110. The microneedle capsule may provide a protective environment or enclosure in which the microneedle array 140 may be safely contained, thereby ensuring the integrity of the microneedle array 140 during certain stages of manufacture and shipping of the analyte monitoring device 110 prior to application of the analyte monitoring device 110. The microneedle capsule may be released or removed from the analyte monitoring device 110 to allow the microneedle array 140 to be exposed and ready for insertion into the skin of a user, as further described herein.

[0127] In some variations, the microneedle enclosure provides an environment in which the microneedle array 140 can be sterilized by providing a closed and sealed environment in which the microneedle array 140 can be contained. For example, the microneedle enclosure with the microneedle array 140 can be sterilized, during which the sterilization penetrates the microneedle enclosure, sterilizing the microneedle array 140. Because the microneedle array 140 is contained in a closed environment, the microneedle array 140 remains sterile until removed from the closed environment.

[0128] Figures 5A-5D Various aspects of the microneedle package 500 are depicted in exploded view, first side view and side cross-sectional view, second side view and side cross-sectional view, and bottom perspective view, respectively. The microneedle package 500 includes a sheath 510, a clamp 520, and a biasing element 530 (e.g., a spring). In some variations, the microneedle package 500 may also include a force concentrator 540.

[0129] The sheath 510 is a housing, capsule, or the like, whose sidewalls surround and / or enclose the microneedle array 140 and provide a closed, sealed environment for the microneedle array 140. The sheath 510 has an opening at a distal end through which the microneedle array 140 is positioned, such that the interior of the sidewalls of the sheath 510 surrounds the microneedle array 140. A bumper 512 can be located at the distal end of the sheath 510 such that the bumper 512 surrounds the opening of the sheath 510 at the distal end. The bumper 512 can be an annular elastomeric bumper or the like that provides a tight seal around the distal end of the sheath 510. The bumper 512 is sized to correspond to the size and shape of the opening of the sheath 510 at the distal end. The inner perimeter of the sheath 510 (e.g., the perimeter of the opening) can be aligned or substantially aligned with the footprint / occupancy of the microneedle array 140. For example, the inner perimeter of the sheath 510 can be sized and shaped to align with the outer perimeter of the microneedle array 140 such that the microneedle array 140 is fully contained within the sheath 510 , with the microneedles extending into the sheath 510 .

[0130] The clamp 520 includes a cavity defined by the sidewalls of the clamp 520. The cavity may include a first cavity 522 and a second cavity 524, each of which is defined by the sidewalls of the clamp 520. The second cavity 524 is adjacent to the first cavity 522 in an area proximal to the first cavity 522 and is a proximal extension of the first cavity 522, such that the first and second cavities 522, 524 are fluidically connected. The first cavity 522 is sized and shaped to accommodate the sheath 510. An opening at the distal end of the clamp 520 provides an access point into the first cavity 522, thereby allowing the sheath 510 to be assembled into the first cavity 522 through the opening. The second cavity 524 is sized and shaped to accommodate the biasing element 530. When the biasing element 530 and the sheath 510 are positioned within the clamp 520 (e.g., through an opening at the distal end of the clamp 520), the biasing element 530 is securely but removably contained within the second cavity 524, and the outer sidewalls of the sheath 510 are aligned with and can abut against the sidewalls of the first cavity 522. In some variations, one or more portions of the outer sidewalls of the sheath 510 contact corresponding one or more portions of the first cavity 522, such that the sheath 510 is wedged or tightly fitted within the first cavity 522, such that the sheath 510 is integral / unitary with the clamp 520. The biasing element 530 can generally correspond in size and shape to the second cavity 524 and extend distally from an upper region of the second cavity 524 to or near the top surface of the sheath 510. The diameter of the biasing element 530 can be slightly smaller than the inner diameter of the second cavity 524 to limit the horizontal movement of the biasing element 530 within the clamp 520. The biasing element 530 can be a coiled metal spring, a plastic leaf spring, a coiled plastic spring, or any form of spring capable of providing compliance between the clamp 520 and the sleeve 510, as further described herein.

[0131] In some variations, a force concentrator 540 may be positioned within the biasing element 530, with its distal region extending beyond the biasing element 530 and contacting the top surface of the sheath 510. For example, the force concentrator 540 may include a shaft and a head. The shaft may be mounted within the biasing element 530, and the head may extend distally through the biasing element 530 to contact the top surface of the sheath 510. The biasing element 530 and the optional force concentrator 540 are combined to provide a sealing downward force on the sheath 510 and the bumper 512, thereby maintaining the sealed enclosure of the microneedle array 140 when the clamp 520 is engaged with the analyte monitoring device 110, as further described herein. The force concentrator 540 provides a downward force against the engaged top surface of the sheath 510 to eliminate the transfer of torque to the bumper 512 during manufacturing and / or assembly. For example, the force concentrator 540 eliminates rotation of the bumper 512 during manufacturing and / or assembly.

[0132] The clamp 520 also includes an external engagement feature 526 and a locking tab 528. The external engagement feature 526 is configured to engage with a portion of an applicator device, as further described herein. The locking tab 528 is formed on a corresponding inner portion of the side wall of the clamp 520 at the distal end of the clamp 520, as shown in FIG. Figure 5D The locking tab 528 can be a protrusion extending orthogonally outward from the interior of the sidewall of the clamp 520 and can be configured to releasably engage the base plate 330, as further described below.

[0133] Figures 5E-5G Depicted are aspects of a microneedle capsule 500, a substrate 330 of an analyte monitoring device 110, and a releasable coupling therebetween. The microneedle capsule 500 is configured to be releasably attached or coupled to the substrate 330 by engaging with a connecting member 332. The microneedle array assembly 360 of the sensor assembly 350 is partially assembled within a cavity formed by the substrate 330 and the connecting member 332, with the microneedle array 140 extending through the aperture 334 of the substrate 330. Figure 5G As shown in the side cross-sectional view of FIG, when the microneedle package 500 is attached to the substrate 330, the microneedle array 140 is contained within the sheath 510, with the bumper 512 providing a seal between the sheath 510 and the substrate 330. In some variations, the bottom edge of the sidewall of the microneedle package 500 interfaces and / or abuts the first surface of the substrate 330 around and / or adjacent to the outer edge of the connecting member 322. In some variations, the bottom edge of the sidewall of the sheath 510 and the bottom edge of the bumper 512 interfaces and / or abuts the first surface of the connecting member 332 around and / or adjacent to the outer edge of the aperture 334. In some variations, the outer diameter of the sheath 510 is equal to or slightly smaller than the diameter of the first surface of the connecting member 322. The diameter of the opening of the sheath 510 is of sufficient size to accommodate the aperture 334 without interfering with the microneedle array 140. The sidewalls of the opening of the encasement 510 may interface with and / or abut the edge surrounding the microneedle array 140 , such that the sidewalls of the opening of the encasement 510 surround the edge of the microneedle array 140 .

[0134] To form a releasable attachment or coupling between the substrate 330 and the microneedle capsule 500, the connector features 336 of the connecting member 332 releasably engage with the locking tabs 528 of the microneedle capsule 500. In some variations, the connector features 336 may be bayonet connectors that engage and disengage with the locking tabs 528 via a twisting or rotational motion. For example, the connector features 336 may include extension blades that protrude orthogonally from the upper region of the connecting member 332. Each extension blade may terminate at one end in a stop feature (e.g., a vertical wall or vertically extending barrier) that extends from the upper edge of the respective extension blade to the first surface of the substrate 330. These connector features 336 may be positioned circumferentially around the outer edge of the connecting member 332, and each connector feature 336 may correspond to a respective locking tab 528 of the microneedle capsule 500. The locking tabs 528 engage with the connector features 336 by sliding under the extension blades and engaging the stop features as the microneedle capsule 500 rotates relative to the substrate 330. In some variations, the microneedle package 500 is placed over the connecting member 332 and rotated until further rotation is stopped by the locking tab 528 engaging the stop feature of the connector feature 336. Rotation in the opposite direction disengages the locking tab 528 from the stop feature, thereby allowing the microneedle package 500 to be disengaged from the connecting member 332, at which point the microneedle package 500 can be lifted or pulled away from the substrate 330. Other types of connecting members that form a releasable connection may be used. In some variations, three connector features 336 and three locking tabs 528 may be combined. In other variations, one, two, four, or more pairs of connector features 336 and locking tabs 528 may be combined.

[0135] like Figure 5G As shown, when the microneedle capsule 500 is connected to the substrate 330 including the microneedle array assembly 360, the sleeve 510 is aligned on the first surface of the connecting member 322 around the microneedle array 140. When the microneedle capsule 500 is positioned over the connecting member 322 and twisted to engage the one or more connector features 336, the biasing element 530 is biased to maintain a stable connection between the sleeve 510 and the clamp 520. The force concentrator 540 provides a downward force to the sleeve 510 and the bumper 512 to eliminate the transfer of torque to the bumper 512, so that the bumper 512 does not rotate during the twisting operation. The sterile barrier provided by the sleeve 510 and the bumper 512 is thereby maintained. The inner periphery of the opening of the sleeve 510 and the edge of the microneedle array 140 are tightly sealed, so that the clamp 520, the sleeve 510, the bumper 512, the biasing element 530, and the force concentrator 540 provide a tight enclosure / envelope around the microneedle array 140.

[0136] The microneedle array assembly 360 (including the microneedle array 140) can be sterilized, wherein the microneedle array assembly 360 is assembled within the substrate 330 and the microneedle enclosure 500 is coupled to the microneedle array assembly 360. For example, a radiation sterilization method can be applied. In some variations, the components are sterilized to 10 -6 500 ). It is noteworthy that sterilization is performed with the microneedle array assembly 360 not connected to the electronic assembly 370. After the sterilization process, the base plate 330 is attached to the housing cover 320, and the electronic assembly 370 is positioned in the housing cover 320. The attachment includes establishing a connection between the microneedle array assembly 360 and the electronic assembly 370 via corresponding PCB connectors 430 and 470. Because the microneedle array 140 is contained within the sealed microneedle enclosure 500, the sterile environment containing the microneedle array 140 is not compromised. The assembled analyte monitoring device 110 and the attached microneedle enclosure 500 can be contained in an applicator device, as further described herein.

[0137] The configuration of the microneedle package 500 described herein allows for large-scale sterilization. For example, multiple components including the microneedle array assembly 360, the substrate 330, and the microneedle package 500 can be assembled as described herein. The multiple components can then be exposed to radiation to sterilize each microneedle array 140. In some variations, one or more trays, containers, etc. containing the multiple components can be placed in a closed environment or sterilization chamber to which the radiation can be applied. This allows multiple components to be sterilized simultaneously, thereby enabling large-scale manufacturing of analyte monitoring devices.

[0138] In some variations, the electronic system of the analyte monitoring device may include an analog front end. The analog front end may include sensor circuitry (e.g., Figure 2A1 (a) a sensor circuit 124 shown in FIG. 1 ), which converts the analog current measurement into a digital value that can be processed by the microcontroller. For example, the analog front end can include a programmable analog front end suitable for an electrochemical sensor. For example, the analog front end can include the MAX30131, MAX30132, or MAX30134 components available from Maxim Integrated (San Jose, CA) (which have 1, 2, and 4 channels, respectively), which are ultra-low power programmable analog front ends for electrochemical sensors. The analog front end can also include the AD5940 or AD5941 devices available from Analog Devices (Norwood, MA), which are high-precision impedance and electrochemical front ends. Similarly, the analog front end can also include the LMP91000 available from Texas Instruments (Dallas, TX), which is a configurable analog front end regulator for low-power chemical sensing applications. The analog front end can provide biasing and a complete measurement path, including an analog-to-digital converter (ADC). Ultra-low power allows for continuous biasing of the sensor to maintain accuracy and fast response when measurements are required over long periods of time (e.g., 7 days) using body-worn battery-powered devices.

[0139] In some variations, the analog front-end device is compatible with two-terminal and three-terminal electrochemical sensors, for example, enabling DC current measurement, AC current measurement, and electrochemical impedance spectroscopy (EIS) measurement capabilities. Furthermore, the analog front-end can include an internal temperature sensor and a programmable voltage reference, support external temperature monitoring and an external voltage reference, and integrate voltage monitoring of bias and supply voltages to ensure safety and regulatory compliance.

[0140] In some variations, the analog front end may include a multi-channel regulator to multiplex sensor inputs and process multiple signal channels. For example, the analog front end may include a multi-channel regulator, such as the multi-channel regulator described in U.S. Patent No. 9,933,387, the entire contents of which are incorporated herein by reference.

[0141] In some variations, the analog front end and peripheral electronics may be integrated into an application specific integrated circuit (ASIC), which may, for example, help reduce costs. In some variations, this integrated solution may include a microcontroller as described below.

[0142] In some variations, the electronic system of the analyte monitoring device may include at least one microcontroller (e.g., Figure 2AController 122 shown). The microcontroller may include, for example, a processor with integrated flash memory. In some variations, the microcontroller in the analyte monitoring device may be configured to perform analysis to correlate sensor signals with analyte measurements (e.g., glucose measurements). For example, the microcontroller may execute programmed routines in firmware to interpret digital signals (e.g., from an analog front end), perform any relevant algorithms and / or other analysis, and route the processed data to and / or from the communication module. Keeping the analysis on the analyte monitoring device can, for example, enable the analyte monitoring device to broadcast / transmit analyte measurements to multiple devices (e.g., mobile computing devices such as smart phones or smart watches, therapeutic delivery systems such as insulin pens or pumps, etc.) in parallel while ensuring that each connected device has the same information.

[0143] In some variations, the microcontroller can be configured to activate and / or deactivate the analyte monitoring device under one or more detection conditions. For example, the device can be configured to power on the analyte monitoring device after the microneedle array is inserted into the skin. For example, this can implement a power-saving feature in which the battery is disconnected until the microneedle array is placed in the skin, at which point the device can begin transmitting sensor data. Such a feature can, for example, help improve the shelf life of the analyte monitoring device and / or simplify the analyte monitoring device-external device pairing process for the user.

[0144] like Figure 6A As shown in the schematic diagram of FIG, in some variations, a microneedle array 600 for sensing one or more analytes may include one or more microneedles 610 protruding from a substrate surface 602. For example, the substrate surface 602 may be substantially flat, and the one or more microneedles 610 may extend perpendicularly from the flat surface. Figure 6B As shown, the microneedle 610 may include a body portion 612 (e.g., a shaft) and a tapered distal portion 614 that is configured to puncture the user's skin. In some variations, the tapered distal portion 614 may terminate at an insulated distal apex 616. The microneedle 610 may also include an electrode 620 on the surface of the tapered distal portion. In some variations, electrode-based measurements may be performed at the interface of interstitial fluid and the electrode located within the body (e.g., performed on the entire outer surface of the microneedle). In some variations, the microneedle 610 may have a solid core (e.g., a solid body portion), but in some variations, the microneedle 610 may include one or more lumens, which may be used, for example, for drug delivery or sampling of dermal interstitial fluid. Other microneedle variations, such as those described below, may similarly include a solid core or one or more lumens.

[0145] The microneedle array 600 may be formed at least in part from a semiconductor (e.g., silicon) substrate and include various material layers applied and formed using various suitable microelectromechanical systems (MEMS) manufacturing techniques (e.g., deposition and etching techniques), as further described below. Similar to a typical integrated circuit, the microneedle array can be reflow soldered to a circuit board. In addition, in some variations, the microneedle array 600 may include a three-electrode arrangement including a working (sensing) electrode having an electrochemical sensing coating (including biorecognition elements, such as enzymes) capable of detecting a target analyte, a reference electrode, and a counter electrode. In other words, the microneedle array 600 may include at least one microneedle 610 comprising a working electrode, at least one microneedle 610 comprising a reference electrode, and at least one microneedle 610 comprising a counter electrode. Other details of these types of electrodes will be described in further detail below.

[0146] In some variations, the microneedle array 600 may include a plurality of microneedles that are insulated such that the electrode on each microneedle in the plurality of microneedles is individually addressable / accessible and electrically isolated from all other electrodes on the microneedle array. The resulting individual addressability of the microneedle array 600 allows for greater control over the function of each electrode because each electrode can be probed individually. For example, the microneedle array 500 can be used to provide multiple independent measurements of a given target analyte, which improves the sensing reliability and accuracy of the device. Furthermore, in some variations, the electrodes of multiple microneedles can be electrically connected to produce enhanced signal levels. As another example, the same microneedle array 600 can additionally or alternatively be interrogated to measure multiple analytes simultaneously, thereby providing a more comprehensive assessment of the physiological state. For example, as Figure 7 As shown in the schematic diagram of , the microneedle array may include a microneedle portion for detecting a first analyte A, a microneedle second portion for detecting a second analyte B, and a microneedle third portion for detecting a third analyte C. It should be understood that the microneedle array can be configured to detect any suitable number of analytes (e.g., 1, 2, 3, 4, 5 or more, etc.). Suitable target analytes for detection may, for example, include glucose, ketones, lactate, and cortisol. For example, in some variations, ketones may be detected in a manner similar to that described in U.S. Patent Application No. 16 / 701,784, which is incorporated herein by reference in its entirety. Therefore, the individual electrical addressing capabilities of the microneedle array 600 provide greater control and flexibility for the sensing function of the analyte monitoring device.

[0147] In some variations of the microneedle (e.g., a microneedle having a working electrode), the electrode 620 may be located proximal to the insulated distal apex 616 of the microneedle. In other words, in some variations, the electrode 620 does not cover the apex of the microneedle. Instead, the electrode 620 may be offset from the apex or tip of the microneedle. The electrode 620 being proximal to or offset from the insulated distal apex 616 of the microneedle advantageously provides more accurate sensor measurements. For example, this arrangement prevents the electric field from being concentrated at the microneedle apex 616 during the manufacturing process, thereby avoiding uneven electrodeposition of the sensing chemical on the surface of the electrode 620, which can lead to erroneous sensing.

[0148] As another example, placing the electrode 620 at a position offset from the microneedle apex can further improve sensing accuracy by reducing unwanted signal artifacts and / or erroneous sensor readings caused by stress during microneedle insertion. The distal apex of the microneedle is the first area to penetrate the skin and is therefore subject to the greatest stress caused by mechanical shear phenomena associated with skin tearing or cutting. If the electrode 620 is placed at the apex or tip of the microneedle, this mechanical stress may cause the electrochemical sensing coating on the electrode surface to delaminate when the microneedle is inserted, and / or cause a small but interfering amount of tissue to be transported to the active sensing portion of the electrode. Therefore, placing the electrode 620 sufficiently offset from the microneedle apex can improve sensing accuracy. For example, in some variations, the distal edge of the electrode 620 can be located at least about 10 μm (e.g., about 20 μm to about 30 μm) from the distal apex or tip of the microneedle, as measured along the longitudinal axis of the microneedle.

[0149] The main body portion 612 of the microneedle 610 may also include a conductive path extending between the electrode 620 and the back electrode or other electrical contacts (e.g., arranged on the back side of the microneedle array substrate). The back electrode can be soldered to a circuit board so that it can be electrically connected to the electrode 620 via the conductive path. For example, during use, the in vivo sensing current measured at the working electrode (in the dermis) is interrogated by the back electrical contact, and the conductive path promotes the electrical connection between the back electrical contact and the working electrode. In some variations, the conductive path can be promoted by passing through the metal inside the microneedle main body portion (e.g., shaft) between the proximal and distal ends of the microneedle. Alternatively, in some variations, the conductive path can be provided by the entire main body portion formed by a conductive material (e.g., doped silicon). In some of these variations, the complete substrate on which the microneedle array 600 is constructed can be conductive, and each microneedle 610 in the microneedle array 600 can be electrically isolated from adjacent microneedles 610, as described below. For example, in some variations, each microneedle 610 in the microneedle array 600 can be electrically isolated from adjacent microneedles 610, wherein the insulating barrier comprises an electrically insulating material (e.g., a dielectric material such as silicon dioxide) surrounding a conductive path extending between the electrode 620 and the backside electrical contact. For example, the body portion 612 can include an insulating material that forms a sheath around the conductive path, thereby preventing electrical communication between the conductive path and the substrate. Other example variations of structures that can achieve electrical isolation between microneedles are described in more detail below.

[0150] This electrical isolation between the microneedles in the microneedle array allows the sensors to be individually addressable. This individually addressable capability advantageously enables independent and parallel measurements between sensors, as well as dynamic reconfiguration of sensor assignments (e.g., for different analytes). In some variations, the electrodes in the microneedle array can be configured to provide redundant analyte measurements, which is an advantage over traditional analyte monitoring devices. For example, redundancy can improve performance by increasing the reliability of the device and / or increasing accuracy by reducing the likelihood of complete failure (e.g., averaging multiple analyte measurements of the same analyte, which reduces the impact of extremely high or low sensor signals on the determination of analyte levels).

[0151] In some variations, as described in further detail below for various variations of microneedles, the microneedle array may be formed at least in part using suitable semiconductor and / or MEMS fabrication techniques and / or mechanical cutting or dicing. Such processes may facilitate, for example, large-scale, low-cost manufacturing of microneedle arrays. For example, in some variations, the microneedle array may be formed at least in part using the techniques described in U.S. Patent Application No. 15 / 913,709, which is incorporated herein by reference in its entirety.

[0152] Several example variations of microneedle structures are described herein that incorporate one or more of the microneedle features of the microneedle arrays in the analyte monitoring devices described above.

[0153] In some variations, a microneedle may have a generally cylindrical body portion and a tapered distal portion with an electrode. For example, Figures 8A-8C An exemplary variation of a microneedle 800 extending from a substrate 802 is shown. Figure 8A is a schematic side cross-sectional view of microneedle 800, and Figure 8B This is a perspective view of the microneedle 800. Figure 8C 8 is a detailed perspective view of the distal portion of the microneedle 800. Figure 8B and 8C As shown, the microneedle 800 may include a cylindrical body portion 812, a tapered distal portion 814 terminating in an insulated distal apex 816, and a ring electrode 820 comprising a conductive material (e.g., Pt, Ir, Au, Ti, Cr, Ni, etc.) and disposed on the tapered distal portion 814. Figure 8A As shown, the annular electrode 820 can be located proximal to (or offset from or spaced apart from) the distal apex 816. For example, the electrode 820 can be electrically isolated from the distal apex 816 by a distal insulating surface 815a comprising an insulating material (e.g., SiO2). In some variations, the electrode 820 can also be electrically isolated from the columnar body portion 812 by a second distal insulating surface 815b. The electrode 820 can be electrically connected to a conductive core 840 (e.g., a conductive path) that extends along the body portion 812 to a backside electrical contact 830 (e.g., made of a Ni / Au alloy) or other electrical welding area in or on the substrate 802. For example, the body portion 812 can include a conductive core material (e.g., highly doped silicon). As shown Figure 8A As shown, in some variations, an insulating protective sleeve 813 comprising an insulating material (e.g., SiO2) can be arranged around the main body 812 (e.g., around its periphery) and extend at least partially through the substrate 802. Thus, the insulating protective sleeve 813 can, for example, help prevent electrical contact between the conductive core 840 and the surrounding substrate 802. The insulating protective sleeve 813 can further extend over the entire surface of the main body 812. The upper and / or lower surfaces of the substrate 802 can also include a layer composed of a substrate insulator 804 (e.g., SiO2). Thus, the insulation provided by the insulating protective sleeve 813 and / or the substrate insulator 804 can at least partially contribute to the electrical isolation of the microneedles 800, which enables the microneedles 800 to be individually addressed within the microneedle array. In addition, in some variations, the insulating protective sleeve 813 extending over the entire surface of the main body 812 can be used to increase the mechanical strength of the microneedle 800 structure.

[0154] The microneedle 800 can be formed at least in part by a suitable MEMS fabrication technique, such as plasma etching, also known as dry etching. For example, in some variations, the insulating protective sheath 813 surrounding the main body portion 812 of the microneedle can be made by first forming a trench in a silicon substrate from the back side of the substrate by deep reactive ion etching (DRIE), and then filling the trench with a sandwich structure of SiO2 / polycrystalline silicon (poly-Si) / SiO2 by low pressure chemical vapor deposition (LPCVD) or other suitable process. In other words, the insulating protective sheath 813 can passivate the surface of the main body portion 812 of the microneedle and continue as a buried feature in the substrate 802 near the proximal portion of the microneedle. By primarily comprising a silicon compound, the insulating protective sheath 813 can provide good filling and adhesion to adjacent silicon walls (e.g., the walls of the conductive core 840, the walls of the substrate 802, etc.). The sandwich structure of the insulating protective sheath 813 may further help provide a good match in coefficient of thermal expansion (CTE) with adjacent silicon, thereby advantageously reducing defects, cracks, and / or other thermally induced weaknesses in the insulating sheath 813 .

[0155] The tapered distal portion can be formed from the front side of the substrate by isotropic dry etching, and the main body portion 812 of the microneedle 800 can be made by DRIE. The front side metal electrode 820 can be deposited and patterned on the distal portion by specialized photolithography (e.g., electron beam evaporation) that allows metal to be deposited in the desired annular region to obtain the electrode 820 without coating the distal apex 816. In addition, the back side electrical contact 830 of Ni / Au can be deposited by suitable MEMS manufacturing techniques (e.g., sputtering).

[0156] The microneedle 800 may have any suitable dimensions. For example, in some variations, the microneedle 800 may have a height of about 300 μm to about 500 μm. In some variations, the tapered distal portion 814 may have an apex angle of about 60 degrees to about 80 degrees and an apex diameter of about 1 μm to about 15 μm. In some variations, the surface area of ​​the ring electrode 820 may be about 9,000 μm. 2 to approximately 11,000 μm 2 , or about 10,000 μm 2 . Figure 9 Various dimensions are shown for an exemplary variation of a cylindrical microneedle having a tapered distal portion and a ring electrode similar to microneedle 800 described above.

[0157] Figures 10A-10F Another example variation of a microneedle 1000 is shown having a generally cylindrical body portion extending from a substrate 1002 having an upper / top surface 1004. Microneedle 1000 can be similar to microneedle 800 described above, except as described below. For example, Figure 10BAs shown, similar to microneedle 800, microneedle 1000 may include a cylindrical main body portion 1012, and a tapered distal portion 1014 disposed on a cylinder 1013 and terminating in an insulated distal apex 1016. Cylinder 1013 may be insulated and have a smaller diameter than cylindrical main body portion 1012. Microneedle 1000 may also include a ring electrode 1020 comprising a conductive material and disposed on the tapered distal portion at a position proximal to (or offset from or spaced apart from) distal apex 1016. Figures 10A-10F As shown, other elements of microneedle 1000 have similar reference numerals as corresponding elements of microneedle 800 .

[0158] However, the electrode 1020 on the microneedle 1000 may include a tip contact groove 1022. This contact groove may be configured to facilitate establishing ohmic contact between the electrode 1020 and the underlying conductive core 1040 of the microneedle. In some variations, the shape of the tip contact groove 1022 may include an annular groove formed in the surface of the conductive core 1040 (e.g., entering / opening into the main body of the microneedle or otherwise contacting the conductive path in the main body), such that when the electrode 1020 material is deposited onto the conductive core 1040, the electrode 1020 with the tip contact groove 1022 may have a stepped profile when viewed from the side. The tip contact groove 1022 may advantageously help provide a tolerance to ensure contact between the electrode 1020 and the underlying conductive core 1040. Any other microneedle variations described herein may also have a similar tip contact groove to help ensure contact between the electrode (e.g., which may be a working electrode, a reference electrode, a counter electrode, etc.) and the conductive path within the microneedle.

[0159] Figure 11A and 11B Various other sizes are shown for example variations of cylindrical microneedles having tapered distal portions and ring electrodes similar to microneedle 1000 described above. For example, Figure 11A and 11BA variation of the microneedle shown in can have a tapered distal portion that generally has a cone angle of about 80 degrees (or about 78 degrees to about 82 degrees, or about 75 degrees to about 85 degrees) and a cone diameter of about 140 μm (or about 133 μm to about 147 μm, or about 130 μm to about 150 μm). The cone of the tapered distal portion can be arranged on the cylinder so that the total combined height of the cone and the cylinder is about 110 μm (or about 99 μm to about 116 μm, or about 95 μm to about 120 μm). The ring electrode on the tapered distal portion can have an outer diameter or base diameter of about 106 μm (or about 95 μm to about 117 μm, or about 90 μm to about 120 μm) and an inner diameter of about 33.2 μm (or about 30 μm to about 36 μm, or about 25 μm to about 40 μm). The length of the ring electrode can be about 57 μm (or about 55 μm to about 65 μm) measured along the incline of the tapered distal portion, and the total surface area of ​​the electrode can be about 12,700 μm 2 (or about 12,500 μm 2 to approximately 12,900 μm 2 , or about 12,000 μm 2 to approximately 13,000 μm 2 ).like Figure 11B As shown, the electrode may also have a tip contact groove extending around the central region of the cone of the tapered distal portion, wherein the contact portion / contact groove may have a width of about 11 μm (or about 5 μm to about 50 μm, about 10 μm to about 12 μm, or about 8 μm to about 14 μm) and a groove depth of about 1.5 μm (or about 0.1 μm to about 5 μm, or about 0.5 μm to about 1.5 μm, or about 1.4 μm to about 1.6 μm, or about 1 μm to about 2 μm) when measured along the slope of the tapered distal portion. The microneedle has an insulated distal apex with a diameter of about 5.5 μm (or about 5.3 μm to about 5.8 μm, or about 5 μm to about 6 μm).

[0160] Details of exemplary variations of microneedle array configurations are described further below.

[0161] As described above, each microneedle in the microneedle array may include an electrode. In some variations, multiple different types of electrodes may be included between the microneedles in the microneedle array. For example, in some variations, the microneedle array can be used as an electrochemical cell that can operate electrolytically with three types of electrodes. In other words, the microneedle array can include at least one working electrode, at least one counter electrode, and at least one reference electrode. Thus, the microneedle array can include three different electrode types, but one or more of each electrode type can form a complete system (e.g., the system can include multiple different working electrodes). In addition, multiple different microneedles can be electrically connected to form an effective electrode type (e.g., a single working electrode can be formed by two or more connected microneedles with working electrode sites). Each of these electrode types can include a metallization layer and can include one or more coatings or layers on the metallization layer that help promote the function of the electrode.

[0162] Typically, the working electrode is the electrode at which the oxidation and / or reduction reactions of interest occur to detect the analyte of interest. The function of the counter electrode is to maintain the electrons required for the electrochemical reaction at the working electrode by sourcing (providing) or sinking (accumulating) current. The function of the reference electrode is to provide a reference potential for the system; that is, the potential of the working electrode when biased is referenced to the reference electrode. A fixed, time-varying, or at least controlled potential relationship is established between the working and reference electrodes, and within practical limits, no current flows from or into the reference electrode. Furthermore, to implement such a three-electrode system, the analyte monitoring device can include a suitable potentiostat or electrochemical analog front end to maintain a fixed potential relationship between the working and reference electrodes within the electrochemical system (via an electronic feedback mechanism), while allowing the counter electrode to dynamically swing to the potential required to maintain the redox reaction of interest.

[0163] A plurality of microneedles can be arranged in a microneedle array (e.g., any of the microneedle variations described herein, each of which can have a working electrode, a counter electrode, or a reference electrode as described above). Considerations for how to configure the microneedles include factors such as the insertion force required to penetrate the skin with the microneedle array, optimization of electrode signal levels and other performance aspects, and manufacturing cost and complexity.

[0164] For example, a microneedle array may include a plurality of microneedles spaced apart at a predetermined spacing (the distance between the center of one microneedle and the center of its nearest adjacent microneedle). In some variations, the microneedles may be spaced apart at a sufficient spacing to distribute the force applied to the user's skin (e.g., to avoid a "bed of nails" effect) so that the microneedle array penetrates the skin. As the spacing increases, the force required to insert the microneedle array tends to decrease, while the penetration depth tends to increase. However, it has been found that the spacing only begins to affect the insertion force at low values ​​(e.g., less than about 150 μm). Therefore, in some variations, the microneedles in the microneedle array may have a spacing of at least 200 μm, at least 300 μm, at least 400 μm, at least 500 μm, at least 600 μm, at least 700 μm, or at least 750 μm. For example, the spacing may be from about 200 μm to about 800 μm, from about 300 μm to about 700 μm, or from about 400 μm to about 600 μm. In some variations, the microneedles can be arranged in a periodic grid, and the spacing can be uniform in all directions and across all regions of the microneedle array. Alternatively, the spacing measured along different axes (e.g., X, Y directions) can be different, and / or some regions of the microneedle array can include smaller spacing, while other regions can include larger spacing.

[0165] In addition, to achieve more consistent puncture, the microneedles can be spaced equidistantly from each other (e.g., the same spacing in all directions). To this end, in some variations, the microneedles in the microneedle array can be as follows: Figures 12A-12C , 13A-13B and 14A-14J are arranged in a hexagonal configuration. Alternatively, the microneedles in the microneedle array can be arranged in a rectangular array (e.g., a square array) or in another suitable symmetrical manner.

[0166] Another consideration in determining the configuration of a microneedle array is the total signal level provided by the microneedles. Typically, the signal level for each microneedle in the total number of microneedle elements in the array is the same. However, the signal level can be enhanced by electrically interconnecting multiple microneedles in the array. For example, an array with a large number of electrically connected microneedles is expected to produce a greater signal strength (and therefore improved accuracy) than an array with fewer microneedles. However, a greater number of microneedles on a carrier sheet will increase the cost of the carrier sheet (assuming constant spacing) and also require greater force and / or speed to insert into the skin. Conversely, a smaller number of microneedles on a carrier sheet can reduce the cost of the carrier sheet and can be inserted into the skin with reduced applied force and / or speed. In addition, in some variations, a lower number of microneedles on a carrier sheet can reduce the total coverage area of ​​the carrier sheet, which can result in less undesirable local edema and / or erythema. Therefore, in some variations, a device such as a microneedle array can be used. Figures 13A-13B The microneedle array shown includes 37 microneedles or Figures 12A-12CThe microneedle array shown includes 7 microneedles to achieve a balance between these factors. However, in other variations, there may be fewer microneedles in the array (e.g., from about 5 to about 35, from about 5 to about 30, from about 5 to about 25, from about 5 to about 20, from about 5 to about 15, from about 5 to about 100, from about 10 to about 30, from about 15 to about 25, etc.) or there may be more microneedles in the array (e.g., more than 37, more than 40, more than 45, etc.).

[0167] Furthermore, as described in further detail below, in some variations, only a subset of the microneedles in a microneedle array may be active during operation of an analyte monitoring device. For example, a portion of the microneedles in a microneedle array may be inactive (e.g., no signal is read from the electrodes of the inactive microneedles). In some variations, a portion of the microneedles in a microneedle array may be activated at some time during operation and remain active for the remainder of the device's operational life. Furthermore, in some variations, a portion of the microneedles in a microneedle array may additionally or alternatively be deactivated at some time during operation and remain inactive for the remainder of the device's operational life.

[0168] When considering the characteristics of microneedle array substrates, substrate size is a function of the number of microneedles in the microneedle array and the spacing between the microneedles. Manufacturing cost is also a consideration, as smaller substrate sizes will help reduce costs because the number of substrates that can be formed from a single wafer of a given area will increase. Additionally, due to the relative fragility of the substrate, smaller substrate sizes are also less prone to brittle fracture.

[0169] Furthermore, in some variations, microneedles at the periphery of the microneedle array (e.g., near an edge or border of the carrier sheet, near an edge or border of the housing, near an edge or border of the adhesive layer on the housing, along the outer periphery of the microneedle array, etc.) may be found to have better performance (e.g., sensitivity) due to their greater penetration compared to microneedles at the center of the microneedle array or the carrier sheet. Thus, in some variations, the working electrodes may be disposed primarily or entirely on microneedles located at the periphery of the microneedle array to obtain more accurate and / or precise analyte measurements.

[0170] Figure 13A and 13B A schematic diagram depicts 37 microneedles arranged in an example variation of microneedle array 1300. For example, the 37 microneedles may be arranged in a hexagonal array with an inter-needle center-to-center spacing of about 750 μm (or about 700 μm to about 800 μm, or about 725 μm to about 775 μm) between the center of each microneedle and the center of its immediate neighbor in any direction. Figure 13ASchematic diagrams of exemplary variations of carrier sheets including microneedle configurations are depicted. Example dimensions of the microneedle array and carrier sheet (e.g., about 4.4 mm x about 5.0 mm) are as follows Figure 13B shown.

[0171] Figure 12A and 12B A schematic perspective view of seven microneedles 1210 arranged in an exemplary variation of the microneedle array 1200 is depicted. The seven microneedles 1210 are arranged in a hexagonal array on a substrate 1202. Figure 12A As shown, the electrode 1220 is disposed on the distal portion of the microneedle 1210 extending from the first surface of the substrate 1202. Figure 12B As shown, the proximal portions of the microneedles 1210 are conductively connected to corresponding backside electrical contacts 1230 located on a second surface of the substrate 1202 opposite the first surface of the substrate 1202. Figure 12C and 12D Schematic plan and side views of a microneedle array similar to microneedle array 1200 are depicted. Figure 12C and 12D As shown, seven microneedles are arranged in a hexagonal array, wherein the center-to-center spacing between the center of each microneedle and the center of its immediate neighbor in any direction is about 750 μm. In other variations, the center-to-center spacing between the needles can be, for example, about 700 μm to about 800 μm, or about 725 μm to about 775 μm. The microneedles can have an outer shaft diameter of approximately about 170 μm (or about 150 μm to about 190 μm, or about 125 μm to about 200 μm) and a height of about 500 μm (or about 475 μm to about 525 μm, or about 450 μm to about 550 μm).

[0172] Furthermore, the microneedle arrays described herein can be highly configurable with respect to the positions of the working electrode, counter electrode, and reference electrode within the microneedle array. This configurability can be facilitated by an electronic system.

[0173] In some variations, the microneedle array may include two or more groups of electrodes distributed in a symmetrical or asymmetrical manner in the microneedle array, with each group having the same or different numbers of electrode components depending on the signal sensitivity and / or redundancy requirements. For example, electrodes of the same type (e.g., working electrodes) may be distributed in a microneedle array in a bilaterally symmetrical or radially symmetrical manner. For example, Figure 14AA variation of the microneedle array 1400A is depicted that includes two symmetrical groups of seven working electrodes (WE), the two working electrode groups being labeled "1" and "2." In this variation, the two working electrode groups are distributed in the microneedle array in a bilaterally symmetrical manner. The working electrodes are typically arranged between a central region occupied by three reference electrodes (RE) and a peripheral region occupied by twenty counter electrodes (CE). In some variations, each of the two working electrode groups may include seven working electrodes that are electrically connected (e.g., to enhance the sensor signal). Alternatively, only a portion of one or both working electrode groups may include a plurality of electrodes electrically connected therebetween. Alternatively, a working electrode group may include working electrodes that are independent and not electrically connected to other working electrodes. In addition, in some variations, the working electrode groups may be distributed in the microneedle array in an asymmetric or random configuration.

[0174] As another example, Figure 14B A variation of a microneedle array 1400B is depicted that includes four symmetrical groups of three working electrodes (WE), the four working electrode groups being labeled "1," "2," "3," and "4." In this variation, the four working electrode groups are distributed in a radially symmetrical manner in the microneedle array. Each working electrode group is adjacent to one of the two reference electrode (RE) components in the microneedle array and are arranged in a symmetrical manner. The microneedle array also includes a counter electrode (CE) arranged around the periphery of the microneedle array, but two electrodes that are inactive / invalid or can be used for other features or operating modes occupy two vertices of the hexagon.

[0175] In some variations, only a portion of the microneedle array may include active electrodes. For example, Figure 14C A variation of the microneedle array 1400C is depicted having 37 microneedles and a reduced number of active electrodes, including four bilaterally symmetrically arranged working electrodes (labeled "1," "2," "3," and "4"), twenty-two counter electrodes, and three reference electrodes. The remaining eight electrodes in the microneedle array are inactive / ineffective. Figure 19C In the microneedle array shown, each working electrode is surrounded by a set of counter electrodes. Two such clusters of working and counter electrodes are separated by a row of three reference electrodes.

[0176] As another example, Figure 14D A variation of the microneedle array 1400D is depicted having 37 microneedles and a reduced number of active electrodes, including four bilaterally symmetrically arranged working electrodes (labeled "1," "2," "3," and "4"), twenty counter electrodes, and three reference electrodes, where the remaining ten electrodes in the microneedle array are inactive electrodes.

[0177] As another example, Figure 14E A variation of the microneedle array 1400E is depicted, having 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1," "2," "3," and "4"), eighteen counter electrodes, and two reference electrodes. The remaining thirteen electrodes in the microneedle array are inactive / ineffective. The inactive electrodes are located along a portion of the perimeter of the entire microneedle array, thereby reducing the effective size and shape of the active microneedle arrangement to a smaller hexagonal array. In the active microneedle arrangement, the four working electrodes are generally arranged in radial symmetry, and each working electrode is surrounded by a set of counter electrodes.

[0178] Figure 14F Another example variation of a microneedle array 1400F is depicted, having 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1," "2," "3," and "4"), two counter electrodes, and one reference electrode. The remaining thirty electrodes in the microneedle array are inactive / inactive. The inactive electrodes are arranged in two layers around the perimeter of the entire microneedle array, reducing the effective size and shape of the active microneedle arrangement to a smaller hexagonal array centered around the reference electrode. In the active microneedle arrangement, the four working electrodes are arranged bilaterally symmetrically, and the two counter electrodes are equidistant from the central reference electrode.

[0179] Figure 14G Another example variation of a microneedle array 1400G is depicted, having 37 microneedles and a reduced number of active electrodes. The active electrodes in the microneedle array 1400G are arranged in the same pattern as the reference electrodes, except that the microneedle array 1400G includes one counter electrode and two reference electrodes, and the smaller hexagonal active microneedle array is centered on the counter electrode. Figure 14F The microneedle array 1400F is shown arranged in a similar manner. In an effective microneedle arrangement, the four working electrodes are arranged bilaterally symmetrically, and the two reference electrodes are equidistant from the central counter electrode.

[0180] Figure 14H Another example variation of a microneedle array 1400H having seven microneedles is depicted. This microneedle arrangement includes two microneedles assigned as independent working electrodes (1 and 2), a counter electrode group consisting of four microneedles, and a single reference electrode. The working and counter electrode arrangements are bilaterally symmetrical, with equal distances from the central reference electrode. In addition, the working electrode is arranged as far away from the center of the microneedle array as possible (e.g., at the periphery of the carrier sheet or array) to take advantage of the location where the working electrode is expected to have higher sensitivity and overall performance.

[0181] Figure 14IAnother example variation of a microneedle array 1400I is depicted, having seven microneedles. The microneedle arrangement includes four microneedles divided into two separate groups (1 and 2), each containing two working electrodes; a counter electrode group consisting of two microneedles; and a single reference electrode. The working and counter electrodes are arranged bilaterally symmetrically, with each being equidistant from the central reference electrode. Furthermore, the working electrode is positioned as far from the center of the microneedle array as possible (e.g., at the periphery of the carrier sheet or array) to take advantage of the location where the working electrode is expected to have higher sensitivity and overall performance.

[0182] Figure 14J Another example variation of a microneedle array 1400J is depicted, having seven microneedles. The microneedle arrangement includes four microneedles assigned as independent working electrodes (1, 2, 3, and 4), a counter electrode group consisting of two microneedles, and a single reference electrode. The working and counter electrodes are arranged bilaterally symmetrically, with equal distances from the central reference electrode. In addition, the working electrode is arranged as far away from the center of the microneedle array as possible (e.g., at the periphery of the carrier sheet or array) to take advantage of the location where the working electrode is expected to have higher sensitivity and overall performance.

[0183] Although Figures 14A-14J Exemplary variations of microneedle array configurations are illustrated, but it should be understood that these figures are not limiting and that other microneedle configurations (including different numbers and / or distributions of working electrodes, counter electrodes, and reference electrodes, and different numbers and / or distributions of active and inactive electrodes, etc.) may be suitable for other variations of microneedle arrays.

[0184] like Figure 1 As shown, in some variations, analyte monitoring device 110 may be applied to the skin using a suitable applicator 160. The applicator may, for example, be configured to push analyte monitoring device 110 toward the user's skin so that microneedle array 140 can be inserted into the skin (e.g., to a desired target depth) and the one or more adhesive layers adhere to the skin to securely hold analyte monitoring device 110 in place.

[0185] The applicator may include an actuatable housing (also referred to as an actuator and / or housing) comprising a housing body defining a cavity therein. The housing body has a distal opening, and the components of the applicator may be located and / or positioned within the cavity of the housing body. The applicator components are aligned and configured to securely hold the analyte monitoring device 110 so that the analyte monitoring device 110 is positioned for inserting the microneedle array 140 into the skin (e.g., the microneedle array is positioned so that the tips of the microneedles are facing distally). In addition, the applicator components are aligned and configured to move the analyte monitoring device 110 and release the analyte monitoring device 110 at a speed that allows the microneedles of the microneedle array 140 to be inserted into the skin with sufficient force.

[0186] In some variations, the applicator may include a housing body, a ferrule assembly, a transfer member, and a removable base (also referred to as a base). The housing body, ferrule assembly, transfer member, and base may be engaged with each other via one or more releasable coupling features and / or engagement features. The base may be released from engagement with the housing body so that the ferrule assembly and transfer member are aligned and positioned in a configuration in which the analyte monitoring device 110 held by the transfer member is ready for insertion into the skin. The transfer member and ferrule assembly may be independently translated relative to the housing body. During an application procedure, actuation of the housing body (e.g., manually by the user, or using an additional external actuator) causes the transfer member and analyte monitoring device 110 to move at a speed that enables the microneedle array 140 to be inserted into the user's skin with a force that allows the microneedles of the microneedle array 140 to penetrate the skin.

[0187] The housing, the hoop assembly, and the transmission member can be axially aligned (e.g., concentrically) and / or nested together and / or telescopically arranged. The transmission member can releasably hold (e.g., grasp, encase, or otherwise carry) the analyte monitoring device 110. The applicator can be transformed from a first "contracted" configuration to a second "stretched" configuration, and then to a third "released" configuration. In the contracted configuration, the components of the applicator are locked relative to each other so that the engagement between the various components of the applicator is fixed, the components cannot move relative to each other, and the analyte monitoring device 110 cannot be deployed. In the contracted configuration, the base engages with the housing. In the extended configuration, the components of the applicator are arranged and constructed so that the analyte monitoring device can be deployed (e.g., released) from the applicator in response to actuation of the housing. The base is removed, and the transmission member is moved to a firing position in the extended configuration. In the released configuration, the analyte monitoring device 110 is released from the applicator and inserted into the user's skin. Each configuration and the conversion between them are described in detail below.

[0188] The hoop assembly can be a single component, or in some variations, can comprise two or more components to form the hoop assembly.For example, the hoop and friction ring can be engaged and / or locked together as further described herein.

[0189] In some variations, in the collapsed configuration, the analyte monitoring device 110 is retained within the transmission member with the distal edge of the cuff and the transmission member in a proximal-most position. In the expanded configuration, the distal edge of the cuff is in a distal-most position and the transmission member is in a neutral position. In the released configuration, the analyte monitoring device 110 is released from the transmission member with the distal edge of the cuff in a neutral position and the transmission member in a distal-most position.

[0190] The housing can include a first retaining surface or feature that releasably couples to a coupling member of the ferrule assembly. The housing can also include a second retaining surface or feature that releasably engages an engagement member of the transmission member. In response to actuation of at least a portion of the housing toward the transmission member (e.g., the applicator can be compressed and placed, for example, against a user's skin surface), the first retaining surface of the housing can be decoupled from the coupling member of the ferrule assembly, which can allow the engagement between the second retaining surface of the housing and the engagement member of the transmission member to be released. During axial movement of the transmission member in response to actuation of the housing, the transmission member can engage at least one transmission member curved surface (e.g., a hard stop) of the ferrule assembly. Engagement of the transmission member with the transmission member curved surface can cause the transmission member to flex radially outward, thereby causing the analyte monitoring device 110 to be released from the transmission member.

[0191] In addition, the applicator may include one or more biasing elements (e.g., springs) for urging adjacent components distally. For example, in some variations, the applicator may include a first biasing element disposed between the housing and the ferrule assembly. The first biasing element may be loaded to store potential energy prior to actuation of the housing (e.g., the first biasing element may include a compression spring that is pre-compressed prior to actuation of the housing). When the housing is actuated during an application procedure, the first biasing element may provide a force to the ferrule assembly that causes the first retaining surface of the housing to decouple from the coupling member of the ferrule assembly. Additionally or alternatively, the applicator may include a second biasing element disposed between the housing and the transfer member. The second biasing element may be loaded to store potential energy prior to actuation of the housing (e.g., the second biasing element may include a compression spring that is pre-compressed prior to actuation of the housing). When the transfer member is disengaged from the housing due to actuation of the housing during an application procedure, the energy stored in the loaded second biasing element may be transferred to the transfer member, thereby driving the analyte monitoring device (e.g., suitable skin puncture for a microneedle array) with an appropriate application force. The combination of two biasing elements for deploying analyte monitoring device 110 allows control of the speed (e.g., impact velocity) of the actuation force and the conveyor moving in response to the actuation of the housing. The dual biasing element design allows control of the impact velocity independently of the force used to actuate. In some variations, the force provided to the ferrule assembly by the first biasing element can be in the range of about 5 Newtons to about 45 Newtons. In some variations, the range of the residual force provided to the conveyor by the second biasing element can be from about 5 Newtons to about 45 Newtons. The range of impact velocity can be from about 2 meters per second to about 10 meters per second. The force provided by the first biasing element and the second biasing element and the resulting impact velocity can be controlled by adjusting the compression and characteristics of the biasing element.

[0192] The components of the applicator may be made using any suitable manufacturing process, including injection molding, casting, 3D printing, machining techniques (eg, using a mill or lathe), and the like.

[0193] Figures 15A-15D An example variation of an applicator 1500 for an analyte monitoring device (eg, analyte monitoring device 110 ) is depicted. Figure 15A and 15B is a side view of the applicator 1500, Figure 15C is a top perspective view of the applicator 1500, and Figure 15D is a bottom perspective view of the applicator 1500. Figure 15A and Figure 15B The applicator 1500 is depicted in a collapsed configuration with the base 1550 engaged with the housing, which is covered by an outer capsule 1570 .

[0194] Figure 15C and Figure 15DAn exploded view of the applicator 1500 is depicted. Figure 15C and Figure 15D As shown, applicator 1500 includes a housing 1510, a ferrule 1520, a friction ring 1530, a transmission member 1540, and a base 1550. Housing 1510 includes a housing body defining a cavity therein. The housing body has a distal opening, and components of the applicator can be located and / or positioned within and / or connected to the cavity of the housing body through the distal opening.

[0195] Friction ring 1530 is axially aligned with ferrule 1520 and is configured to be nested and arranged (e.g., telescopically arranged) within ferrule 1520. Ferrule 1520 and friction ring 1530 are axially aligned with the cavity of the housing body and are configured to be nested and arranged within the cavity of the housing body. Transmission member 1540 is axially aligned with the nested arrangement of ferrule 1520 and friction ring 1530 in the cavity of the housing body and is configured to be nested and arranged within the nested arrangement.

[0196] Applicator 1500 also includes a base 1550 that is arranged to engage the housing body at the distal opening of the housing body. A locking member 1560, an outer capsule 1570, and a top plug 1580 are also provided. In some variations, the outer capsule 1570 and / or the top plug 1580 are optional and need not be included in applicator 1500 for operation.

[0197] like Figure 15C and Figure 15D As further shown, a first biasing element 1582 (eg, a first compression spring) may be disposed between the housing 1510 and the ferrule 1520 , and a second biasing element 1584 (eg, a second compression spring) may be disposed between the housing 1510 and the transmission 1540 .

[0198] Figure 15E and Figure 15F Various aspects of the transport 1540 and the analyte monitoring device 110 relative to each other are shown in exploded and perspective views, respectively. Figure 15E and Figure 15F As shown, the analyte monitoring device 110 with the attached microneedle capsule 500 can be held in the transport 1540, and the microneedle array 140 (in Figure 15E and Figure 15F When the transmission member 1540 is arranged in the cavity of the housing body, the analyte monitoring device 110 is located at the distal end.

[0199] The base 1550 is removably coupled to the housing body to completely enclose the analyte monitoring device 110 within the cavity defined by the housing body (e.g., to maintain the sterility of the device 110 prior to application, as further described herein). The base 1550 is a removable distal cover or cap that releasably engages the housing body when the applicator is in the collapsed configuration. The base 1550 is coupled to the microneedle enclosure 500 that provides a sterile environment for the microneedle array 140. In some variations, when the base 1550 is removed from the housing body, the microneedle enclosure 500 is removed along with the base 1550, thereby making the microneedle array 140 accessible through the distal opening of the housing body. Additional details are provided herein.

[0200] Figure 16A 、 Figure 16B 、 Figure 16C and Figure 16D Various aspects of conveyor 1540 are depicted in greater detail. Figure 16A is a perspective view of the conveyor 1540, Figure 16B This is a bottom view. Figure 16C It is a side view. Figure 16D It is along Figure 16C 15. A cross-sectional side view taken along line AA is shown. Transport member 1540 is configured to retain analyte monitoring device 110 when applicator 1500 is in the retracted and extended configurations. Transport member 1540 is configured to respond to actuation of housing 1510 and deploy analyte monitoring device 110 at a speed and force required to insert the microneedles of microneedle array 140 into the skin of a user. In the released configuration of the applicator, analyte monitoring device 110 is released from transport member 1540.

[0201] As shown, the conveyor 1540 includes a base portion 1610 and a conveyor shaft 1630. The conveyor shaft 1630 defines an internal cavity 1632 in which the second biasing element 1584 is disposed.

[0202] The conveyor 1540 may include an engagement member or feature for releasably engaging a conveyor holding surface or feature of the housing 1510. The engagement member or feature may be formed at one or more portions around the periphery of the conveyor shaft 1630 and may be configured to releasably engage a conveyor holding surface of the housing 1510. In some variations, such as Figure 16CAs shown, the engaging member may include a distal surface 1636 of a shelf 1634. The shelf 1634 may be a portion of the conveyor shaft 1630 that extends horizontally outward from the conveyor shaft 1630. The span (e.g., width or diameter) of the shelf 1634 is greater than the span (e.g., width or diameter) of the conveyor shaft 1630, wherein the span is measured in a direction orthogonal to the axial arrangement direction of the conveyor 1540 within the cavity of the housing body. The distal surface 1636 may be a surface extending between the shelf 1634 and the conveyor shaft 1630, such as a shoulder. In some variations, the distal surface 1636 may be an angled surface. In some variations, the distal surface 1636 may be flat or substantially flat. As further described herein, the distal surface 1636 releasably engages with the housing 1510 at the conveyor retaining surface.

[0203] The base portion 1610 located at the distal end of the conveyor shaft 1630 includes one or more flexible blades 1612 extending from the conveyor shaft 1630, one or more flexible support petals 1614 extending from the conveyor shaft 1630, and one or more tracking protrusions 1616 extending from the outer side walls of the one or more flexible blades 1612.

[0204] The configuration or orientation of the flexible blade 1612 defines the configuration (e.g., the loaded configuration and the released configuration) of the transport member 1540, as described herein. The flexible blade 1612 defines a receptacle 1640 in which the analyte monitoring device 110 can be received. For example, Figure 16A and Figure 16B As shown, each flexible blade 1612 comprises an arcuate or curved member extending from a flexible connecting member that is attached at its proximal end to the conveyor shaft 1630. The flexible connecting member allows the flexible blade 1612 to bend relative to the conveyor shaft 1630. For example, in some variations, the flexible blade 1612 is a cantilever that can bend radially outward. The flexible blades 1612 can be arranged circumferentially around the conveyor shaft 1630 to define a receptacle 1640 for supporting / enclosing the analyte monitoring device 110 proximate the footprint of the analyte monitoring device 110. Figure 16A and Figure 16BAs shown, the receiving portion 1640 can be substantially circular. When the flexible blade 1612 is in a natural, unbent state, the transport member 1540 is in a load-bearing configuration, wherein the analyte monitoring device 110 is supported or retained in the receiving portion 1640. In the load-bearing configuration, the analyte monitoring device 110 is retained in the receiving portion 1640 due to the engagement of the inner sidewall of the flexible blade 1612 with the periphery of the analyte monitoring device 110. For example, external pressure can be applied to the flexible blade 1612, causing the transport member 1540 to transition to a release configuration. In the release configuration, the analyte monitoring device 110 is not retained by the flexible blade 1612, and the analyte monitoring device 110 can be released from the receiving portion 1640. The external pressure can be provided at least in part by the second biasing element 1584. For example, when the housing 1510 is actuated during an application procedure, the transmission member 1540 is moved axially downward by the concentric (e.g., telescoping) arrangement within the cuff 1520, and the second biasing element 1584 is compressed within the lumen 1632. During the axial movement of the transmission member 1540, the tracking protrusions 1616 extending from the outer sidewalls of the flexible blades 1612 of the transmission member 1540 engage and interfere with the transmission member curved surface (e.g., a hard stop) of the cuff 1520. The transmission member curved surface of the cuff 1520 resists axial movement of the transmission member 1540, and the energy stored in the second biasing element 1584 is transferred to the transmission member 1540, thereby causing the flexible blades 1612 to bend radially outward, ejecting the analyte monitoring device 110 with an appropriate applied force (e.g., for properly inserting the microneedle array 140 into the user's skin). The construction of the flexible blades 1612 is similar and / or analogous to a collet construction in which, in the loaded configuration of the collet construction, the collet arms are biased radially inwardly and engage and retain the components. At the end of the loaded path, the collet arms are released from their biased state, thereby disengaging the components.

[0205] In some variations, each flexible blade 1612 may further include one or more optional coupling features disposed at the distal end of the flexible blade 1612 and configured to help enclose the analyte monitoring device 110. For example, Figure 16B and Figure 16D As shown, at least one flexible blade 1612 may include a flange 1622 or other protrusion or flange-like support surface at the distal end of the arcuate or curved member of the flexible blade 1612. The flange 1622 or other protrusion or flange-like support surface may extend inward at the distal end to help provide stable support for the distal surface of the analyte monitoring device 110.

[0206] In some variations, each flexible support flap 1614 is a tab-like member extending from a flexible connecting member that is attached at its proximal end to the conveyor shaft 1630. The flexible support flaps 1614 may be arranged circumferentially around the conveyor shaft 1630 in an alternating configuration with the flexible blades 1612. Each flexible support flap 1614 may have a rounded or curved distal surface to retain and / or support and / or stabilize the proximal surface of the analyte monitoring device 110. For example, in some variations, a portion of the proximal surface of the analyte monitoring device 110 fits tightly within the arcuate configuration formed by the distal surfaces of the flexible support flaps 1614.

[0207] Each flexible support flap 1614 may also include one or more optional coupling or clamping features. For example, a support clamp 1624 in the form of a protrusion or extension of a tab-like member may be positioned at the distal end of one or more flexible support flaps 1614. The support clamp 1624, together with the rounded or curved distal surface of the flexible support flap 1614, helps stabilize and retain the analyte monitoring device 110.

[0208] When the analyte monitoring device 110 is placed in the receptacle 1640, the flange 1622 and / or the clamping member 1624 provide additional support for enclosing or retaining the analyte monitoring device 110. When the transport 1540 is in the stowed configuration, the engagement between the circumferential edge of the analyte monitoring device 110 and the flange 1622 and / or the engagement between the proximal surface of the analyte monitoring device 110 and the clamping member 1624 helps provide additional stability to the analyte monitoring device 110 within the receptacle 1640. When the flexible blades 1612 are bent radially outward (in the released configuration of the transport 1540), the flange 1622 does not engage the analyte monitoring device 110 and, therefore, does not provide additional stability to the analyte monitoring device 110 and / or does not prevent its release.

[0209] Although the conveyor 1540 is shown as having four flexible blades 1612 and four flexible support flaps 1614, in other variations, the conveyor 1540 may have any suitable number of flexible blades 1612 (e.g., one, two, three, five, six, or more) and any suitable number of flexible support flaps 1614 (e.g., one, two, three, five, six, or more). In some variations, flexible support flaps 1614 are not included. In some variations, the number of flexible blades 1612 may be different from the number of flexible support flaps 1614. For example, the conveyor 1540 may include fewer or more flexible support flaps 1614 than flexible blades 1612.

[0210] Although the conveyor 1540 is shown as having flexible blades 1612 that are substantially the same size and shape, in other variations, one or more flexible blades 1612 may be sized and shaped differently than one or more other flexible blades 1612. For example, the conveyor 1540 may include two flexible blades 1612 that have a longer circumference than the other two flexible blades 1612. Similarly, although the conveyor 1540 is shown as having flexible support petals 1614 that are substantially the same size and shape as one another, in other variations, one or more flexible support petals 1614 may be sized and shaped differently than one or more other flexible support petals 1614.

[0211] Although the housing 1640 is shown as having a circular or substantially circular footprint formed by the shape and configuration / configuration of the flexible blades 1612 and the flexible support flaps 1614, the housing 1640 may define footprints of other shapes, such as square, oval, rectangular, etc., to illustrate / according to the shape of the analyte monitoring device 110. The flexible blades 1612 and the flexible support flaps 1614 may have different configurations / configurations (e.g., curvature, size, shape, etc.) to provide retention and release of analyte monitoring devices of any shape. In some variations, the curvature of the flexible support flaps 1614 is substantially similar to the curvature of the proximal surface of the analyte monitoring device, such that the flexible support flaps 1614 hug the proximal surface.

[0212] refer to Figure 16E and 16F, which illustrate additional features of the transport member 1540 in bottom perspective and bottom views, respectively. In some variations, a clamping layer 1650 may be disposed on the distal surfaces of the flexible blade 1612, the flexible support flap 1614, and the transport member shaft 1630. The clamping layer 1650 may be an elastomeric layer deposited and / or applied to provide additional clamping capability between the analyte monitoring device 110 and the distal surfaces of the flexible blade 1612, the flexible support flap 1614, and / or the transport member shaft 1630. In some variations, one or more proximal surfaces of the analyte monitoring device 110 may be smooth or substantially smooth surfaces, and the incorporation of the clamping layer 1650 may help retain the analyte monitoring device 110 within the receptacle 1640 defined by the flexible blade 1612. In some variations, a clamping layer 1650 is disposed on one or more distal surfaces of the flexible paddle 1612, the flexible support flap 1614, and / or the conveyor shaft 1630 that contact the analyte monitoring device 110 when the analyte monitoring device 110 is retained in the receptacle 1640. In some variations, the clamping layer 1650 is uniformly distributed. In some variations, the clamping layer 1650 is non-uniformly distributed. In some variations, the clamping layer 1650 is disposed at one or more points of contact between the analyte monitoring device 110 and the distal surfaces of the flexible paddle 1612, the flexible support flap 1614, and / or the conveyor shaft 1630.

[0213] Figure 16G and Figure 16H Aspects of the conveyor 1540 modified with the shelf 1634 are shown in side view and side cross-sectional view, respectively. Additional aspects and features of the conveyor 1540 may be compared to those of the reference Figures 16A-16F Same as shown and described.

[0214] In some variations, shelf 1634 has a proximal surface 1638. Proximal surface 1638 can be a surface extending between shelf 1634 and conveyor shaft 1630, such as a shoulder. In some variations, proximal surface 1638 can be an angled surface. In some variations, proximal surface 1638 can be flat or substantially flat. In some variations, proximal surface 1638 of shelf 1634 can serve as a conveyor locking feature. For example, it may be desirable to incorporate a feature that prevents conveyor 1540 from being reloaded so that applicator 1500 cannot move from a released configuration to an extended configuration. This may be desirable in situations where the sterility and / or condition of analyte monitoring device 110 is unknown. For example, if analyte monitoring device 110 has been released from applicator 1500, microneedle array 140 or other components of analyte monitoring device 110 may be damaged. In reaction to the axial movement of the transport member 1540 toward the proximal end of the housing 1510 after the distal surface 1636 of the transport member 1540 and the housing 1510 disengages at the transport member retaining surface, the axial movement of the transport member 1540 is stopped by the distal end of the transport member retaining surface. In particular, the proximal surface 1638 will abut the distal end of the transport member retaining surface, thereby preventing the transport member 1540 from axially moving toward the proximal end of the housing 1510. The distal end of the transport member retaining surface can be a flat or substantially flat surface to prevent the proximal surface 1638 from pushing past the transport member retaining surface.

[0215] In some variations (e.g., Figures 16A-16D In the embodiment shown and described above, the applicator 1500 can be reloaded and / or reused. For example, the transmission member 1540 is reloadable to allow the transmission member 1540 to be moved axially toward the proximal end of the housing 1510 so that the applicator components can be reengaged in the extended configuration.

[0216] In some variations, alternative and / or additional transfer member locking features may be incorporated. In one variation, a spring clip feature is nested within the transfer member shaft 1630 in a retaining post within the transfer member shaft 1630. The distal ends of the spring-loaded fingers are bent inward to be retained by the retaining post. The proximal ends of the spring-loaded fingers are retained at the proximal end of the cavity of the housing body. When the applicator 1500 is transitioned to the extended configuration and the transfer member 1540 moves toward the distal end of the housing body, the retaining post moves with the transfer member 1540 and the spring-loaded fingers expand to a larger radial configuration. If an attempt is made to reload or reposition the transfer member (e.g., to move the transfer member 1540 toward the proximal end of the housing body), the spring-loaded fingers in the larger radial configuration form a blocking surface for the transfer member 1540.

[0217] In another variation, a locking post is positioned within the conveyor shaft 1630. The locking post includes a spring-loaded finger at the distal end that engages with an inner surface feature of the conveyor shaft 1630. At the proximal end, the locking post engages within a footprint defined by a locking arm extending from the proximal end of the cavity of the housing body. The engagement of the locking post within the footprint defined by the locking arm causes the locking arm to deflect outward. When the applicator 1500 is rotated to the extended configuration and the conveyor 1540 moves toward the distal end of the housing body, the locking post moves with the conveyor 1540 and the locking arm deflects inward to a natural, unbent state. If an attempt is made to reload or reposition the conveyor, the distal end of the locking arm provides a blocking surface for the conveyor 1540.

[0218] Figures 17A-17E Various aspects of the ferrule 1520 are depicted in greater detail. Figure 17A A top perspective view of the ferrule 1520 is provided. Figure 17B is the bottom view, Figure 17C It is a top view. Figure 17D is a first side and corresponding side sectional view, Figure 17E is a second side and corresponding side cross-sectional view.

[0219] The cuff 1520 is disposed in the cavity defined by the housing body and is configured to retain the applicator 1500 in a collapsed configuration (wherein the position of the housing 1510 and the position of the transmission member 1540 are fixed relative to each other) when the base 1550 is engaged with the housing 1510. The cuff 1520 is also configured to disengage the base 1550 from the housing 1510 and transform the applicator 1500 into an expanded configuration when the locking member 1560 is depressed. The cuff 1520 interacts and engages with the friction ring 1530 to transform the transmission member 1540 into a fired position of the expanded configuration, as further described herein. The transmission member 1540 can be substantially axially aligned and nested within the cuff 1520, and the transmission member 1540 can move axially within the cuff 1520. When the housing 1510 is actuated, the cuff 1520 is used to disengage the analyte monitoring device 110 from the transmission member 1540.

[0220] like Figure 17A As shown, the ferrule 1520 is a tubular structure having a sidewall and a lumen 1720 extending through the sidewall. The ferrule 1520 has a proximal opening and a distal opening. The firing ring 1530 and the transmission member 1540 are axially aligned and move axially within the lumen 1720 through the proximal opening and / or the distal opening.

[0221] In some variations, the ferrule 1520 is generally cylindrical, having a circular or substantially circular cross-section along a plane perpendicular to the height of the ferrule 1520. In some variations, the ferrule 1520 may have other configurations. For example, the ferrule 1520 may have a square, rectangular, or oval cross-section. The effective inner diameter, or the internal span between opposing sidewalls, may be consistent along the height of the ferrule 1520. In some variations, the effective inner diameter or internal span of the ferrule 1520 may vary slightly along its height. An upper shoulder 1722 is located at the proximal end of the ferrule 1520 along the proximal opening, and a bottom flange 1732 is located at the distal end of the ferrule 1520 along the distal opening.

[0222] The cuff 1520 includes a retaining wall 1712 formed on an outer sidewall that generally extends along the height of the cuff 1520 at locations corresponding to corresponding locking members 1560. As shown, in some variations, the cuff 1520 has two retaining walls 1712 corresponding to two locking members 1560. In some variations, the cuff 1520 has fewer or more retaining walls 1712 and corresponding locking members 1560. For example, in some variations, there may be one retaining wall 1712 and one locking member 1560. Each retaining wall 1712 is defined by a retaining lip 1714 that extends around at least a portion of the outer periphery of the retaining wall 1712. Each retaining wall 1712 may be sized and shaped to generally correspond to the outer periphery of the locking member 1560, such that the retaining lip 1714 closely conforms to and / or aligns with the outer periphery of the movable locking member 1560. The exterior exposed surface of the retaining wall 1712 may be flat or substantially flat. In some variations, the outer curvature of ferrule (1520) forms the outer exposed surface of retaining wall (1712).

[0223] 17. The top edge of the retaining lip 1714 can engage the upper edge of a corresponding locking member 1560. In the collapsed configuration of the applicator 1500, the locking member 1560 is positioned within the retaining wall 1712 such that the upper edge of the locking member 1560 engages below the top edge of the retaining lip 1714, thereby preventing the ferrule 1520 from moving downward relative to the housing 1510. When the locking member 1560 is depressed, the vertical movement of the ferrule 1520 is no longer impeded as the locking member 1560 is removed from engagement with the top edge of the retaining lip 1714. Additional details are further described herein.

[0224] The rotational alignment of the transfer member 1540 within the ferrule 1520 can be guided by one or more tracking features. The one or more tracking features can also guide the axial movement of the transfer member 1540 within the ferrule 1520. For example, the ferrule 1520 can include one or more tracks 1716 that extend along at least a portion of the height of the ferrule 1520, and one or more tracking protrusions 1616 on the transfer member 1540 can travel within the tracks. The tracks 1716 can include, for example, Figure 17A 1540 . The track 1716 may be configured to receive other suitable types of tracking features on the conveyor 1540 (e.g., ball bearings). The ferrule 1520 and the conveyor 1540 may include any suitable number of tracking features (e.g., one, two, three, four, or more), and the tracking features may be distributed circumferentially in equal or unequal amounts. For example, four tracking features may be evenly spaced 90 degrees apart around the conveyor 1540 and the ferrule 1520. In some variations, two tracking features may be evenly spaced 180 degrees apart or directly opposite each other, three tracking features may be evenly spaced 120 degrees apart, and so on.

[0225] Each track 1716 can terminate at the bottom end of the track 1716 with a conveyor curved surface 1718. The conveyor curved surface 1718 can be a portion of the bottom surface or bottom flange 1732 of the ferrule 1520, or another shoulder-like surface that acts as a stop for axial movement of the conveyor 1540 to help the flexible blades 1612 of the conveyor 1540 flex radially outward. For example, the conveyor curved surface 1718 of each track 1716 prevents the conveyor 1540 from moving further beyond the bottom edge of the ferrule 1520.

[0226] The upper shoulder 1722 of the ferrule 1520 may include features for engaging with and locking to the friction ring 1530. In the collapsed configuration of the applicator 1500, the friction ring 1530 is retracted within the lumen 1720 of the ferrule 1520. During the transition from the collapsed configuration to the expanded configuration, the friction ring 1530 protrudes and / or extends outwardly from the proximal opening of the ferrule 1520 at the proximal end. In the collapsed configuration of the applicator 1500, the retracted arrangement of the friction ring 1530 within the ferrule 1520 provides a compact overall height for the applicator 1500. In some variations, the friction ring 1530 is not retracted within the ferrule 1520, resulting in a taller applicator in the retracted configuration. In some variations, the friction ring 1530 and the ferrule 1520 are not separate components.

[0227] A shoulder formed circumferentially around the top edge of ferrule 1520 can secure engagement of friction ring 1530 with ferrule 1520. In some variations, a portion of upper shoulder 1722 can include a bottom beam 1724 with guide walls 1726. Bottom beam 1724 can be a flat or substantially flat surface extending outward from a portion of upper shoulder 1722, such that bottom beam 1724 extends over a corresponding portion of lumen 1720. Two guide walls 1726 can be disposed at either end of bottom beam 1724, comprising vertically extending members extending upward from or adjacent to bottom beam 1724. Bottom beam 1724 provides a flat surface for engaging the flexible tab of friction ring 1530, and a pair of guide walls 1726 secure the flexible tab to bottom beam 1724 by preventing rotational movement of friction ring 1530. For example, a pair of guide walls 1726 are positioned at either end of the bottom beam 1724 to lock the flexible tab in place on the bottom beam 1724. The collar 1520 may include more than one engagement and locking feature for securing engagement with the friction ring 1530, and the engagement and locking features may be distributed circumferentially around the upper shoulder 1722 in equal or unequal fashion. For example, Figure 17A 、 17B 17C , three bottom beams 1724 with corresponding pairs of guide walls 1726 are evenly spaced 120 degrees apart from each other around upper shoulder 1722. In some variations, four bottom beams 1724 with corresponding pairs of guide walls 1726 may be evenly spaced 90 degrees apart from each other, two bottom beams 1724 with corresponding pairs of guide walls 1726 may be evenly spaced 180 degrees apart from each other or directly opposite each other, etc.

[0228] An underside 1728 of upper shoulder 1722 may also interface with friction ring 1530. For example, underside 1728 may interface with a portion of a circumferential edge of friction ring 1530 to maintain the axial position of ferrule 1520 and friction ring 1530. Additional details regarding engagement and locking are further described herein.

[0229] The outer sidewall of the ferrule 1520 may have features that interface with the base 1550. For example, a base retaining surface 1730 may be formed at one or more portions of the ferrule 1520 around the periphery and near or at the distal end of the ferrule 1520. The base retaining surface 1730 may be a rib protruding from the outer sidewall of the ferrule 1520 and may be configured to provide a retaining surface for one or more components of the base 1550, as further described herein.

[0230] Figure 17F and Figure 17G Various aspects of the ferrule 1520 with a modified bottom flange 1732 are shown in bottom and side views, respectively. Additional aspects and features of the ferrule 1520 may be compared to those of the reference Figures 17A-17E Same as shown and described. Figure 17F and Figure 17G As shown, the bottom flange 1732 has a Figures 17A-17C 17A-17C ). The bottom flange 1732 has an increased surface area compared to the bottom flange shown. During actuation of the applicator 1500, the distal end of the bottom flange 1732 is the contact area that contacts the user's skin at the insertion site of the analyte monitoring device 110. The increase in the surface area of ​​the bottom flange 1732 disperses the forces applied during actuation, making the application process a more comfortable experience for the user. For bottom flanges with a smaller surface area (e.g., 17A-17C), the forces applied during actuation are concentrated in a smaller area, resulting in the user feeling a more noticeable force at the distal end of the cuff 1520.

[0231] The increased surface area bottom flange 1732 has cutouts 1734 formed therethrough for accommodating the arms of the base 1550, as described herein.

[0232] The bottom flange 1732 creates a contact surface area for insertion of the microneedle array 140 of the analyte monitoring device 110. When the applicator 1500 is in the extended configuration, the contact surface area, together with the actuation force required to actuate the housing body, causes the user's skin to bulge convexly within the perimeter of the bottom flange 1732, distal to the microneedle array 140. When the skin is bulged (in some variations, approximately 3-6 mm, depending on skin type), the skin is stretched and tightened, providing a preferred insertion position for insertion of the microneedle array because the stretched / tightened skin improves insertion efficiency and consistency. The bulged / dome-shaped convex shape of the skin reduces the well-known nail bed effect that can occur during standard microneedle insertion. The result is that the microneedles in the center of the microneedle array can penetrate first, followed by the microneedles around the perimeter of the microneedle array, resulting in consistent and effective insertion.

[0233] Figures 18A-18D Various aspects of friction ring 1530 are depicted in greater detail. Figure 18A A first top perspective view of friction ring 1530 is provided, Figure 18B A second top perspective view is provided, Figure 18C A first bottom perspective view is provided, Figure 18D A second bottom perspective view is provided.

[0234] Friction ring 1530 has an annular structure that is concentrically and axially disposed within ferrule 1520 and serves as an extension of ferrule 1520 for application of analyte monitoring device 110. In the collapsed configuration of applicator 1500, friction ring 1530 is retracted within ferrule 1520. Friction ring 1530 includes a coupling member that prevents launch of transmission member 1540 until base 1550 is removed. During transition from the collapsed configuration to the expanded configuration of applicator 1500, and upon removal of base 1550, ferrule 1520 is axially moved toward the distal opening of the housing body, causing friction ring 1530 to extend and / or outwardly extend from the proximal opening of ferrule 1520 and lock into ferrule 1520. During actuation of housing 1510, friction ring 1530 and ferrule 1520 are locked together as a single component and serve to disengage analyte monitoring device 110 from transmission member 1540. The transmission member 1540 can be substantially axially aligned and nested within the friction ring 1530 , and the transmission member 1540 can move axially within the friction ring 1530 .

[0235] like Figures 18A-18D As shown, the friction ring 1530 has an annular core that defines a friction ring cavity 1810 extending through the annular core. The transmission member 1540 is axially aligned within the friction ring cavity 1810 and moves within the friction ring cavity 1810. The outer sidewall of the annular core is axially aligned with the hoop 1520, moves within the hoop 1520, and at least partially extends out of the hoop 1520.

[0236] The ferrule 1520 can be locked to the friction ring 1530 via one or more engagement and locking features. For example, the friction ring 1530 can include one or more features that engage and lock with corresponding features on the ferrule 1520. In some variations, the engagement and locking features can be arranged circumferentially around the annular core of the friction ring 1530. For example, the flexible tab 1812 can extend along at least a portion of the height of the outer sidewall of the annular core and be circumferentially aligned with the base 1724 of the ferrule 1520. The proximal or top end of the flexible tab 1812 is attached or fixed to the top shoulder 1814 of the friction ring 1530, while the distal or bottom end of the flexible tab 1812 is not fixed, thereby allowing the distal end of the flexible tab 1812 to flex or move relative to the fixed proximal end. When the applicator 1500 is in the collapsed configuration, the proximal end of the flexible tab 1812 is aligned with a portion of the inner diameter of the upper shoulder 1722 of the ferrule 1520. During the transition from the collapsed configuration to the expanded configuration of the applicator 1500, the ferrule 1520 moves axially relative to the friction ring 1530 along the length of the flexible tab 1812 toward and through the distal opening of the housing body. The flexible tab 1812 is bent or pushed inward until the ferrule 1520 passes the distal end of the flexible tab 1812, at which point the flexible tab 1812 snaps onto the base beam 1724 and is retained between the pair of guide walls 1726.

[0237] The friction ring 1530 may include more than one flexible tab 1812, and the flexible tabs 1812 may be distributed circumferentially around the outer sidewall of the annular core in an equal or unequal manner. Figures 18A-18D As shown, three flexible tabs 1812 are evenly spaced 120 degrees apart around the outer sidewall of the annular core. In some variations, four flexible tabs 1812 may be evenly spaced 90 degrees apart, two flexible tabs 1812 may be evenly spaced 180 degrees apart or directly opposite each other, etc. The number of flexible tabs 1812 generally corresponds to the number of base beams 1724 and the associated pair of guide walls 1726.

[0238] The friction ring 1530 may further include an outwardly extending surface for engaging and locking with the ferrule 1520. For example, the underside 1728 of the upper shoulder 1722 of the ferrule 1520 may interface with the friction ring 1530 at the outwardly extending surface. The interface between the underside 1728 of the ferrule 1520 and the outwardly extending surface of the friction ring 1530 may be used to maintain the axial position of the ferrule 1520 relative to the friction ring 1530. For example, the friction ring 1530 may include a protruding circumferential edge 1816. The protruding circumferential edge 1816 may protrude outwardly at a distal end or region of the outer sidewall of the annular core, perpendicular to the height of the outer sidewall, as shown in FIG. Figure 18B The raised circumferential edge 1816 provides an interface or engagement point for the underside 1728 of the cuff 1520. When the cuff 1520 moves axially downward relative to the friction ring 1530 during the transition of the applicator 1500 from the contracted configuration to the expanded configuration, the underside 1728 abuts the raised circumferential edge 1816, which prevents the cuff 1520 from further downward axial movement.

[0239] A cushioning member 1818 can be positioned on an upper surface of the raised circumferential edge 1816. The cushioning member 1818 can be an elastomer or rubber strip or the like that cushions or softens the contact between the underside 1728 of the cuff 1520 and the raised circumferential edge 1816.

[0240] The friction ring 1530 may include more than one protruding circumferential edge 1816, and the protruding circumferential edges 1816 may be distributed circumferentially around the outer sidewall of the annular core in an equal or unequal manner. Figures 18A-18D As shown, three protruding circumferential edges 1816 are evenly spaced 120 degrees apart around the outer sidewall of the annular core. In some variations, four protruding circumferential edges 1816 can be evenly spaced 90 degrees apart, two protruding circumferential edges 1816 can be evenly spaced 180 degrees apart or directly opposite each other, etc.

[0241] The friction ring 1530 may include a coupling member that releasably couples to a ring retaining surface of the housing 1510 to help lock the delivery member 1540 when the base 1550 is engaged with the housing 1510. For example, in some variations, in the collapsed configuration of the applicator 1500, the friction ring 1530 is retracted within the ferrule 1520 and prevents firing of the delivery member 1540 until the base 1550 is removed.

[0242] For example, the housing 1510 can include at least one ring-retaining surface, and the friction ring 1530 can be disposed within a cavity defined by the housing body and include a protrusion 1820 that is removably coupled to the ring-retaining surface. In response to actuation of at least a portion of the housing 1510 toward the transmission member 1540 (e.g., the applicator can be placed in compression against the skin surface of a user, for example), the ring-retaining surface of the housing can be decoupled from the protrusion 1820, which can result in release of the releasable coupling feature coupling the transmission member 1540 and the housing 1510.

[0243] like Figure 18C As shown, a protrusion 1820 can be disposed on the inner sidewall of the annular core and extend into the friction ring cavity 1810. The protrusion 1820 can include a surface, such as a flat surface that is normal or substantially normal to the inner sidewall of the annular core, that forms a releasable engagement with a ring retaining surface of the housing 1510, as further described herein.

[0244] The friction ring 1530 may include more than one protrusion 1820, and the protrusions 1820 may be circumferentially distributed around the inner sidewall of the annular core in an equal or unequal manner. Figures 18A-18D As shown, three protrusions 1820 are evenly spaced 120 degrees apart around the inner sidewall of the annular core 120. In some variations, four protrusions 1820 may be evenly spaced 90 degrees apart, two protrusions 1820 may be evenly spaced 180 degrees apart or directly opposite each other, and so on.

[0245] Figures 19A-19E Depicted are aspects of a ferrule-ring assembly 1900, including a ferrule 1520 and a friction ring 1530 of an analyte monitoring device 1500. Figures 19A-19E The ferrule-ring assembly 1900 is shown in a top perspective view, a bottom view, a top view, a side view, a side cross-sectional view, and two detailed views of FIG. 1 , wherein the ferrule 1520 and the friction ring 1530 are locked together.

[0246] The cuff 1520 and the friction ring 1530 can be locked or secured to one another by one or more engaging and locking features. When the applicator 1500 is in the collapsed configuration, the friction ring 1530 is retracted within the cuff 1520, and the engaging and locking features are disconnected from one another. When the base 1550 is removed from the housing 1510, the applicator 1500 transitions from the collapsed configuration to the expanded configuration. During this transition, the cuff 1520 is moved or pushed downward, during which the engaging and locking features become engaged, thereby locking the cuff 1520 and the friction ring 1530 to one another.

[0247] like Figure 19A 、 19D 19E , when the ferrule-ring assembly 1900 is in the locked state, the top portion of the friction ring 1530 extends upward and is exposed outside the proximal end of the ferrule 1520 , such that the upper shoulder 1722 surrounds the top exposed portion of the friction ring 1530 .

[0248] Figure 19E The detailed view provided in FIG. 1 is a close-up view illustrating a portion of the engagement and locking features of ferrule 1520 and friction ring 1530 in a locked state.

[0249] As shown in close-up view D, in the locked state, the underside 1728 of the upper shoulder 1722 of the ferrule 1520 interfaces with the friction ring 1530 at a protruding circumferential edge 1816. This interface serves to maintain the axial position of the ferrule 1520 relative to the friction ring 1530. For example, the protruding circumferential edge 1816 acts as a stop for the ferrule 1520. As shown in close-up view C, the flexible tab 1812 is snapped onto the base beam 1724 and is retained in alignment between a pair of guide walls 1726.

[0250] Figures 20A-20F Depicted are aspects of a housing 1510 of an applicator 1500 for an analyte monitoring device 110 according to some variations. Figures 20A-20F15. The housing 1510 is configured to be manipulated (e.g., manually by a user) to actuate the applicator 1500 to deploy the analyte monitoring device 110 releasably retained within the transmission member 1540. The housing 1510 has a housing body 2002 that defines a cavity 2010 that receives the ferrule 1520, the friction ring 1530, and the transmission member 1540. The housing body 2002 has a distal opening 2004. A first biasing element 1582 (e.g., a first compression spring) can be disposed within the cavity 2010 on or around a mount 2014 (e.g., a mounting or support structure) that extends downwardly from a proximal surface 2012 of the housing body 2002 through the cavity 2010. For example, the mount 2014 can extend from the underside of the proximal surface 2012 of the housing body 2002 such that the mount 2014 extends within the cavity 2010. The mount 2014 can be concentrically aligned with or nested with the ferrule 1520, the friction ring 1530, and the transmission 1540. For example, the mount 2014 can extend through the locking friction ring cavity 1810 of the friction ring 1530, and the transmission shaft 1630 can extend through at least a portion of the mount 2014.

[0251] In some variations, such as Figure 20C Figure 20F As shown, the mounting base 2014 includes a plurality of downwardly extending fingers 2016 arranged in a circumferential configuration. For example, the plurality of downwardly extending fingers 2016 are arranged so that the configuration defines a circular or substantially circular footprint. The circular or substantially circular footprint can correspond to the outer periphery of the conveyor shaft 1630, so that the conveyor shaft 1630 (e.g., the upper portion of the conveyor shaft 1630) fits within the circular or substantially circular footprint. The shape and configuration of the footprint defined by the downwardly extending fingers 2016 can vary based on the shape and configuration of the conveyor shaft 1630 and / or the first biasing element 1582. Each downwardly extending finger 2016 can be configured to flex or bend outward along a portion of the length of the downwardly extending finger 2016 in response to a force.

[0252] One or more retaining surfaces and / or features may be formed on the mount 2014. For example, each downwardly extending finger 2016 may have one or more retaining members formed thereon. The retaining surfaces and / or features may include a ring retaining surface including a shoulder 2018 for releasably coupling with a protrusion 1820 of the friction ring 1530 to prevent firing of the transmission 1540 until the base 1550 is removed. For example, the shoulder 2018 may be formed along an outwardly facing (e.g., first) surface of the downwardly extending finger 2016 and may couple with the shoulder 2018 by a distal surface of the protrusion 1820 contacting or resting on the shoulder 2018. In some variations, a ring retaining slot (e.g., a groove or channel) may be formed through or along the outwardly facing surface of the downwardly extending finger 2016, wherein the ring retaining slot terminates distally at the shoulder 2018. The ring retaining slot can be sized so that the protrusion 1820 runs smoothly but securely along its length. For example, the thickness of the protrusion 1820 can be approximately the width of the ring retaining slot. When the housing 1510 is actuated, the housing 1510 moves downward relative to the ferrule 1520 and the friction ring 1530. During this downward movement of the housing 1510, the ring retaining slot slides downward along the protrusion 1820, and the coupling (e.g., contact) between the shoulder 2018 and the protrusion 1820 is released.

[0253] The retaining surface and / or features of each downwardly extending finger 2016 may further include a transport retaining surface including a shoulder 2020 for releasably engaging a shelf 1634 of the transport 1540 to control axial movement of the transport 1540 upon release of the analyte monitoring device 110. For example, the shoulder 2020 may be formed along an inwardly facing (e.g., second) surface of the downwardly extending finger 2016, and the shoulder 2020 may engage a distal surface 1636 of the shelf 1634. The shelf 1634 and the distal surface 1636 may extend circumferentially along the transport axis 1630. During actuation of the housing 1510 , as the engagement between the shoulder 2018 and the protrusion 1820 is released, downward movement of the transfer member 1540 toward the distal opening 2004 of the housing body 2002 causes the shelf 1634 to push past (e.g., deflect or bend) the shoulder 2020 , which is no longer restrained by the friction ring 1530 .

[0254] In some variations, each downwardly extending finger 2016 may include a shoulder 2018 formed along an outwardly facing surface of the downwardly extending finger 2016 and a shoulder 2020 formed along an opposite inwardly facing surface of the downwardly extending finger 2016. The number of downwardly extending fingers 2016 may correspond to the number of protrusions 1820. The downwardly extending fingers 2016 may be distributed circumferentially in equal or unequal manner. For example, Figure 20DAs shown, three downwardly extending fingers 2016 are evenly spaced 120 degrees apart from each other within cavity 2010. In some variations, four downwardly extending fingers 2016 may be evenly spaced 90 degrees apart from each other, two downwardly extending fingers 2016 may be evenly spaced 180 degrees apart from each other or directly opposite each other, etc.

[0255] In certain variations, the housing 1510 may include one or more guide members positioned within the cavity 2010 along the inner sidewall of the housing body 2002. For example, one or more ribs may extend along the length or a portion of the length of the inner sidewall of the housing body 2002 and may interface with corresponding outwardly facing members disposed along the length or a portion of the length of the ferrule 1520. The guide members may help maintain axial and rotational alignment of the ferrule 1520 within the housing body 2002.

[0256] The housing 1510 may also include features that align with and retain the locking member 1560 in a configurable configuration. For example, a first side opening 2022 formed through the sidewall of the housing body 2002 may be sized and shaped to retain the depressible member of the locking member 1560 therein. A pivot surface 2024 may be formed at a height above the first side opening 2022 and may provide a pivot surface for the locking member 1560. For example, the pivot surface 2024 may provide a point along which the locking member 1560 may pivot to release the locking member 1560 from engagement with the ferrule 1520. A second side opening 2026 may be formed through the sidewall of the housing body 2002 at a height above the pivot surface 2024. The second side opening 2026 may be sized and shaped to retain the pivot member of the locking member 1560 therein. A flexible contact member 2028 may be formed at a height above the second side opening 2026. The flexible contact member 2028 can be fixed at its proximal end to the sidewall of the housing body 2002. The distal end of the flexible contact member 2028 can be free from the sidewall of the housing body 2002 and can be configured to flex outward from the sidewall in response to an applied force. For example, the distal end of the flexible contact member 2028 can engage a portion of the pivot member of the locking member 1560. When the pivot member pivots outward along the pivot rod 2024, the flexible contact member 2028 flexes outward in response to the pivoting motion, but restricts the outward pivoting or flexing motion of the locking member 1560.

[0257] In certain variations, the housing 1510 may include features for connecting / interfacing with the base 1550 and / or for securing the base 1550. For example, one or more grooves or slots may be formed in one or more portions of the distal end of the housing body 2002 to receive a portion of a base sidewall of the base 1550, and / or one or more grooves or slots may be formed in the inner sidewall of the housing body 2002 to receive a corresponding one or more arms of the base 1550, as further described herein.

[0258] In some variations, housing 1510 may include or be coupled to an outer shell 1570. For example, outer shell 1570 may be a gripping member that may include a sheath or ring that slides around housing 1510 or is coupled to housing 1510 via a suitable mechanical fit (e.g., threads, an interference fit, etc.). In some variations, outer shell 1570 may be integrally formed with housing 1510 (e.g., overmolded) and / or housing 1510 may include one or more gripping features. In some variations, outer shell 1570 may include one or more features that enhance a user's ability to manipulate housing 1510. For example, outer shell 1570 may include one or more concave or otherwise recessed contours having finger-receiving surfaces to enhance manual grip. Additionally or alternatively, outer shell 1570 may include one or more convex textured features (ridges, ridges, ribs, rings, etc.) to increase friction. Additionally or alternatively, the outer shell 1570 may comprise one or more materials having greater friction (e.g., polysiloxane / silicone or other elastomers). In some variations, the outer shell 1570 is an elastomeric material that provides an environmental enclosure for the housing body 2002 and the components disposed therein (e.g., by substantially surrounding the housing body 2002). The outer shell 1570 may also control acoustics (e.g., reducing sounds generated by actuation of the applicator) and vibrations (e.g., dampening vibrations between the user and the applicator components generated by actuation of the applicator).

[0259] Figures 21A-21BVarious aspects of the locking member 1560 of the applicator 1500 for the analyte monitoring device 110 are depicted in front and rear perspective views, respectively. The movable locking member 1560 fits within a corresponding feature of the housing body 2002 and is aligned with and at least partially fits within the retaining wall 1712 formed on the outer sidewall of the ferrule 1520. For example, the outer periphery of the locking member 1560 at the rear surface can be an elongated member that fits within the retaining wall 1712 defined by the retaining lip 1714. The locking member 1560 includes a depressible member 2110, a pivot rod 2112, and a pivot member 2114 having a flat or substantially flat upper edge 2116. The depressible member 2110 can be in the form of a button or nub and can be configured to fit within and extend through the first side opening 2022 of the housing 1510. The size and shape of the depressible member 2110 generally allow a user to contact and depress the depressible member 2110. The pivot rod 2112 is a rod-shaped member that passes through the second side opening 2026 of the housing 1510 and extends along the pivot surface 2024. For example, the pivot rod 2112 is movably engaged with the pivot surface 2024 such that when the depressible member 2110 is pressed inward (e.g., depressed), the locking member 1560 pivots at the interface between the pivot rod 2112 and the pivot surface 2024. The pivoting movement of the locking member 1560 causes the pivot member 2114 to move outward. That is, when the depressible member 2110 is pressed or pushed inward in the first opening 2022, the pivot member 2114 moves outward from the second side opening 2026. The outward movement of the pivot member 2114 is controlled or limited by the flexible contact member 2028 of the housing 1510.

[0260] The pivot member 2114 has a flat or substantially flat upper edge 2116 that releasably engages the top edge of the retaining lip 1714 of the retaining wall 1712 that defines the cuff 1520. In the collapsed configuration of the applicator 1500, the locking member 1560 is positioned within the retaining wall 1712 such that the upper edge 2116 of the movable locking member 1560 engages below the top edge of the retaining lip 1714, thereby preventing the cuff 1520 from moving downwardly relative to the housing body 2002. When the locking member 1560 is depressed, vertical movement of the cuff 1520 is no longer impeded due to the outward movement of the pivot member 2114 away from the top edge of the retaining lip 1714.

[0261] Thus, locking member 1560 is engaged with ferrule 1520 in the first configuration and disengaged from ferrule 1520 in the second configuration. In some variations, movement of locking member 1560 from the first configuration to the second configuration releases ferrule 1520, thereby decoupling the proximal surface of base 1550 from housing body 2002, as further described herein.

[0262] In some variations, one locking member 1560 is provided. In some variations, two locking members 1560 are provided. The combination of the two locking members 1560 provides a locking system for the applicator 1500 that requires a deliberate and controlled user action (e.g., simultaneous or nearly simultaneous depression of both locking members 1560) to unlock the applicator 1500 and transition the applicator 1500 from the collapsed configuration to the expanded configuration for deployment of the analyte monitoring device 110.

[0263] Figures 22A-22G Depicted are aspects of a base 1550 for an applicator 1500 of an analyte monitoring device 110 according to some variations. Figures 22A-22G 15. The base 1550 is shown in a top perspective view, a top view, a bottom view, a first side view, a first side cross-sectional view, a second side view, and a second side cross-sectional view, respectively. Generally, the base 1550 provides an enclosed area for the analyte monitoring device 110 before a user is ready to apply the analyte monitoring device 110. The base 1550 is removably coupled to the housing body 2002 at the distal opening 2004. The base 1550 is held in place by releasable engagement between features of the base 1550, the ferrule 1520, and the housing body 2002, as further described herein. When the locking member 1560 is moved from the first configuration to the second configuration, the base 1550 is disengaged from its releasable engagement with the ferrule 1520 and the housing body 2002, and a removal force is subsequently applied to the base 1550 by the user. Release of locking member 1560 from engagement with the top edge of retaining lip 1714 of ferrule 1520 allows ferrule 1520 to translate vertically toward distal opening 2004 of housing body 2002. Movement of ferrule 1520 toward distal opening 2004 contacts and pushes base 1550 in the same direction.

[0264] As the ferrule 1520 is advanced downward, the transfer member 1540 moves to a position where the shoulder 2020 of the one or more downwardly extending fingers 2016 engages a shelf 1634 (e.g., at distal surface 1636) formed on the transfer member shaft 1630. The ferrule 1520 travels further downward until it is stopped by the protruding circumferential edge 1816 of the friction ring 1530 and the friction ring 1530 is locked into the ferrule 1520 by the flexible tabs 1812 engaging the bottom beam 1724. As the ferrule 1520 moves axially downward, further movement of the transfer member 1540 is stopped by the shoulder 2020 of the one or more downwardly extending fingers 2016. Simultaneously, further downward movement causes the base 1550 to be pushed further downward, such that the locking arms of the base 1550 prevent the base 1550 from being reattached, and the retaining arms of the base 1550 are in a position to cause the base 1550 to be released by the user applying a removal force to the base 1550. After the user applies a removal force to the base 1550, the applicator 1500 is in an extended configuration, wherein the components of the applicator 1500 are aligned with the analyte monitoring device 110 and are ready to apply the analyte monitoring device 110 when the housing 1510 is actuated.

[0265] In some variations, such as Figures 22A-22G As shown, the base 1550 has a proximal surface 2210, and a base sidewall 2212 extends upward from a portion of the proximal surface 2210. The proximal surface 2210 can have a substantially flat surface with a curved edge that abuts against the bottom edge of the housing body 2002 and / or the outer shell 1570 to form a sealed enclosure therebetween. In some variations, the base sidewall 2212 can extend continuously in a circular or substantially circular arrangement. In some variations, the base sidewall 2212 can be a separate and discrete component that together form a circular or substantially circular footprint. The upper edge of the base sidewall 2212 can fit into a corresponding groove formed in the bottom edge of the housing body 2002 so that when the applicator 1500 is in the retracted configuration, the base sidewall 2212 is surrounded by the housing body 2002.

[0266] The base 1550 can be configured to form a secure attachment to the microneedle capsule 500 connected to the analyte monitoring device 110. For example, the size and shape of the interior portion of the base 1550 can be determined so that the fixture 520 (of the microneedle capsule 500) can be assembled and / or contained within the interior portion. In some variations, the base 1550 includes a receiving area or compartment that provides an encapsulating enclosure for the microneedle capsule 500. When the microneedle capsule 500 and the substrate 330 of the analyte monitoring device 110 are attached to each other via the locking tabs 528 and the connecting member 332, the microneedle capsule 500 and the substrate 330 can be contained within the receiving area of ​​the base 1550. As further described herein, engagement can be performed between the external engagement features 526 of the microneedle capsule 500 and the fixture engagement features formed within the receiving area of ​​the base 1550.

[0267] Figure 22H Figure 22J Various aspects of the base 1550 and the microneedle enclosure 500 are depicted in exploded view, top perspective view, and side cross-sectional view, respectively, as described herein.

[0268] In some variations, the receiving area may include a capsule sidewall 2214 extending upward from a central region of the proximal surface 2210 within the interior of the base sidewall 2212. The capsule sidewall 2214 may form a perimeter around the periphery of, or interface with, the substrate 330 of the analyte monitoring device 110. Within the capsule sidewall 2214, the clamp engagement feature may include a plurality of upwardly extending flexible fingers 2216 and a plurality of walls 2217, each upwardly extending flexible finger having a chamfered or beveled edge, each wall engaging an external engagement feature 526 of the clamp 520. The upwardly extending flexible fingers 2216 bend outward to receive the microneedle capsule 500, the chamfered or beveled edges secure the microneedle capsule 500, and the walls 2217 limit rotational movement of the microneedle capsule 500. The flexible fingers 2216 may be arranged alternately with the walls 2217 , and the flexible fingers 2216 and walls 2217 may be positioned circumferentially around the inner perimeter of the enclosure sidewall 2214 such that the flexible fingers 2216 and walls 2217 form a footprint for the clamp 520 .

[0269] For example, the external engagement feature 526 of the clamp 520 may include an extension surface that extends orthogonally from a mid-region of the clamp 520 and terminates in a fin-like portion that extends orthogonally from the extension surface to or near the proximal end of the clamp 520, such as Figure 5E and 5FThe external engagement features 526 of the clamp 520 can be positioned circumferentially around the outer edge of the clamp 520, and each external engagement feature 526 (including the extended surface and the fin-like portion) can correspond to a corresponding flexible finger 2216 and wall 2217 of the base 1550. The extended surface of the clamp 520 can interface with the flexible fingers 2216 such that when pressure is applied therebetween, the extended surface is secured under the upper edge of the flexible fingers 2216 (e.g., the flexible fingers 2216 flex outward under pressure to allow the extended surface to snap fit under the chamfered or beveled upper edge of the flexible fingers 2216).

[0270] The rotational movement of the clamp 520 is limited or constrained due to the interface between the fin-shaped portion of the clamp 520 and the wall 2217. For example, the rotational movement of the clamp 520 stops when the fin-shaped portion of the clamp 520 contacts the wall 2217 of the base 1550. Since the clamp 520 has a rotatable connection with the connecting member 332 of the base 330 (as described above with reference to FIG. Figure 5E 、 5F 5G ), rotation of the clamp 520 while held within the clamp engagement features of the base 1550 can result in disengagement of the clamp 520 and the substrate 330. For example, by rotating the clamp 520 such that the clamp's locking tabs 528 disengage from the connector features 336 of the substrate 330, the microneedle capsule 500 (held within the base 1550 by the clamp engagement features (e.g., engagement of the flexible fingers 2216 and the extended surfaces of the clamp 520)) can be lifted off the substrate 330.

[0271] Thus, when the analyte monitoring device 110 having the microneedle capsule 500 is mounted within the base 1550, the microneedle array 140 of the analyte monitoring device 110 is contained within the sterile environment provided by the sheath 510 until the compressive engagement between the clamp 520 and the substrate 330 is released. In some variations, once the microneedle capsule 500 is attached to the base 1550 and the base 1550 is attached to the housing 1510, the rotational locking arrangement between the microneedle capsule 500 and the substrate 330 can be disengaged by, for example, a manufacturing operation that maintains engagement between the flexible fingers 2216 and the microneedle capsule 500. The microneedle array 140 is then retained within its sterile environment due to compression from the biasing elements 530, 1582, and 1584 until the base 1550 is released from the housing 1510. Disengagement of the base 1550 results in removal of the microneedle enclosure 500 along with the base 1550 , as the microneedle enclosure 500 is rotated out of the substrate 330 (by the previous manufacturing disengagement operation) and secured in the base 1550 by the snap attachment with the flexible fingers 2216 .

[0272] In some variations, the base 1550 includes arms that facilitate engagement and release between the base 1550, the ferrule 1520, and the housing body 2002. The base 1550 may include locking arms 2218 that extend from the proximal surface 2210 in an upwardly protruding configuration. The locking arms 2218 may be configured to flex or snap into locking retention grooves formed in the sidewalls of the housing body 2002 when the base 1550 is coupled to the housing body 2002. For example, during assembly of the applicator 1500, the locking arms 2218 may flex inwardly to allow the outwardly protruding surfaces of the locking arms 2218 to be positioned (e.g., snap into) the locking retention grooves and be biased radially outwardly. In the process of releasing the base 1550 as the base 1550 is pushed downward, the locking arm 2218 disengages (e.g., is pulled out) from the lock retaining groove and is pushed beyond a wall surface formed in the side wall of the housing body 2002 during the downward axial movement of the base 1550. Once the locking arm 2218 moves beyond the wall surface, the user is prevented from reattaching the base 1550 to the housing body 2002 because the wall surface prevents the locking arm 2218 from moving upward axially.

[0273] In some variations, the base 1550 may include more than one locking arm 2218, which may be circumferentially distributed and / or positioned in an equal or unequal manner around the proximal surface 2210. For example, Figure 22A As shown, the base 1550 includes four locking arms 2218 distributed around the proximal surface 2210.

[0274] In some variations, the locking arms 2218 may bend outwardly to allow the outwardly protruding surfaces of the locking arms 2218 to be positioned (eg, snapped into) the lock retention grooves and biased radially inwardly.

[0275] The base 1550 includes a retaining arm that releasably engages the base retaining surface of the ferrule 1520. When the applicator 1500 is in the collapsed configuration, the configuration / arrangement of the retaining arm with the base retaining surface of the ferrule 1520 and with the housing body 2002 prevents the base 1550 from being separated from its engagement with the ferrule 1520 and the housing body 2002. For example, the base 1550 may include a retaining arm 2220 that extends from the proximal surface 2210 in an upwardly protruding configuration. When the applicator 1500 is in the collapsed configuration, the retaining arm 2220 can be sandwiched between the outer side surface of the ferrule 1520 and the inner side surface of the housing body 2002. The inwardly protruding surface of the retaining arm 2220 can engage the base retaining surface 1730 of the ferrule 1520. This engagement or locking configuration prevents separation between the base 1550 and the housing body 2002. In releasing the base 1550, the base 1550 is pushed downwardly along with the ferrule 1520 and maintains engagement between the retaining arms 2220 and the base retaining surface 1730. With the engagement point beyond the housing body 2002, the base 1550 is in a configuration where it can be removed by a user-applied removal force.

[0276] In some variations, the base 1550 may include more than one retention arm 2220, and the releasable retention arms 2220 may be distributed circumferentially around the proximal surface 2210 in equal or unequal manner. Figure 22A As shown, the base 1550 includes four releasable retention arms 2220 distributed about the proximal surface 2210.

[0277] In some variations, the length of locking arm 2218 is greater than the length of retaining arm 2220. In some variations, the length of retaining arm 2220 is greater than the length of locking arm 2218. In some variations, the length of locking arm 2218 is equal to or approximately equal to the length of retaining arm 2220.

[0278] Figure 22K Various aspects of the applicator base 1550 are shown in a top perspective view engaged with the ferrule 1520. As shown, the ferrule 1520 includes a bottom flange 1732 having an increased surface area and a cutout 1734 formed therethrough for accommodating the arms of the base 1550 (e.g., the locking arm 2218 and the retaining arm 2220).

[0279] Figures 23A-23O Views of an applicator 1500 in assembled form are shown in cross-section and close-up, according to variations described herein. Figures 23A-23F Applicator 1500 is shown in a collapsed configuration. Figures 23G-23KThe applicator 1500 is shown in the process of releasing the base 1550 from engagement with the housing body 2002 to transition the applicator 1500 from the collapsed configuration to the expanded configuration. Figures 23L-23O The movement of the applicator 1500 from the extended configuration, in which the analyte monitoring device 110 is ready to be released, to the released configuration, in which the analyte monitoring device 110 is released from the applicator 1500, is shown sequentially. Figures 23A-23O 1. In some of the views of FIG. 1 , the analyte monitoring device 110 is shown. Where details of the analyte monitoring device 110 are not necessary for the particular aspect shown, the analyte monitoring device 110 may be omitted from the view. Figures 23A-23O 5. In some of the views, details of the microneedle enclosure 500 are shown, but omitted in other views where details of the microneedle enclosure 500 are not necessary for the particular aspect shown.

[0280] refer to Figures 23A-23F , the applicator 1500 is depicted in a collapsed configuration, wherein the components are locked (eg, fixed) relative to each other and the analyte monitoring device 110 cannot be deployed.

[0281] In the collapsed configuration, the friction ring 1530 is retracted within the ferrule 1520, and the locking member 1560 is engaged with the ferrule 1520. The second biasing element 1584 is located in the inner cavity 1632 defined by the transport shaft 1630 and is compressed to a first compressed state of the second biasing element 1584. The first biasing element 1582 is positioned within the cavity 2010 defined by the housing body 2002 and is compressed to a first compressed state of the first biasing element 1582. The shelf 1634 (e.g., distal surface 1636) of the transport shaft 1630 is positioned proximal to (e.g., with a gap therebetween) the shoulder 2020 of the downwardly extending finger 2016. The analyte monitoring device 110 is held by the transport 1540.

[0282] In the collapsed configuration of the applicator 1500, the locking tabs 528 of the microneedle enclosure and the connector features 336 of the substrate 330 are disengaged. The sterile seal provided by the microneedle enclosure 500 is maintained by the opposing forces of the microneedle enclosure biasing element 530 and the opposing forces of the first and second biasing elements 1582, 1584. Furthermore, when the analyte monitoring device 110 is held between these opposing forces, the analyte monitoring device 110 is able to move relative to the components of the applicator 1500. This movement allows the bumper 512 (e.g., a seal around the sheath 510) to reliably remain in contact with the analyte monitoring device, thereby maintaining sterility under vibration, temperature changes, and other environmental conditions.

[0283] like Figure 23AAs shown, the microneedle capsule 500 is contained within the base 1550 and connected to the analyte monitoring device 110. The external engagement features 526 of the microneedle capsule 500 are secured beneath the chamfered or beveled upper edge of the flexible fingers 2216 formed in the base 1550, thereby allowing the microneedle capsule 500 to be removed when the base 1550 is released from the housing body 2002. Figure 23A As shown, in the collapsed configuration, the transmission member 1540 and the distal edge of the ferrule 1520 are in a proximal-most position and are located proximal to the distal opening 2004 of the housing body 2002. In some variations of the collapsed configuration, the distal edge of the ferrule 1520 and the transmission member 1540 are located proximal to the distal opening 2004 of the housing body 2002.

[0284] refer to Figure 23B , provides a detailed view of the locking member 1560 mounted within the retaining wall 1712 formed on the outer sidewall of the ferrule 1520. The close-up view depicts the upper edge 2116 of the locking member 1560 engaging below the top edge of the retaining lip 1714 of the retaining wall 1712. This engagement between the locking member 1560 and the ferrule 1520 prevents the ferrule 1520 from moving downwardly relative to the housing body 2002. When the applicator 1500 is in the collapsed configuration, the engagement and locking features of the ferrule 1520 and friction ring 1530 are not connected to each other because the friction ring 1530 is retracted within the ferrule 1520.

[0285] like Figure 23C and 23D As shown, the configuration of the friction ring 1530 within the ferrule 1520 can prevent the transmission member 1540 from being triggered / fired in the collapsed configuration. This is because when the friction ring 1530 is collapsed within the ferrule 1520 and sandwiched between the ferrule 1520 and the mount 2014 of the housing 1510, the friction ring 1530 prevents the transmission member 1540 from vertically displacing toward the distal opening 2004; due to the position of the friction ring 1530, the downwardly extending fingers 2016 of the mount cannot flex a sufficient amount to allow vertical displacement of the transmission member 1540. In other words, when the applicator 1500 is in the collapsed configuration, the transmission member 1540 is locked in place due to the concentric arrangement of the mount 2014, friction ring 1530, and ferrule 1520.

[0286] Figure 23E and 23FVarious aspects of the base 1550 are depicted as being engaged with the housing body 2002 and the ferrule 1520 when the applicator 1500 is in the collapsed configuration. The upper edge of the base sidewall 2212 fits into a corresponding groove formed in the distal edge of the housing body 2002 such that the base sidewall 2212 is surrounded by the housing body 2002. The locking arms 2218 of the base 1550 fit into the locking retention grooves formed in the sidewalls of the housing body 2002, as shown. Figure 23E As shown in the close-up view of Figure 23F As shown in the close-up view of FIG, the retaining arms 2220 of the base 1550 are sandwiched between the outer side surface of the ferrule 1520 and the inner side surface of the housing body 2002. For example, the inwardly projecting surfaces of the retaining arms 2220 engage the base retaining surface 1730 of the ferrule 1520 to prevent separation between the base 1550 and the housing body 2002.

[0287] refer to Figures 23G-23K , illustrates aspects related to releasing the engagement of the base 1550 with the housing body 2002, transitioning the applicator 1500 from the retracted configuration to the extended configuration. When the locking members 1560 are depressed (e.g., when the depressible members 2110 are depressed inwardly to move from the first configuration to the second configuration), each locking member 1560 pivots at the interface between the pivot rod 2112 of the locking member 1560 and the pivot surface 2024 of the housing body 2002. This pivoting motion causes the pivot members 2114 of the locking members 1560 to move outward within the second side opening 2026, and the upper edges 2116 of the pivot members 2114 are no longer locked beneath the top edge of the retaining lip 1714 of the ferrule 1520. Thus, when the locking members 1560 are depressed, the vertical movement of the ferrule 1520 is no longer impeded due to the outward movement of the pivot members 2114 away from the top edge of the retaining lip 1714. In the expanded configuration of applicator 1500, the distal edge of ferrule 1520 is in a distal-most position and transmission member 1540 is in an intermediate position. In some variations of the expanded configuration, the distal edge of ferrule 1520 is distal to the distal opening 2004 of housing body 2002 and transmission member 1540 is proximal to the distal opening 2004 of housing body 2002. In some variations of the expanded configuration, the distal edge of ferrule 1520 is distal to the distal opening 2004 of housing body 2002 and transmission member 1540 is proximal to the distal opening 2004 of housing body 2002.

[0288] Figure 23G 17. Disengagement between the ferrule 1520 and the locking member 1560 is shown. The release of the locking member 1560 from engagement with the top edge of the retaining lip 1714 of the ferrule 1520 allows the ferrule 1520 to move vertically in a downward direction, as shown. Figure 23GThe downward movement of the ferrule 1520 pushes the base 1550 in the same downward direction (eg, at the proximal surface 2210). Figure 23G The close-up view in illustrative figures depicts the release of locking member 1560 from engagement with the top edge of retention lip 1714 of ferrule 1520 , and the outward movement of pivot member 2114 being limited by flexible contact member 2028 of housing body 2002 .

[0289] Figure 23H The details of the engagement between the ferrule 1520 and the friction ring 1530 are depicted. During the downward movement of the ferrule 1520, the ferrule 1520 moves axially, causing the friction ring 1530 to extend from the top surface of the ferrule 1520 and lock into the ferrule 1520. More specifically, the ferrule 1520 moves axially downward relative to the friction ring 1530 along the length of the flexible tab 1812. The flexible tab 1812 is bent or pushed inward until the ferrule 1520 passes the distal end of the flexible tab 1812, at which point the flexible tab 1812 snaps onto the bottom beam 1724 (and is retained between the pair of guide walls 1726, Figure 23H 1520). Further downward advancement of the ferrule 1520 is blocked by the protruding circumferential edge 1816 of the friction ring 1530, which provides an interface or engagement point with the underside 1728 of the ferrule 1520. The engagement between the ferrule 1520 and the friction ring 1530 prevents the ferrule 1520 from moving distally relative to the distal opening 2004 of the housing body 2002.

[0290] Figure 23I Detail of the microneedle capsule 500 is depicted with the base 1550 removed. The microneedle capsule 500 is removed along with the base 1550 due to the secure engagement of the external engagement features 526 of the clamp 520 with the upper edges of the flexible fingers 2216 formed in the base 1550. Figure 23I , depicts the interface between the extended surface (of the external engagement feature 526) and the flexible fingers 2216. As shown and described herein, the flexible fingers 2216 flex outward under pressure to allow the extended surface to snap fit and remain under the chamfered or beveled upper edge of the flexible fingers 2216. The axial displacement of the ferrule 1520 pushes the base 1550, and the microneedle package 500, which is fixed below the flexible fingers 2216, moves with the base 1550. This movement of the microneedle package 500 breaks the sterile seal between the sheath 510 and the microneedle array 140. Therefore, in the expanded configuration, the microneedle package 500 does not enclose / encapsulate the microneedle array 140.

[0291] Figure 23J and 23KDepicted are various aspects of the arms of the base 1550 as the base 1550 is pushed downward during the transition of the applicator 1500 to the expanded configuration. Figure 23J The locking arm 2218 is shown disengaged from the locking retaining groove of the housing body 2002. Figure 23J As shown in the close-up view of , when the locking arm 2218 is pushed beyond the locking retaining groove, the wall surface below the locking retaining groove blocks the upward axial movement of the locking arm 2218, preventing the user from reattaching the base 1550 to the shell body 2002. Figure 23K The engagement between the retaining arms 2220 and the base retaining surface 1730 is shown to be maintained as the base 1550 is pushed downwardly along with the ferrule 1520. When the engagement point is beyond the housing body 2002, the base 1550 is in a configuration in which the base 1550 can be removed by a user-applied removal force. For example, the user can grasp the base 1550 and pull it down, with the pulling force overcoming the engagement between the retaining arms 2220 and the base retaining surface 1730.

[0292] refer to Figures 23L-23O , illustrates aspects related to the applicator 1500 moving from an extended configuration to a released configuration. In the extended configuration, the components of the applicator 1500 are arranged and configured so that the analyte monitoring device 110 can be deployed (e.g., released) from the applicator 1500 in response to actuation of the housing 1510. The base 1550 is removed, and the transmission member 1540 is moved to a firing position in the extended configuration. In the released configuration, the analyte monitoring device 110 is released from the applicator 1500 and inserted into the user's skin.

[0293] During actuation of housing 1510, friction ring 1530 and ferrule 1520 act as a single component and are used to disengage analyte monitoring device 110 from transmission member 1540. Transmission member 1540 is axially aligned and nested within friction ring 1530. Figure 23L Detail of the transfer member 1540 is depicted positioned in an extended configuration. In the extended configuration, the mount 2014 is releasably engaged with the friction ring 1530, and the mount 2014 is releasably engaged with the transfer member 1540. In this configuration, the transfer member 1540 moves to a position in which the shoulder 2020 of the downwardly extending finger 2016 engages the shelf 1634 of the transfer member shaft 1630, and the shoulder 2018 of the downwardly extending finger 2016 engages the protrusion 1820 of the friction ring 1530, as shown. Figure 23L A close-up view of the .

[0294] Figure 23M 、 Figure 23N and Figure 23O Details of the applicator 1500 in the released configuration are shown in first, second and third cross-sectional views, respectively. Figure 23M 、 23N 230 depict the arrangement of applicator components when the applicator 1500 is in a released configuration, wherein the analyte monitoring device 110 is deployed from the transport 1540. Figure 23M 、 23N 23O, the second biasing element 1584 is less compressed because the energy stored in the second biasing element 1584 when loaded has been transferred to the transmission member 1540 to drive the analyte monitoring device 110 with an appropriate applied force. In the released configuration, the analyte monitoring device 110 is released from the transmission member 1540. In the released configuration, the distal edge of the cuff 1520 is in an intermediate position and the transmission member 1540 is in a distal-most position. In some variations of the released configuration, the distal edges of the cuff 1520 and the transmission member 1540 are both located distal to the distal opening 2004 of the housing body 2002. In some variations of the released configuration, the distal edge of the cuff 1520 is located distal to the distal opening 2004 of the housing body 2002 and the transmission member 1540 is located distal to the distal opening 2004 of the housing body 2002.

[0295] Figure 23M The details of the disengagement between the friction ring 1530 and the housing body 2002 are depicted. More specifically, as Figure 23M As shown in the close-up view of FIG, when the housing body 2002 is actuated (e.g., pushed downward), the protrusion 1820 of the friction ring 1530 decouples from the shoulder 2018 of the housing 1510. When the downward movement causes the decoupling between the friction ring 1530 and the downwardly extending fingers 2016 on which the shoulder 2018 is formed, the releasable coupling feature between the transfer member 1540 and the downwardly extending fingers 2016 is released. More specifically, the downward movement of the transfer member 1540 causes the shelf 1634 to push over the shoulder 2020 (e.g., the downwardly extending fingers 2016 bend away from the transfer member 1540). This bending or flexing is possible because the downwardly extending fingers 2016 are no longer restrained or blocked by the protrusion 1820. Furthermore, during actuation of housing body 2002 , as housing body 2002 moves downwardly relative to ferrule 1520 and friction ring 1530 , the ring retention slot formed in the outwardly facing sidewall of downwardly extending fingers 2016 slides in a distal direction along protrusion 1820 .

[0296] Figure 23N and Figure 23ODetail is depicted of a track 1716 formed along the ferrule 1520 through which one or more tracking protrusions 1616 on the transfer member 1540 travel during actuation of the housing body 2002. Each track 1716 terminates at a distal end in a transfer member curved surface 1718, wherein the transfer member curved surface 1718 acts as a stop for axial movement of the transfer member 1540 to assist in flexing the flexible blades 1612 of the transfer member 1540 radially outward, as shown. Figure 23O As shown in a close-up view of FIG. , the analyte monitoring device 110 is released from the transmission member 1540 as the flexible blades 1612 bend radially outward. When the second biasing element 1584 is compressed in the inner cavity 1632 of the transmission member 1540, the second biasing element 1584 provides external pressure for the radial outward bending. The transmission member curved surface 1718 of the sleeve 1520 blocks the axial movement of the transmission member 1540, and the energy stored in the second biasing element 1584 is transferred to the transmission member 1540, thereby causing the flexible blades 1612 to bend radially outward, thereby pushing the analyte monitoring device 110 out with a suitable force (e.g., for appropriately inserting the microneedle array 140 into the user's skin). When the microneedle array 140 is inserted into the user's skin, the adhesive layer (e.g., the outer adhesive layer 344) adheres the analyte monitoring device 110 to the user's skin. The analyte monitoring device 110 can be removed by applying sufficient force to overcome the adhesive layer.

[0297] Figure 24 A process flow chart P2400 is shown, including a process of moving the applicator 1500 from a collapsed configuration to an extended configuration to move the analyte monitoring device 110 to a ready-to-release position. The process proceeds sequentially along the left side of the process flow chart from S2410 to S2420 to S2430 to S2440 and to S2450. The aspects connected by dashed lines and dashed boxes depict different states and configurations of the applicator components after each process step. The order in which the different states and configurations appear can vary and is not limited to Figure 24 in the order shown.

[0298] At S2410 , the locking member 1560 is depressed (eg, moved from the first configuration to the second configuration). The depression of the locking member 1560 includes disengagement of the locking member 1560 from the ferrule 1520 .

[0299] At S2420, the ferrule 1520 is axially displaced toward the distal end 2004 of the housing body 2002. This axial displacement of the ferrule 1520 results in engagement between the ferrule 1520 and the friction ring 1530. Specifically, the flexible tabs of the friction ring 1530 snap onto the base of the ferrule 1520, and the protruding edge of the friction ring 1530 engages the underside of the proximal end of the ferrule 1520. Additionally, the first biasing element 1582 is moved from its first compressed state to a first biasing element second compressed state that is less than the first compressed state.

[0300] At S2430, as the ferrule 1520 pushes against the proximal surface 2210 of the base, the base 1550 is axially displaced. The axial displacement of the base 1550 causes the sterile seal provided by the microneedle package 500 to be broken. The axial displacement of the base 1550 further causes the locking arm of the base 1550 to disengage from the locking groove of the housing body 2002.

[0301] At S2440, the transport member 1540 is dropped into the firing position. In the firing position, the transport member 1540 is configured to fire or propel the analyte monitoring device 110 for insertion into the user's skin. When the transport member 1540 is dropped into the firing position, the shoulder 2020 of the downwardly extending finger engages the shelf 1634 of the transport member shaft. The second biasing element 1584 moves from its first compressed state to a second compressed state of the second biasing element, which is slightly less than its first compressed state due to the axial movement of the transport member 1540 into the firing position.

[0302] At S2450, the base 1550 is pulled down. The user can pull down the base 1550 by applying appropriate force. At this point, the applicator 1500 is in the extended configuration.

[0303] Figure 25 A process flow chart P2500 is shown, including a process for moving the applicator 1500 from an extended configuration to a released configuration for inserting an analyte monitoring device. The process proceeds sequentially along the left side of the process flow chart from S2510 to S2520 to S2530 and S2540. The aspects connected by dashed lines and dashed boxes depict different states and configurations of the applicator components after each process step. The order in which the different states and configurations appear can vary and is not limited to Figure 25 in the order shown.

[0304] At S2510, the applicator 1500 in the expanded configuration is placed on the user. The distal end of the cuff 1520 contacts the human skin at the insertion site where the applicator 1500 is placed.

[0305] At S2520, the housing body 2002 is actuated (e.g., pushed downward for axial displacement). This actuation causes a gap or separation between the protrusion 1820 of the friction ring 1530 and the shoulder 2018 formed on the downwardly extending finger 2016. Due to the connection within the cavity 2010 of the housing body 2002, the axial displacement of the downwardly extending finger 2016 causes the separation. The shelf 1634 of the conveyor shaft pushes over the shoulder 2020 of the downwardly extending finger. This actuation further causes the first biasing element 1582 to move to a third compressed state of the first biasing element, which is greater than its second compressed state. In addition to the movement and / or change of the applicator component during actuation, the actuation also causes the human skin within the area defined by the distal edge of the cuff 1520 to bulge.

[0306] At step S2530, the transmission member 1540 is axially displaced toward the distal opening 2004 of the housing body 2002. The second biasing element 1584 is moved to a third compression state of the second biasing element, which is less than its second compression state. The axial displacement of the transmission member 1540 causes the microneedle array 140 to contact the human skin and be inserted into the insertion site. The continued axial displacement of the transmission member 1540 causes the adhesive to adhere to the human skin at the insertion site.

[0307] At S2540, tracking protrusions on the conveyor 1540 engage the conveyor curved surface of the ferrule 1520. The engagement between the tracking protrusions and the conveyor curved surface causes the flexible leaves of the conveyor 1540 to splay or bend radially outward, thereby releasing the analyte monitoring device.

[0308] Figure 26A and Figure 26B Various aspects of the conveyor locking mechanism are shown in cross-sectional and close-up views. As shown, a shelf 1634 formed on the conveyor shaft 1630 includes a distal surface 1636 and a proximal surface 1638. In some variations, the proximal surface 1638 of the shelf 1634 can be used as a conveyor locking feature. Figure 26A The applicator 1500 is shown in an extended configuration, wherein the distal surface 1636 of the shelf 1634 of the delivery member shaft 1630 engages the shoulder 2020 of the downwardly extending finger 2016 to control movement of the delivery member 1540 toward the distal opening 2004 of the housing body 2002 .

[0309] Figure 26B2002. The diagram shows how the proximal surface 1638 of the shelf 1634 prevents the transport member 1540 from axially moving toward the proximal end of the housing body 2002. Axial movement toward the proximal end is prevented after the distal surface 1636 of the shelf 1634 and the transport member retaining surface (e.g., shoulder 2020) are disengaged. The proximal surface 1638 abuts the distal end of the shoulder 2020, thereby preventing the transport member 1540 from axially moving toward the proximal end of the housing body 2002. The distal end of the transport member retaining surface can be a flat or substantially flat surface to prevent the proximal surface 1638 from pushing past the transport member retaining surface.

[0310] As described above, the analyte monitoring device may include a housing. The housing may at least partially surround or enclose other components (e.g., electronic components) of the analyte monitoring device, for example, to protect these components. For example, the housing may be configured to help prevent dust and moisture from entering the analyte monitoring device. In some variations, an adhesive layer may be attached to the housing to the surface (e.g., skin) of the user while allowing the microneedle array to extend outward from the housing and into the user's skin. In addition, in some variations, the housing may typically include rounded edges or corners and / or a low profile to prevent damage and reduce interference with clothing, etc., worn by the user.

[0311] For example, Figures 27A-27E As shown, an example variation of the analyte monitoring device 300 may include a housing 310 configured to at least partially surround various other internal components of the device 300 and a microneedle array 331 extending outwardly from a skin-facing surface (e.g., an underside) of the housing 310.

[0312] For example, the housing 310 may include one or more rigid or semi-rigid protective shell components that may be coupled together by suitable fasteners (e.g., mechanical fasteners), mechanical interlocking or mating features, and / or engineered fits. Figure 27E As shown, the housing can include a housing cover 310a and a housing base 310b, wherein the cover 310a and the base 310b can be secured together with one or more threaded fasteners (e.g., fasteners that engage threaded holes in the upper and / or lower housing portions). The cover 310a and the base 310b can include rounded / radiused edges and corners, and / or other damage-resistant features. When coupled together, the cover 310a and the base 310b can form an interior volume that houses other internal components, such as a device printed circuit board 351 (PCB), a sensor assembly 321, and / or other components, such as a gasket 312. For example, the internal components arranged in the interior volume can be arranged in a compact, low-profile stack, such as Figure 27E As shown. Although Figure 27EThe housing 310 is shown as comprising multiple housing components, but in some variations, the housing 310 may comprise a single component defining an interior volume for housing internal device components. In some embodiments, the housing 310 may be filled with a suitable potting compound (e.g., epoxy) to reduce harmful environmental influences such as temperature, humidity, pressure, and light.

[0313] Additionally, the analyte monitoring device 300 may include an adhesive layer 340 configured to attach the housing 310 to a surface (e.g., skin) of a user. The adhesive layer 340 may be attached to the skin-facing side of the housing 310, for example, via a double-sided adhesive liner 345. Figure 27D Alternatively, adhesive layer 340 may be coupled directly to the skin-facing side of housing 310 using one or more suitable fasteners (e.g., adhesives, mechanical fasteners, etc.). Adhesive layer 340 may be protected by a release liner that is removed by the user prior to application to the skin to expose the adhesive. In some variations, the analyte monitoring device may include a removable Obtained 1504XL TM Double-sided adhesive and 4076 TM Skin-Facing Adhesives: These materials were chosen for their: breathability, abrasion resistance, mean water vapor transmission rate (MWVTR), biocompatibility, compatibility with sensor sterilization methods / strategies, appearance, durability, adhesion, and ability to maintain said adhesion while the sensor is worn.

[0314] In some variations, the perimeter of the adhesive layer 340 may extend further than the perimeter or outer periphery of the housing 310 (e.g., to increase the surface area for attachment, improve retention stability, or improve attachment to the user's skin). Additionally, in some variations, the adhesive layer 340 may include openings 342 that allow the outwardly extending microneedle array 331 to pass through. The openings 342 may closely / immediately circumscribe / define the shape of the microneedle array 331, such as Figure 27C as shown (e.g., a square opening that closely corresponds in size and shape to the square microneedle array), or has another suitable size and shape that is larger than the coverage area of ​​the microneedle array (e.g., a circular opening that is larger than the square microneedle array).

[0315] although Figures 27A-27E The housing 310 is shown as being hexagonal and generally prismatic, but it will be appreciated that in other variations, the housing 310 may be any suitable shape. For example, in other variations, the housing may be generally prismatic and have a base that is oval (e.g., circular), triangular, rectangular, pentagonal, or other suitable shape. As another example, Figures 28A-28CAn example variation of an analyte monitoring device 400 is shown that includes a dome-shaped housing 411. Figures 28A-28C The dome-shaped housing 411 shown in FIG. 4 is generally circular, but in other variations, the dome-shaped housing may have a base having another suitable oval or polygonal shape.

[0316] Similar to housing 310, housing 411 may include an interior volume configured to at least partially surround other components of analyte monitoring device 400. For example, Figure 28D As shown in the cross-sectional view of , the housing 411 may include a dome-shaped cover 411a coupled to a base 411b to form an interior volume in which the device PCB 451 and the sensor assembly having the microneedle array 431 may be disposed. In addition, the housing 411 may be configured to be coupled to a surface via an adhesive layer 440, and the microneedle array 431 may extend outward from the housing and beyond the adhesive layer 440. In addition, as shown Figure 28D and 28E As shown, adhesive layer 440 may extend beyond the outer perimeter of housing 411 .

[0317] In some variations, the analyte monitoring system may provide user status, analyte monitoring device status, and / or other appropriate information directly on the analyte monitoring device via a user interface (e.g., a display, indicator light, etc., as described below). Thus, compared to analyte monitoring systems that can only transmit information to a separate peripheral device (e.g., a mobile phone, etc.) that in turn conveys the information to the user, in some variations, such information may be provided directly by the analyte monitoring device. Advantageously, in some variations, such a user interface on the analyte monitoring device may reduce the need for the user to continuously maintain a separate peripheral device (which may be impractical due to cost, inconvenience, etc.) in order to monitor the user status and / or analyte monitoring device status. In addition, the user interface on the analyte monitoring device may reduce the risk associated with loss of communication between the analyte monitoring device and the separate peripheral device, such as the user having an inaccurate understanding of their current analyte level (e.g., causing the user to believe that their analyte level is high when in fact their analyte level is low, which may, for example, cause the user to self-administer an inaccurate dose of medication or cause the user to refuse a therapeutic intervention when medically necessary).

[0318] Furthermore, the ability to convey information to a user via the analyte monitoring device itself without reliance on a separate peripheral device may reduce or eliminate the need to maintain compatibility between the analyte monitoring device and such peripheral devices when the separate peripheral devices are upgraded (e.g., replaced with a new device model or other hardware, running a new version of an operating system or other software, etc.).

[0319] Thus, in some variations, the housing may include a user interface, such as an interface that provides information in a visual, auditory, and / or tactile manner to provide information about the user state and / or the analyte monitoring device state, and / or other suitable information. Examples of user states that can be conveyed via the user interface include information representing an analyte measurement in the user (e.g., below a predetermined target analyte measurement value threshold or range, within a predetermined target analyte measurement value range, above a predetermined target analyte measurement value threshold or range, an increase or decrease in the analyte measurement value over time, a rate of change of the analyte measurement value, other information related to the trend of the analyte measurement value, other suitable alarms associated with the analyte measurement value, etc.). Examples of analyte monitoring device states that can be conveyed via the user interface include device operating modes (e.g., associated with device preheating state, analyte monitoring state, battery power state such as low power, etc.), device error states (e.g., operating errors, pressure-induced sensing attenuation, faults, failure modes, etc.), device power states, device life states (e.g., expected sensor life end), connection states between the device and the mobile computing device, etc.

[0320] Figure 29 Another example variation of a microneedle 900 is shown, which has a generally cylindrical body portion. Except as described below, microneedle 900 can be similar to microneedle 700 as described above. For example, similar to microneedle 700, microneedle 900 can include a cylindrical body portion 912 and a tapered distal portion 914 terminating in an insulated distal apex 916. Microneedle 900 can also include a ring electrode 920 that includes a conductive material and is disposed on the tapered distal portion 914 at a position proximal to (or offset from or spaced apart from) the distal apex 916. Other elements of microneedle 900 have similar reference numerals to corresponding elements of microneedle 700.

[0321] However, compared to microneedle 700, microneedle 900 may have a sharper tip at distal apex 916 and an improved insulating protective sheath 913. For example, distal apex 916 may have a sharper apex angle (e.g., an apex angle of about 25 degrees to about 45 degrees) and a apex radius of less than about 100 nanometers, which provides a sharper microneedle profile that can penetrate the skin more easily, at a lower speed, with less energy, and / or with less trauma. In addition, compared to insulating protective sheath 713 (e.g., Figure 33A28 , which extends through substrate 702 and along the height of microneedle body portion 712), the improved insulating protective sleeve 913 can extend only through substrate 902, so that the sandwich structure filling the groove (e.g., as produced by DRIE as described above) only forms a buried feature in the substrate. Although the sidewalls of microneedle 900 are shown in FIG. 28 as extending generally orthogonal to the substrate surface, it should be understood that because the improved insulating protective sleeve 913 need not extend the entire height of the microneedle body portion 712, in some variations, the sidewalls of microneedle 900 can be at a non-orthogonal angle relative to the substrate (e.g., the sidewalls can have a slight positive taper of about 1 degree to about 10 degrees, or about 5 degrees to about 10 degrees).

[0322] In some variations, the remainder of the microneedle surface 900 (excluding the ring electrode 920) may include insulating material extending from the base insulator 904. For example, a layer of insulating material (e.g., SiO2) may extend from the front surface of the base 902 to provide the body portion insulator 918 and may further extend upward onto the proximal edge of the electrode 920, as shown. Figure 29 As shown. Another region of insulating material can similarly cover the distal edge of electrode 920 and insulate distal apex 916. This region of insulating material and / or a modified insulating protective sheath 913 can help prevent electrical contact between conductive core 940 and surrounding substrate 902. Thus, similar to microneedles 700, microneedles 900 can remain electrically isolated for individual addressing within a microneedle array. In some variations, the process for forming microneedles 900 can result in higher yields and / or provide lower production costs than the process for forming microneedles 700.

[0323] Microneedle 900 may have any suitable dimensions. For example, in some variations, microneedle 900 may comprise a height of about 400 μm to about 600 μm, or about 500 μm. In some variations, tapered distal portion 914 may have a tip angle of about 25 degrees to about 45 degrees, with a tip radius of less than about 100 nm. Furthermore, the microneedle may have a shaft diameter of about 160 μm to about 200 μm. Figure 30 Various other sizes are shown for exemplary variations of cylindrical microneedles having tapered distal portions and ring electrodes similar to microneedle 900 described above.

[0324] Although Figures 31A-31C Exemplary variations of microneedle array configurations are illustrated, but it should be understood that these figures are not limiting and that other microneedle configurations (including different numbers and / or distributions of working electrodes, counter electrodes, and reference electrodes, and different numbers and / or distributions of active and inactive electrodes, etc.) may be suitable for other variations of microneedle arrays.

[0325] As shown in FIG. 1 , the analyte monitoring device 110 Figure 2AAs shown schematically, the electronic system 120 can be integrated within the housing 112, so that the electronic system 120 can be combined with the sensing element (e.g., the microneedle array) as part of a single unit, in contrast to conventional CGM systems that typically integrate components into multiple physically distinct units. Further details of example variations of the electronic system 120 are described below.

[0326] In some variations, an analyte monitoring device may include one or more printed circuit boards (PCBs). For example, an analyte monitoring device may include at least one PCB in a sensor assembly 321 including a microneedle array, such as a microneedle array, and at least one device PCB 351. Figure 27E shown.

[0327] For example, Figures 27F-27I As shown, the sensor assembly 321 may include a sensor support printed circuit board (PCB) 322 coupled to a connecting printed circuit board (PCB) 324. The microneedle array 331 may be attached to the sensor support PCB 322 (e.g., FR-4, PTFE, Rogers 4350B), such as by a soldering process combined with an epoxy underfill for mechanical strength. In some variations, an epoxy skirt may be deposited along the edge of the silicon microneedle array 331 to mitigate the sharp edges during the silicon cutting process described above. The epoxy may also provide a transition from the silicon substrate edge of the microneedle array silicon to the edge of the PCB 322. Alternatively, such epoxy may be replaced or supplemented by a rubber gasket or the like.

[0328] like Figure 27J As shown, the sensor holder PCB 322 can serve as a holder that at least partially determines the desired distance that the microneedle array 331 extends from the housing 310. Therefore, the holder height of the sensor holder PCB 322 can be selected to help ensure that the microneedle array 331 is properly inserted into the user's skin. During the needle insertion process, the bottom surface of the housing 310 will act as a stop for the needle insertion. If the sensor holder PCB 322 has a reduced height and its lower surface is flush or nearly flush with the bottom surface of the housing, the housing 310 will prevent the microneedle array 331 from fully inserting into the skin. However, increasing the holder height may result in greater pressure of the microneedle array against the skin during microneedle insertion, which may cause skin irritation and / or erythema (redness of the skin).

[0329] The sensor support PCB 322 may be secured to the housing 310 and / or within a stack within the housing, for example, using suitable fasteners or the like. Figures 27H-27JAs shown, the sensor support PCB 322 (having the microneedle array 331) can be coupled to a first side of the connection PCB 324, while the opposite second side of the connection PCB 324 can be coupled to the interposer PCB connector 326. Figure 27J As shown, interposer PCB connector 326 can be communicatively coupled to device PCB 351, for example, for signal processing as described below. Thus, signals from microneedle array 331 can pass through sensor support PCB 322 and be transmitted to device PCB via sensor support PCB 322, connection PCB 324, and interposer PCB connector 326. However, in some variations, the analyte monitoring device may include fewer PCBs. For example, in some variations, sensor assembly 321 may eliminate sensor support PCB 322 so that microneedle array 331 can be directly electrically connected to connection PCB 324 (or directly electrically connected to device PCB 351).

[0330] Additionally or alternatively, in some variations, at least one printed circuit board in sensor assembly 321 may include or be coupled to one or more additional sensors in conjunction with microneedle array 331. For example, sensor assembly 321 may include a temperature sensor (e.g., a thermistor, a resistance temperature detector, a thermocouple, a bandgap reference, a non-contact temperature sensor, etc.). In some variations, temperature measurements may additionally or alternatively be performed by one or more analyte-insensitive electrodes in the microneedle array.

[0331] In some variations, the thickness of the sensor holder PCB 322 may be from about 0.05 inches to about 0.15 inches, or from about 0.093 inches to about 0.127 inches. In some variations, the sensor holder PCB 322 may include one or more conductive through-substrate vias configured to route / conduct electrical signals from the front surface of the PCB to the rear surface of the PCB. In some variations, the sensor holder PCB 322 may include a semiconductor (e.g., silicon) having conductive through-substrate vias configured to route / conduct electrical signals from the front surface of the semiconductor to the rear surface of the semiconductor. In other variations, the microneedle array 331 may be mounted directly to the PCB 324 without the sensor holder PCB 322.

[0332] In some variations, the electronic system of the analyte monitoring device may include an analog front end. The analog front end may include sensor circuitry (e.g., Figure 2A1 (a) a sensor circuit 124 shown in FIG. 1 ), which converts the analog current measurement into a digital value that can be processed by the microcontroller. For example, the analog front end can include a programmable analog front end suitable for an electrochemical sensor. For example, the analog front end can include the MAX30131, MAX30132, or MAX30134 components available from Maxim Integrated (San Jose, CA) (which have 1, 2, and 4 channels, respectively), which are ultra-low power programmable analog front ends for electrochemical sensors. The analog front end can also include the AD5940 or AD5941 devices available from Analog Devices (Norwood, MA), which are high-precision impedance and electrochemical front ends. Similarly, the analog front end can also include the LMP91000 available from Texas Instruments (Dallas, TX), which is a configurable analog front end regulator for low-power chemical sensing applications. The analog front end can provide biasing and a complete measurement path, including an analog-to-digital converter (ADC). Ultra-low power allows for continuous biasing of the sensor to maintain accuracy and fast response when measurements are required over long periods of time (e.g., 7 days) using body-worn battery-powered devices.

[0333] In some variations, the analog front-end device is compatible with two-terminal and three-terminal electrochemical sensors, for example, enabling DC current measurement, AC current measurement, and electrochemical impedance spectroscopy (EIS) measurement capabilities. Furthermore, the analog front-end can include an internal temperature sensor and a programmable voltage reference, support external temperature monitoring and an external voltage reference, and integrate voltage monitoring of bias and supply voltages to ensure safety and regulatory compliance.

[0334] In some variations, the analog front end may include a multi-channel regulator to multiplex sensor inputs and process multiple signal channels. For example, the analog front end may include a multi-channel regulator, such as the multi-channel regulator described in U.S. Patent No. 9,933,387, the entire contents of which are incorporated herein by reference.

[0335] In some variations, the analog front end and peripheral electronics may be integrated into an application specific integrated circuit (ASIC), which may, for example, help reduce costs. In some variations, this integrated solution may include a microcontroller as described below.

[0336] In some variations, the electronic system of the analyte monitoring device may include at least one microcontroller (e.g., Figure 2AController 122 shown). The microcontroller may include, for example, a processor with integrated flash memory. In some variations, the microcontroller in the analyte monitoring device may be configured to perform analysis to correlate sensor signals with analyte measurements (e.g., glucose measurements). For example, the microcontroller may execute programmed routines in firmware to interpret digital signals (e.g., from an analog front end), perform any relevant algorithms and / or other analysis, and route the processed data to and / or from the communication module. Keeping the analysis on the analyte monitoring device can, for example, enable the analyte monitoring device to broadcast / transmit analyte measurements to multiple devices (e.g., mobile computing devices such as smart phones or smart watches, therapeutic delivery systems such as insulin pens or pumps, etc.) in parallel while ensuring that each connected device has the same information.

[0337] In some variations, the electronic system of an analyte monitoring device may include at least one communication module (e.g., Figure 2AThe communication module 126 shown is a wireless communication module that communicates with one or more devices. For example, the communication module may include a wireless transceiver integrated into the microcontroller device. However, the electronic system may additionally or alternatively include a communication module separate from the microcontroller device. In some variations, the communication module can communicate via a wireless network (e.g., via Bluetooth, NFC, WiFi, RFID, or any type of data transmission method that is not connected via a cable). For example, devices can communicate directly with each other in a paired connection (1:1 relationship, i.e., unicast transmission) or in a hub-and-spoke or broadcast connection ("one to many" or 1:m relationship, i.e., multicast transmission). As another example, devices can communicate with each other via a mesh network connection (e.g., "many to many", or m:m relationship, or ad-hoc), such as via a Bluetooth mesh network. Wireless communication can use any of a variety of communication standards, protocols and technologies, including but not limited to Global System for Mobile Communications (GSM), Enhanced Data GSM Environment (EDGE), High Speed ​​Downlink Packet Access (HSDPA), High Speed ​​Uplink Packet Access (HSUPA), Evolution, Data-Only (EV-DO), HSPA, HSPA+, Dual Cell HSPA (DC-HSPDA), Long Term Evolution (LTE), Near Field Communication (NFC), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TDMA), Bluetooth, Wireless Fidelity (WiFi) (e.g., IEEE 802.11a, IEEE 802.11b, IEEE 802.11g, IEEE 802.11n, etc.), or any other suitable communication protocol. Some wireless network deployments may combine networks from multiple cellular networks, or use a mix of cellular, Wi-Fi and satellite communications. In an example variation, the communication module may include a wireless transceiver integrated into a microcontroller and include a Bluetooth low energy compatible radio that complies with the Bluetooth Special Interest Group 5.0 specification.

[0338] The communication module may also include or be coupled to one or more antennas (e.g., Figure 2A 128). For example, the electronic system may include a chip antenna mounted on a PCB, or an antenna implemented directly on the PCB, which may provide better range while reducing cost and complexity. In some variations, a user wearing the analyte monitoring device 110 may act as the antenna (e.g., antenna 128). For example, the antenna input / output portion 128 of the communication module 126 may be electrically connected to a single microneedle or multiple microneedles (e.g., similar to a microneedle) inserted into the wearer's skin. Figure 2B140). This can increase the effective cross-sectional area of ​​the antenna, provide adequate impedance matching between the antenna input / output of the communication module and free space, and / or help improve operating metrics such as antenna gain, antenna diversity, omnidirectionality, and communication module receiver sensitivity / transmitter efficiency.

[0339] Devices can move in and out of range of the communication module to connect and reconnect, enabling users to seamlessly connect and transfer information between devices. In some variations, the microcontroller on each analyte monitoring device may have a unique serial number, which enables tracking of a specific analyte monitoring device during production and / or field use.

[0340] As described above, in some variations, the analyte monitoring device may include one or more sensors in addition to the microneedle array. For example, the analyte monitoring device may include one or more temperature sensors configured to measure skin temperature, thereby enabling temperature compensation of the analyte sensor. For example, in some variations, a temperature sensor (e.g., a thermistor, an RTD, a semiconductor junction, a bimetallic sensor, a thermopile sensor) may be coupled to a device PCB within the housing such that the temperature sensor is disposed near the skin-facing portion or bottom of the housing 112. The housing may be thinned to reduce thermal resistance and improve heat transfer, thereby improving measurement accuracy. Additionally or alternatively, a thermally conductive material may thermally couple the surface-mounted temperature sensor to the user's skin. In variations in which the temperature sensor is coupled to the device PCB near the base of the microneedle array carrier sheet, the thermally conductive material may, for example, be molded into a skirt to mitigate the sharp edges of the carrier sheet and wrapped along the edges of the carrier sheet and along the surface of the main PCB.

[0341] In some variations, the temperature sensor can be used to develop a glucose interpolation characteristic based on the measured current and a priori sensitivity (e.g., nA / mM or pA / mg / dL). Under constant temperature conditions, the current characteristic can be modeled by the following relationship: G [G], where y is the measured current, m G is the glucose sensitivity, and [G] is the interpolated glucose concentration. In some cases, such as introducing a channel b that is insensitive to the analyte, a background signal can be introduced into the above equation: y = mG [G] + b. Introducing the measurement value from the temperature sensor, the current characteristic can be expressed by the following relationship: y = m G [G]+m T [T] + b, where m Tis the temperature sensitivity (e.g., pA / °C), T is the measured temperature, and b is the background signal (e.g., pA). In other operating situations, the current characteristic is modeled by the following relationship: y = m1[G][T] + b, where m1 is a weighting factor determined a priori. In other operating scenarios, the current characteristic can be modeled as the convolution of temperature and glucose: y = {m T [T] + m2} [G] + b, where m2 is a weighting factor determined a priori. In other operating conditions, the current characteristic is provided by the following relationship: y = {m G [G] + m2} [T] [G] + b. In other operating conditions, the current characteristic is given by the following nonlinear relationship: y = {m G2 [G] 2 +m G [G]}[T]+b, where m G2 is a nonlinear weighting factor. In other operating conditions, the current characteristic is given by the following Gaussian relationship: y = m G [G]exp{-([T]-[T OPT ]) 2 / (2σ 2 )}+b, where T OPT is the optimum temperature of the enzyme for maximum catalytic turnover, and σ is the operating temperature range of the enzyme.

[0342] In some variations, the analyte monitoring device may include at least one microneedle whose electrodes are configured to function as an analyte-insensitive channel (e.g., a glucose-insensitive channel) with a known temperature sensitivity, where such known temperature sensitivity can be used to compensate for temperature. For example, one advantage of using a glucose-insensitive channel includes proximity to a glucose sensor (e.g., resulting in smaller errors from thermal gradients) and cost (e.g., by reducing external components and reducing specialized processes for thermally coupling the sensor to the skin). In some variations, the analyte monitoring device may include an analyte-insensitive channel as well as a thermistor, with an algorithm that utilizes information from both. Additionally or alternatively, the analyte monitoring device may include an additional sensor that measures ambient temperature, which may also be used in the temperature compensation algorithm.

[0343] In some variations, the analyte-insensitive channel can be used to make differential measurements and / or subtract background noise levels from the analyte-sensitive channel to improve signal fidelity and / or signal-to-noise ratio. The analyte-insensitive channel may be sensitive to common-mode signals that also appear on the analyte-sensitive channel (e.g., endogenous and pharmacological interferences, pressure decay, etc.).

[0344] Additionally or alternatively, in some variations, the analyte monitoring device may include at least one kinetic sensor / motion sensor. The motion sensor may, for example, include an accelerometer, a gyroscope, and / or an inertial measurement unit to capture position, displacement, trajectory, speed, acceleration, and / or device orientation values. For example, such measurements may be used to infer the wearer's physical activity (e.g., number of steps, strenuous exercise) over a limited duration. Additionally or alternatively, in some variations, a motion sensor may be used to detect the wearer's interaction (e.g., touching or tapping) with the analyte monitoring device. For example, touch or tap detection may be used to mute or pause notifications, warnings, and alarms, control wirelessly connected mobile computing devices, or enable / disable the user interface (e.g., embedded display or indicator light) on the analyte monitoring device. Touch or tap can be performed in a defined order and / or predetermined duration (e.g., at least 3 seconds, at least 5 seconds) to trigger certain actions (e.g., display or indicator light deactivation / activation). Additionally or alternatively, in some embodiments, the analyte monitoring device may enter a power save mode when limited motion or activity (e.g., no significant acceleration) is detected for at least a predetermined time period (e.g., 15 minutes, 30 minutes, 45 minutes, 1 hour, or other suitable time) as measured by a motion sensor.

[0345] Additionally or alternatively, in some variations, the analyte monitoring device may include at least one real-time clock (RTC). When the analyte monitoring device is in storage or during use, the real-time clock can be used to track absolute time (e.g., coordinated universal time, UTC, or local time). In some variations, synchronization with absolute time can be performed after the analyte monitoring device is manufactured. The real-time clock can be used to time-stamp analyte measurements (e.g., glucose measurements) during operation of the analyte monitoring device to create a time series data set that is transmitted to a connected peripheral device (e.g., a mobile computing device), cloud storage, or other suitable data storage device, such as for later viewing by a user (e.g., the wearer of the analyte monitoring device), their support network, or their healthcare provider, etc.

[0346] like Figure 2A As shown, the analyte monitoring device may include one or more power sources 130 (such as batteries) in the housing 112, which are configured to supply power to other components. For example, the analyte monitoring device may include an AgO battery, which has a high energy density and is more environmentally friendly than a lithium battery. In some variations, a primary (e.g., non-rechargeable) battery may be used. In addition, in some variations, a secondary (e.g., rechargeable) battery may be used. However, any suitable power source may be used, including a lithium-based battery.

[0347] In some variations, a low-profile holder or mount may be used to connect the power source to the device PCB, which reduces the overall height of the electronics, thereby minimizing the height or profile of the analyte monitoring device. For example, while conventional battery holders use a conductive metal with a spring force to apply force to the top side of the battery, in some variations, a laterally mounted battery holder may contact the side of the battery to complete the circuit. In some variations, the size and / or shape of the housing may be determined with appropriate tolerances to apply a vertical or downward force on the battery toward the device PCB, thereby maintaining contact between the battery and the PCB.

[0348] In some variations, the analyte monitoring device can be applied manually. For example, a user can remove a protective film from the adhesive layer and manually press the device onto his or her skin at the desired location. Additionally or alternatively, as Figure 1 As shown, in some variations, an analyte monitoring device can be applied to the skin using a suitable applicator 160. Applicator 160 can be configured, for example, to push analyte monitoring device 110 toward the user's skin so that microneedle array 140 of analyte monitoring device 110 can be inserted into the skin (e.g., to a desired target depth). Various exemplary variations of applicators for applying an analyte monitoring device are described below.

[0349] In some variations, the applicator may include an actuatable housing, a trigger, and a conveyor. The conveyor can releasably receive (e.g., grasp, encase, or otherwise carry) an analyte monitoring device. Typically, the housing, the trigger, and the conveyor can be engaged with each other by one or more releasable coupling features so that in an application procedure, actuation of the housing (e.g., directly or indirectly manually actuated by a user, or by an additional external actuator) can cause a change in the state of the trigger, which in turn can cause a change in the state of the conveyor to release the analyte monitoring device from the conveyor. For example, the housing, the trigger, and the conveyor can be axially aligned (e.g., concentrically) and / or nested together. The components of the applicator can be formed with any suitable manufacturing process, including injection molding, casting, 3D printing, machining technology (e.g., with a rolling mill or lathe), etc.

[0350] For example, the housing may include at least one trigger retaining surface, the trigger may be arranged in the housing and include at least one trigger member that is releasably engaged with the trigger retaining surface. The transmission member may be releasably engaged with the trigger member via one or more releasable coupling features and may be configured to receive an analyte monitoring device. The transmission member may have a first "carrying" configuration or form in which the transmission member retains the analyte monitoring device, and a second "releasing" configuration or form in which the transmission member releases the analyte monitoring device. In response to actuation of at least a portion of the housing toward the transmission member (e.g., the applicator may be compressed and placed, for example, against a patient surface), the trigger member member may disengage from the trigger retaining surface of the housing, which may result in release of the releasable coupling features coupling the transmission member and the trigger member. As a result, the transmission member may transition from its carrying configuration to its releasing configuration, thereby allowing the analyte monitoring device to be deployed from the applicator.

[0351] In addition, in some variations, such as those described below, the applicator may include one or more biasing elements (such as springs) that are arranged to push away adjacent components. For example, in some variations, the applicator may include at least one biasing element that is arranged between an actuatable housing and a trigger member so that when the housing is actuated during the application procedure, the biasing element may provide a trigger force to the trigger member that causes the trigger member to disengage from the trigger member holding surface of the housing. Additionally or alternatively, the applicator may include at least one biasing element that is arranged between the trigger member and the transmission member. The biasing element may be loaded to store potential energy before the housing is actuated (for example, the biasing element may include a compression spring that is pre-compressed before the housing is actuated). When the transmission member is disengaged from the trigger member due to the housing being actuated during the application procedure, the energy stored in the loaded biasing element may be transferred to the transmission member, thereby driving the analyte monitoring device (for example, for suitable skin puncture) with a suitable applied force.

[0352] Figures 31A-31D An example variation of an applicator 1600 for an analyte monitoring device is depicted. The applicator 1600 includes an actuatable housing 1620, a trigger member 1631 disposed in the housing 1620, and a transmission member 1651 disposed in the trigger member 1631. Figure 31D As shown, a first biasing element 1628 (e.g., a compression spring) may be disposed between the housing 1620 and the trigger member 1631, and a second biasing element 1648 (e.g., a compression spring) may be disposed between the trigger member 1631 and the transmission member 1651. Figure 31C As shown, the analyte monitoring device 10 can be housed in a transport 1651 with the microneedle array in a distal direction away from the housing 1620. A cap 1608 can be removably coupled to the housing 1620 to completely enclose the analyte monitoring device 10 within the housing (e.g., to maintain the sterility of the device 10 prior to application).

[0353] refer to Figures 32A-32G , which depicts a conveyor 1651 in greater detail, which may include a base portion having one or more flexible members 1662 extending from a conveyor core 1652, wherein the flexible members 1662 define a receptacle 1660 that can accommodate the analyte monitoring device 10. For example, Figure 32C As shown, bendable member 1662 comprises an arcuate or helical member attached at its proximal end to conveyor core 1652. Bendable members 1662 can be arranged circumferentially around conveyor core 1652 to define a generally circular receptacle 1660 proximate the footprint of analyte monitoring device 10 for enclosing analyte monitoring device 10. Although conveyor 1651 is shown as having three bendable members 1662, it should be understood that in other variations, conveyor 1651 can have any suitable number of bendable members (e.g., one, two, four, five, six, or more).

[0354] Each bendable member 1662 may further include one or more coupling features (e.g., disposed at a distal end of the bendable member 1662), each coupling feature configured to mate with a corresponding coupling feature on the analyte monitoring device 10. For example, Figure 32C As shown, at least one of the flexible members may include a tab 1664 or other protrusion that can be inserted into a corresponding opening 12 ( ) on the analyte monitoring device when the analyte monitoring device 10 is placed in the receptacle 1660. Figure 31D 1664 is engaged with the corresponding opening 12 on the analyte monitoring device, this engagement between the bendable member 1662 and the analyte monitoring device can thereby securely engage the analyte monitoring device within the receptacle 1660. When the distal end of the bendable member 1662 is bent sufficiently radially outward (the "release configuration" of the transmitter), the tab 1664 can disengage from the opening 12 of the analyte monitoring device. As described in further detail below, this disengagement of the coupling features on the transmitter and the analyte monitoring device can enable the analyte monitoring device to be released from the applicator.

[0355] although Figures 32A-32G The delivery member is shown with tabs as coupling features for securing the analyte monitoring device to the delivery member, but it should be understood that the delivery member may additionally or alternatively include other types of coupling features. Figures 32A-32GA generally rectangular tab on the bendable member is depicted, but the tab may have any suitable shape (e.g., triangular, circular, semicircular, etc.) and / or suitable cross-sectional profile (e.g., the tab may have a substantially uniform thickness, or may be thinner on the radially outer side than on the radially inner side of the bendable member 1662, so that the tab more easily self-aligns and mates with the opening 12 on the analyte monitoring device). As another example, in some variations, the bendable member 1662 may include an opening on its distal end that is configured to receive a tab or other outward projection (not shown) on the analyte monitoring device.

[0356] although Figures 32A-32G A coupling scheme is depicted in which coupling features on the bendable member 1662 face radially inward to engage the side edges of the analyte monitoring device, but the coupling features on the bendable member may be oriented in any suitable orientation to engage the analyte monitoring device. For example, in some variations, at least a portion of the bendable member 1662 may include a shoulder along its length that forms a shoulder-like surface that supports a lower surface (e.g., a skin-facing surface) of the analyte monitoring device that rests on the shoulder. In these variations, similar to Figures 32A-32G In the illustrated variation, when the shoulder portion of the bendable member 1662 bends radially outward, the shoulder may disengage from the lower surface of the analyte monitoring device, thereby enabling the analyte monitoring device to be released from the applicator.

[0357] Furthermore, different types of coupling features can be combined in a single transmission member design. For example, the transmission member can include at least one bendable member having a tab similar to tab 1664 that engages an opening on an analyte monitoring device, at least one bendable member having an opening that receives a tab on an analyte monitoring device, at least one bendable member having a shoulder, or any combination thereof.

[0358] Figures 33A-33F Depicted is a detailed view of a trigger member 1631, which may be configured to engage a transmission member 1651 housed therein, such as Figure 31C For example, the transmission member 1651 can be substantially axially aligned with and nested within the trigger member 1631, and the transmission member 1651 can move axially within the trigger member 1631. When the trigger member 1631 is activated by actuation of the housing, it functions to disengage the analyte monitoring device from the transmission member 1651.

[0359] like Figure 33AAs shown, the trigger 1631 may include a base portion 1633. The bendable member 1662 of the transport member (when the transport member is placed in the trigger member) may generally be biased outwardly toward the interior of the base portion 1633. However, the effective inner diameter of the base portion 1633 may vary along the height of the base portion, which controls the degree to which the bendable member 1662 is allowed to bend outward. For example, the interior of the trigger 1631 may include one or more beveled edges against which the bendable member 1662 engages. The beveled edges may, for example, be located on one or more angled trigger ribs 1639, such as Figure 33G , where the outwardly angled bevel or ramp on the trigger rib 1639 allows the bendable member 1662 to be moved away from the housing (e.g., Figure 33G Thus, if the conveyor moves in a direction away from the housing, the bendable members 1662 can gradually bend outward and gradually transition the conveyor from its load-bearing configuration to its release configuration.

[0360] The rotational alignment of the transport 1651 within the trigger 1631 can be guided by one or more tracking features. For example, the trigger 1631 can include one or more tracks 1637 within which the outward tracking features 1656 on the transport can travel. The tracks 1637 can include, for example, Figures 33A-33G 16. Track 1637 may also be configured to receive other suitable types of tracking features on the conveyor (e.g., ball bearings). Additionally or alternatively, conveyor 1651 may alternatively include one or more tracks within which outward-facing tracking features on the trigger member can travel. Conveyor 1651 and / or trigger member 1631 may each include any suitable number of tracking features (e.g., one, two, three, four, or more), and the tracking features may be distributed equally or unequally around the circumference. For example, a conveyor may have two tracking features evenly distributed around the conveyor (180 degrees apart or directly opposite each other), three tracking features evenly distributed around the conveyor (120 degrees apart), four tracking features evenly distributed around the conveyor (90 degrees apart), and so on.

[0361] The crown portion 1641 of the trigger member 1631 can be configured to control when the transmission member can move axially within the trigger member. Figure 37AAs shown, the crown portion 1641 of the trigger 1631 can receive and engage the transmission core 1652, and the firing biasing element 1648 (e.g., a spring) is disposed within the transmission core 1652 and is loaded between the transmission and the trigger. The crown portion 1641 may include one or more trigger members 1644 having a latch portion 1646 (e.g., a hook, a lip, and / or the like) that can engage a transmission lip 1654 that extends at least partially around the transmission core 1652. The trigger member 1644 may include a slender structure having a proximal end fixed to the base portion 1633 and a distal free end extending into the crown portion 1641. As shown Figure 33A As shown, for example, trigger member 1644 may include a trigger retaining slot 1644 (or channel, etc.) along its longitudinal length that engages with retaining member 1617 of the housing. In some variations, one or more trigger members 1644 may have an arcuate cross-section with a radius of curvature similar to the radius of curvature of the remainder of crown portion 1641. Trigger 1631 may include any suitable number of trigger members 1644 (e.g., one, two, three, four, or more), and the trigger members may be distributed circumferentially in equal or unequal amounts. For example, the trigger may have two trigger members evenly distributed around the trigger (180 degrees apart or directly opposite each other), three trigger members evenly distributed around the trigger (120 degrees apart), four trigger members evenly distributed around the trigger (90 degrees apart), and so on.

[0362] Figures 34A-34G The housing 1620 of the applicator 1600 is depicted. The housing 1620 may include a housing cavity that receives a trigger member 1631 and a transmission member 1651. Figure 37A As shown, first biasing element 1628 (e.g., a spring) can be disposed within the housing cavity and positioned on mount 1642 and / or a similar mount within the housing cavity. Housing 1620 can be configured to be manipulated (e.g., manually by a user) to actuate applicator 1600 to deploy the analyte monitoring device loaded within transport member 1651.

[0363] The housing 1620 may include one or more retaining members 1617 within the housing cavity. The one or more retaining members 1617 may include at least one trigger retaining surface for releasably engaging the trigger member 1644 of the trigger 1631 and retaining the trigger in a loaded (unfired) state until the housing 1620 is actuated during an application procedure. For example, the retaining member 1617 may include a wall extending radially inward from the inner surface of the housing 1620 and engaging (e.g., inserting) into the trigger retaining slot 1644 as described above. As such, the thickness of the retaining member (measured in a circumferential direction around the housing 1620) may approximate the width of the trigger retaining slot 1644. In some variations, the retaining member 1617 may have a stepped profile, wherein one step is configured to engage the trigger member 1644 when the trigger is in the loaded state, and another step is configured to engage the trigger member 1644 after the trigger has been actuated and is in the fired state, as further described below.

[0364] In some variations, housing 1620 may include or be coupled to gripper 1613. For example, gripper 1613 may include a sheath or ring that slides around housing 1620 or be coupled to housing 1620 via a suitable mechanical fit, such as threads, an interference fit, or the like. Figure 34B As shown, the housing may include one or more ribs 1611a that are configured to engage and rotationally align with the grip 1613, and / or shoulders 1611b that are configured to engage and axially align with the grip 1613. In some variations, the grip 1613 may be integrally formed with the housing 1620 (e.g., overmolded) and / or the housing 1620 may include one or more gripping features described herein. In some variations, the grip 1613 may include one or more features for enhancing the user's ability to manipulate the housing 1620. For example, the grip may include one or more concave or otherwise recessed contours having finger-receiving surfaces to improve manual gripping, such as Figure 34A The housing 1620 shown in Figure 34H Additionally or alternatively, the gripping member may include one or more raised structural features (ridges, ridges, ribs, rings, etc.) to increase friction, such as Figure 34I 16. Additionally or alternatively, the gripping member 1613 can comprise one or more materials having greater friction (e.g., silicone / polysiloxane or other elastomers). The overall shape of the housing can vary. For example, the housing can be generally prismatic or dome-shaped and / or have a circular or polygonal cross-section, or any other suitable shape.

[0365] Furthermore, in some variations, as described above with respect to Figure 31DAs described, the applicator may include an applicator cap 1608 that is coupled to the housing to enclose the analyte monitoring device 10 within the applicator and to help maintain the sterility of the analyte monitoring device 10 until it is applied to the user. Examples of other techniques for maintaining the sterility of the analyte monitoring device 10 and that can be used in conjunction with the applicator are described in U.S. patent application Ser. No. 63 / 249,399, which is incorporated herein by reference. In some variations, the cap 1608 may be coupled to the housing 1620 by mechanical interfitting (e.g., threads, snap fit) and / or other suitable means (e.g., an epoxy that can be overcome with a sufficiently applied separation force). In addition, in some variations, the coupling of the cap 1608 and the housing 1620 may include one or more seals (e.g., gaskets). Similar to the grip 1613, the cap 1608 may include one or more features for enhancing the user's ability to manipulate the cap (e.g., to separate the cap from the housing before using the applicator). For example, as Figure 34H As shown, cap 1608' may include ribs to increase the friction and grip of the cap. As another example, as shown in FIG. Figure 34I As shown, cap 1608" may include concave features and a polygonal edge to enhance the grippability of the cap.

[0366] Turning now to the use of applicator 1600, Figures 35A-35B and Figures 36A-36C An example method of loading the analyte monitoring device 10 into the applicator 1600, such as during the manufacturing process, is shown. As described above, the analyte monitoring device 10 can be inserted into or received by the transport 1651. Specifically, as shown in FIG. Figure 35A and 35B , the analyte monitoring device 10 can be placed between the flexible members 1662 of the transport (with the microneedle array pointing away from the housing). The analyte monitoring device 10 can be rotated to align its opening 12 with the tab 1664 on the flexible members 1662, and the tab 1664 can be inserted into the opening 12 (or groove, etc.) to carry the analyte monitoring device 10 in the space between the flexible members 1662.

[0367] like Figure 36A As shown, when the trigger member 1631 is arranged in the housing 1620, the transmission member 1651 with the analyte monitoring device 10 can be pushed into the interior of the trigger member 1631. Figure 36A As shown in the detailed view of FIG, as the transfer member 1651 is pushed further into the trigger member 1631, the transfer member lip 1654 (which can be an outward protrusion positioned around at least a portion of the transfer member core) can push into at least one trigger member latch 1646 of the trigger member. At least in part due to the transfer member lip 1654 (e.g., Figure 37CDue to the angled nature of the interface between the transmission member lip 1654') and the trigger latch 1646, pushing the transmission member lip 1654 into the trigger can push the trigger latch 1646 upward over the lower step of the stepped retaining member 1617 of the housing ( Figure 37C 1617a)( Figure 36B As the trigger latch 1646 is pushed upward over the lower step, the trigger member can flex radially outward, allowing the transmission lip 1654 to bypass the trigger latch 1646. Once the transmission lip 1654 is pushed further into the trigger and past the trigger latch 1646, the trigger latch 1646 is allowed to fall back into place on the lower step of the retaining member 1617. Figure 36C Once the trigger latch 1646 reengages the lower step of the retaining member 1617, the transmitter lip 1654 is secured over the trigger latch 1646, thereby locking the transmitter in place within the trigger and housing in its loaded configuration and simultaneously locking the analyte monitoring device 10 in the transmitter.

[0368] Figures 37A-37E Other cross-sectional views of the coupling between the transmission member, trigger member, and housing when the analyte monitoring device is loaded in the applicator are shown and further described below. Figure 35B Also shown is a lower side view of the analyte monitoring device 10 loaded in the applicator, showing the bendable member 1662 engaged with the opening 12 of the analyte monitoring device 10 and also locked into a radially inward bent position (the load-bearing form of the transport member) to secure the analyte monitoring device 10 in the applicator.

[0369] As described above, the analyte monitoring device 10 can be oriented so that its opening 12 is aligned with the tab 1664 on the flexible member 1662, and the tab 1664 can be inserted into the opening 12 to carry the analyte monitoring device 10 in the space between the flexible members 1662. When the transmission member is locked in place within the trigger member, as described above with respect to Figures 36A-36C As described above, the bendable member 1662 is additionally pushed radially inward by the trigger rib 1639 on the interior of the trigger ( Figure 37E ) so that tab 1664 is locked in opening 12 of analyte monitoring device 10.

[0370] In addition, if Figure 37AAs shown, a first biasing element 1628 (e.g., a compression spring) can be arranged between the trigger and the housing in a relaxed or unloaded state. In this state, the first biasing element 1628 can cause the trigger and the housing to separate, and when the housing is pushed into the trigger, the first biasing element transmits the actuation force to the trigger. In addition, a second biasing element 1648 can be arranged between the transmission member and the trigger in a compressed or loaded state, storing energy for forcing the transmission member to be ejected from the trigger to deploy the analyte monitoring device 2. Although the first and second biasing elements 1628 and 1648 are Figure 37A 1628 and / or the second biasing element 1648. Although shown as a compression spring, it should be understood that other biasing elements (e.g., spring arms, leaf springs, etc.) may additionally or alternatively be used as the first biasing element 1628 and / or the second biasing element 1648.

[0371] During the application procedure, at least a portion of the housing 1620 can be actuated toward the transfer member 1651 (or toward the trigger member 1631). For example, at least a portion of the housing 1620 can be pushed or compressed. Alternatively, at least a portion of the housing 1620 can be rotated, tilted, or actuated in any manner to move the housing 1620 toward the transfer member and / or trigger member. The entire housing can be actuated, or can include a depressible button (or other suitable actuator) to achieve appropriate mechanical force transmission similar to that described below. Figure 37B , when the housing 1620 is pushed toward the transfer member 1651 or the trigger member 1631, the first biasing element 1628 compresses, which transmits or provides a triggering force to the trigger member 1644. This triggering force can cause the trigger member 1644 to disengage from the trigger member retaining surface 1617a on the lower step portion of the retaining member 1617 and bend radially outward to move into the gap, thereby resting on the second step portion 1617b of the retaining member 1617 in the housing. This outward movement of the trigger member 1644 causes the transfer member lip 1654 to disengage from the trigger member 1644, which unlocks the transfer member 1651 and allows it to move axially within the trigger member 1631. When the transfer member 1651 is unlocked in this manner, the second biasing element 1648 relaxes and releases its stored energy to accelerate or forcibly eject the transfer member 1651 axially downward (at Figure 381637). The transport member 1651 continues to move axially until the tracking feature 1656, engaged in the slot 1637 of the track, reaches the lower edge of the slot 1637 of the track. Simultaneously, as the transport member 1651 moves axially downward, its bendable member 1662 is gradually allowed to flex radially outward from the transport member's loaded configuration to the transport member's released configuration, as permitted by the outwardly inclined surfaces or ramps on the trigger ribs 1639. When the bendable member 1662 has sufficiently flexed radially outward, the bendable member 1662 disengages from the analyte monitoring device 10, allowing the analyte monitoring device 10 to be fully separated from the applicator 1600. The longer the length of the outwardly inclined surfaces or ramps on the trigger ribs 1639, the later it will take for the bendable member 1662 to flex outward and ultimately release the analyte monitoring device 10. Thus, the longer inclined surfaces or ramps on the trigger ribs 1639 can help ensure that the analyte monitoring device 10 remains in a fixed position for a longer period of time when the transport member is released. During the application procedure, the analyte monitoring device 10 is ejected from the delivery member, and therefore from the applicator, but the delivery member 1651 is retained within the trigger 1631 at least in part due to the continued engagement of the delivery member lip 1654 within the slot of the trigger member 1644 .

[0372] Figures 39A-39D An exemplary variation of an applicator 2400 is depicted that is similar to the applicator 1600 described above, with certain differences as described below. For example, the applicator 2400 can include a housing 2410 (which can include or be coupled to a gripping member 2412), a triggering member 2430, and a transmission member 2450 coupled to one another. A first biasing element 2428 can be disposed between the housing 2410 and the triggering member 2430 to provide a triggering force, and a second biasing element 2448 can be disposed between the triggering member 2430 and the transmission member 2450 to provide a firing force, similar to the first and second biasing elements described above with respect to the applicator 1600. The applicator 2400 can also include a cap 2408 removably coupled to the housing 2410, and the cap 2408 can be similar to the cap 1608 described above with respect to the applicator 1600.

[0373] refer to Figure 40A and 40B The conveyor 2450 shown in Figures 41A-41E The trigger member 2430 and Figures 42A-42E With reference to the features shown in the detailed view of housing 2410 shown in FIG, an operating description of applicator 2400 follows. Figure 43The applicator 2400 is shown in a loaded state, wherein an analyte monitoring device 10 (not shown) can be carried in a receptacle in the transport member 2450, the receptacle being at least partially defined by one or more coupling members 2464 and / or an annular rim (or a partial annular rim), within or on which the analyte monitoring device can be placed. The transport member 2450 can engage with the trigger member 2430 such that the outer periphery of the transport member 2450 can interfere with (e.g., press radially outwardly on) the inner sidewall surface of the trigger member 2430, and the trigger member sidewall urges the transport member 2450 into a loaded configuration in which the coupling members 2464 are locked around the analyte monitoring device 10. In some variations, the periphery of the transport member 2450 may include one or more outwardly projecting members 2462 that engage and travel within corresponding tracks 2416 (e.g., slots, grooves) in the sidewall of the trigger member 2430, thereby maintaining rotational alignment between the transport member 2450 and the trigger member 2430. The transport member 2450 may include a transport member rod 2452 extending from a central portion of the transport member 2450 and configured to engage a central opening between the collet-arm-like blades 2432 of the trigger member 2430. The blades 2432 may be arranged circumferentially around the trigger member 2430. Each blade 2432 may have a proximal end that is integral / integrally formed with or otherwise attached to the periphery of the trigger member 2430 (e.g., around the annular or partially annular base 2439, or at the sidewall of the trigger member) to support the blade. In addition, each blade 2432 may have a free distal end extending toward the center of the trigger 2430 and having a surface 2432a that engages the surface 2452a of the transmission rod. Although the trigger 2430 is shown in the figure as including three blades, it should be understood that the trigger 2430 may include any suitable number of blades (e.g., one, two, four, or more, etc.). The blades may be arranged circumferentially in equal or unequal manner. For example, the trigger may have two blades evenly distributed around the trigger (180 degrees apart or directly opposite each other), or three blades evenly distributed around the trigger (120 degrees apart), or four blades evenly distributed around the trigger (90 degrees apart), etc.

[0374] The trigger member 2430 can be engaged with the interior of the housing 2410. Figure 43As shown. A trigger protrusion 2436 is disposed around the exterior of blade 2438 and projects radially outward, causing the inner surface of housing 2410 to interfere with protrusion 2436 and push blade 2438 inward. This radially inwardly directed force urges blade 2438 into a closed configuration around transmission rod 2452 and further locks transmission 2450 axially in engagement with trigger 2430, in which position a second biasing element 2448 (e.g., a spring) is compressed or otherwise energized for firing transmission 2450 in response to trigger actuation. Additionally, similar to applicator 1600, a first biasing element 2428 may be disposed between housing 2410 and trigger 2430 to provide a trigger force.

[0375] Figure 44 The applicator 2400 is depicted in a fired state after the trigger 2430 has been activated (e.g., by actuating the housing 2410 toward the transfer member 2450 and / or the trigger 2430). For example, when at least a portion of the housing 2410 is pushed and actuated toward the transfer member 2450 and / or the trigger 2430, the housing 2410 moves toward the transfer member and / or the trigger, and the protrusion 2436 on the trigger blade 2432 slides into the track 2416 in the housing. When the trigger blade 2432 is located in the track 2416, this relieves the central pressure on the trigger blade 2432 and allows the blade 2432 to expand radially outward, causing the central opening to widen and releasing the transfer rod 2452. Once the transfer rod 2452 is released, the transfer member 2450 is free to move axially with the trigger (in Figure 44 2416. The analyte monitoring device 10 is released from the applicator 2400 and ejected from the applicator 2400.

[0376] Figures 45A-45DAn exemplary variation of an applicator 3000 is depicted that is similar to the applicator 1600 described above, with certain differences as described below. For example, the applicator 3000 can include a housing 3010, a trigger member 3030, and a transmission member 3050 coupled to one another. A first biasing element 3028 can be disposed between the housing 3010 and the trigger member 3030 to provide a triggering force, and a second biasing element 3048 can be disposed between the trigger member 3030 and the transmission member 3050 to provide a firing force, similar to the first and second biasing elements described above with respect to the applicator 1600. The applicator 3000 can also include a base ring 3006 that can be coupled to the housing 3010 (e.g., with one or more fasteners).

[0377] refer to Figures 46A-46E The transmission member 3050 shown, Figures 47A-47D The trigger member 3030 and Figures 48A-48E The features described in the detailed view of the housing 3010 are shown, and an operating description of the applicator 3000 follows. Figure 49 The applicator 3000 is shown in a loaded state, wherein an analyte monitoring device (not shown) can be carried in a receptacle in a transport member 3050, the receptacle being at least partially defined by one or more coupling members 3064 and / or an annular rim (or a portion of an annular rim), and the analyte monitoring device can be placed in or on the receptacle. The transport member 3050 can be arranged interior to the trigger member 3030, with the receptacle portion (carrying the analyte monitoring device) engaging the inner sidewall surface 3036 of the trigger member 3030. The protrusion 3062 of the transport member 3050 can engage a track 3034 (e.g., a groove, a channel) within the inner sidewall surface 3036, for example to maintain rotational alignment between the transport member 3050 and the trigger member 3030. The transport member 3050 can also have a transport member mating connector 3052 located at the center of the transport member and extending upwardly (at the center) from the receptacle portion of the transport member 3050 that carries the analyte monitoring device. Figure 4930). The transport member 3050 can be engaged with the housing 3010 by an actuator member 3014 that extends longitudinally within a central portion of the housing 3010. Each actuator member 3014 can have an inner latch portion 3014a that extends through a corresponding opening in the transport member mating connector 3052 and engages the transport member mating connector 3052. In addition, each actuator member 3014 can have an outer latch portion 3014b that engages the trigger member retaining cylinder 3032 such that the actuator member 3014 can be trapped between the transport member mating connector 3052 and the trigger member retaining cylinder 3032. Thus, the actuator member 3014 in this locked position holds the transport member 3030 in a loaded position in which the loaded form of the transport member holds the analyte monitoring device (with the receptacle portion engaged against the inner sidewall surface 3036, as described above).

[0378] Figure 50 The applicator 3000 is depicted in a fired state, and the trigger 3030 has been activated (e.g., by activating the housing 3010 toward the transmission 3050 and / or the trigger 3030). For example, when at least a portion of the housing 3010 is pushed and actuated toward the transmission 3050 and / or the trigger 3030, the housing 3010 moves toward the transmission and / or the trigger, and the actuator member 3014 is released from the trigger retaining cylinder 3032. The free actuator member 3014 is allowed to flex radially outward, which causes the inner latch portion 3014a to disengage from the transmission mating connector 3052. Once the transmission mating connector 3052 is disengaged and unlocked from the actuator member 3014, the transmission 3050 is free to move axially within the trigger (in Figure 50 orientation shown) to the inner sidewall surface 3036 widens and allows the coupling member 3064 (in Figure 50 The point at which the analyte monitoring device 10 is bent radially outward and released in the form of a release member (hidden behind the analyte monitoring device 10).

[0379] The axial movement of the transport member 3050 is accelerated by the second biasing element 3048, which pushes the transport member 3050 and the analyte monitoring device 10 carried therein downward until the transport member tabs 3062 on the periphery of the transport member reach the lowest edge of the track 3034 where the tabs 3062 engage. As a result, the analyte monitoring device 10 is ejected from the applicator 3000, and the fired transport member 3050 is retained within the trigger member 3030.

[0380] The above-described applicator variations (e.g., applicator 1600, applicator 2400, and applicator 3000) can each include a specific combination of housing, trigger, and conveyor variations that interact with each other. However, it should be understood that one or more features of the housing, trigger, and / or conveyor variations described herein can be combined in any suitable manner. In addition, one or more features of the housing, trigger, and / or conveyor variations described herein can be combined with other housing, trigger, and / or conveyor designs not described herein. Thus, any conveyor feature described herein can be implemented with various embodiments of the trigger and / or housing. Similarly, any trigger feature described herein can be implemented with various embodiments of the conveyor and / or housing, and any housing feature described herein can be implemented with various embodiments of the conveyor and / or trigger.

[0381] For example, described below are additional transmission member variations that may be combined with any of the housing and / or trigger member variations described above, or any suitable housing and / or trigger member variations.

[0382] refer to Figures 51A to 51N Another conveyor variation 3600 is depicted that includes a deformable ring. Figures 51A to 51F Various aspects of conveyor 3600 are depicted in FIG. Figure 51A 、 Figure 51B and Figure 51C A bottom perspective view, a side view, and a bottom view of a first embodiment of a conveyor 3600 are depicted. Figure 51D 、 Figure 51E and Figure 51F A bottom perspective view, a side view, and a bottom view of a second embodiment of a conveyor 3600 are depicted.

[0383] The bottom ring portion 3610 of the transport member 3600 can be configured to retain the analyte monitoring device in a restrained (eg, closed, stored, or otherwise contained) configuration. The bottom ring portion 3610 can be configured to release the analyte monitoring device in an expanded (eg, open or released) configuration.

[0384] In the first embodiment, as Figure 51A 、 51B 51C , the bottom ring portion 3610 can be generally elliptical or oval in the constrained configuration. In the expanded configuration, the bottom ring portion can be generally circular. In the constrained configuration, the analyte monitoring device can contact the inner sidewall of the bottom ring portion 3610, while in the expanded configuration, the analyte monitoring device does not contact the inner sidewall of the bottom ring portion 3610, thereby allowing release of the analyte monitoring device.

[0385] In the second embodiment, if Figure 51D 、 51EAs shown in Figures 51F and 51F, the bottom ring portion 3610 can be generally triangular in the constrained configuration; for example, the bottom ring portion 3610 can have a trilobal shape. In the expanded configuration, the bottom ring portion can be generally circular. When the bottom ring portion 3610 is in the constrained configuration, the triangular shape provides three points of contact between the wearable device and the inner sidewall of the bottom ring portion 3610.

[0386] The transmission member 3600 has two or more movable ribs 3620 that facilitate movement of the bottom ring portion 3610 between a constrained configuration and an expanded configuration. The two or more ribs 3620 are connected between the bottom ring portion 3610 and the spring retention cavity of the transmission member 3600. The spring retention member forms a recess that accommodates the firing spring and interferes / interfaces with the trigger member used to deploy the wearable device from the transmission member 3600.

[0387] Figures 51G to 51I The transmission member 3600 is depicted in the loaded position engaged with the trigger member 3650. In the loaded position, the bottom ring portion 3610 is in a restraining configuration. Figures 51J to 51L The transmission member 3600 is depicted in a deployed position engaged with the trigger member 3650. In the deployed position, the bottom ring portion 3610 is in an expanded configuration.

[0388] The conveyor 3600 may include one or more pairs of guide walls on the outer wall of the bottom ring portion 3610. Each of the one or more pairs of conveyor guide walls may interface (e.g., align and / or engage) with a corresponding one of the trigger wall ramps. One or more trigger wall ramps may be formed on the inner sidewall of the trigger 3650. The conveyor 3600 may further include one or more conveyor notches that interface (e.g., align and / or engage) with corresponding channels of the trigger 3650. The trigger channel may be formed through the sidewall of the trigger 3650. Each conveyor notch may be formed on a corresponding portion of the rib 3620.

[0389] In the loaded position, the pair of transmission member guide walls interface with the trigger member wall ramps, and the transmission member recess interfaces with the trigger member channel. In the deployed position, the pair of transmission member guide walls no longer interface with the trigger member wall ramps, thereby allowing the bottom ring portion 3610 to move from the constrained configuration to the expanded configuration, thereby releasing the wearable device.

[0390] Figure 51M and Figure 51N Depicted is an alternative embodiment of a bottom wall portion 3610 of a conveyor 3600. In this embodiment, two upper extensions extend across a top portion of the bottom wall portion 3610, which help retain a wearable device within the bottom wall portion 3610.

[0391] Figure 52A and Figure 52BAnother transport member variation is depicted. Transport member 3700 includes three or more retaining walls 3710 that are movable from a restrained position to an expanded position. In the restrained position, the retaining walls engage the analyte monitoring device, such that the analyte monitoring device is retained within the inner portion of the retaining walls 3710. In the expanded position, the retaining walls are moved such that the engagement between the inner portion of the retaining walls 3710 and the analyte monitoring device is broken. This allows the analyte monitoring device to be deployed from transport member 3700.

[0392] The transport 3700 has a spring retention cavity for receiving a firing spring therein, which interfaces with a trigger for deploying the analyte monitoring device from the transport 3700, as described in accordance with other embodiments herein.

[0393] In some embodiments, each retaining wall 3710 may have a corresponding notch that interfaces with a first opening of the trigger in the constrained configuration and interfaces with a second opening of the trigger in the expanded configuration. The first opening is laterally located at a height above the second opening and has a smaller transverse circumference along the first opening than along the second opening. When the transport member 3700 is released, the notch moves from the first opening to the second opening, thereby allowing the retaining wall 3710 to move from the constrained configuration to the expanded configuration.

[0394] According to another alternative or additional embodiment, one or more wedges can be provided along the bottom portion of the trigger to move the retaining wall from the constrained configuration to the expanded configuration. In some embodiments, each wedge can correspond to a groove or opening between adjacent retaining walls 3710.

[0395] Figures 53A to 53K Aspects of an applicator 3800 are depicted having an actuatable housing 3810, a trigger member 3820, and a transmission member 3830. Figure 53A 38 is an enlarged view of the applicator 3800, showing the alignment of the housing 3810, the trigger 3820, and the transport 3830. The housing 3810 is the outermost component and defines an interior cavity into which the trigger 3820 is removably mounted. The trigger 3820 is generally concentric with the housing 3810. The trigger 3820 defines an interior cavity into which the transport 3830 is removably mounted. The transport 3830 includes a mechanism for retaining and releasing the analyte monitoring device.

[0396] A trigger spring and a firing spring (not shown) are provided. The trigger spring provides the trigger force and is located between the inner surface of the actuator 3810 and the outer surface of the trigger member 3820. The firing spring provides the deployment force and is located between the inner surface of the trigger member 3820 and the outer surface of the transmission member 3830. Figure 53AAlso shown is an exemplary analyte monitoring device that may be contained within an applicator 3800 for deployment and insertion into the dermis of a user.

[0397] Figures 53B to 53E Various aspects of a transport member 3830 are shown. The transport member includes a spring post for firing a spring and three or more retaining walls that can be moved...

Claims

1. An applicator for an analyte monitoring device, the applicator comprising: a housing including a body defining a cavity therein and defining a distal opening; a cuff slidably received within the cavity and including a lumen therethrough; a transmission member slidably received within the lumen and configured to releasably retain the analyte monitoring device; a first biasing element disposed between the housing and the ferrule; a second biasing element disposed between the housing and the transmission member; a microneedle enclosure releasably engageable with the analyte monitoring device and configured to encapsulate a portion of the analyte monitoring device when engaged, the microneedle enclosure comprising a third biasing element and a sheath having an opening surrounding a microneedle array and sealed against the analyte monitoring device when the microneedle enclosure is engaged with the analyte monitoring device, thereby providing a closed and sterile environment for the microneedle array; as well as A base is releasably engaged with the housing and attached to the microneedle enclosure.

2. The applicator of claim 1, wherein: The first biasing element is configured to bias the ferrule toward the distal opening.

3. The applicator of claim 1, wherein: The second biasing element is configured to bias the transmission member toward the distal opening.

4. The applicator of claim 1, wherein: The transmission member is configured to slide relative to the ferrule and the housing body.

5. The applicator of claim 1 , wherein: The ferrule is configured to slide relative to the transmission member and the housing body.

6. The applicator of claim 1, wherein: The microneedle enclosure further includes a cavity in which the sheath is slidably received, the cavity containing the third biasing element.

7. The applicator of claim 6, wherein: The third biasing element biases the encasement toward the analyte monitoring device.

8. The applicator of claim 6, wherein: The microneedle enclosure further comprises a force concentrator disposed within the cavity, the force concentrator comprising a shaft and a head, the shaft being disposed within the third biasing element, wherein the force concentrator and the third biasing element are combined to bias the sheath toward the analyte monitoring device, thereby maintaining a closed and sterile environment for the microneedle array.

9. The applicator of claim 1, wherein: The transmission member and the ferrule are telescopically arranged within the housing body.

10. The applicator of claim 1, wherein: The first biasing element, the second biasing element, and the third biasing element are each selected from the group consisting of a helical metal spring, a plastic leaf spring, and a helical plastic spring.

11. The applicator of claim 1 , wherein: The microneedle array is oriented away from the proximal end of the housing body.

12. The applicator of claim 1, wherein: The first biasing element is further disposed about a mount extending from a proximal end of the housing body to a distal opening of the housing body.

13. The applicator of claim 12, wherein: The mount includes at least one downwardly extending finger configured to releasably engage the transfer member.

14. The applicator of claim 12, further comprising a friction ring disposed about the mount and about an axis of the transmission extending away from the analyte monitoring device and toward the proximal end of the housing body.

15. The applicator of claim 14, wherein: The mount includes at least one downwardly extending finger configured to releasably engage the friction ring.

16. The applicator of claim 14, further comprising a locking member at least partially received within the side opening of the housing body and releasably engaged with the ferrule.

17. The applicator of claim 16, wherein: Actuation of the locking member releases the engagement between the locking member and the ferrule, thereby allowing the ferrule to move.

18. The applicator of claim 1, wherein: The microneedle enclosure includes a locking tab configured to engage a connector feature of the analyte monitoring device.

19. The applicator of claim 1, wherein: The base includes a retaining arm configured to be received between the ferrule and an inner surface of the housing body.

20. The applicator of claim 19, wherein The retaining arm is configured to releasably engage a retaining surface on the ferrule.

21. The applicator of claim 20, wherein The retaining arms prevent separation between the base and the ferrule when the retaining arms engage the retaining surfaces on the ferrule.

22. The applicator of claim 19, wherein: The base includes a plurality of retaining arms, each of the plurality of retaining arms being configured to be received between the ferrule and an inner surface of the housing body.

23. The applicator of claim 1, wherein: The base includes a locking arm configured to be releasably received in a recess of the housing body.

24. The applicator of claim 23, wherein When the locking arm is received in the recess of the housing body, the locking arm is biased radially outward toward the housing body.

25. The applicator of claim 23, wherein The base includes a plurality of locking arms, wherein the plurality of locking arms are positioned circumferentially around the base.

26. The applicator of claim 1, wherein The ferrule includes one or more tracks within which corresponding one or more tracking protrusions on the conveyor are slidably engageable.

27. The applicator of claim 26, wherein The one or more tracks are disposed circumferentially around the ferrule, and the corresponding one or more tracking projections are disposed circumferentially around the conveyor at corresponding locations.

28. The applicator of claim 1, wherein The housing body includes one or more guides on an inner surface thereof, and the ferrule includes one or more corresponding guided protrusions on an outer surface thereof, the corresponding one or more guided protrusions slidably engaging the one or more guides.

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