Wearable Analyte Monitoring Device

Abstract

Aspects of the present subject matter are directed to a wearable analyte monitoring device having an integrated applicator for deploying a microneedle array-based sensor into a skin surface of a subject. The microneedle array is held within a housing body of the wearable analyte monitoring device in a first, worn configuration. Upon actuation, a biasing element accelerates the microneedle array into the skin of the subject, thereby transitioning the microneedle array to a second, deployed configuration in which the microneedle array protrudes through a distal opening of the housing body, enabling the microneedle array to sense one or more target analytes in the subject's cutaneous interstitial fluid.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 296,830, filed January 5, 2022, the contents of which are incorporated by reference in their entirety herein.

[0002] The present invention relates generally to the field of analyte monitoring, such as continuous glucose monitoring. [Background technology]

[0003] Diabetes is a chronic disease in which the body does not produce or properly utilize insulin, a hormone that regulates blood glucose. Insulin can be administered to diabetic patients to help regulate blood glucose levels, but blood glucose levels must still be carefully monitored to help ensure that timing and dosage are appropriate. If diabetic patients do not properly manage their condition, they can suffer from a variety of complications resulting from hyperglycemia (high blood sugar levels) or hypoglycemia (low blood sugar levels).

[0004] Blood glucose monitors help diabetic patients manage their condition by measuring blood glucose levels from a blood sample. For example, a diabetic patient may draw a blood sample via a finger prick sampling mechanism, transfer the blood sample to a test strip with suitable reagent(s) that react with the blood sample, and use a blood glucose monitor to analyze the test strip and measure the glucose level in the blood sample. However, patients using this process are typically only able to measure their glucose levels at discrete time instances and may not be able to capture hyperglycemic or hypoglycemic conditions in a timely manner. A more recent variety of glucose monitor is the continuous glucose monitor (CGM) device, which includes an implantable transcutaneous electrochemical sensor used to continuously detect and quantify blood glucose levels by proxy measurement of glucose levels in subcutaneous interstitial fluid. However, conventional CGM devices also have weaknesses including tissue trauma from insertion and signal delays (e.g., due to the time required for glucose analytes to diffuse from a capillary source to the sensor). These weaknesses also lead to several drawbacks, such as the pain experienced by the patient when the electrochemical sensor is inserted and limited accuracy of glucose measurements, especially when blood glucose levels are changing rapidly. Thus, there is a need for new and improved analyte monitoring systems. Summary of the Invention [Means for solving the problem]

[0005] According to one embodiment, the present disclosure relates to analyte monitoring.

[0006] In an embodiment, the present disclosure further relates to a wearable analyte monitoring device comprising: a housing including a body defining a cavity therein, the housing body including a distal opening; an adhesive layer coupled to a distal end of the housing and surrounding the distal opening, the adhesive layer configured to secure the device to a skin surface of a user; a biasing element contained within the cavity; a microneedle array coupled to the biasing element and including a plurality of microneedles; a retaining element contained within the cavity and configured to releasably retain the biasing element; and an actuating member coupled to the retaining element, wherein engagement of the actuating member transitions the microneedle array between a first configuration and a second configuration, wherein in the first configuration the microneedle array is retained within the cavity of the housing body and in the second configuration the microneedle array protrudes through the distal opening of the housing body.

[0007] In an embodiment, the present disclosure further relates to a method of inserting a microneedle array into a skin surface of a user, the method comprising: providing a wearable analyte monitoring device including a microneedle array in a first configuration, the microneedle array including a plurality of microneedles, the microneedle array coupled to a biasing element housed within a cavity of a housing, the housing including a body defining a cavity therein, the biasing element being releasably held by a retaining element housed within the cavity, the retaining element being coupled to an actuation member; and transitioning the microneedle array from the first configuration to a second configuration, wherein in the first configuration the microneedle array is held within the cavity of the housing body and in the second configuration the microneedle array protrudes through a distal opening of the housing body.

[0008] In an embodiment, the present disclosure further relates to an analyte monitoring device comprising a housing including a body defining a cavity therein, the housing body including a distal opening, a biasing element contained within the cavity, a microneedle array coupled to the biasing element, and an actuating member, wherein engagement of the actuating member transitions the microneedle array from a first configuration to a second configuration under influence of the biasing element, wherein in the first configuration the microneedle array is retained within the cavity of the housing body and in the second configuration at least a portion of the microneedle array protrudes through the distal opening of the housing body.

[0009] In an embodiment, the present disclosure further relates to a method of monitoring a user using a wearable analyte monitoring device, the method comprising: providing a wearable analyte monitoring device including a microneedle array in a first configuration, the microneedle array including a plurality of microneedles, the microneedle array coupled to a biasing element housed within a cavity of a housing, the housing including a body defining a cavity therein, the biasing element being releasably held by a retaining element housed within the cavity, the retaining element coupled to an actuation member; adhering the wearable analyte monitoring device to a skin surface of the user; transitioning the microneedle array from the first configuration to a second configuration, wherein in the first configuration the microneedle array is held within the cavity of the housing body and wherein in the second configuration the microneedle array protrudes through a distal opening of the housing body; and measuring a target analyte level in skin interstitial fluid of the subject with the microneedle array.

[0010] In an embodiment, the disclosure further relates to a method of inserting a microneedle array into a skin surface, the method comprising: providing a microneedle array within a cavity of a housing, the housing including a body defining a cavity therein, the microneedle array being coupled to a biasing element within the cavity; loading the microneedle array in a first configuration in which the microneedle array is biased by the biasing element towards a distal end of the housing body; and providing an actuating member engaged to release the microneedle array from the first configuration and transition the microneedle array to a second configuration in which a plurality of microneedles of the microneedle array protrude from a distal opening of the housing body, wherein in transitioning from the first configuration to the second configuration, the microneedle array moves within the cavity towards the distal end of the housing body under the influence of the biasing element. [Brief description of the drawings]

[0011] [Figure 1] 1 shows an exemplary schematic diagram of an analyte monitoring system having a microneedle array.

[0012] [Figure 2A] 1 shows an exemplary schematic diagram of an analyte monitoring device.

[0013] [Figure 2B] 1 shows an exemplary schematic of microneedle insertion depth in an analyte monitoring device.

[0014] [Figure 3A] 1A-1D show top perspective, side, bottom and exploded views, respectively, of an analyte monitoring device. [Figure 3B] 1A-1D show top perspective, side, bottom and exploded views, respectively, of an analyte monitoring device. [Figure 3C] 1A-1D show top perspective, side, bottom and exploded views, respectively, of an analyte monitoring device. [Figure 3D]1A-1D show top perspective, side, bottom and exploded views, respectively, of an analyte monitoring device.

[0015] [Figure 4A] 1A-1C show exploded perspective, exploded side, bottom perspective, side and top perspective views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4B] 1A-1C show exploded perspective, exploded side, bottom perspective, side and top perspective views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4C] 1A-1C show exploded perspective, exploded side, bottom perspective, side and top perspective views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4D] 1A-1C show exploded perspective, exploded side, bottom perspective, side and top perspective views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4E] 1A-1C show exploded perspective, exploded side, bottom perspective, side and top perspective views, respectively, of a sensor assembly in an analyte monitoring device.

[0016] [Figure 4F] 1A-1D show exploded perspective, exploded side, and side views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4G] 1A-1D show exploded perspective, exploded side, and side views, respectively, of a sensor assembly in an analyte monitoring device. [Figure 4H] 1A-1D show exploded perspective, exploded side, and side views, respectively, of a sensor assembly in an analyte monitoring device.

[0017] [Figure 5A] 1 shows an exemplary schematic diagram of a microneedle array. [Figure 5B] 5B shows an exemplary schematic diagram of a microneedle of the microneedle array shown in FIG. 5A.

[0018] [Figure 6]FIG. 1 shows an exemplary schematic diagram of a microneedle array configuration used for sensing multiple analytes.

[0019] [Figure 7A] FIG. 1 shows a side cross-sectional view of a cylindrical microneedle having a tapered distal end. [Figure 7B] 7B is an image showing a perspective view and a detailed view of the microneedle embodiment shown in FIG. 7A. [Figure 7C] 7B is an image showing a perspective view and a detailed view of the microneedle embodiment shown in FIG. 7A.

[0020] [Figure 8] FIG. 1 shows an exemplary schematic diagram of a cylindrical microneedle with a tapered distal end.

[0021] [Figure 9A] 1A and 1B show exemplary schematic diagrams of a microneedle array and a microneedle, respectively. [Figure 9B] 1A and 1B show exemplary schematic diagrams of a microneedle array and a microneedle, respectively. [Figure 9C] 1A-1C show detailed partial views of exemplary variations of microneedles. [Figure 9D] 1A-1C show detailed partial views of exemplary variations of microneedles. [Figure 9E] 1A-1C show detailed partial views of exemplary variations of microneedles. [Figure 9F] 1A-1C show detailed partial views of exemplary variations of microneedles.

[0022] [Figure 10A] 1 illustrates an exemplary variation of a microneedle. [Figure 10B] 1 illustrates an exemplary variation of a microneedle.

[0023] [Figure 11A] 1 shows an exemplary schematic diagram of a microneedle array configuration. [Figure 11B]1 shows an exemplary schematic diagram of a microneedle array configuration. [Figure 11C] 1 shows an exemplary schematic diagram of a microneedle array configuration. [Figure 11D] 1 shows an exemplary schematic diagram of a microneedle array configuration.

[0024] [Figure 12A] 1A and 1B show perspective and orthogonal views, respectively, of an exemplary variation of a die containing a microneedle array. [Figure 12B] 1A and 1B show perspective and orthogonal views, respectively, of an exemplary variation of a die containing a microneedle array.

[0025] [Figure 13A] 1A-1D show exemplary schematic diagrams of different variations of microneedle array configurations. [Figure 13B] 1A-1D show exemplary schematic diagrams of different variations of microneedle array configurations. [Figure 13C] 1A-1D show exemplary schematic diagrams of different variations of microneedle array configurations. [Figure 13D] 1A-1D show exemplary schematic diagrams of different variations of microneedle array configurations. [Figure 13E] 1A-1D show exemplary schematic diagrams of different variations of microneedle array configurations.

[0026] [Figure 14A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14C] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14D] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14E] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14F]1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 14G] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device.

[0027] [Figure 15A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 15B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 15C] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 15D] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 15E] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device.

[0028] [Figure 16A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 16B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 16C] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device.

[0029] [Figure 17A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 17B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 17C] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 17D] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 17E] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device.

[0030] [Figure 18A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 18B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 18C] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device.

[0031] [Figure 19A] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. [Figure 19B] 1 shows an exemplary schematic diagram of an embodiment of a wearable analyte monitoring device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] Non-limiting examples of various aspects and variations of the present invention are described herein and illustrated in the accompanying drawings.

[0033] Aspects of the present subject matter are directed to microneedle array-based analyte monitoring devices having an integrated applicator. In some variations, the integrated applicator mechanism allows a user to position the analyte monitoring device over a desired area for insertion into the skin and deploy the microneedle array to pierce the user's skin. In some variations, the analyte monitoring device is secured to the skin via an adhesive in the desired area before the microneedle array is deployed.

[0034] In some variations, the microneedle array-based analyte monitoring device (also referred to herein as an analyte monitoring device, a wearable analyte monitoring device, and / or a wearable analyte monitoring device with an integrated applicator) transitions the microneedle array from a first configuration to a second configuration. In some variations, the first configuration is a loaded configuration (e.g., when the microneedle array is in the first configuration, the analyte monitoring device and / or the biasing element are loaded ready to deploy the microneedle array) and the second configuration is a deployed configuration (e.g., when the microneedle array is in the second configuration, the analyte monitoring device and / or the biasing element are deployed such that the microneedle array is inserted into the user's skin). In the first configuration, the microneedle array is held within the housing of the wearable analyte monitoring device, away from surrounding electronics and housing components. By holding the microneedle array within the housing in the first configuration, the multiple microneedles of the microneedle array may be protected from damage prior to deployment. This arrangement allows the microneedle array to move in a generally vertical direction (e.g., transition to a deployed or second configuration) independent of the supporting electronics and housing. By isolating or separating the microneedle array from other components, the mass of the support structure holding the microneedle array is reduced, allowing the microneedle array to be accelerated quickly with relatively small displacements due to relatively small forces compared to moving the entire device body (e.g., as would be necessary with a separate applicator device). This arrangement minimizes impact momentum and reduces discomfort to the user upon impact. The reduced moving mass also allows the spring size and required spring force to be reduced to the extent that the components for effective insertion are small enough to fit inside the wearable sensor body housing.

[0035] In a variant, during assembly of the analyte monitoring device, the microneedle array is positioned in a first loading configuration, in which the microneedle array is retracted into the housing body and held in the first configuration by a holding element (such as a movable clip) that can be displaced by an actuation member, for example, from outside the housing body. In the first configuration, the biasing element is compressed under pressure and presses the microneedle array with a constant force (e.g., about 15 to about 35 Newtons). When the biasing element is released from the holding element via actuation by the user, the biasing element exerts an acceleration force on the microneedle array in the application direction. Due to its small mass, this force accelerates the microneedle array to a relatively high velocity (e.g., about 7 to about 14 m / s) over a very short displacement distance (e.g., about 1.5 to about 3 mm) to impact the skin. This velocity overcomes the viscoelastic mechanical properties of the skin surface, thus effectively and reliably inserting the microneedle array.

[0036] In some variations, the microneedle array maintains electrical connectivity with the electronics of the analyte monitoring device via a mechanically flexible connection. In some variations, the electrical connection with the electronics of the analyte monitoring device is established when the microneedle array reaches a deployed configuration or a second configuration in which the microneedle array protrudes from a distal opening for insertion into the user's skin. In some variations, a seal is maintained between the microneedle array and the housing during the transition from the first configuration to the second configuration. In some variations, the seal is established when the microneedle array reaches the deployed configuration or the second configuration.

[0037] Before providing further details regarding aspects of wearable analyte monitoring devices with integrated applicators, the following provides a description of some example analyte monitoring devices that may be used in conjunction with the wearable analyte monitoring devices described herein. The following description is intended to be illustrative, and aspects related to wearable analyte monitoring devices with integrated applicators consistent with the present subject matter are not limited to the example analyte monitoring devices described herein.

[0038] As generally described herein, an analyte monitoring system can include an analyte monitoring device that is worn by a user and includes one or more sensors for monitoring at least one analyte of the user. The sensor can include, for example, one or more electrodes configured to perform electrochemical detection of the at least one analyte. The analyte monitoring device can communicate sensor data to an external computing device for storage, display, and / or analysis of the sensor data.

[0039] For example, as shown in FIG. 1 , analyte monitoring system 100 may include an analyte monitoring device 110 worn by a user, which may be a continuous analyte monitor (e.g., a continuous glucose monitor). 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 bodily fluid of a user. Analyte monitoring device 110 may include one or more processors for performing analysis of the sensor data and / or a communication module (e.g., a wireless communication module) configured to communicate the sensor data to mobile computing device 102 (e.g., a smartphone) or other suitable computing device. In some variations, mobile computing device 102 may include one or more processors for executing a mobile application to process the sensor data (e.g., display the data, analyze the data for trends, etc.) and / or provide appropriate alerts or other notifications related to the sensor data and / or its analysis. It should be appreciated that, in some variations, the mobile computing device 102 may perform the sensor data analysis locally, while other computing devices may alternatively or additionally analyze the sensor data and / or communicate information related to such analysis to the mobile computing device 102 (or other suitable user interface) for display to a user. Further, in some variations, the mobile computing device 102 may be configured to communicate the sensor data and / or an analysis of the sensor data to one or more storage devices 106 (e.g., a server) via the network 104 for archiving data and / or other suitable information relevant to a user of the analyte monitoring device.

[0040] The analyte monitoring devices described herein have features that improve several properties advantageous to continuous analyte monitoring devices, such as continuous glucose monitoring (CGM) devices. For example, the analyte monitoring devices described herein have improved sensitivity (amount of sensor signal generated per given concentration of target analyte), improved selectivity (rejection of endogenous and exogenous circulating compounds that may interfere with detection of the target analyte), and improved stability to help minimize changes in sensor response over time due to storage and operation of the analyte monitoring device. Furthermore, compared to conventional continuous analyte monitoring devices, the analyte monitoring devices described herein have a shorter warm-up time that allows the sensor to quickly provide a stable sensor signal after implantation, as well as a shorter response time that allows the sensor to quickly provide a stable sensor signal after changes in the user's analyte concentration. Furthermore, as described in more detail below, the analyte monitoring devices described herein can be applied to and function within a variety of application sites, providing the user with a painless sensor insertion. Other properties, such as biocompatibility, sterilizability, and mechanical integrity, are also optimized in the analyte monitoring devices described herein.

[0041] Although the analyte monitoring systems described herein may be described with reference to monitoring glucose (e.g., in users with type 2 diabetes, type 1 diabetes), it should 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 include, for example, 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 enable monitoring of other indications such as stress (e.g., through detection of elevated cortisol and glucose) and ketoacidosis (e.g., through detection of elevated ketones).

[0042] As shown in FIG. 2A, in some variations, the analyte monitoring device 110 may generally include a housing 112 and a microneedle array 140. In some variations, the microneedle array extends outwardly from the housing when in a deployed configuration. The housing 112 may be a wearable housing configured to be worn on the skin of a user, such that the microneedle array 140 extends at least partially into the user's skin after deployment. For example, the housing 112 may include an adhesive such that the analyte monitoring device 110 is a simple and easy skin-adhesive patch for application to a user. The microneedle array 140 may include one or more electrochemical sensors (e.g., electrodes) configured to pierce the user's skin and to measure one or more target analytes accessible after the microneedle array 140 pierces 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., used for a period of time and replaced with another instance of the analyte monitoring device 110).

[0043] The electronics system 120 may include various electronic components, such as a sensor circuit 124 disposed at least partially within the housing 112 and configured to perform signal processing (e.g., biasing and readout of an electrochemical sensor, converting an analog signal from the electrochemical sensor to a digital signal, etc.). The electronics 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 source 130, and / or various other suitable passive circuitry 127. The microcontroller 122 may be configured, for example, to interpret digital signals output from the sensor circuit 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 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. In some variations, one or more antennas 128 of the communication module 126 are configured for near-field wireless communication. For example, the communication module 126 may be configured to provide unidirectional and / or bidirectional communication of data with an external computing device 102 to which the analyte monitoring device 110 is paired. The power source 130 may provide power to the analyte monitoring device 110 for the electronics system, and the like. The power source 130 may include a battery or other suitable power source, and in some variations may be rechargeable and / or replaceable. The passive circuitry 127 may include various non-powered electrical circuits (e.g., resistors, capacitors, inductors, and the like) that provide interconnections between other electronic components, and the like. The passive circuitry 127 may be configured to perform, for example, noise reduction, biasing, and / or other purposes. In some variations, the electronic components in the electronics system 120 may be disposed on one or more printed circuit boards (PCBs), which may be, for example, rigid, semi-rigid, or flexible.Further details of electronic device system 120 are described further below.

[0044] 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 the sensor measurements obtained by the microneedle array electrochemical sensor.

[0045] The microneedle array 140 in the analyte monitoring device 110 is configured to pierce the skin of a user. As shown in FIG. 2B, when the device 110 is worn by a user, the microneedle array 140 may be deployed to extend into the user's skin such that the electrodes on the distal regions of the microneedles reside in the dermis. Specifically, in some variations, the microneedles may be designed to penetrate the skin and access the upper skin regions of the skin (e.g., the papillary dermis and upper reticular dermis layers) to allow the electrodes to access the interstitial fluid surrounding the cells of these layers. For example, in some variations, the microneedles may have a height generally ranging from at least 350 μm to about 515 μm. In some variations, one or more microneedles may extend from the housing such that in the deployed configuration, the distal ends of the electrodes on the microneedles are positioned less than about 5 mm from the skin contacting surface 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.

[0046] In contrast to conventional continuous analyte monitoring devices (e.g., CGM devices), which typically include sensors embedded about 8 mm to about 10 mm below the skin surface in the subcutaneous tissue or fat layer of the skin, the analyte monitoring device 110 has a shallower microneedle insertion depth of about 0.25 mm (such that the electrodes are embedded in the upper dermal region of the skin), which provides many advantages. These advantages include at least access to the skin interstitial fluid, which contains one or more target analytes for detection, since it has been found that at least some types of analyte measurements in skin interstitial fluid are closely correlated with analyte measurements in blood. For example, glucose measurements performed using electrochemical sensors that access skin interstitial fluid have been found to be advantageously highly linearly correlated with blood glucose measurements. Thus, glucose measurements based on skin interstitial fluid are highly representative of blood glucose measurements.

[0047] Additionally, the shallower microneedle insertion depth of the analyte monitoring device 110 results in reduced time delay in analyte detection compared to conventional continuous analyte monitoring devices. Such shallower insertion depth positions the sensor surface in close proximity (e.g., within a few hundred micrometers or less) to the dense, well-perfused capillary bed of the reticular dermis, resulting in negligible diffusion lag from the capillaries to the sensor surface. The diffusion time is t=x 2 / (2D), where t is the diffusion time, x is the diffusion distance, and D is the mass diffusivity of the analyte of interest. Thus, positioning the analyte sensing element twice as far away from the analyte source in the capillary increases the diffusion delay time by four times. Thus, conventional analyte sensors (which reside in the very poorly vascularized adipose tissue below the dermis) experience significantly longer diffusion distances from the vasculature in the dermis, resulting in substantial diffusion latencies (e.g., typically 5-20 minutes). In contrast, the shallower microneedle insertion depth of the analyte monitoring device 110 benefits from low diffusion latencies from the 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 latencies can be less than 10 minutes, less than 5 minutes, or less than 3 minutes.

[0048] Furthermore, when the microneedle array is in the upper skin region, the lower dermis below the microneedle array contains very high levels of vascularization and perfusion to support dermal metabolism, which allows for thermoregulation (via vasoconstriction and / or vasodilation) and provides a barrier function that helps stabilize the sensing environment around the microneedles. Yet another advantage of a shallower insertion depth is that the upper dermal layer lacks pain receptors, thus reducing the sensation of pain when the microneedle array pierces the user's skin, providing a more comfortable and less invasive user experience.

[0049] Thus, the analyte monitoring devices and methods described herein allow for improved continuous monitoring of one or more target analytes in a user. For example, as described above, the analyte monitoring devices can be simple and easy to apply, thereby improving ease of use and user compliance. Furthermore, analyte measurement in skin interstitial fluid can provide highly accurate analyte detection. Furthermore, compared to conventional continuous analyte monitoring devices, insertion of the microneedle array and its sensors can be less invasive and less painful for the user. Additional advantages of other aspects of the analyte monitoring devices and methods are further described below.

[0050] Figures 3A-3D show an embodiment of an analyte monitoring device 110. Figures 3A-3D show a top perspective view, a side view, a bottom view, and an exploded view, respectively, of analyte monitoring device 110.

[0051] The analyte monitoring device 110 may include a housing that defines a cavity that at least partially surrounds or encloses other components (e.g., electronic components) of the analyte monitoring device 110, such as to protect such components. For example, the housing may be configured to help prevent dust and moisture from entering the analyte monitoring device 110. In some variations, an adhesive layer may be provided at a distal end of the housing to attach the housing to a surface (e.g., skin) of a user. In some variations, after the housing is attached to a surface, the microneedle array 140 may be deployed to extend outwardly from the housing and into the skin of the user. Additionally, in some variations, the housing may generally include rounded edges or corners and / or may be low-profile to reduce interference with clothing worn by the user, and the like.

[0052] 3A-3D, an exemplary variation of analyte monitoring device 110 can include a housing cover 320 and a base plate 330 configured to at least partially enclose the internal components of analyte monitoring device 110. For example, housing cover 320 and base plate 330 can provide an enclosure for a sensor assembly 350 that includes microneedle array 140 and electronic components. When deployed, microneedle array 140 extends outwardly from a portion of base plate 330 in a skin-facing direction (e.g., underside) of analyte monitoring device 110.

[0053] The housing cover 320 and the base plate 330 may include one or more rigid or semi-rigid protective shell components that may be coupled to one another via, for example, suitable fasteners (e.g., mechanical fasteners), mechanical interlocking or mating features, and / or engineered fits. The housing cover 320 and the base plate 330 may include rounded edges and corners, and / or other atraumatic features. When coupled to one another, the housing cover 320 and the base plate 330 may form a cavity that includes an interior volume that houses internal components, such as the sensor assembly 350. For example, the internal components disposed within the interior volume may be arranged in a compact, low-profile stack as the sensor assembly 350.

[0054] Analyte monitoring device 110 may include one or more adhesive layers provided at a distal end of the housing for attaching analyte monitoring device 110 (e.g., housing cover 320 and base plate 330 coupled together) to a surface (e.g., skin) of a user. As shown in FIG. 3D , the one or more adhesive layers may include an inner adhesive layer 342 and an outer adhesive layer 344. Inner adhesive layer 342 may adhere to base plate 330, and outer adhesive layer 344 may adhere to inner adhesive layer 342 and provide an adhesive on its outwardly facing side for (e.g., temporarily) adhering to the skin of a user. Inner adhesive layer 342 and outer adhesive layer 344 together function as a double-sided adhesive for adhering analyte monitoring device 110 to the skin of a user. Outer adhesive layer 344 may be protected by a release liner that a user removes to expose the adhesive prior to application to the skin. In some variations, a single adhesive layer is provided. In some variations, the outer adhesive layer 344, the inner adhesive layer 342, and / or the single adhesive layer may have an outer periphery that extends further than the outer periphery or perimeter of the housing cover 320 and the base plate 330. This may increase the surface area for attachment and increase the stability of retention or attachment to the user's skin. The inner adhesive layer 342, the outer adhesive layer 344, and / or the single adhesive layer may each have an opening that allows the outwardly extending microneedle array 140 to pass through when deployed, as described further below. The openings in the inner adhesive layer 342 and the outer adhesive layer 344 may generally be aligned with one another, but in some variations may differ in size such that one opening is smaller than the other. In some variations, the openings are substantially the same size.

[0055] The base plate 330 has a first surface (e.g., an outer exposed surface) opposite a second surface and functions as a support and / or connection structure as well as a protective cover for the sensor assembly 350. The base plate 330 is sized and shaped to attach to the housing cover 320. The base plate 330 may be molded to fit securely within the housing cover 320 such that an outer edge of the base plate 330 aligns with a corresponding edge of the opening in the housing cover 320. The alignment may be such that there is no gap between the outer edge of the base plate 330 and the corresponding edge of the opening in the housing cover 320.

[0056] A central or near-central region of the first surface of the base plate 330 may have a connecting member 332 formed therein. The connecting member 332 is a protrusion (e.g., a protruding hub) having a sidewall extending from the first surface of the base plate 330 and a first surface substantially parallel to the first surface of the base plate 330. The sidewall extends from an edge of the first surface of the connecting member 332 to the first surface of the base plate 330. The remaining portion of the first surface of the base plate 330 surrounding the connecting member 332 may be flat or substantially flat. One or more connector features 336 extend outwardly from the sidewall of the connecting member 332 to releasably engage with a corresponding connector of, for example, a microneedle enclosure providing a sterile environment for the microneedle array 140. The first surface and the sidewall of the connecting member 332 partially define a chamber. The chamber may be further defined by a portion of the base plate 330 adjacent (e.g., below) the connecting member 332. The chamber is accessible through an opening on the second surface of the base plate 330. An aperture or distal opening 334 is formed through the first surface of the connecting member 332. The distal opening 334 may be sized and shaped such that the microneedle array 140 fits securely within and extends through the distal opening 334 when in the deployed configuration. For example, the sidewalls of the microneedle array 140 may align with corresponding sidewalls of the distal opening 334. In some variations, the distal opening 334 may be sized and shaped to correspond to an 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) may be sized such that the connecting member 332 extends through the opening 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 those of 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 a single adhesive layer) is adjacent to a sidewall of the connecting member 332 with clearance to accommodate one or more connector features 336.In some variations, one or more slits or notches may be formed in the inner adhesive layer 342, the outer adhesive layer 344, and / or the single adhesive layer, extending from the opening to aid in positioning of the respective adhesive layers.

[0057] Although the housing cover 320 and base plate 330 shown in Figures 3A-3D are substantially circular, with the housing cover 320 having a dome shape, in other variations the housing cover 320 and base plate 330 may have any suitable shape. For example, in other variations the housing cover 320 and base plate 330 may be generally prismatic, may have an elliptical, triangular, rectangular, pentagonal, hexagonal, or other suitable shape. The outer adhesive layer 344 (or single adhesive layer) may extend outwardly from the housing cover 320 and base plate 330 and may extend beyond the outer periphery of the housing cover 320. The outer adhesive layer 344 (or single adhesive layer) may be circular, as shown in Figures 3A-3D, or may have an elliptical, 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.

[0058] 4A-4E show an embodiment of a sensor assembly 350 of an analyte monitoring device 110 in exploded perspective, exploded side, bottom perspective, side, and top perspective views, respectively.

[0059] The sensor assembly 350 includes microneedle array components and electronics for implementing the analyte detection and processing aspects of the microneedle array-based continuous analyte monitoring device 110 for analyte detection and measurement. In some variations, the sensor assembly 350 is a compact, low-profile laminate that is at least partially contained within a cavity that includes an interior volume defined by the housing cover 320 and the base plate 330.

[0060] In some variations, the sensor assembly 350 includes a microneedle array assembly 360 and an electronics assembly 370 that connect to each other to implement the microneedle array analyte detection and processing aspects described further herein. In some variations, the electronics assembly 370 includes a primary printed circuit board (PCB) 450 to which the electronic components are connected, and the microneedle array assembly 360 includes a secondary printed circuit board (PCB) 420 to which the microneedle array 140 is connected.

[0061] In some variations, the microneedle array assembly 360 includes, in addition to the secondary PCB 420 and the microneedle array 140, an epoxy skirt 410 and a secondary PCB connector 430. The microneedle array 140 is coupled to a top side (e.g., an outwardly facing side) of the secondary PCB 420 such that the individual microneedles of the microneedle array 140 are exposed, as described with reference to Figures 3A-3D. The secondary PCB connector 430 is coupled to a back side opposite the top side of the secondary PCB 420. The secondary PCB connector 430 may be an electromechanical connector and may be communicatively coupled to the primary PCB 450 via a primary PCB connector 470 on a top side (e.g., an outwardly facing side) of the primary PCB 450 to enable signal communication between the secondary PCB 420 and the primary PCB 450. For example, signals from the microneedle array 140 can be communicated to the primary PCB 450 via the secondary PCB 420, the secondary PCB connector 430, and the primary PCB connector 470.

[0062] The secondary PCB 420 may in part determine the distance that the microneedle array 140 protrudes from the base plate 330 of the housing. Thus, the height of the secondary PCB 420 may 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 outwardly facing surface) of the connecting member 332 of the base plate 330 may act as a stop for the microneedle insertion. If the height of the secondary PCB 420 is low and its top surface is flush or nearly flush with the first surface of the connecting member 332, the connecting member 332 may prevent the microneedle array 140 from being fully inserted into the skin.

[0063] In some variations, other components (e.g., electronic components such as sensors or other components) may also be connected to secondary PCB 420. For example, secondary PCB 420 may be sized and shaped to accommodate electronic components on the top or back side of secondary PCB 420.

[0064] In some variations, the epoxy skirt 410 may be deposited along the edges (e.g., periphery) of the microneedle array 140 to provide a tight fit of the microneedle array 140 into the distal opening 334 formed in the connecting member 332 of the base plate 330 and / or to soften sharp edges along the microneedle array 140, as shown in Figures 3C and 3D. For example, the epoxy skirt 410 may occupy the portion of the distal opening 334 not filled by the microneedle array 140 and / or the portion of the chamber defined in the base plate 330 not filled by the secondary PCB 420. The epoxy skirt 410 may also provide a transition from the edge of the microneedle array 140 to the edge of the secondary PCB 420. In some variations, the epoxy skirt 410 may be replaced or supplemented by a gasket (e.g., a rubber gasket) or the like.

[0065] The electronics assembly 370 with the primary PCB 450 includes a battery 460 coupled to a back side of the primary PCB 450, opposite the top side to which the primary PCB connector 470 is coupled. In some variations, the battery 460 may be coupled to the top side of the primary PCB 450 and / or in other arrangements.

[0066] Figures 4F-H show an embodiment of an alternative variation of a sensor assembly 350 of analyte monitoring device 110. Perspective exploded views, side exploded views, and side views of sensor assembly 350 are provided in Figures 4F-H, respectively.

[0067] As shown, the sensor assembly 350 incorporates an additional PCB component, the intermediate PCB 425. In some variations, the intermediate PCB 425 is part of the microneedle array assembly 360 and is positioned between and connected to the secondary PCB 420 and the microneedle array 140. The intermediate PCB 425 may be added to increase the height of the microneedle array assembly 360, so that the microneedle array 140 extends a greater distance from the base plate 330, which may aid in the insertion of the microneedle array 140 into the skin of a user. The microneedle array 140 is coupled to a top side (e.g., an outwardly facing side) of the intermediate PCB 425 such that the individual microneedles of the microneedle array 140 are exposed, as described with reference to Figures 3A-3D. The secondary PCB 420 is bonded to the back side, opposite the top side, of the intermediate PCB 425, and the secondary PCB connector 430 is bonded to the back side, opposite the top side, of the secondary PCB 420. An epoxy skirt 410 (which may be replaced or supplemented by an equivalent gasket) provides a transition from the edge of the microneedle array 140 to the edge of the intermediate PCB 425.

[0068] The intermediate PCB 425 with the secondary PCB 420 determines, in part, the distance that the microneedle array 140 protrudes through the distal opening 334 of the base plate 330. The incorporation of the intermediate PCB 425 provides additional height that helps ensure that the microneedle array 140 is properly inserted into the user's skin. In some variations, the top side (e.g., the outwardly facing side) of the intermediate PCB 425 extends out through the distal opening 334, such that the first surface (e.g., the exposed top surface) of the connection member 332 surrounding the distal opening 334 does not prevent the microneedle array from being fully inserted into the skin. In some variations, the top side (e.g., the outwardly facing side) of the intermediate PCB 425 does not extend out of the distal opening 334, but the increased height (by incorporating the intermediate PCB 425) ensures that the microneedle array 140 protrudes a sufficient distance from the base plate 330 of the housing.

[0069] In some variations, a microneedle enclosure may be provided for releasable attachment to the analyte monitoring device 110. The microneedle enclosure 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 manufacturing and shipping of the analyte monitoring device 110 prior to application of the analyte monitoring device 110. The microneedle enclosure is releasable or removable from the analyte monitoring device 110 so that the microneedle array 140 is exposed and / or ready for insertion into a user's skin, as described further herein.

[0070] In some variations, the microneedle enclosure provides an environment in which the microneedle array 140 may be sterilized by providing an enclosed and sealed environment in which the microneedle array 140 may be contained. For example, the microneedle enclosure with the microneedle array 140 may be subjected to a sterilization process in which the sterilization penetrates the microneedle enclosure such that the microneedle array 140 is also sterilized. Because the microneedle array 140 is contained within an enclosed environment, the microneedle array 140 remains sterile until it is removed from the enclosed environment. In some variations, a removable film is provided at the distal end of the housing to cover the distal opening 334 prior to application of the analyte monitoring device 110 to a skin surface of a subject. The removable film may maintain a sterile environment and prevent the entry of foreign objects or extraneous substances prior to application of the analyte monitoring device 110. A user may remove or peel off the film immediately prior to application and / or adhesion of the analyte monitoring device 110 to a skin surface of a subject.

[0071] In some variations, the electronics system of the analyte monitoring device 110 may include an analog front end. The analog front end may include a sensor circuit (e.g., sensor circuit 124 as shown in FIG. 2A) that converts analog current measurements into digital values ​​that can be processed by a microcontroller. The analog front end may include, for example, a programmable analog front end suitable for use with an electrochemical sensor. For example, the analog front end may include MAX30131, MAX30132, or MAX30134 components (having 1, 2, and 4 channels, respectively) available from Maxim Integrated (San Jose, Calif.), which are ultra-low power programmable analog front ends for use with electrochemical sensors. The analog front end may also include AD5940 or AD5941 components available from Analog Devices (Norwood, Mass.), which are high-precision, impedance, and electrochemical front ends. Similarly, the analog front end may also include the LMP91000 available from Texas Instruments (Dallas, TX), which is a configurable analog front end potentiostat for low power chemical sensing applications. The analog front end may provide bias and a complete measurement path including an analog to digital converter (ADC). The ultra-low power may allow continuous biasing of the sensor to maintain accuracy and fast response when measurements are required for extended periods (e.g., 7 days) using a body-worn battery-operated device.

[0072] In some variations, the analog front-end device may be compatible with both two and three terminal electrochemical sensors, such as to enable both DC current measurement, AC current measurement, and electrochemical impedance spectroscopy (EIS) measurement capabilities. Additionally, the analog front-end may include an internal temperature sensor and programmable voltage reference, support external temperature monitoring and external reference sources, and integrate voltage monitoring of bias and supply voltages for safety and compliance.

[0073] In some variations, the analog front end may include a multi-channel potentiostat for multiplexing the sensor inputs and processing multiple signal channels, for example, the analog front end may include a multi-channel potentiostat such as that described in U.S. Patent No. 9,933,387, which is incorporated herein by reference in its entirety.

[0074] In some variations, the analog front end and peripheral electronics may be integrated into an application specific integrated circuit (ASIC), which may help to reduce costs, for example. This integrated solution may include a microcontroller, as described below.

[0075] In some variations, the electronics system of the analyte monitoring device may include at least one microcontroller (e.g., controller 122 shown in FIG. 2A). 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 that correlates the sensor signal to an analyte measurement (e.g., a glucose measurement). For example, the microcontroller may execute programmed routines in firmware to interpret the digital signal (e.g., from the analog front end), perform any associated algorithms and / or other analysis, and route the processed data to and from the communications module. By keeping the analysis on-board the analyte monitoring device, for example, the analyte monitoring device may broadcast analyte measurements in parallel to multiple devices (e.g., mobile computing devices such as smartphones or smartwatches, therapy delivery systems such as insulin pens or pumps, etc.) while ensuring that each connected device has the same information.

[0076] In some variations, the microcontroller may be configured to activate and / or deactivate the analyte monitoring device upon one or more detected conditions. For example, the device may be configured to power up the analyte monitoring device upon deployment or insertion of the microneedle array into the skin. This may enable a power saving feature, for example, where the battery is disconnected until the microneedle array is deployed, at which point the device may begin broadcasting sensor data. Such a feature may help, for example, to improve the shelf life of the analyte monitoring device and / or simplify the analyte monitoring device-external device pairing process for a user.

[0077] As shown in the schematic diagram of FIG. 5A, in some variations, a microneedle array 510 for use in sensing an analyte may include one or more microneedles 510 protruding from a substrate surface 502. The substrate surface 502 may be, for example, a substantially planar semiconductor (e.g., silicon) substrate, and the one or more microneedles 510 may protrude orthogonally from the plane. In general, as shown in FIG. 5B, the microneedle 510 may include a body portion 512 (e.g., shaft) and a tapered distal portion 514 configured to pierce the skin of a user. In some variations, the tapered distal portion 514 may terminate in an insulated distal tip 516. The microneedle 510 may further include an electrode 520 on a surface of the tapered distal portion. In some variations, the electrode-based measurement may be performed at the interface of an electrode placed inside the body and interstitial fluid (e.g., on the outer surface of the entire microneedle). In some variations, the microneedle 510 may have a solid core (e.g., a solid body portion), while in some variations, the microneedle 510 may include one or more lumens that may be used, for example, for drug delivery or sampling of skin interstitial fluid. Other microneedle variations, as described below, may similarly include either a solid core or one or more lumens.

[0078] The microneedle array 500 may be at least partially formed from a semiconductor (e.g., silicon) substrate and includes various layers of materials applied and shaped using various suitable microelectromechanical systems (MEMS) fabrication techniques (e.g., deposition and etching techniques), as described further below. The microneedle array may be reflow soldered to the circuit board, similar to a typical integrated circuit. Furthermore, in some variations, the microneedle array 500 may include a three-electrode configuration including a working (sensing) electrode having an electrochemical sensing coating (including a biorecognition element such as an aptamer or enzyme) that allows for detection of an analyte, a reference electrode, and a counter electrode. In other words, the microneedle array 500 may include at least one microneedle 510 that includes a working electrode, at least one microneedle 510 that includes a reference electrode, and at least one microneedle 510 that includes a counter electrode. Further details of these types of electrodes are described in more detail below.

[0079] In some variations, the microneedle array 500 may include multiple microneedles that are insulated such that the electrodes on each microneedle in the multiple microneedles are individually addressable and electrically isolated from all other electrodes on the microneedle array. The resulting individual addressability of the microneedle array 500 may allow greater control over the function of each electrode since each electrode can be probed separately. For example, the microneedle array 500 may be used to provide multiple independent measurements of a given analyte, thereby improving the sensing reliability and accuracy of the device. Furthermore, in some variations, the electrodes of the multiple microneedles may be electrically connected to generate enhanced signal levels. As another example, the same microneedle array 500 may additionally or alternatively be interrogated to measure multiple analytes simultaneously to provide a more comprehensive assessment of a physiological condition. For example, as shown in the schematic diagram of FIG. 6, the microneedle array may include a portion of microneedles for detecting a first analyte A, a second portion of microneedles for detecting a second analyte B, and a third portion of microneedles for detecting a third analyte C. It should be understood that the microneedle array may be configured to detect any suitable number of analytes (e.g., 1, 2, 3, 4, 5 or more, etc.), provided that at least one of the analytes detected is an analyte.

[0080] In some variations of the microneedle (e.g., a microneedle having a working electrode), the electrode 520 may be positioned proximal to the insulated distal apex 516 of the microneedle. In other words, in some variations, the electrode 520 does not cover the apex of the microneedle. Rather, the electrode 520 may be offset from the apex or tip of the microneedle. The electrode 520 is proximal to or offset from the insulated distal apex 516 of the microneedle, advantageously providing more accurate sensor measurements. For example, this arrangement prevents concentration of the electric field at the microneedle apex 516 during manufacturing, thereby avoiding uneven deposition of the sensing chemistry on the electrode surface 520 that would result in erroneous sensing. The electrode 520 may be configured to have an annular shape and may include a distal edge 521a and a proximal edge 521b.

[0081] As another example, placing the electrode 520 offset from the microneedle apex further improves sensing accuracy by reducing undesirable signal artifacts and / or erroneous sensor readings caused by stresses during microneedle insertion. The distal apex of the microneedle is the first area to penetrate the skin and therefore experiences the greatest stresses caused by mechanical shear phenomena associated with tearing or cutting the skin. If the electrode 520 were placed at the apex or tip of the microneedle, this mechanical stress could peel off the electrochemical sensing coating on the electrode surface when the microneedle is inserted and / or cause a small but interfering amount of tissue to be transported onto the active sensing portion of the electrode. Thus, placing the electrode 520 sufficiently offset from the microneedle apex can improve sensing accuracy. For example, in some variations, the distal edge 520 of the electrode 521a can be placed 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.

[0082] The body portion 512 of the microneedle 510 may further include a conductive path extending between the electrode 520 and a back electrode or other electrical contact (e.g., disposed on the back side of the substrate of the microneedle array). The back electrode may be soldered to a circuit board and may be in electrical communication with the electrode 520 via the conductive path. For example, during use, the in vivo sensed current measured at the working electrode (inside the dermis) is interrogated by the back electrical contact, and the electrical connection between the back electrical contact and the working electrode is facilitated by the conductive path. In some variations, this conductive path may be facilitated by a metal via running through the interior of the microneedle body portion (e.g., shaft) between the proximal and distal ends of the microneedle. Alternatively, in some variations, the conductive path may be provided by the entire body portion formed from a conductive material (e.g., doped silicon). In some of these variations, the complete substrate on which the microneedle array 500 is constructed may be conductive, and each microneedle 510 of the microneedle array 500 may be electrically isolated from adjacent microneedles 510 as described below. For example, in some variations, each microneedle 510 in the microneedle array 500 may be electrically isolated from adjacent microneedles 510 using an insulating barrier including an electrically insulating material (e.g., a dielectric material such as silicon dioxide) that surrounds the conductive pathway extending between the electrode 520 and the backside electrical contact. For example, the body portion 512 may include an insulating material that forms a sheath around the conductive pathway, thereby preventing electrical communication between the conductive pathway and the substrate. Other exemplary variations in structures that provide electrical isolation between microneedles are described in more detail below.

[0083] Such electrical isolation between the microneedles in the microneedle array allows the sensors to be individually addressable. This individual addressability advantageously allows for independent parallelized measurements between sensors, as well as dynamic reconfiguration of sensor assignments (e.g., for different analytes). In some variations, the electrodes of the microneedle array can be configured to provide redundant analyte measurements, which is an advantage over conventional analyte monitoring devices. For example, redundancy can improve performance by improving accuracy (e.g., averaging multiple analyte measurements from different microneedles, which reduces the impact of extremely high or low sensor signals on the determination of analyte levels) and / or can improve device reliability by reducing the likelihood of overall failure.

[0084] In some variations, as described in further detail below with each different variation of microneedles, the microneedle array may be at least partially formed by suitable semiconductor and / or MEMS manufacturing techniques and / or mechanical cutting or dicing. Such processes may be advantageous, for example, to enable large-scale, cost-effective manufacture of microneedle arrays.

[0085] Further exemplary variations of microneedle structures incorporating one or more of the microneedle features described above for microneedle arrays in analyte monitoring devices are described herein.

[0086] In some variations, the microneedle may have a generally cylindrical body portion and a tapered distal portion having an electrode. For example, Figures 7A-7C show an exemplary variation of a microneedle 700 extending from a substrate 702. Figure 7A is a schematic side cross-sectional view of the microneedle 700, Figure 7B is a perspective view of the microneedle 700, and Figure 7C is a detailed perspective view of the distal portion of the microneedle 700. As shown in Figures 7B and 7C, the microneedle 700 may include a cylindrical body portion 712, a tapered distal portion 714 terminating in an insulated distal apex 716, and a ring electrode 720. The ring electrode 720 includes a conductive material (e.g., Pt, Ir, Au, Ti, Cr, Ni, combinations thereof, etc.) disposed on the tapered distal portion 714, e.g., on a segment thereof, and includes a distal edge 721a and a proximal edge 721b. 7A, the ring electrode 720 may be proximal to (or offset or spaced from) the distal apex 716. The ring electrode 720 may be electrically insulated from the distal apex 716 by a distal insulating surface 715a that includes an insulating material (e.g., SiO2). For example, the distal edge 721a of the ring electrode 720 may be proximate to the proximal edge of the distal insulating surface 715a of the insulated distal apex 716. In some variations, the distal edge 721 a of the ring electrode 720 may be proximal (e.g., immediately proximal, adjacent, abutting) the proximal edge of the distal apices 716 (the proximal edge of the distal insulating surface 715 a), while in other variations, the distal edge 721 a of the ring electrode 720 may be distal (e.g., immediately distal, adjacent) to the proximal edge of the insulated distal apices 716 (the proximal edge of the distal insulating surface 715 a), but remain proximal to the apices themselves. Thus, in some variations, the ring electrode 720 may overlie a portion of the distal insulating surface 715 a, but remain proximal to (and may be offset from) the insulated distal apices themselves.

[0087] 7A, the proximal edge 721b of the ring electrode 720 may be distal to the cylindrical body portion 712, or in some variations may be offset or spaced therefrom. In some variations, the proximal edge 721b of the ring electrode 720 may also be electrically insulated from the cylindrical body portion 712 by a second distal insulating surface 715b comprising an insulating material (e.g., SiO2) at the proximal end or region of the tapered distal portion 714. For example, the proximal edge 721b of the ring electrode 720 may be proximate to the distal edge of the second distal insulating surface 715b. In some variations, the proximal edge 721b of the ring electrode 720 may be proximal (e.g., immediately proximal, adjacent, abutting) to the distal edge of the second distal insulating surface 715b, while in other variations, the proximal edge 721b of the ring electrode 720 may be distal (e.g., immediately distal, adjacent) to the distal edge of the second distal insulating surface 715b, but remain proximal to the cylindrical body portion 712. Thus, in some variations, the ring electrode 720 may overlie a portion of the second distal insulating surface 715b, but remain proximal to (and offset from) the cylindrical body portion 712. As shown in FIG. 7A and in some other variations, the ring electrode 720 may be on only a portion of the surface of the tapered distal portion 714, and may or may not extend to the cylindrical body portion 712.

[0088] The electrode 720 may be in electrical communication with a conductive core 740 (e.g., a conductive path) that passes along the body portion 712 to a backside electrical contact 730 (e.g., made from a Ni / Au alloy) or other electrical pad in or on the substrate 702. For example, the body portion 712 may include a conductive core material (e.g., heavily doped silicon). As shown in FIG. 7A, in some variations, an insulating moat 713 including an insulating material (e.g., SiO2) may be disposed around (e.g., around the periphery) the body portion 712 and extend at least partially through the substrate 702. The insulating moat 713 may thus help to prevent electrical contact between, for example, the conductive core 740 and the surrounding substrate 702. The insulating moat 713 may extend further over the surface of the body portion 712. The top and / or bottom surface of the substrate 702 may also include a substrate insulating layer 704 (e.g., SiO2). Thus, the insulation provided by the insulating moat 713 and / or the substrate insulator 704 may at least partially contribute to the electrical insulation of the microneedle 700 enabling addressability of the microneedle 700 within a microneedle array. Additionally, in some variations, the insulating moat 713 extending over a surface of the body portion 712 may function to increase the mechanical strength of the microneedle 700 structure.

[0089] The microneedle 700 may be formed at least in part by a suitable MEMS fabrication technique, such as plasma etching, also referred to as dry etching. For example, in some variations, the insulating moat 713 around the body portion 712 of the microneedle may be fabricated by first forming a trench in a silicon substrate by deep reactive ion etching (DRIE) from the backside of the substrate, and then filling the trench with a SiO2 / polycrystalline silicon (poly-Si) / SiO2 sandwich by low pressure chemical vapor deposition (LPCVD) or other suitable process. In other words, the insulating moat 713 passivates the surface of the body portion 712 of the microneedle and may continue as a recessed feature in the substrate 702 near the proximal portion of the microneedle. By including a compound that is primarily silicon, the insulating moat 713 may provide good filling and adhesion to adjacent silicon walls (e.g., conductive core 740, substrate 702, etc.). The sandwich structure of the insulating moat 713 can further help provide an excellent coefficient of thermal expansion (CTE) match with the adjacent silicon, thereby advantageously reducing failure, cracking, and / or other thermally induced weaknesses of the insulating structure 713.

[0090] The tapered distal portion may be formed by isotropic dry etching from the front side of the substrate, and the body portion 712 of the microneedle 700 may be formed by DRIE. A front metal electrode 720 may be deposited and patterned on the distal portion by special lithography (e.g., electron beam evaporation) that allows metal deposition on the desired annular region of the electrode 720 without coating the distal tip 716. Additionally, a Ni / Au backside electrical contact 730 may be deposited by an appropriate MEMS fabrication technique (e.g., sputtering).

[0091] The microneedle 700 may have any suitable dimensions. By way of example, the microneedle 700 may have a height of about 300 μm to about 500 μm in some variations. In some variations, the tapered distal portion 714 may have a tip angle of about 60 degrees to about 80 degrees and a top diameter of about 1 μm to about 15 μm. In some variations, the surface area of ​​the ring electrode 720 may be about 9000 μm. 2 ~about 11000μm 2 , or about 10,000 μm 2 FIG. 8 illustrates various dimensions of an exemplary variation of a cylindrical microneedle having a tapered distal portion and an annular electrode, similar to the microneedle 700 described above. The cylindrical microneedle of FIG. 8 includes a cylindrical body portion, a tapered distal portion terminating in an insulated distal apex, a contact trench formed in the tapered distal portion, and an annular electrode (labeled "Pt" in FIG. 8) disposed on the tapered distal portion and covering the contact trench, similar to the microneedle 700 described above. The annular electrode may include a conductive material (e.g., Pt, Ir, Au, Ti, Cr, Ni, combinations thereof, etc.). In some variations, the contact trench may have a width of about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 35 μm, about 40 μm, about 45 μm, about 50 μm, or about 20 μm as shown in Figure 8. The ring electrode may include a distal edge and a proximal edge, and in some variations, the distance between the distal and proximal edges of the ring electrode may be about 20 μm, about 30 μm, about 40 μm about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, or about 60 μm as shown in Figure 8. In some variations, as shown in FIG. 8 by the dimension callouts 60 μm and 20 μm, the annular electrode may overlap the contact trench and, possibly, a portion of the insulating surface of the tapered distal portion (labeled "Oxide" in FIG. 8).

[0092] 9A-9F show another exemplary variation of a microneedle 900 having a generally cylindrical body portion extending from a substrate 902 having an upper surface 904. The microneedle 900 may be similar to the microneedle 700 described above, except as described below. For example, as shown in FIG. 9B, similar to the microneedle 700, the microneedle 900 may include a cylindrical body portion 912 and a tapered distal portion disposed on a cylinder 913 and terminating in an insulated distal apex 916. The cylinder 913 may be insulated and may have a smaller diameter than the cylindrical body portion 912. The microneedle 900 may further include a ring electrode 920 comprising a conductive material and disposed on the tapered distal portion proximal to (or offset or spaced from) the distal apex 916. The electrode 920 may be in electrical communication with a conductive core 940 (e.g., a conductive pathway) that passes along the body portion 912 to a backside electrical contact 930 (e.g., made from a Ni / Au alloy) or other electrical pad in or on the substrate 902. Other elements of the microneedle 900 shown in Figures 9A-9F are numbered similarly to corresponding elements of the microneedle 700.

[0093] As can be seen most easily in Figures 9B, 9C, and 9F, the tapered distal portion 914, and more specifically, the electrode 920 on the tapered distal portion 914 of the microneedle 900, can include a tip contact trench 922. This contact trench can be configured to establish an ohmic contact between the electrode 920 and the underlying conductive core 940 of the microneedle. In some variations, the shape of the tip contact trench 922 can include an annular recess formed in a surface of the tapered distal portion 914. In some variations, the shape of the tip contact trench 922 can include an annular recess formed in a surface of the conductive core 940 (e.g., in contact with a conductive path within or otherwise within the body portion of the microneedle). In some variations, the tip contact trench 922 can be formed in an insulating material on the tapered distal portion 914 and can have a depth approximately equal to a thickness of the insulating material (e.g., distal insulating surface 915a and / or second distal insulating surface 915b). In some examples, the depth of the contact trench may be greater than the thickness of the insulating material such that the contact trench extends beyond the surface of the conductive core 940 (e.g., into the conductive core 940). The electrode 920 may overlie the tip contact trench 922 such that an ohmic contact is established between the electrode 920 and the conductive core 940. In some variations, the electrode 920 may extend beyond the tip contact trench 922 such that when the material of the electrode 920 is deposited on the conductive core 940, the electrode 920 with the tip contact trench 922 may have a stepped profile in side view. Thus, the tip contact trench 922 may advantageously help ensure contact between the electrode 920 and the underlying conductive core 940. Any of the other microneedle variations described herein may have a similar tip contact trench to help ensure contact between the electrode (which may be, for example, a working electrode, a reference electrode, a counter electrode, etc.) and the conductive pathway within the microneedle.

[0094] 10A and 10B show further various dimensions of an exemplary variation of a cylindrical microneedle having a tapered distal portion and a ring electrode similar to the microneedle 900 described above. For example, the microneedle variation shown in FIG. 10A and 10B may have a tapered distal portion having a taper angle of generally 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 may be disposed on the cylinder such that the combined height of the cone and 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 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 measured along the slope of the tapered distal portion can be about 57 μm (or about 55 μm to about 65 μm), and the total surface area of ​​the electrode can be about 12,700 μm. 2 (or about 12,500 μm 2 ~Approx. 12,900μm 2 , or about 12,000 μm 2 ~Approx. 13,000μm 2 10B, the electrode may further have a tip contact trench extending around the central region of the cone of the tapered distal portion, the contact having 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) as measured along the slope of the tapered distal portion, and a trench 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). The microneedle has an insulated distal tip having 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).

[0095] Details of exemplary variations in microneedle array configurations are described in further detail below.

[0096] As mentioned above, each microneedle in the microneedle array may include an electrode. In some variations, multiple different types of electrodes may be included among the microneedles of the microneedle array. For example, in some variations, the microneedle array may function as an electrochemical cell capable of electrolytic operation using three types of electrodes. In other words, the microneedle array may include at least one working electrode, at least one counter electrode, and at least one reference electrode. Thus, the microneedle array may include three different electrode types, but one or more of each electrode type may form a complete system (e.g., the system may include multiple separate working electrodes). Furthermore, multiple separate microneedles may be electrically joined to form an effective electrode type (e.g., a single working electrode may be formed from two or more connected microneedles having working electrode sites). Each of these electrode types may include a metallization layer and one or more coatings or layers on the metallization layer that help facilitate the function of that electrode.

[0097] In general, the working electrode is the electrode at which the oxidation and / or reduction reaction of interest occurs for detection of the analyte of interest. The counter electrode functions to source (supply) or sink (store) the electrons necessary to sustain the electrochemical reaction at the working electrode via current. The reference electrode functions to provide a reference potential for the system; that is, the potential at which the working electrode is 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 is sourced from or sunk to the reference electrode. Furthermore, to implement such a three-electrode system, the analyte monitoring device may include a suitable potentiostat or electrochemical analog front end to maintain (via an electronic feedback mechanism) a fixed potential relationship between the working and reference electrode contingencies in the electrochemical system, while dynamically varying the counter electrode to the potential required to sustain the redox reaction of interest.

[0098] A plurality of microneedles (e.g., any of the microneedle variations described herein, each of which may have a working electrode, counter electrode, or reference electrode as described above) may be arranged in a microneedle array. Considerations for how to configure the microneedles include factors such as the desired insertion force for penetrating the skin with the microneedle array, optimization of electrode signal levels and other performance aspects, and manufacturing cost and complexity.

[0099] For example, a microneedle array may include multiple microneedles spaced apart at a predetermined pitch (the distance between the center of one microneedle and the center of its nearest neighboring microneedle). In some variations, the microneedles may be spaced apart at a pitch sufficient to distribute the force applied to the user's skin to penetrate the microneedle array into the skin (e.g., avoiding a "needle-rat" effect). As the pitch increases, the force required to insert the microneedle array tends to decrease and the depth of penetration tends to increase. However, it has been found that the pitch only begins to affect the insertion force at low values ​​(e.g., less than about 150 μm). Thus, in some variations, the microneedles of the microneedle array may have a pitch 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 pitch 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 may be arranged in a periodic grid and the pitch may be uniform across all directions and areas of the microneedle array. Alternatively, the pitch may be different when measured along different axes (e.g., X, Y directions) and / or some areas of the microneedle array may include a smaller pitch and other areas may include a larger pitch.

[0100] Additionally, for more consistent penetration, the microneedles may be spaced equidistant from one another (e.g., same pitch in all directions). To that end, in some variations, the microneedles in the microneedle array may be arranged in a hexagonal configuration as shown in Figures 11A-11C, 12A-12B, and 13A-13E. Alternatively, the microneedles in the microneedle array may be arranged in a rectangular array (e.g., a square array) or in another suitable symmetrical manner.

[0101] Another consideration for determining the configuration of a microneedle array is the overall signal level provided by the microneedles. In general, the signal level at each microneedle is invariant to the total number of microneedle elements in the array. 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 generate a greater signal strength (and therefore improve accuracy) than an array with fewer microneedles. However, a larger number of microneedles on a die increases the die cost (given a constant pitch) and also requires a greater force and / or speed to insert into the skin. In contrast, a smaller number of microneedles on a die reduces the die cost and allows insertion into the skin with a reduced applied force and / or speed. Furthermore, in some variations, a smaller number of microneedles on a die may reduce the overall footprint area of ​​the die, which may result in less undesirable local edema and / or erythema. Thus, in some variations, a balance of these factors can be achieved with a microneedle array including 37 microneedles as shown in Figures 12A-12B, or a microneedle array including 7 microneedles as shown in Figures 11A-11C, but in other variations, the number of microneedles in the array may be low (e.g., about 5 to about 35, about 5 to about 30, about 5 to about 25, about 5 to about 20, about 5 to about 15, about 5 to about 100, about 10 to about 30, about 15 to about 25, etc.) or the number of microneedles in the array may be high (e.g., greater than 37, greater than 40, greater than 45, etc.).

[0102] Additionally, as described in more detail below, in some variations, only a subset of the microneedles in the microneedle array may be active during operation of the analyte monitoring device. For example, some of the microneedles in the microneedle array may be inactive (e.g., no signal is read from the electrodes of the inactive microneedles). In some variations, some of the microneedles in the microneedle array may be activated at a particular time during operation and remain active for the remainder of the operational life of the device. Furthermore, in some variations, some of the microneedles in the microneedle array may additionally or alternatively be deactivated at a particular time during operation and remain inactive for the remainder of the operational life of the device.

[0103] Considering the characteristics of the die for microneedle array, the die size is a function of the number of microneedles in the microneedle array and the pitch of the microneedles.Manufacturing cost should also be considered, since a smaller die size contributes to lower costs, since the number of dies that can be formed from a single wafer of a given area increases.In addition, a smaller die size is also less susceptible to brittle fracture due to the relative fragility of the substrate.

[0104] Furthermore, in some variations, microneedles on the periphery of the microneedle array (e.g., near the edge or border of the die, near the edge or border of the housing, near the edge or border of an adhesive layer on the housing, along the outer edge of the microneedle array, etc.) may be found to have better performance (e.g., sensitivity) due to better penetration compared to microneedles in the center of the microneedle array or die. Thus, in some variations, the working electrode may be located mostly or completely on microneedles located on the periphery of the microneedle array to obtain more accurate and / or precise analyte measurements.

[0105] 12A and 12B show an exemplary schematic diagram of 37 microneedles arranged in an exemplary variation of a microneedle array 1200. The 37 microneedles may be arranged in a hexagonal array with, for example, a needle-to-needle center-to-center pitch 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. FIG. 12A shows an exemplary schematic diagram of an exemplary variation of a die including the microneedle arrangement. Exemplary dimensions of the die (e.g., about 4.4 mm by about 5.0 mm) and the microneedle array 1200 are shown in FIG. 12B.

[0106] 11A and 11B show perspective views of an exemplary schematic of seven microneedles 1110 arranged in an exemplary variation of a microneedle array 1100. The seven microneedles 1110 are arranged in a hexagonal array on a substrate 1102. As shown in FIG. 11A, electrodes 1120 are disposed on distal portions of the microneedles 1110 extending from a first surface of the substrate 1102. As shown in FIG. 11B, proximal portions of the microneedles 1110 are conductively connected to respective backside electrical contacts 1130 on a second surface of the substrate 1102 opposite the first surface of the substrate 1102. FIGS. 11C and 11D show plan and side views of an exemplary schematic of a microneedle array similar to the microneedle array 1100. As shown in Figures 11C and 11D, the seven microneedles are arranged in a hexagonal array with a needle-to-needle center-to-center pitch of about 750 μm between the center of each microneedle and the center of its immediate neighbor in any direction. In other variations, the needle-to-needle center-to-center pitch may be, for example, about 700 μm to about 800 μm, or about 725 μm to about 775 μm. The microneedles may have an approximate outer axial diameter of 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).

[0107] Additionally, the microneedle arrays described herein can have a high degree of configurability with respect to where the working, counter, and reference electrodes are located within the microneedle array, and this configurability can be facilitated by the electronics system.

[0108] In some variations, the microneedle array may include electrodes distributed symmetrically or asymmetrically in two or more groups within the microneedle array, with each group featuring the same or different number of electrode components depending on the requirements of signal sensitivity and / or redundancy. For example, electrodes of the same type (e.g., working electrodes) may be distributed bilaterally or radially symmetrically within the microneedle array. For example, FIG. 13A shows a variation of a microneedle array 1300A including two symmetric groups of seven working electrodes (WE), with two working electrode groups labeled "1" and "2". In this variation, the two working electrode groups are distributed bilaterally symmetrically within the microneedle array. The working electrodes are generally positioned between a central region of three reference electrodes (RE) and a peripheral region of twenty counter electrodes (CE). In some variations, each of the two working electrode groups may include seven working electrodes electrically connected between them (e.g., to enhance the sensor signal). Alternatively, only a portion of one or both of the working electrode groups may include multiple electrodes electrically connected between them. As yet another alternative, the working electrodes may include working electrodes that are stand-alone and not electrically connected to other working electrodes.Furthermore, in some variations, the working electrodes may be distributed across the microneedle array in an asymmetric or random configuration.

[0109] As another example, FIG. 13B shows a variation of a microneedle array 1300B that includes four symmetric groups of three working electrodes (WE) with the four working electrode groups labeled "1," "2," "3," and "4." In this variation, the four working electrode groups are radially symmetrically distributed in the microneedle array. Each working electrode group is adjacent to and symmetrically positioned with one of the two reference electrode (RE) components in the microneedle array. The microneedle array also includes counter electrodes (CE) positioned around the periphery of the microneedle array, except for two electrodes on the vertices of a hexagon that may be inactive or used for other features or modes of operation.

[0110] 13C shows another exemplary variation of a microneedle array 1300C having seven microneedles. The microneedle arrangement includes two microneedles assigned as independent working electrodes (1 and 2), a counter electrode condition consisting of four microneedles, and a single reference electrode. There is a symmetry in the arrangement of the working and counter electrodes that are equidistant from the central reference electrode. Furthermore, the working electrodes are placed as far away from the center of the microneedle array (e.g., the periphery of the die or array) as possible to take advantage of the location where the working electrodes are expected to have higher sensitivity and overall performance.

[0111] FIG. 13D shows another exemplary variation of a microneedle array 1300D having seven microneedles. The microneedle arrangement includes four microneedles assigned as two independent groups (1 and 2) of two working electrodes each, a counter electrode consisting of two microneedles, and a single reference electrode. There is a symmetry in the arrangement of the working and counter electrodes, which are equidistant from the central reference electrode. Furthermore, the working electrodes are placed as far away as possible from the center of the microneedle array (e.g., the periphery of the die or array) to take advantage of the location where the working electrodes are expected to have higher sensitivity and overall performance.

[0112] 13E shows another exemplary variation of a microneedle array 1300E having seven microneedles. The microneedle arrangement includes four microneedles assigned as independent working electrodes (1, 2, 3, and 4), a counter electrode condition consisting of two microneedles, and a single reference electrode. There is a symmetry in the arrangement of the working and counter electrodes that are equidistant from the central reference electrode. Furthermore, the working electrodes are placed as far away from the center of the microneedle array (e.g., the periphery of the die or array) as possible to take advantage of the location where the working electrodes are expected to have higher sensitivity and overall performance.

[0113] While Figures 13A-13E show exemplary variations in microneedle array configurations, it should be understood that these figures are not limiting and other microneedle configurations (including different numbers and / or distributions of working, counter, and reference electrodes, as well as different numbers and / or distributions of active and inactive electrodes, etc.) may be suitable for other variations in microneedle arrays.

[0114] As mentioned above, the analyte monitoring device (or various embodiments thereof as described above) may be integrated with an applicator or application component configured to urge the microneedle array 140 towards the user's skin such that the microneedle array 140 is inserted into the skin (e.g., to a desired target depth). In some variations, one or more adhesive layers are provided on the distal end of the housing of the analyte monitoring device and adhered to the skin to hold the analyte monitoring device 110 firmly in place during or prior to deployment of the microneedle array 140 into the skin.

[0115] 14A and 14B show an embodiment of a wearable analyte monitoring device 1400 with an integrated applicator (also referred to herein as an analyte monitoring device). FIG. 14A provides a top perspective view of the analyte monitoring device 1400 with an integrated applicator, and FIG. 14B provides a side view. In some variations, the analyte monitoring device 1400 includes a housing cover 1410 and a housing base 1420, which together form a body of the housing and define an interior cavity. An adhesive layer may be provided on a distal outwardly facing region of the housing base 1420 or on a distal end of the housing to adhere the analyte monitoring device 1400 to a user's skin.

[0116] In some variations, the actuating member 1430 is formed on a proximal surface of the housing cover 1410. The actuating member 1430 is a depressible or releasable (e.g., flexible) member that responds to a user force. For example, when a user presses the actuating member 1430 downward, the actuating member responds by depressing inward. After the user force is removed, the actuating member 1430 can assume its original shape. In some variations, the actuating member 1430 can be a deformable portion of the housing cover 1410. For example, the actuating member 1430 can be made from a material that responds to force and / or pressure. The surrounding portion of the housing cover 1410, in some variations, can be made from a stronger, more resilient material that maintains its shape and structure as the actuating member 1430 deforms in response to a force applied by a user. In some variations, the actuating member 1430 can be a component that is separate from, but coupled with, the housing cover 1410. For example, the actuating member 1430 can be a releasable member, such as a cap or button, that fits within or is mated with a peripheral portion of the housing cover 1410. In some variations, the actuating member 1430 can be a diaphragm.

[0117] Figures 14C and 14D show internal aspects of the analyte monitoring device 1400. Figure 14C is a cross-sectional side view taken along line 14C:14C shown in Figure 14A of the analyte monitoring device 1400 in a configuration for deploying the microneedle array 140 of the analyte monitoring device 1400. In Figure 14C, the microneedle array 140 is in a first configuration in which the microneedle array 140 is held within a cavity of the housing body. Figure 14D is a cross-sectional side view taken along line 14C:14C shown in Figure 14A of the analyte monitoring device 1400 in a configuration in which the microneedle array 140 is deployed. In Figure 14D, the microneedle array 140 is in a second configuration in which the microneedle array 140 protrudes through a distal opening of the housing body.

[0118] In some variations, the printed circuit board assembly 1440 including the first assembly portion 1442 and the second assembly portion 1444 is disposed within a housing (e.g., within a cavity defined by the housing cover 1410 and the housing base 1420). The first assembly portion 1442 may be configured to connect to the microneedle array 140. That is, the microneedle array 140 may be electrically connected to the first assembly portion 1442, for example, via a connection component 1422. The connection component 1422 may be similar or equivalent to the secondary PCB components and / or secondary PCB connectors described above (e.g., the secondary PCB 420 and secondary PCB connector 430 shown in Figures 4B and 4G), whereby the connection component 1422 provides an electrical connection between the electrical contacts on the back side of the microneedle array 140 and the first assembly portion 1442 of the printed circuit board assembly 1440.

[0119] In some variations, the microneedle array 140 is provided as part of a microneedle array assembly, similar to the microneedle array assemblies described above (e.g., microneedle array assembly 360 shown in Figures 4B and 4G). Additionally, a microneedle array assembly utilized in an analyte monitoring device with an integrated applicator may include a skirt (similar to skirt 410 shown in Figures 4B and 4G) and a spacer or intermediate PCB (similar to intermediate PCB 425 shown in Figure 4G).

[0120] The second assembly part 1444 generally surrounds the first assembly part 1442 and includes other components of the analyte monitoring device as described elsewhere herein (e.g., electronics for processing and communicating analyte signals). In some variations, the first assembly part 1442 includes a flexible PCB that provides an electrical connection between the microneedle array 140 and the second assembly part 1444, thereby providing the microneedle array in electrical communication with other components of the analyte monitoring device. In some variations, the first assembly part 1442 includes a resilient material and can be utilized as a biasing element without the need for additional components. For example, the printed circuit board assembly 1440 can include a resilient substrate (e.g., a fiberglass reinforced PCB) that allows the first assembly part 1442 to be cut away and utilized as a biasing element while remaining integral with the second assembly part 1444.

[0121] 14E, 14F, and 14G show an embodiment of a printed circuit board assembly 1440. FIG. 14E provides a top perspective view, FIG. 14F provides a side cross-sectional view in a configuration for deploying the microneedle array 140, and FIG. 14G provides a side cross-sectional view in a configuration for deploying the microneedle array 140. The first assembly part 1442 may be a flexible circuit board, the flexibility of which allows for movement of the first assembly part 1442 relative to the second assembly part 1444. In some variations, the battery 160 is coupled to the second assembly part 1444. The battery 160 may be offset from the center of the device / second assembly 1444 to allow space for translation of the microneedle array and the biasing element during transition of the microneedle array 140 from the first configuration to the second configuration during deployment of the microneedle array 140.

[0122] As shown in Figures 14C-14G, the biasing element 1450 is disposed within a cavity of the housing body of the analyte monitoring device 1400. The biasing element 1450 is attached to or otherwise connected to a first assembly portion 1442 of a printed circuit board assembly 1440 that includes the microneedle array 140. The biasing element 1450 thus serves as a support structure for the microneedle array 140. The biasing element 1450 may be a moveable clip, a leaf spring, a compression coil spring, an extension spring, or the like, and is positioned in a loaded or first configuration upon assembly of the analyte monitoring device 1400, as shown in Figure 14C. In this position, the microneedle array 140 is retracted within the cavity defined by the housing cover 1410 and the housing base 1420 and is held in place by the engagement of the biasing element 1450 and the retaining element 1460.

[0123] The biasing element 1450 may be disengaged from the retaining element 1460 upon actuation of the actuation member 1430. For example, by applying a force or pressure to an outer surface of the actuation member 1430, the retaining element 1460 is released from the biasing element 1450. The release or disengagement of the biasing element 1450 and the retaining element 1460 creates an acceleration force on the microneedle array 140, causing insertion into the user's skin surface. The biasing element 1450 transitions from a first, loaded configuration to a second, deployed configuration, in which the first biasing element 1450 is compressed under pressure, thus pressing against the microneedle array 140 with a constant force (e.g., about 15 to about 35 Newtons). When the biasing element 1450 is released via actuation by the user, the first biasing element 1450 exerts an acceleration force on the microneedle array 140 in the application direction.

[0124] When loaded, the biasing element is compressed and / or bent under pressure, thus providing potential energy when the microneedle array is in the first configuration. When the biasing element is released from the holding element via actuation by a user, the biasing element exerts an acceleration force on the microneedle array in the direction of application. Because the biasing element acts only on the microneedle array and not the entire monitoring device, the force accelerates the microneedle array to a relatively high speed over a very short displacement distance to impact the skin.

[0125] In some variations, the biasing element accelerates the microneedle array to a velocity of about 7 to about 14 meters per second (m / s) before penetrating the user's skin surface. In some variations, the biasing element may move the microneedle array at about 2.5 m / s to about 5 m / s, about 2.5 m / s to about 7 m / s, about 2.5 m / s to about 10 m / s, about 2.5 m / s to about 12.5 m / s, about 2.5 m / s to about 15 m / s, about 2.5 m / s to about 20 m / s, about 2.5 m / s to about 25 m / s, about 5 m / s to about 7 m / s, about 5 m / s to about 10 m / s, about 5 m / s to about 12.5 m / s, about 5 m / s to about 15 m / s, about 5 m / s to about 20 m / s, about 5 m / s to about 25 m / s, about 7 m / s to about 25 m / s, about 2.5 m / s to about ... Approx. 10m / s, Approx. 7m / s~Approx. 12.5m / s, Approx. 7m / s~Approx. 15m / s, Approx. 7m / s~Approx. 20m / s, Approx. 7m / s~Approx. 25m / s, Approx. 10m / s~Approx. 12.5m / s, Approx. 10m / s~Approx. 15m / s, Approx. 10m / s~Approx. 20m / s, Approx. 10m / s s~about 25m / s, about 12.5m / s~about 15m / s, about 12.5m / s~about 20m / s, about 12.5m / s~about 25m / s, about 15m / s~about 20m / s, about 15m / s~about 25m / s, or about 20m / s~about 25m / s. In some variations, the biasing element accelerates the microneedle array to a velocity of at least about 2.5 m / s, about 5 m / s, about 7 m / s, about 10 m / s, about 12.5 m / s, about 15 m / s, about 20 m / s, or about 25 m / s.

[0126] In some variations, the microneedle array is translated about 1.5 to about 3 millimeters (mm) when deployed from the first configuration to the second configuration. In some variations, the microneedle array is translated about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 5 mm, about 0.5 mm to about 7 mm, about 0.5 mm to about 10 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2.5 mm, about 1 mm to about 3 mm, about 1 mm to about 5 mm, about 1 mm to about 7 mm, about 1 mm to about 10 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm. m, about 1.5 mm to about 3 mm, about 1.5 mm to about 5 mm, about 1.5 mm to about 7 mm, about 1.5 mm to about 10 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 5 mm, about 2 mm to about 7 mm, about 2 mm to about 10 mm, about 2.5 mm to about 3 mm, about 2.5 mm to about 5 mm, about 2.5 mm to about 7 mm, about 2.5 mm to about 10 mm, about 3 mm to about 5 mm, about 3 mm to about 7 mm, about 3 mm to about 10 mm, about 5 mm to about 7 mm, about 5 mm to about 10 mm, or about 7 mm to about 10 mm. In some variations, the microneedle array is translated a maximum of about 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 5 mm, 7 mm, or 10 mm.

[0127] In a variation, the retaining element 1460 is integral with and / or coupled to the actuation member 1430. The retaining element 1460 may include an extension arm 1462 having a retaining ledge 1464. The retaining ledge 1464 provides a support surface for the first biasing element 1450. An outer edge of the biasing element 1450 rests on, interfaces with, and / or is otherwise engaged with the retaining ledge 1464 when loaded.

[0128] In response to actuation of the actuation member 1430 (e.g., pressure or force applied by a user), the biasing element 1450 and the retaining element 1460 disengage. The retaining element 1460 may bend and / or move downward in response to actuation, allowing disengagement between the biasing element 1450 and the retaining element 1460. In some variations, the actuation member 1430 is integrated with the housing cover 1430, as shown in FIG. 14D. The actuation member 1430 may be provided as a flexible portion of the housing cover 1410 that inverts when pressed down by a user. When the actuation member 1430 is inverted, the extension arm 1462 of the retaining element 1460 moves outwardly away from the biasing element 1450, releasing the biasing element 1450 from the retaining ledge 1462. In some variations, the actuation member 1430 remains inverted, decreasing the profile (e.g., height) of the wearable analyte monitoring device 1400. In some variations, the actuation member 1430 may return to its original shape.

[0129] In some variations, a second biasing element may be disposed within the cavity of the housing body to provide additional compression to the microneedle array 140 inserted into the skin of the user. For example, the second biasing element may be positioned within a volume defined between the housing body and the biasing element 1450. The second biasing element may be a spring, such as a compression coil spring. The second biasing element may be in a first compressed state when the biasing element 1450 is in the loaded configuration and in a second compressed state when the biasing element 1450 is in the deployed configuration. The second compressed state may provide additional force to the biasing element 1450 while in the deployed configuration.

[0130] 15A-15E show embodiments of a wearable analyte monitoring device 1500 with an integrated applicator according to several variations. FIG. 15A provides a top perspective view of the analyte monitoring device 1500 with an integrated applicator. FIGS. 15B, 15C, 15D, and 15E show internal embodiments of the analyte monitoring device 1500. FIG. 15B is a side cross-sectional view of the analyte monitoring device 1500 in a loaded configuration for deploying the microneedle array 140 of the analyte monitoring device 1500. FIG. 15C is a side cross-sectional view of the analyte monitoring device 1500 in a deployed configuration. FIG. 15D is a detailed view of the analyte monitoring device 1500 in a loaded configuration for deploying the microneedle array 140. FIG. 15E is a detailed view of the analyte monitoring device 1500 in a deployed configuration.

[0131] The analyte monitoring device 1500 includes a housing body that includes an interior cavity in which various components of the analyte monitoring device 1500 are retained. In some variations, the housing includes a cover 1510 and a housing base 1515, which together form the housing body and define the interior cavity. An adhesive layer 1520 may be provided on a distal end of the housing body (e.g., on a bottom, outwardly facing area of ​​the housing base 1515) to adhere the analyte monitoring device 1500 to the skin of a user.

[0132] In some variations, the actuating member 1530 is formed on the top surface of the housing cover 1510. The actuating member 1530 is a depressible or releasable (e.g., flexible) member that responds to a user force. For example, when a user presses the actuating member 1530 downward, the actuating member responds by depressing inward. After the user force is removed, the actuating member 1530 can assume its original shape. In some variations, the actuating member 1530 can be a deformable portion of the housing cover 1510. For example, the actuating member 1530 can be made from a material that responds to force and / or pressure. The surrounding portion of the housing cover 1510 can be made from a stronger, more resilient material that maintains its shape and structure as the actuating member 1530 deforms in response to a force applied by a user, in some variations.

[0133] As shown in Figures 15B-15E, the biasing element 1550 is disposed within a cavity of the housing of the analyte monitoring device 1500. The biasing element 1550 is coupled or otherwise connected to the microneedle array 140. Thus, the biasing element 1550 serves as a support structure for the microneedle array 140. In some variations, the biasing element 1500 includes a flat or contoured portion 1555 to facilitate attachment to the microneedle array 140. The biasing element 1550 may be a leaf spring fixed at two points to bias the microneedle array 140 toward the user's skin surface when the analyte monitoring device 1500 is loaded and deploys the microneedle array 140, as shown in Figures 15B and 15D. In this position, the microneedle array 140 is retracted into the cavity defined by the housing cover 1510 and the housing base 1515 and is held in place by engagement of the biasing element 1550 and the retaining element 1560 .

[0134] The biasing element 1550 may be disengaged from the retaining element 1560 upon actuation of the actuation member 1530. For example, by applying a force or pressure to an outer surface of the actuation member 1530, the retaining element 1560 is released from the biasing element 1550. The release or disengagement of the biasing element 1550 and the retaining element 1560 creates an acceleration force on the microneedle array 140, causing it to insert into the skin surface of a user. When the biasing element 1550 transitions from the loaded configuration to the deployed configuration, the biasing element 1550 transitions from a loaded, pressured state, and thus presses the microneedle array 140 into the skin surface with a constant force (e.g., about 15 to about 35 Newtons) when the device 1500 is applied to a user.

[0135] In some variations, the biasing element 1550 has two opposing ends that are coupled, attached, or otherwise secured to an inner surface of the housing cover 1510, a surface of the main PCB 1544, or a surface of the housing base 1515. During assembly, an intermediate portion of the biasing element 1550 (which may be configured for attachment to a microneedle array and / or a connecting component) is translated and engaged with the holding element 1560, thereby resulting in the biasing element 1550 in a loaded configuration. In the loaded configuration, the biasing element 1550 is provided in a bent, pressured state such that when the biasing element 1550 is disengaged from the holding element 1560, the intermediate portion of the biasing element 1550 accelerates the attached microneedle array 140 towards the skin surface.

[0136] In variations, the retaining element 1560 is integral with and / or coupled to the actuation member 1530. The retaining element 1560 may include a retaining ledge 1565. In some variations, the retaining ledge 1565 provides a support surface for the biasing element 1550 or an outer edge of the biasing element 1550 to rest on, interface with, and / or otherwise engage with the retaining ledge 1565 to retain the analyte monitoring device 1500 in the loaded configuration. In some variations, the retaining ledge engages the connecting component 1522 to retain the analyte monitoring device 1500 in the loaded configuration.

[0137] In some variations, a second biasing element (not shown) may be disposed within the cavity of the housing to provide additional compression to the microneedle array 140 inserted into the user's skin. For example, the second biasing element may be positioned within a volume defined between the housing and the biasing element 1550. The second biasing element may be a spring, such as a compression coil spring. The second biasing element may be in a first compressed state when the biasing element 1550 is loaded and in a second compressed state when the biasing element 1550 is deployed. The second compressed state may provide additional compressive force to the microneedle array 140 while transitioning the microneedle array 140 from the first configuration to the second configuration.

[0138] In some variations, the analyte monitoring device 1500 includes a printed circuit board (PCB) assembly disposed within the housing (e.g., within a cavity defined by the housing cover 1510 and the housing base 1515), the PCB assembly including a main PCB portion 1544 and a flexible PCB portion 1542. The flexible PCB 1542 may be configured to connect the microneedle array 140 to the main PCB 1544 to allow movement of the microneedle array 140 relative to the main PCB 1544 while maintaining an electrical connection. In some variations, the main PCB portion 1544 is also a flexible printed circuit board. Thus, the main PCB portion 1544 and the flexible PCB portion 1542 may be integrated and no connection needs to be established between them. In some variations, the microneedle array 140 may be electrically connected to the flexible PCB 1542, for example, via a connecting component 1522. The connection component 1522 may be similar to the secondary PCB components and / or secondary PCB connectors described above (e.g., the secondary PCB 420 and secondary PCB connector 430 shown in Figures 4B and 4G), whereby the connection component 1522 provides an electrical connection between the electrical contacts on the back side of the microneedle array 140 and the flexible PCB 1542 of the printed circuit board assembly.

[0139] In some variations, the housing base 1515, adhesive layer 1520, and / or main PCB 1544 include apertures that form a distal opening of the housing body to allow at least a portion of the microneedle array 140 to extend outwardly from the device. During deployment (transition from a first configuration to a second configuration), a portion of the microneedle array 140 may be translated from within the cavity through the distal opening such that the microneedles extend from the housing body and penetrate the user's skin surface. In some variations, a sealing element is provided such that the internal cavity is sealed when the microneedle array 140 is deployed. The sealing element may provide a water-resistant or waterproof seal to prevent ingress of moisture into the internal cavity of the housing.

[0140] 15B, 15C, 15D, and 15E show a sealing element 1512 including a ledge 1514 and an inner wall 1516. In some variations, in the deployed configuration (as shown in FIGS. 15C and 15E), a connecting component 1522 coupled to the microneedle array 140 contacts the sealing element 1512 to seal the distal opening, thereby sealing the interior cavity of the housing. In some variations, the connecting component 1522 abuts the ledge 1514, the inner wall 1516, or both, of the sealing element 1512 to create a seal. In some variations, an outer edge of the microneedle array 140 abuts the ledge 1514, the inner wall 1516, or both, of the sealing element 1512 to create a seal. In some variations, the inner wall 1516 of the sealing element 1512 is tapered to facilitate an interference, press, or friction fit between the sealing element 1512 and the connecting component 1522 and / or the microneedle array 140. The sealing element 1512 may be formed from silicone, a waterproof polymer, rubber, or similar material suitable for creating a waterproof seal.

[0141] In some variations, the seal element 1512 is integral with the housing base 1515. In some variations, the seal element 1512 is adhered or otherwise coupled to the housing base 1515. Although the seal element 1512 is shown as substantially rectangular or square, the features of the seal element 1512 may substantially correspond to the shape of the microneedle array 140 and / or the connecting component 1522. For example, if the microneedle array 140 and / or the connecting component 1522 are substantially circular, the inner wall 1516 and ledge 1514 of the seal element 1512 may also be substantially circular and dimensioned to create an interference fit.

[0142] In some variations, components of the analyte monitoring device may have a conformal waterproof coating to prevent corrosion, destruction, or other adverse effects resulting from exposure to liquids or moisture. The seal may also be provided by a flexible and / or bellows-like membrane. For example, a bellows-like membrane may be provided between the microneedle array and the base of the housing, such that moisture cannot pass between them. Such a configuration may allow the microneedle array to move relative to the housing (e.g., during transition from a first configuration to a second configuration) while maintaining a waterproof seal and preventing moisture from entering the interior cavity of the housing.

[0143] In some variations, the biasing element applies a constant force to the microneedle array in the second configuration to hold the microneedles within the user's skin surface. In some variations, a locking mechanism is utilized to maintain the position of the deployed microneedle array. For example, the ledge 1514 of the sealing element 1512 may be coated with a contact adhesive such that the outer edges of the microneedle array 140 and / or the connecting component 1522 adhere to the ledge 1514 when they contact the ledge 1514 of the sealing element 1512 during deployment. Additional or alternative lockout mechanisms may be utilized, such as detents, spring-loaded slides, etc. For example, the retaining element 1560 may have a bottom that extends beyond the retaining ledge 1565 such that in the deployed configuration, the bottom surface of the retaining element 1560 abuts the top surface of the biasing element 1550. In such an example, the retaining element 1560 may move outward during actuation to allow the biasing element 1550 to transition to the deployed configuration, and then move back to its home position after the actuation force is removed, with the bottom surface of the retaining element abutting the top surface of the biasing element.

[0144] 16A-16C show an embodiment of a wearable analyte monitoring device 1600 with an integrated applicator according to several variations. FIGS. 16A-16C show variations of an actuation mechanism for triggering deployment of a microneedle array 140 configured to monitor the level of a target analyte present in a subject's skin interstitial fluid. FIG. 16A is a side cross-sectional view of the analyte monitoring device 1600 in a loaded configuration (e.g., when the microneedle array 140 is in a first configuration). FIG. 16B is a side cross-sectional view of the analyte monitoring device 1600 in a deployed configuration (e.g., when the microneedle array 140 is in a second configuration). FIG. 16C is an exploded perspective view of the actuation member 1630, shuttle 1640, and housing base 1615 of the analyte monitoring device 1600.

[0145] In some variations, the wearable analyte monitoring device 1600 includes a base 1615 having a protrusion 1617. In some variations, the protrusion 1617 is cylindrical and holds the shuttle 1640 when in a loaded configuration (as shown in FIG. 16A ). In some variations, the protrusion 1617 has an inner diameter and an outer diameter and is substantially tubular. The protrusion 1617 extends from a proximal surface of the base 1615 into a cavity formed by the base 1615 and the housing 1610.

[0146] In some variations, the shuttle 1640 is a substantially cylindrical member having one or more flexible arms 1642 extending from its outer sidewall. The flexible arms 1642 allow retention of the shuttle 1640 when the analyte monitoring device 1600 is in a loaded configuration (e.g., as shown in FIG. 16A ) as a distal surface (e.g., protrusion) of the flexible arms 1642 abuts a distal surface of a corresponding aperture 1612 of the protrusion 1617. The microneedle array 140 is coupled at its distal end to the shuttle 1640 such that the microneedles of the microneedle array 140 extend distally from the distal end of the shuttle 1640. A biasing element 1650 (e.g., a compression spring) may bias the shuttle 1640 and the microneedle array 140 toward the base 1615 of the analyte monitoring device 1600 and away from the actuating member 1630.

[0147] In some variations, during deployment of the microneedle array 140, the protrusions of the flexible arms 1642 of the shuttle 1640 are forced inward by the inner surface of the actuation member 1630, thereby releasing the flexible arms 1642 from engagement with the aperture 1612 and allowing the shuttle 1640 and attached microneedle array 140 to be translated towards the base and to the user's skin surface. In some variations, as described above, the base 1615 includes an aperture that forms a distal opening of the housing body to allow the multiple microneedles of the microneedle array 140 to pass through and extend from the device in the deployed configuration (as shown in FIG. 16B). A seal may be provided or formed in the deployed configuration.

[0148] In some variations, the actuating member 1630 is integrated with the top of the housing 1610. Thus, the actuating member 1630 may be engaged by a user depressing the top of the housing. In some variations, the actuating member 1630 may be a separate component from the housing 1610. The biasing element 1650 may also function to provide a bias to the actuating member 1630 to prevent accidental deployment of the microneedle array 140. In some variations, if the actuating member 1630 is engaged by deforming a portion of the housing 1610, the biasing element 1650 may function to push the housing 1610 back to its original shape after deployment.

[0149] In some variations, the actuation member 1630 has one or more protrusions 1632 that fit into the aperture 1612 upon actuation to ensure that the flexible arm 1642 of the shuttle 1640 is fully retracted into the inner portion of the protrusion 1617 of the base. In some variations, the protrusion 1632 of the actuation member 1630 is provided on the flexible arm to facilitate sliding of the actuation member 1630 over the protrusion 1617 of the base. In some variations, the protrusion 1617 of the base 1615 includes one or more slots or tracks 1631 to guide the actuation member 1630 and / or the shuttle 1640 as they are translated during actuation and deployment.

[0150] 16A-16C show a variation of a shuttle 1640 having two flexible arms 1642 and two corresponding apertures 1612 provided by a protrusion 1617 of a base 1615, it should be understood that the number of flexible arms and corresponding apertures may be varied. For example, the shuttle may have one, two, three, four, five, six, or more flexible arms and the protrusion of the base may include a corresponding number of apertures. Additionally, the size of the flexible arms and corresponding apertures may be varied.

[0151] In some variations, the microneedle array 140 is coupled to the shuttle 1640, which is coupled to a biasing element 1650 (e.g., a coil spring), thereby facilitating indirect coupling of the microneedle array 140 to the biasing element. In some variations, the electronic components of the wearable analyte monitoring device 1600 (e.g., a battery, a wireless transceiver, a microprocessor, etc.) are coupled to and / or provided within the shuttle 1640. In some variations, the electronic components are provided elsewhere within a cavity formed by the housing, or are attached to the base 1615 and connected to the microneedle array 140 by a flexible PCB or wire array. An aperture 1644 provided through the shuttle 1640 may correspond to a slot 1614 formed in the protrusion 1617 of the base 1615 to allow the flexible PCB or wire connection to be maintained during translation of the shuttle 1642 and the microneedle array 140 from the first configuration to the second configuration.

[0152] 17A-17E show an embodiment of a wearable analyte monitoring device 1700 with an integrated applicator according to several variations. FIGS. 17A-17E show variations of an actuation mechanism for triggering deployment of a microneedle array 140 configured to monitor levels of a target analyte present in a subject's skin interstitial fluid. FIG. 17A is a side cross-sectional view of the analyte monitoring device 1700 in a loaded configuration (e.g., when the microneedle array 140 is in a first configuration). FIG. 17B is a side cross-sectional view of the analyte monitoring device 1700 in a deployed configuration (e.g., when the microneedle array 140 is in a second configuration). FIG. 17C is a top view of the actuation member 1730 and housing base 1715 of the analyte monitoring device 1700 in a loaded configuration (e.g., when the microneedle array 140 is in a first configuration). Figure 17D is a top view of the actuating member 1730 and housing base 1715 of the analyte monitoring device 1700 in a deployed configuration (e.g., when the microneedle array 140 is in the second configuration), and Figure 17E is an exploded perspective view of the actuating member 1730, microneedle array 140, and housing base 1715 of the analyte monitoring device 1700.

[0153] In some variations, the wearable analyte monitoring device 1700 has a base 1715 having one or more protrusions 1717. The microneedle array 140 may be coupled to the actuation member 1730. A biasing element 1750 (e.g., a coil spring) may bias the actuation member 1730 and the microneedle array 140 toward the base 1715. In some variations, the actuation member 1730 may have one or more protrusions 1732 on its distal surface that provide a retention element as the bottom surface of the protrusions 1732 abut against the proximal surface of the protrusions 1717 of the base 1715 in the loaded configuration (as shown in FIG. 17C). In some variations, the top of the actuation member 1730 is provided outside the housing and is rotatable by the user. To deploy the microneedle array 140, the actuation member 1730 is rotated such that the protrusions 1732 are positioned within the slots or spaces provided between the protrusions 1717 of the base 1715 (as shown in FIG. 17D), thereby releasing and translating the actuation member 1730 and attached microneedle array 140 towards the base 1715 such that the microneedle array 140 protrudes through the distal opening and into the skin surface of the user under the influence of the biasing element 1750. In some variations, as described above, the base 1715 includes a distal opening formed by an aperture to allow the multiple microneedles of the microneedle array 140 to pass through and extend from the device in the second configuration. A seal may be provided or formed around the microneedle array 140.

[0154] 17C-17E show a variation of an actuation member 1730 having four protrusions 1732 and four corresponding protrusions 1717 on the base 1715, it should be understood that the number of protrusions on the actuation member and corresponding protrusions on the base may be varied. For example, the actuation member may have one, two, three, four, five, six, or more protrusions and the base may include a corresponding number of protrusions. Additionally, the size of the protrusions may be varied. For example, as shown in FIG. 17E, larger protrusions with smaller spacing between them on the base may form tracks or slots that facilitate guiding and aligning the microneedle array 140 during deployment.

[0155] In some variations, the biasing element 1750 abuts an inner surface of the top of the housing 1710 at a first end. In some variations, the biasing element 1750 abuts an upper surface of one or more of the protrusions 1732 of the actuating member 1730 at a second end opposite the first end. In some variations, an inner surface of the protrusion 1717 of the base 1715 forms a guide for the actuating member 1730 during translation. In some variations, the biasing element 1750 is wrapped around a portion of the actuating member 1730, and the outer periphery of the biasing element 1750 fits within the inner surface of the protrusion 1717 of the base 1715. In some variations, translation of the actuating member 1730 is stopped when the protrusion 1732 abuts a portion of the base 1715 or when a bottom surface of the top of the actuating member abuts the housing 1710.

[0156] 18A-18C show an embodiment of a wearable analyte monitoring device 1800 with an integrated applicator according to several variations. FIGS. 18A-18C show variations of an actuation mechanism for triggering deployment of a microneedle array 140 configured to monitor the level of a target analyte present in a subject's skin interstitial fluid. FIG. 18A is a side cross-sectional view of the analyte monitoring device 1800 in a loaded configuration (e.g., when the microneedle array 140 is in a first configuration). FIG. 18B is a side cross-sectional view of the analyte monitoring device 1800 in a deployed configuration (e.g., when the microneedle array 140 is in a second configuration). FIG. 18C is an exploded perspective view of the biasing element 1850, the retaining element 1840, and the base protrusion 1817 of the analyte monitoring device 1800.

[0157] In some variations, the wearable analyte monitoring device 1800 includes a base 1815 having a protrusion 1817. The microneedle array 140 may be coupled to a biasing element 1850. The biasing element 1850 (e.g., a leaf spring) may bias the microneedle array 140 toward the base 1815 of the device 1800. In some variations, the retaining element 1840 fits within the protrusion of the base 1817 and has one or more flexible wings 1847. The biasing element 1850 may be attached or fixed to a first end. A second end of the biasing element 1850 may include a slot 1855 having a width slightly larger than an outer diameter of the protrusion 1817 of the base 1815. In the loaded configuration (as shown in FIG. 18A ), the retaining element may be biased away from the base by the spring 1845 such that the wings 1847 are outside the projection 1817 and extend outward from the body of the retaining element 1840. In the loaded configuration, the wings 1847 extend beyond the width of the slot 1855 of the biasing element 1850 such that the bottom surface of the biasing element 1850 abuts the wings 1847 and the wings 1847 abut the projection. In some variations, engagement of the actuating member 1830 forces the retaining element 1840 into the projection 1817 and the wings 1847 are forced inward as the retaining element 1840 is forced into the projection. With the wings 1847 forced inward, the biasing element 1850 is released and the wings 1847 no longer impede translation of the biasing element. When the biasing element 1850 is translated towards the base 1815, the protrusions 1817 move through the slots 1855 in the biasing element and the microneedle array 140 is deployed (as shown in FIG. 18B).

[0158] 18C shows a variation of a retaining element 1840 having four wings 1847, it should be understood that the number of wings may be varied. For example, the retaining element may have one, two, three, four, five, six, or more flexible wings. Additionally, the size of the flexible wings may be varied.

[0159] In some variations, the actuating member 1830 includes a flexible portion of the housing 1810 that is depressed to abut the retaining element 1840. In some variations, the actuating member 1830 has a protrusion that abuts the retaining element 1840. The protrusion may be coupled to or integral with the flexible portion of the housing 1810 that is depressed by the user. In some variations, the retaining element 1840 is coupled to or integral with the actuating member 1830. As described above, the base 1815 may include an aperture that forms a distal opening of the housing body to allow the plurality of microneedles of the microneedle array 140 to pass through and extend from the device in the second configuration. A seal may be provided or formed in the deployed configuration.

[0160] 19A-19B show an embodiment of a wearable analyte monitoring device 1900 with an integrated applicator according to several variations. FIGS. 19A-19B show variations of an actuation mechanism for triggering deployment of a microneedle array 140 configured to monitor levels of a target analyte present in a subject's skin interstitial fluid. FIG. 19A is a side cross-sectional view of the analyte monitoring device 1900 in a loaded configuration (e.g., when the microneedle array 140 is in a first configuration). FIG. 19B is a side cross-sectional view of the analyte monitoring device 1900 in a deployed configuration (e.g., when the microneedle array 140 is in a second configuration).

[0161] In some variations, the wearable analyte monitoring device 1900 has a base 1915 with one or more protrusions 1917. The protrusions 1917 extend from a proximal surface of the base 1915 into a cavity formed by the base 1915 and the housing 1910. In some variations, the protrusions 1917 form a retention element to retain the shuttle 1940 when in a loaded configuration (as shown in FIG. 19A ). The microneedle array 140 may be coupled to the shuttle 1940 (e.g., coupled to a distal end of the shuttle 1940). A biasing element 1950 (e.g., a compression spring) may bias the shuttle 1940 and the microneedle array 140 towards the base 1915 of the device and away from the actuation member 1930. In the loaded configuration, movement of the shuttle 1940 and the microneedle array 140 is prevented by one or more opposing surfaces of the protrusions 1917. For example, protrusion 1917 forms a stop that prevents vertical translation of shuttle 1940 and microneedle array 140 in the distal direction.

[0162] In some variations, a user engages the actuating member 1930 such that one or more surfaces of the actuating member 1930 abut the shuttle 1940. A depression applied to the actuating member 1930 translates the shuttle 1940, forcing a portion of the shuttle 1940 into the opening created by the protrusion 1917. In some variations, the shuttle 1940 is tapered to facilitate one-way passage of the shuttle 1940 through the protrusion 1917. After the distal end of the shuttle 1940 passes through the opening created by the protrusion 1917, the biasing element 1950 translates the microneedle array 140 to the second configuration (as shown in FIG. 19B ). In some variations, the depth of the microneedle array 140 is locked or fixed once the shuttle 1940 passes through the protrusion 1917. The thickness or depth of the proximal portion of the shuttle 1940 may be varied to control the insertion depth of the microneedle array 140 in the second configuration.

[0163] In some variations, the protrusions 1917 are flexible (e.g., formed from a flexible material) and are biased outwardly by the shuttle 1940 upon depression of the actuating member 1930, allowing the shuttle 1940 to pass through the opening. In some variations, the shuttle 1940 has one or more flexible members that are biased inwardly by the protrusions 1917 upon depression of the actuating member 1930, allowing the shuttle 1940 to pass through. The abutment surfaces of the shuttle 1940 and / or the protrusions 1917 may be chamfered (e.g., beveled, tapered, etc.) to facilitate translation of the shuttle 1940 through the protrusions 1917. Although FIGS. 19A-19B show a variation of a base having two flexible protrusions 1917, it should be understood that the number of protrusions may be varied. For example, the base may have one, two, three, four, five, six, or more protrusions. Additionally, the size and spacing of the protrusions may be varied. In some variations, the protrusions 1917 are substantially annular and flexible (e.g., formed from a flexible material). In some variations, the proximal ends of the protrusions 1917 are flexible to facilitate passage of the shuttle upon application of force to the actuation member 1930 by a user.

[0164] In some variations, the actuating member 1930 is integrated with the top of the housing 1910. Thus, the actuating member 1930 may be engaged by a user depressing the top of the housing. In some variations, the actuating member 1930 may be a separate component from the housing 1910. The biasing element 1950 may also function to provide a bias to the actuating member 1930 to prevent accidental deployment of the microneedle array 140. In some variations, if the actuating member 1930 is engaged by deforming a portion of the housing 1910, the biasing element 1950 may function to urge the housing 1910 back to its original shape after deployment. In some variations, the protrusion 1917 defines a distal opening in the base 1915 to allow the multiple microneedles of the microneedle array 140 to extend through and out of the analyte monitoring device 1900 when in the deployed configuration. As discussed above, a seal may be provided or formed in the deployed configuration. In some variations, a seal is provided between a distal portion of the shuttle 1940 and the inner surface formed by the protrusion 1917 .

[0165] In some variations, one or more electrical connections are established when the microneedle array reaches the second configuration (e.g., the microneedle array is deployed). As disclosed above, features of the device (e.g., flexible PCB connections) may allow the microneedle array to maintain electrical connection with the main PCB as it transitions from the first configuration to the second configuration. Additionally, additional electrical connections may be established when the microneedle array 140 is in the second configuration (e.g., when the microneedle array 140 is deployed). For example, one or more electrical contacts may be provided to provide an open circuit in the first configuration and establish a closed circuit in the second configuration. Establishing new electrical connections in the second configuration may be utilized to power up components of the analyte monitoring device, establish a connection to the battery of the analyte monitoring device, wake the analyte monitoring device from a sleep state, and / or transition the analyte monitoring device from a low power mode to a full power mode.

[0166] In some variations, some or all of the components of the analyte monitoring system may be provided (e.g., to a user, clinician, etc.) in a kit. For example, the kit may include at least one analyte monitoring device. In some variations, the kit may include multiple analyte monitoring devices, which may form a supply of analyte monitoring devices sufficient for a given period of time (e.g., 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, etc.).

[0167] In some variations, the kit may further include user instructions for operating the analyte monitoring device and / or applicator (e.g., instructions for applying the analyte monitoring device manually or with an applicator, instructions for pairing the analyte monitoring device with one or more peripheral devices (e.g., a computing device such as a mobile phone), etc.).

[0168] Below is provided an overview of various aspects of the methods of use and operation of the analyte monitoring system, including the analyte monitoring device and peripherals.

[0169] As described above, the analyte monitoring device is applied to the skin of a user such that the microneedle array in the device penetrates the skin and the electrodes of the microneedle array are positioned in the upper dermis for access to dermal interstitial fluid. For example, in some variations, the microneedle array may be geometrically configured to penetrate the outer layer of the skin, the stratum corneum, penetrate the epidermis, and rest within the papillary or upper reticular dermis. The sensing area limited to the electrodes in the distal extent of each microneedle component of the array (as described above) may be configured to remain resting and seated in the papillary or upper reticular dermis after application to ensure adequate exposure to circulating dermal interstitial fluid (ISF) without risk of bleeding or undue influence by nerve endings.

[0170] In some variations, the analyte monitoring device may include a wearable housing or patch having an adhesive layer provided at a distal end of the housing and configured to adhere to the skin and secure the microneedle array in place.

[0171] The analyte monitoring device may be applied at any suitable location, although in some variations it may be desirable to avoid anatomical regions of thick or raw skin (e.g., palmar and plantar regions), or areas that undergo significant flexion (e.g., olecranon or patella). Suitable application sites may include, for example, the arms (e.g., upper arms, lower arms, forearms, or volar forearms), shoulders (e.g., over the deltoids), backs of the hands, neck, face, scalp, torso (e.g., on the back, such as the pectoral region, lumbar region, sacral region, or on the chest or abdomen), buttocks, legs (e.g., upper legs, lower legs, etc.), and / or tops of the feet, etc.

[0172] Once the analyte monitoring device is inserted and warm-up and any calibration is completed, the analyte monitoring device may be ready to provide a sensor measurement of a target analyte. The target analyte (and any necessary cofactors) diffuse from the biological environment through a biocompatible and diffusion-limiting layer on the working electrode to a biorecognition layer that contains a biorecognition element. In the presence of the cofactor (if present), the biorecognition element may convert the target analyte into an electroactive product.

[0173] A bias potential can be applied between the working and reference electrodes of the analyte monitoring device, and a current can be passed from the counter electrode to maintain a fixed potential relationship between the working and reference electrodes. This causes the electroactive product to be oxidized or reduced, causing a current to flow between the working and counter electrodes. The value of the current is proportional to the rate of the redox reaction at the working electrode, and specifically, to the concentration of the analyte of interest according to the Cotterell relationship, as described in more detail above.

[0174] The current may be converted to a voltage signal by a transimpedance amplifier and quantized to a digital bit stream by an analog-to-digital converter (ADC). Alternatively, the current may be directly quantized to a digital bit stream by a current-mode ADC. The digital representation of the current may be processed within an embedded microcontroller within the analyte monitoring device and relayed to a wireless communication module for broadcast or transmission (e.g., to one or more peripheral devices). In some variations, the microcontroller may perform additional algorithmic processing on the data to improve signal fidelity, accuracy, and / or calibration, etc.

[0175] In some variations, the digital representation of the current or sensor signal may be correlated with an analyte measurement (e.g., glucose measurement) by the analyte monitoring device. For example, a microcontroller may execute programmed routines in firmware to interpret the digital signal and perform any associated algorithms and / or other analyses. Keeping the analysis on-board the analyte monitoring device may, for example, allow the analyte monitoring device to broadcast analyte measurements to multiple devices in parallel while ensuring that each connected device has the same information. Thus, in general, a user's target analyte (e.g., glucose) value may be estimated, stored in the analyte monitoring device, and communicated to one or more peripheral devices.

[0176] In the foregoing description, for purposes of explanation, specific nomenclature was used to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that specific details are not required to practice the present invention. Thus, the foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Obviously, many modifications and variations are possible in light of the above teachings. The embodiments were chosen and described in order to explain the principles of the invention and its practical application, thereby enabling those skilled in the art to utilize the present invention and its various embodiments with various modifications as suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the present invention. Numbered embodiments for carrying out the invention

[0177] Without limiting the scope of the appended claims, the present disclosure describes the following numbered embodiments.

[0178] Embodiment I-1. A wearable analyte monitoring device comprising: a housing including a body defining a cavity therein, the housing body including a distal opening; an adhesive layer coupled to a distal end of the housing and surrounding the distal opening, the adhesive layer configured to secure the device to a skin surface of a user; a biasing element contained within the cavity; a microneedle array coupled to the biasing element and including a plurality of microneedles; a retaining element contained within the cavity and configured to releasably retain the biasing element; and an actuating member coupled to the retaining element, wherein engagement of the actuating member transitions the microneedle array between a first configuration and a second configuration, wherein in the first configuration the microneedle array is retained within the cavity of the housing body and in the second configuration the microneedle array protrudes through the distal opening of the housing body.

[0179] Embodiment I-2. A wearable analyte monitoring device as described in embodiment I-1, wherein in the second configuration, a plurality of microneedles are inserted through the user's skin surface.

[0180] Embodiment I-3. A wearable analyte monitoring device according to any one of embodiments I-1 to I-2, wherein the microneedle array achieves a speed of at least 10 meters / second transitioning from the first configuration to the second configuration.

[0181] Embodiment I-4. A wearable analyte monitoring device according to any one of embodiments I-1 to I-3, wherein the microneedle array moves a distance of 1.5 millimeters or less transitioning from the first configuration to the second configuration.

[0182] Embodiment I-5. A wearable analyte monitoring device according to any one of embodiments I-1 to I-4, wherein a seal is formed between the outer periphery of the microneedle array and the distal opening when the microneedle array is in the second configuration.

[0183] Embodiment I-6. The wearable analyte monitoring device of any one of embodiments I-1 to I-5, wherein the cavity is watertight when the microneedle array is in the second configuration.

[0184] Embodiment I-7. A wearable analyte monitoring device according to any one of embodiments I-1 to I-6, wherein the actuating member is integrated with a portion of the housing body.

[0185] Embodiment I-8. A wearable analyte monitoring device as described in any one of embodiments I-1 to I-7, wherein engagement of the actuating member includes depressing a portion of the housing body, thereby releasing the biasing element and transitioning the microneedle array to the second configuration.

[0186] Embodiment I-9. A wearable analyte monitoring device as described in embodiment I-8, wherein the retaining element is integrated with the housing body.

[0187] Embodiment I-10. A wearable analyte monitoring device of embodiment I-8 or embodiment I-9, wherein the housing body includes one or more tapered portions to facilitate bending upon depression of a portion of the housing body.

[0188] Embodiment I-11. The wearable analyte monitoring device of embodiment I-1, wherein engaging the actuating member includes rotating the actuating member.

[0189] Embodiment I-12. A wearable analyte monitoring device according to any one of embodiments I-1 to I-6, wherein a portion of the biasing element is coupled proximal to the interior distal end of the housing body within the cavity.

[0190] Embodiment I-13. A wearable analyte monitoring device of any one of embodiments I-1 to I-12, wherein the biasing element comprises a leaf spring, a coil spring, a compression spring, a flexible member, or a combination thereof.

[0191] Embodiment I-14. A wearable analyte monitoring device described in any one of embodiments I-1 to I-13, wherein the biasing element includes a first end and a second end, the first end of the biasing element is coupled to the microneedle array, and the second end of the biasing element is coupled proximal to the inner distal end of the housing body within the cavity.

[0192] Embodiment I-15. A wearable analyte monitoring device as described in embodiment I-14, wherein a first end of the biasing element is releasably retained by a retaining element.

[0193] Embodiment I-16. A wearable analyte monitoring device as described in embodiment I-15, wherein the retaining element is proximal to the interior proximal end of the housing body within the cavity.

[0194] Embodiment I-17. A wearable analyte monitoring device according to any one of embodiments I-1 to I-16, further comprising a printed circuit board housed within the cavity of the housing body.

[0195] Embodiment I-18. A wearable analyte monitoring device as described in embodiment I-17, wherein the printed circuit board is in electrical communication with the microneedle array via a flexible printed circuit board, and the microneedle array is mounted on the flexible printed circuit board.

[0196] Embodiment I-19. A wearable analyte monitoring device as described in embodiment I-17, wherein the flexible printed circuit board includes actuation contacts that contact corresponding contacts provided on the printed circuit board when the microneedle array is in the second configuration.

[0197] Embodiment I-20. The wearable analyte monitoring device of any one of embodiments I-1 to I-19, wherein the wearable analyte monitoring device is operative when the microneedle array is in the second configuration.

[0198] Embodiment I-21. The wearable analyte monitoring device of embodiment I-17, wherein the printed circuit board moves with the microneedle array.

[0199] Embodiment I-22. A wearable analyte monitoring device according to any one of embodiments I-1 to I-21, wherein a first microneedle of the plurality of microneedles of the microneedle array comprises a working electrode having an electrochemical sensing coating.

[0200] Embodiment I-23. The wearable analyte monitoring device of embodiment I-22, wherein a second microneedle of the plurality of microneedles of the microneedle array comprises a reference electrode.

[0201] Embodiment I-24. The wearable analyte monitoring device of embodiment I-22 or embodiment I-23, wherein a third microneedle of the plurality of microneedles of the microneedle array comprises a counter electrode.

[0202] Embodiment I-25. The wearable analyte monitoring device of any one of embodiments I-1 to I-24, further comprising a shuttle configured to couple the microneedle array to the biasing element.

[0203] Embodiment I-26. A wearable analyte monitoring device as described in embodiment I-25, further comprising a tubular protrusion extending from a distal end of the housing body into the cavity, the tubular protrusion configured to guide the shuttle as the microneedle array transitions between the first configuration and the second configuration.

[0204] Embodiment I-27. A wearable analyte monitoring device as described in embodiment I-26, wherein the tubular protrusion includes an aperture configured to engage a flexible arm of the shuttle, thereby holding the microneedle array in the first configuration.

[0205] Embodiment I-28. A wearable analyte monitoring device as described in embodiment I-27, wherein depression of the actuation member deflects the flexible arms of the shuttle inwardly, thereby releasing the shuttle and transitioning the microneedle array from the first configuration to the second configuration.

[0206] Embodiment I-29. A wearable analyte monitoring device of any one of embodiments I-26 to I-28, wherein the interior sidewall of the tubular protrusion defines a distal opening of the housing body.

[0207] Embodiment I-30. A wearable analyte monitoring device as described in embodiment I-25, further comprising a protrusion extending from a distal end of the housing body into the cavity, the protrusion configured to abut the shuttle when the microneedle array is in the first configuration.

[0208] Embodiment I-31. A wearable analyte monitoring device as described in embodiment I-30, wherein depression of the actuation member deflects the protrusions outward, thereby releasing the shuttle and transitioning the microneedle array from the first configuration to the second configuration.

[0209] Embodiment I-32. A wearable analyte monitoring device of embodiment I-30 or embodiment I-31, wherein an interior sidewall of the protrusion defines a distal opening of the housing body.

[0210] Embodiment I-33. The wearable analyte monitoring device of any one of embodiments I-1 to I-32, further comprising a second biasing element.

[0211] Embodiment I-34. A wearable analyte monitoring device as described in embodiment I-33, wherein the second biasing element is deployed after the microneedle array reaches the second configuration.

[0212] Embodiment I-35. A method of inserting a microneedle array into a skin surface of a user, comprising: providing a wearable analyte monitoring device including a microneedle array in a first configuration, the microneedle array including a plurality of microneedles, the microneedle array coupled to a biasing element housed within a cavity of a housing, the housing including a body defining a cavity therein, the biasing element being releasably held by a retaining element housed within the cavity, the retaining element being coupled to an actuation member; and transitioning the microneedle array from the first configuration to a second configuration, wherein in the first configuration the microneedle array is held within the cavity of the housing body and in the second configuration the microneedle array protrudes through a distal opening of the housing body.

[0213] Embodiment I-36. The method of embodiment I-35, further comprising adhering the wearable analyte monitoring device to a skin surface of the user.

[0214] Embodiment I-37. The method of embodiment I-36, wherein the wearable analyte monitoring device is adhered to the user's skin surface prior to transitioning the microneedle array from the first configuration to the second configuration.

[0215] Embodiment I-38. An analyte monitoring device comprising: a housing including a body defining a cavity therein, the housing body including a distal opening; a biasing element contained within the cavity; a microneedle array coupled to the biasing element; and an actuating member, wherein engagement of the actuating member transitions the microneedle array from a first configuration to a second configuration under influence of the biasing element, wherein in the first configuration the microneedle array is retained within the cavity of the housing body and in the second configuration at least a portion of the microneedle array protrudes through the distal opening of the housing body.

[0216] Embodiment I-39. The analyte monitoring device of embodiment I-38, wherein the microneedle array is configured to penetrate the subject's skin surface and detect target analytes present in the subject's skin interstitial fluid.

[0217] Embodiment I-40. The analyte monitoring device of embodiment I-38 or embodiment I-39, wherein the microneedle array comprises a first microneedle comprising a working electrode having an electrochemical sensing coating.

[0218] Embodiment I-41. The analyte monitoring device of any one of embodiments I-38 through I-40, wherein the microneedle array includes a second microneedle that includes a reference electrode.

[0219] Embodiment I-42. The analyte monitoring device of any one of embodiments I-38 through I-41, wherein the microneedle array includes a third microneedle that includes a counter electrode.

[0220] Embodiment I-43. An analyte monitoring device described in any one of embodiments I-38 to I-42, further comprising a retaining element configured to hold the microneedle array in a first configuration, wherein engagement of the actuation member deflects a portion of the retaining element to enable the microneedle array to transition from the first configuration to the second configuration under the influence of the biasing element.

[0221] Embodiment I-44. The analyte monitoring device of any one of Embodiments I-38 through I-43, wherein in the second configuration, a plurality of microneedles are inserted through the skin surface of the user.

[0222] Embodiment I-45. An analyte monitoring device according to any one of embodiments I-38 to I-44, wherein the microneedle array achieves a speed of at least 7 meters / second transitioning from the first configuration to the second configuration.

[0223] Embodiment I-46. The analyte monitoring device of any one of embodiments I-38 through I-45, wherein the microneedle array moves a distance of 1.5 millimeters or less transitioning from the first configuration to the second configuration.

[0224] Embodiment I-47. An analyte monitoring device according to any one of embodiments I-38 to I-46, wherein a seal is formed between the outer periphery of the microneedle array and the distal opening when the microneedle array is in the second configuration.

[0225] Embodiment I-48. The analyte monitoring device of any one of embodiments I-38 through I-47, wherein the cavity is watertight when the microneedle array is in the second configuration.

[0226] Embodiment I-49. The analyte monitoring device of any one of Embodiments I-38 through I-48, wherein the actuating member is integral with a portion of the housing body.

[0227] Embodiment I-50. An analyte monitoring device described in any one of embodiments I-38 to I-49, wherein engagement of the actuating member includes depressing a portion of the housing body, thereby releasing the biasing element and transitioning the microneedle array to the second configuration.

[0228] Embodiment I-51. The analyte monitoring device of embodiment I-43, wherein the retaining element is integral with the housing body.

[0229] Embodiment I-52. The analyte monitoring device of embodiment I-50 or embodiment I-51, wherein the housing body includes one or more tapered portions to facilitate flexing upon depression of a portion of the housing body.

[0230] Embodiment I-53. The analyte monitoring device of any one of embodiments I-38 through I-42 and embodiments I-45 through I-48, wherein engaging the actuating member includes rotating the actuating member.

[0231] Embodiment I-54. An analyte monitoring device of any one of embodiments I-38 through I-53, wherein a portion of the biasing element is coupled proximal to the interior distal end of the housing body within the cavity.

[0232] Embodiment I-55. The analyte monitoring device of any one of embodiments I-38 through I-54, wherein the biasing element comprises a leaf spring, a coil spring, a compression spring, a flexible member, or a combination thereof.

[0233] Embodiment I-56. An analyte monitoring device described in any one of embodiments I-38 to I-55, wherein the biasing element includes a first end and a second end, the first end of the biasing element is coupled to the microneedle array, and the second end of the biasing element is coupled proximal to the inner distal end of the housing body within the cavity.

[0234] Embodiment I-57. The analyte monitoring device of embodiment I-56, wherein the first end of the biasing element is releasably retained by the retaining element.

[0235] Embodiment I-58. An analyte monitoring device as described in embodiment I-57, wherein the retaining element is proximal to the interior proximal end of the housing body within the cavity.

[0236] Embodiment I-59. An analyte monitoring device according to any one of Embodiments I-38 through I-58, further comprising a printed circuit board housed within the cavity of the housing body.

[0237] Embodiment I-60. An analyte monitoring device as described in embodiment I-59, wherein the printed circuit board is in electrical communication with the microneedle array via a flexible printed circuit board, and the microneedle array is mounted on the flexible printed circuit board.

[0238] Embodiment I-61. An analyte monitoring device as described in embodiment I-59 or embodiment I-60, wherein the flexible printed circuit board includes actuating contacts that contact corresponding contacts provided on the printed circuit board when the microneedle array is in the second configuration.

[0239] Embodiment I-62. The analyte monitoring device of any one of embodiments I-38 through I-61, wherein the analyte monitoring device is activated when the microneedle array is in the second configuration.

[0240] Embodiment I-63. The analyte monitoring device of embodiment I-59, wherein the printed circuit board moves with the microneedle array.

[0241] Embodiment I-64. An analyte monitoring device according to any one of embodiments I-38 to I-63, wherein a first microneedle of the plurality of microneedles of the microneedle array comprises a working electrode having an electrochemical sensing coating.

[0242] Embodiment I-65. The analyte monitoring device of embodiment I-64, wherein a second microneedle of the plurality of microneedles of the microneedle array comprises a reference electrode.

[0243] Embodiment I-66. The analyte monitoring device of embodiment I-64 or embodiment I-65, wherein a third microneedle of the plurality of microneedles of the microneedle array comprises a counter electrode.

[0244] Embodiment I-67. An analyte monitoring device according to any one of embodiments I-38 to I-66, further comprising a shuttle configured to couple the microneedle array to the biasing element.

[0245] Embodiment I-68. The analyte monitoring device of embodiment I-67, further comprising a tubular protrusion extending from the distal end of the housing body into the cavity, the tubular protrusion configured to guide the shuttle as the microneedle array transitions between the first configuration and the second configuration.

[0246] Embodiment I-69. An analyte monitoring device as described in embodiment I-68, wherein the tubular protrusion includes an aperture configured to engage a flexible arm of the shuttle, thereby holding the microneedle array in the first configuration.

[0247] Embodiment I-70. The analyte monitoring device of embodiment I-69, wherein depression of the actuation member deflects the flexible arms of the shuttle inwardly, thereby releasing the shuttle and transitioning the microneedle array from the first configuration to the second configuration.

[0248] Embodiment I-71. An analyte monitoring device according to any one of embodiments I-68 through I-70, wherein the interior sidewall of the tubular projection defines a distal opening of the housing body.

[0249] Embodiment I-72. The analyte monitoring device of embodiment I-67, further comprising a protrusion extending from a distal end of the housing body into the cavity, the protrusion configured to abut the shuttle when the microneedle array is in the first configuration.

[0250] Embodiment I-73. The analyte monitoring device of embodiment I-72, wherein depression of the actuation member deflects the protrusions outward, thereby releasing the shuttle and transitioning the microneedle array from the first configuration to the second configuration.

[0251] Embodiment I-74. The analyte monitoring device of embodiment I-72 or embodiment I-73, wherein the interior sidewall of the protrusion defines a distal opening of the housing body.

[0252] Embodiment I-75. The analyte monitoring device of any one of embodiments I-38 through I-74, further comprising a second biasing element.

[0253] Embodiment I-76. The analyte monitoring device of embodiment I-75, wherein the second biasing element is deployed after the microneedle array reaches the second configuration.

[0254] Embodiment I-77. A method of monitoring a user using a wearable analyte monitoring device comprising: providing a wearable analyte monitoring device including a microneedle array in a first configuration, the microneedle array including a plurality of microneedles, the microneedle array coupled to a biasing element housed within a cavity of a housing, the housing including a body defining a cavity therein, the biasing element being releasably held by a retaining element housed within the cavity, the retaining element coupled to an actuation member; adhering the wearable analyte monitoring device to a skin surface of the user; transitioning the microneedle array from the first configuration to a second configuration, wherein in the first configuration the microneedle array is held within the cavity of the housing body and in the second configuration the microneedle array protrudes through a distal opening of the housing body; and measuring a target analyte level in skin interstitial fluid of the subject with the microneedle array.

[0255] Embodiment I-78. The method of embodiment I-77, further comprising communicating information indicative of the measured value of the target analyte level.

[0256] Embodiment I-79. The method of embodiment I-77 or embodiment I-78, further comprising displaying the measured value of the target analyte level.

[0257] Embodiment I-80. The method of embodiment I-78, wherein communicating information indicative of the measured value of the target analyte level includes transmitting the information to an external device.

[0258] Embodiment I-81. The method of embodiment I-80, wherein transmitting information includes wirelessly transmitting the target analyte level measurement.

[0259] Embodiment I-82. The method of embodiment I-81, wherein wirelessly transmitting the target analyte level measurement comprises transmitting via short-range wireless communication, Bluetooth® communication, or both.

[0260] Embodiment I-83. The method of any one of embodiments I-77 to I-82, wherein measuring the target analyte level further comprises processing signals received from the microneedle array.

[0261] Embodiment I-84. The method of embodiment I-83, wherein processing the signals received from the microneedle array is performed by a microprocessor disposed within the housing of the wearable analyte monitoring device.

[0262] Embodiment I-85. The method of embodiment I-83 or embodiment I-84, wherein the processing includes applying an algorithm to the signals received from the microneedle array.

[0263] Embodiment I-86. A method of inserting a microneedle array into a skin surface comprising: providing a microneedle array within a cavity of a housing, the housing including a body defining a cavity therein, the microneedle array being coupled to a biasing element within the cavity; loading the microneedle array in a first configuration in which the microneedle array is biased by the biasing element towards a distal end of the housing body; and providing an actuating member engaged to release the microneedle array from the first configuration and transition the microneedle array to a second configuration in which a plurality of microneedles of the microneedle array protrude from a distal opening of the housing body, wherein in transitioning from the first configuration to the second configuration, the microneedle array moves within the cavity towards the distal end of the housing body under the influence of the biasing element.

[0264] Embodiment I-87. The method of embodiment I-86, wherein loading the microneedle array in the first configuration further comprises locking the biasing element within the retaining element, the retaining element being disposed a predetermined distance away from the distal end of the housing body.

[0265] Embodiment I-88. The method of embodiment I-86 or embodiment I-87, wherein the actuating member comprises a portion of the housing body.

Claims

1. 1. A wearable analyte monitoring device, comprising: a housing including a body defining a cavity therein, the housing body including a distal opening; an adhesive layer coupled to a distal end of the housing and surrounding the distal opening, the adhesive layer configured to secure the device to a skin surface of a user; and a biasing element housed within the cavity; a microneedle array coupled to the biasing element and including a plurality of microneedles; a retaining element received within the cavity and configured to releasably retain the biasing element; an actuation member coupled to the retention element, wherein engagement of the actuation member transitions the microneedle array between a first configuration and a second configuration; and Including, In the first configuration, the microneedle array is held within the cavity of the housing body; In the second configuration, the microneedle array protrudes through the distal opening of the housing body.

2. The wearable analyte monitoring device of claim 1 , wherein in the second configuration, the plurality of microneedles are inserted through the skin surface of the user.

3. The wearable analyte monitoring device of claim 1 , wherein a seal is formed between an outer periphery of the microneedle array and the distal opening when the microneedle array is in the second configuration.

4. The wearable analyte monitoring device of claim 1 , wherein the actuation member is integral with a portion of the housing body.

5. 5. The wearable analyte monitoring device of claim 4, wherein engagement of the actuation member comprises depressing the portion of the housing body, thereby releasing the biasing element and transitioning the microneedle array to the second configuration.

6. The wearable analyte monitoring device of claim 5 , wherein the retaining element is integral with the housing body.

7. The wearable analyte monitoring device of claim 5 , wherein the housing body includes one or more tapered portions to facilitate flexing upon depression of the portion of the housing body.

8. The wearable analyte monitoring device of claim 1 , wherein engaging the actuation member comprises rotating the actuation member.

9. The wearable analyte monitoring device of claim 1 , wherein a portion of the biasing element is coupled proximal to an interior distal end of the housing body within the cavity.

10. The wearable analyte monitoring device of claim 1 , wherein the biasing element comprises a leaf spring, a coil spring, a compression spring, a flexible member, or a combination thereof.

11. 2. The wearable analyte monitoring device of claim 1, wherein the biasing element includes a first end and a second end, the first end of the biasing element coupled to the microneedle array and the second end of the biasing element coupled proximal to an interior distal end of the housing body within the cavity.

12. The wearable analyte monitoring device of claim 11 , wherein the first end of the biasing element is releasably retained by the retaining element.

13. The wearable analyte monitoring device of claim 12 , wherein the retaining element is proximal to an interior proximal end of the housing body within the cavity.

14. The wearable analyte monitoring device of claim 1 , further comprising a printed circuit board housed within the cavity of the housing body.

15. 15. The wearable analyte monitoring device of claim 14, wherein the printed circuit board is in electrical communication with the microneedle array via a flexible printed circuit board, the microneedle array being mounted on the flexible printed circuit board.

16. 15. The wearable analyte monitoring device of claim 14, wherein the flexible printed circuit board includes actuation contacts that contact corresponding contacts provided on the printed circuit board when the microneedle array is in the second configuration.

17. The wearable analyte monitoring device of claim 16 , wherein the wearable analyte monitoring device is activated when the microneedle array is in the second configuration.

18. The wearable analyte monitoring device of claim 14 , wherein the printed circuit board moves with the microneedle array.

19. The wearable analyte monitoring device of claim 1 , further comprising a second biasing element.

20. 1. A method for inserting a microneedle array into a skin surface of a user, comprising: providing a wearable analyte monitoring device including a microneedle array in a first configuration, the microneedle array including a plurality of microneedles, the microneedle array coupled to a biasing element housed within a cavity of a housing, the housing including a body defining the cavity therein, the biasing element being releasably held by a retaining element housed within the cavity, the retaining element coupled to an actuation member; transitioning the microneedle array from the first configuration to a second configuration; Including, In the first configuration, the microneedle array is held within the cavity of the housing body; In the second configuration, the microneedle array protrudes through a distal opening of the housing body.

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