Patent Application
20250000395
This invention relates generally to the field of analyte monitoring, such as continuous glucose monitoring.
Diabetes is a chronic disease in which the body does not produce or properly utilize insulin, a hormone that regulates blood glucose. Insulin may be administered to a diabetic patient to help regulate blood glucose levels, though blood glucose levels must nevertheless be carefully monitored to help ensure that timing and dosage are appropriate. Without proper management of their condition, diabetic patients may suffer from a variety of complications resulting from hyperglycemia (high blood sugar levels) or hypoglycemia (low blood sugar levels).
Blood glucose monitors help diabetic patients manage their condition by measuring blood glucose levels from a sample of blood. For example, a diabetic patient may obtain a blood sample through a fingerstick 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 to measure glucose level in that blood sample. However, a patient using this process can typically only measure his or her glucose levels at discrete instances in time, which may fail to capture a hyperglycemia or hypoglycemia condition in a timely manner. Yet a more recent variety of glucose monitor is a continuous glucose monitor (CGM) device, which includes implantable transdermal electrochemical sensors that are used to continuously detect and quantify blood glucose levels by proxy measurement of glucose levels in the subcutaneous interstitial fluid. However, conventional CGM devices also have weaknesses including tissue trauma from insertion and signal latency (e.g., due to the time required for the glucose analyte to diffuse from capillary sources to the sensor). These weaknesses also lead to a number of drawbacks, such as pain experienced by the patient when electrochemical sensors are inserted, and limited accuracy in glucose measurements, particularly when blood glucose levels are changing rapidly. Accordingly, there is a need for a new and improved analyte monitoring system.
According to an embodiment, the present disclosure relates to analyte monitoring.
In embodiments, the present disclosure further relates to a wearable analyte monitoring device, comprising a housing comprising a body defining a cavity therein, wherein the housing body comprises 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 the user, a biasing element contained within the cavity, a microneedle array coupled to the biasing element and comprising a plurality of microneedles, a retention element contained within the cavity and configured to releasably retain the biasing element, and an actuation member coupled to the retention element, wherein engagement of the actuation member moves the microneedle array between a first configuration and a second configuration, and 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 the distal opening of the housing body.
In embodiments, 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 comprising the microneedle array in a first configuration, the microneedle array comprising a plurality of microneedles, the microneedle array coupled to a biasing element contained within a cavity of a housing, the housing comprising a body defining the cavity therein, the biasing element releasably retained by a retention element contained within the cavity, and the retention element coupled to an actuation member, and transitioning the microneedle array from the first configuration to a second configuration, and 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.
In embodiments, the present disclosure further relates to an analyte monitoring device, comprising a housing comprising a body defining a cavity therein, wherein the housing body comprises a distal opening, a biasing element contained within the cavity, a microneedle array coupled to the biasing element, and an actuation member, wherein engagement of the actuation member moves the microneedle array from a first configuration to a second configuration under influence of the biasing element, and wherein in the first configuration, the microneedle array is held 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.
In embodiments, the present disclosure further relates to a method of monitoring a user using a wearable analyte monitoring device, the method comprising providing the wearable analyte monitoring device comprising the microneedle array in a first configuration, the microneedle array comprising a plurality of microneedles, the microneedle array coupled to a biasing element contained within a cavity of a housing, the housing comprising a body defining the cavity therein, the biasing element releasably retained by a retention element contained within the cavity, and the retention 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, and 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 dermal interstitial fluid of the subject with the microneedle array.
In embodiments, the present disclosure further relates to a method of inserting a microneedle array into a skin surface, the method comprising providing the microneedle array within a cavity of a housing, the housing comprising a body defining the cavity therein, wherein the microneedle array is coupled to a biasing element within the cavity, loading the microneedle array in first configuration in which the microneedle array is biased by the biasing element toward a distal end of the housing body, and providing an actuation member, wherein the actuation member is 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 the transition from the first configuration to the second configuration, the microneedle array travels within the cavity toward the distal end of the housing body under influence of the biasing element.
Non-limiting examples of various aspects and variations of the invention are described herein and illustrated in the accompanying drawings.
Aspects of the current subject matter are directed to a microneedle array-based analyte monitoring device with integrated applicator. In some variations, an integrated applicator mechanism allows for a user to place the analyte monitoring device on the desired area and deploy the microneedle array to puncture the skin of the user for insertion into the skin. In some variations, the analyte monitoring device is secured to the skin at the desired area via an adhesive prior to the microneedle array being deployed.
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 integrated applicator) transitions a 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 a biasing element are loaded such that the microneedle array is ready to be deployed), 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 a biasing element are deployed such that the microneedle array is inserted into the skin of the user). In the first configuration, the microneedle array is retained inside the housing of the wearable analyte monitoring device away from the surrounding electronics and housing components. By retaining the microneedle array within the housing in the first configuration, the plurality of microneedles of the microneedle array may be protected from damage prior to deployment. This arrangement allows for the microneedle array to travel (e.g., transition to a deployed or second configuration) in a generally vertical direction independent of the supporting electronics and housing. By isolating or separating the microneedle array from other components, the mass of a support structure holding the microneedle array is low, enabling rapid acceleration of the microneedle array over a relatively small displacement with relatively small forces when compared to moving an entire device body (e.g., as would be required with a separate applicator device). This arrangement minimizes impact momentum, which reduces discomfort to the user on impact. The reduced moving mass also enables reduction in spring size and required spring force to the degree that components for effective insertion are small enough to fit inside of a wearable sensor body housing.
In variations, upon assembly of the analyte monitoring device, the microneedle array is positioned in a first, loaded configuration, in which it is retracted inside a housing body and held in the first configuration by a retention element (such as a movable clip) that can be dislocated by an actuation member from, for example, an exterior of the housing body. In the first configuration, a biasing element is compressed into a stressed state and presses on the microneedle array with a force (e.g., between about 15 to about 35 Newtons). Once the biasing element is released from the retention element via actuation by the user, the biasing element applies an accelerating force on the microneedle array in the direction of application. Due to the small mass, the force accelerates the microneedle array to relatively high speeds (e.g., between about 7 to about 14 m/s) in a very short displacement distance (e.g., between about 1.5 to about 3 mm) to impact the skin. The speeds overcome the viscoelastic mechanical properties of the skin surface, thus effectively and reliably inserting the microneedle array.
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, an electrical connection is established with the electronics of the analyte monitoring device when the microneedle array reaches the deployed or second configuration in which the microneedle array protrudes from a distal opening for insertion into the skin of the user. In some variations, a seal is maintained between the microneedle array and the housing while transitioning from the first configuration to the second configuration. In some variations, a seal is established when the microneedle array reaches the deployed or second configuration.
Before providing additional details regarding aspects of the wearable analyte monitoring device with integrated applicator, the following provides a description of some examples of an analyte monitoring device that may be used with the wearable analyte monitoring device described herein. The following descriptions are meant to be exemplary, and aspects related to the wearable analyte monitoring device with integrated applicator consistent with the current subject matter are not limited to the example analyte monitoring device described herein.
As generally described herein, an analyte monitoring system may include an analyte monitoring device that is worn by a user and includes one or more sensors for monitoring at least one analyte of a user. The sensors may, for example, include one or more electrodes configured to perform electrochemical detection of at least one analyte. The analyte monitoring device may communicate sensor data to an external computing device for storage, display, and/or analysis of sensor data.
For example, as shown in
The analyte monitoring devices described herein have characteristics that improve a number of properties that are advantageous for a continuous analyte monitoring device such as a continuous glucose monitoring (CGM) device. For example, the analyte monitoring device described herein have improved sensitivity (amount of sensor signal produced per given concentration of target analyte), improved selectivity (rejection of endogenous and exogenous circulating compounds that can interfere with the detection of the target analyte), and improved stability to help minimize change in sensor response over time through storage and operation of the analyte monitoring device. Additionally, compared to conventional continuous analyte monitoring devices, the analyte monitoring devices described herein have a shorter warm-up time that enables the sensor(s) to quickly provide a stable sensor signal following implantation, as well as a short response time that enables the sensors(s) to quickly provide a stable sensor signal following a change in analyte concentration in the user. Furthermore, as described in further detail below, the analyte monitoring devices described herein may be applied to and function in a variety of wear sites, and provide for pain-free sensor insertion for the user. Other properties such as biocompatibility, sterilizability, and mechanical integrity are also optimized in the analyte monitoring devices described herein.
Although the analyte monitoring systems described herein may be described with reference to monitoring of 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, for example, include glucose, ketones, lactate, and cortisol. One target analyte may be monitored, or multiple target analytes may be simultaneously monitored (e.g., in the same analyte monitoring device). For example, monitoring of other target analytes may enable the monitoring of other indications such as stress (e.g., through detection of rising cortisol and glucose) and ketoacidosis (e.g., through detection of rising ketones).
As shown in
An electronics system 120 may be at least partially arranged in the housing 112 and include various electronic components, such as sensor circuitry 124 configured to perform signal processing (e.g., biasing and readout of electrochemical sensors, converting the analog signals from the electrochemical sensors to digital signals, 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 other various suitable passive circuitry 127. The microcontroller 122 may, for example, be configured to interpret digital signals output from the sensor circuitry 124 (e.g., by executing a programmed routine in firmware), perform various suitable algorithms or mathematical transformations (e.g., calibration, etc.), and/or route processed data to and/or from the communication module 124. In some variations, the communication module 126 may include a suitable wireless transceiver (e.g., Bluetooth transceiver or the like) for communicating data with an 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 communication. For example, the communication module 126 may be configured to provide uni-directional and/or bi-directional communication of data with an external computing device 102 that is paired with the analyte monitoring device 110. The power source 130 may provide power for the analyte monitoring device 110, such as for the electronics system. The power source 130 may include battery or other suitable source, and may, in some variations, be rechargeable and/or replaceable. Passive circuitry 127 may include various non-powered electrical circuitry (e.g., resistors, capacitors, inductors, etc.) providing interconnections between other electronic components, etc. The passive circuitry 127 may be configured to perform noise reduction, biasing and/or other purposes, for example. In some variations, the electronic components in the electronics system 120 may be arranged on one or more printed circuit boards (PCB), which may be rigid, semi-rigid, or flexible, for example. Additional details of the electronics system 120 are described further below.
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 for user monitoring. For example, the analyte monitoring device 110 may further include at least one temperature sensor (e.g., thermistor) configured to measure skin temperature, thereby enabling temperature compensation for the sensor measurements obtained by the microneedle array electrochemical sensors.
The microneedle array 140 in the analyte monitoring device 110 is configured to puncture skin of a user. As shown in
In contrast to traditional continuous analyte monitoring devices (e.g., CGM devices), which include sensors typically implanted between about 8 mm and about 10 mm beneath the skin surface in the subcutis or adipose layer of the skin, the analyte monitoring device 110 has a shallower microneedle insertion depth of about 0.25 mm (such that electrodes are implanted in the upper dermal region of the skin) that provides numerous benefits. These benefits include access to dermal interstitial fluid including one or more target analytes for detection, which is advantageous at least because at least some types of analyte measurements of dermal interstitial fluid have been found to closely correlate to those of blood. For example, it has been discovered that glucose measurements performed using electrochemical sensors accessing dermal interstitial fluid are advantageously highly linearly correlated with blood glucose measurements. Accordingly, glucose measurements based on dermal interstitial fluid are highly representative of blood glucose measurements.
Additionally, because of the shallower microneedle insertion depth of the analyte monitoring device 110, a reduced time delay in analyte detection is obtained compared to traditional continuous analyte monitoring devices. Such a shallower insertion depth positions the sensor surfaces in close proximity (e.g., within a few hundred micrometers or less) to the dense and well-perfused capillary bed of the reticular dermis, resulting in a negligible diffusional lag from the capillaries to the sensor surface. Diffusion time is related to diffusion distance according to t=x2/(2D) where is the diffusion time, x is the diffusion distance, and D is the mass diffusivity of the analyte of interest. Therefore, positioning an analyte sensing element twice as far away from the source of an analyte in a capillary will result in a quadrupling of the diffusional delay time. Accordingly, conventional analyte sensors, which reside in the very poorly vascularized adipose tissue beneath the dermis, result in a significantly greater diffusion distance from the vasculature in the dermis and thus a substantial diffusional latency (e.g., typically 5-20 minutes). In contrast, the shallower microneedle insertion depth of the analyte monitoring device 110 benefits from low diffusional latency from capillaries to the sensor, thereby reducing time delay in analyte detection and providing more accurate results in real-time or near real-time. For example, in some embodiments, diffusional latency may be less than 10 minutes, less than 5 minutes, or less than 3 minutes.
Furthermore, when the microneedle array rests in the upper dermal region, the lower dermis beneath the microneedle array includes very high levels of vascularization and perfusion to support the dermal metabolism, which enables thermoregulation (via vasoconstriction and/or vasodilation) and provides a barrier function to help stabilize the sensing environment around the microneedles. Yet another advantage of the shallower insertion depth is that the upper dermal layers lack pain receptors, thus resulting in a reduced pain sensation when the microneedle array punctures the skin of the user, and providing for a more comfortable, minimally-invasive user experience.
Thus, the analyte monitoring devices and methods described herein enable improved continuous monitoring of one or more target analytes of a user. For example, as described above, the analyte monitoring device may be simple and straightforward to apply, which improves ease-of-use and user compliance. Additionally, analyte measurements of dermal interstitial fluid may provide for highly accurate analyte detection. Furthermore, compared to traditional continuous analyte monitoring devices, insertion of the microneedle array and its sensors may be less invasive and involve less pain for the user. Additional advantages of other aspects of the analyte monitoring devices and methods are further described below.
The analyte monitoring device 110 may include a housing which defines a cavity that at least partially surrounds or encloses other components (e.g., electronic components) of the analyte monitoring device 110, such as for protection of 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 house is attached to the surface, the microneedle array 140 may be deployed to extend outwardly from the housing and into the skin of the user. Furthermore, in some variations, the housing may generally include rounded edges or corners and/or be low-profile to reduce interference with clothing, etc. worn by the user.
For example, as shown in
The housing cover 320 and the base plate 330 may, for example, include one or more rigid or semi-rigid protective shell components that may couple together via suitable fasteners (e.g., mechanical fasteners), mechanically interlocking or mating features, and/or an engineering fit. The housing cover 320 and the base plate 330 may include radiused edges and corners and/or other atraumatic features. When coupled together, the housing cover 320 and the base plate 330 may form a cavity comprising an internal volume that houses internal components, such as the sensor assembly 350. For example, the internal components arranged in the internal volume may be arranged in a compact, low-profile stack-up as the sensor assembly 350.
The analyte monitoring device 110 may include one or more adhesive layers provided on a distal end of the housing to attach the analyte monitoring device 110 (e.g., the coupled together housing cover 320 and the base plate 330) to a surface (e.g., the skin) of a user. As shown in
The base plate 330 has a first surface (e.g., an outwardly exposed surface) opposite a second surface and serves as a support and/or connection structure and 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 shaped to securely fit within the housing cover 320 such that outer edges of the base plate 330 align with corresponding edges of an opening of the housing cover 320. The alignment may be such that there is no gap between the outer edges of the base plate 330 and the corresponding edges of the opening of the housing cover 320.
A connection member 332 may be formed in a central or near central region of the first surface of the base plate 330. The connection member 332 is a protrusion (e.g., a projected hub) with sidewalls that extend from the first surface of the base plate 330 and with a first surface substantially parallel to the first surface of the base plate 330. Sidewalls extend from edges of the first surface of the connection member 332 to the first surface of the base plate 330. A remaining portion of the first surface of the base plate 330 surrounding the connection member 332 may be flat or substantially flat. One or more connector features 336 extend outwardly from the sidewalls of the connection member 332 to releasably engage with corresponding connectors of a microneedle enclosure that provides, for example, a sterile environment for the microneedle array 140. The first surface and the sidewalls of the connection member 332 define, in part, a chamber. The chamber may be further defined through a portion of the base plate 330 adjacent (e.g., below) the connection member 332. The chamber has an opening, and is accessible, on the second surface of the base plate 330. An aperture or distal opening 334 is formed through the first surface of the connection 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, 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 with an area surrounding the microneedle array 140. The openings in the inner adhesive layer 342 and the outer adhesive layer 344 (or the single adhesive layer) may be sized such that the connection member 332 extends through the openings without interference with the adhesive layers. For example, the diameter of the opening of the inner adhesive layer 342 and the diameter of the opening of the outer adhesive layer 344 is larger than that of the connection member 332. In some variations, the opening of the inner adhesive layer 342 and/or the opening of the outer adhesive layer 344 (or that of the single adhesive layer) is in proximity with the sidewalls of the connection member 332 with a clearance to accommodate the 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 placement of the respective adhesive layer.
Although the housing cover 320 and the base plate 330 depicted in
The sensor assembly 350 includes microneedle array components and electronic components to implement analyte detection and processing aspects of the microneedle array-based continuous analyte monitoring device 110 for the detection and measuring of an analyte. In some variations, the sensor assembly 350 is a compact, low-profile stack-up that is at least partially contained within the cavity comprising an internal volume defined by the housing cover 320 and the base plate 330.
In some variations, the sensor assembly 350 includes a microneedle array assembly 360 and an electronics assembly 370 that connect to one another to implement the microneedle array analyte detection and processing aspects further described herein. In some variations, the electronics assembly 370 includes a main printed circuit board (PCB) 450 on which electronic components are connected, and the microneedle array assembly 360 includes a secondary printed circuit board (PCB) 420 on which the microneedle array 140 is connected.
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., outer facing side) of the secondary PCB 420 so that the individual microneedles of the microneedle array 140 are exposed as described with reference to
The secondary PCB 420 may in part determine the distance to which the microneedle array 140 protrudes from the base plate 330 of the housing. Accordingly, the height of the secondary PCB 420 may be selected to help ensure that the microneedle array 140 is inserted properly into a user's skin. During microneedle insertion, the first surface (e.g., outer facing surface) of the connection member 332 of the base plate 330 may act as a stop for microneedle insertion. If the secondary PCB 420 has a reduced height and its top surface is flush or nearly flush with the first surface of the connection member 332, then the connection member 332 may prevent the microneedle array 140 from being fully inserted into the skin.
In some variations, other components (e.g., electronic components such as sensors or other components) may also be connected to the secondary PCB 420. For example, the secondary PCB 420 may be sized and shaped to accommodate electronic components on the top side or the back side of the secondary PCB 420.
In some variations, the epoxy skirt 410 may be deposited along the edges (e.g., the outer perimeter) of the microneedle array 140 to provide a secure fit of the microneedle array 140 within the distal opening 334 formed in the connection member 332 of the base plate 330 and/or to relieve the sharp edges along the microneedle array 140, as shown in
The electronics assembly 370, having the primary PCB 450, includes a battery 460 coupled to a back side of the primary PCB 450, opposite the top side on which the primary PCB connector 470 is coupled. In some variations, the battery 460 may be coupled on the top side of the primary PCB 450 and/or in other arrangements.
As shown, in the sensor assembly 350, an additional PCB component, an intermediate PCB 425, is incorporated. 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 such that the microneedle array 140 extends at a further distance from the base plate 330, which may aid in insertion of the microneedle array 140 into the skin of a user. The microneedle array 140 is coupled to a top side (e.g., outer facing side) of the intermediate PCB 425 so that the individual microneedles of the microneedle array 140 are exposed as described with reference to
The intermediate PCB 425 with the secondary PCB 420, in part, determine the distance to which the microneedle array 140 protrudes through the distal opening 334 of the base plate 330. The incorporation of the intermediate PCB 425 provides an additional height to help ensure that the microneedle array 140 is properly inserted into a user's skin. In some variations, the top side (e.g., outer facing side) of the intermediate PCB 425 extends through and out of the distal opening 334 so that the first surface (e.g., top, exposed 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., outer facing side) of the intermediate PCB 425 does not extend out of the distal opening 334 but the increased height (by virtue of incorporating the intermediate PCB 425) ensures that the microneedle array 140 protrudes at a sufficient distance from the base plate 330 of the housing.
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 manufacture and transport 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 to allow for the microneedle array 140 to be exposed and/or ready for insertion into the skin of the user, as further described herein.
In some variations, the microneedle enclosure, by providing an enclosed and sealed environment in which the microneedle array 140 may be contained, provides an environment in which the microneedle array 140 may be sterilized. For example, the microneedle enclosure with the microneedle array 140 may be subjected to a sterilization process, during which the sterilization penetrates the microneedle enclosure so that the microneedle array 140 is also sterilized. As the microneedle array 140 is contained in an enclosed environment, the microneedle array 140 remains sterilized until removed from the enclosed environment. In some variations, a removeable film is provided on the distal end of the housing, covering the distal opening 334 prior to application of the analyte monitoring device 110 on the skin surface of a subject. The removeable film may maintain a sterile environment and prevent intrusion of foreign objects or substances before application of the analyte monitoring device 110. A user may remove or peel off the film just prior to applying and/or adhering the analyte monitoring device 110 to the skin surface of a subject.
In some variations, the electronics system of the analyte monitoring device 110 may include an analog front end. The analog front end may include sensor circuitry (e.g., sensor circuitry 124 as shown in
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. Furthermore, the analog front end may include an internal temperature sensor and programmable voltage reference, support external temperature monitoring and an external reference source and integrate voltage monitoring of bias and supply voltages for safety and compliance.
In some variations, the analog front end may include a multi-channel potentiostat to multiplex sensor inputs and handle multiple signal channels. For example, the analog front end may include a multi-channel potentiostat such as that described in U.S. Pat. No. 9,933,387, which is incorporated herein in its entirety by this reference.
In some variations, the analog front end and peripheral electronics may be integrated into an application-specific integrated circuit (ASIC), which may help reduce cost, for example. This integrated solution may include the microcontroller described below, in some variations.
In some variations, the electronics system of the analyte monitoring device may include at least one microcontroller (e.g., controller 122 as shown in
In some variations, the microcontroller may be configured to activate and/or inactivate the analyte monitoring device on one or more detected conditions. For example, the device may be configured to power on the analyte monitoring device upon deployment or insertion of the microneedle array into skin. This may, for example, enable a power-saving feature in which the battery is disconnected until the microneedle array is deployed, at which time the device may begin broadcasting sensor data. Such a feature may, for example, help improve the shelf life of the analyte monitoring device and/or simplify the analyte monitoring device-external device pairing process for the user.
As shown in the schematic of
In some variations, electrode-based measurements may be performed at the interface of the electrode and interstitial fluid located within the body (e.g., on an outer surface of the overall microneedle). In some variations, the microneedle 510 may have a solid core (e.g., solid body portion), though in some variations the microneedle 510 may include one or more lumens, which may be used for drug delivery or sampling of the dermal interstitial fluid, for example. Other microneedle variations, such as those described below, may similarly either include a solid core or one or more lumens.
The microneedle array 500 may be at least partially formed from a semiconductor (e.g., silicon) substrate and include various material layers applied and shaped using various suitable microelectromechanical systems (MEMS) manufacturing techniques (e.g., deposition and etching techniques), as further described below. The microneedle array may be reflow-soldered to a circuit board, similar to a typical integrated circuit. Furthermore, in some variations the microneedle array 500 may include a three electrode setup including a working (sensing) electrode having an electrochemical sensing coating (including a biorecognition element such as an aptamer or an enzyme) that enables detection of the 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 including a reference electrode, and at least one microneedle 510 including a counter electrode. Additional details of these types of electrodes are described in further detail below.
In some variations, the microneedle array 500 may include a plurality of microneedles that are insulated such that the electrode on each microneedle in the plurality of microneedles is individually addressable and electrically isolated from every other electrode on the microneedle array. The resulting individual addressability of the microneedle array 500 may enable greater control over each electrode's function, since each electrode may be separately probed. For example, the microneedle array 500 may be used to provide multiple independent measurements of a given analyte, which improves the device's sensing reliability and accuracy. Furthermore, in some variations the electrodes of multiple microneedles may be electrically connected to produce augmented signal levels. As another example, the same microneedle array 500 may additionally or alternatively be interrogated to simultaneously measure multiple analytes to provide a more comprehensive assessment of physiological status. For example, as shown in the schematic of
In some variations of microneedles (e.g., microneedles with a working electrode), the electrode 520 may be located 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 being proximal to or offset from the insulated distal apex 516 of the microneedle advantageously provides more accurate sensor measurements. For example, this arrangement prevents concentration of the electric field at the microneedle apex 516 during manufacturing, thereby avoiding non-uniform electro-deposition of sensing chemistry on the electrode surface 520 that would result in faulty sensing. The electrode 520 may be configured to have an annular shape and may comprise a distal edge 521a and a proximal edge 521b.
As another example, placing the electrode 520 offset from the microneedle apex further improves sensing accuracy by reducing undesirable signal artefacts and/or erroneous sensor readings caused by stress upon microneedle insertion. The distal apex of the microneedle is the first region to penetrate into the skin, and thus experiences the most stress caused by the mechanical shear phenomena accompanying the tearing or cutting of the skin. If the electrode 520 were placed on the apex or tip of the microneedle, this mechanical stress may delaminate the electrochemical sensing coating on the electrode surface when the microneedle is inserted, and/or cause a small yet 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 may improve sensing accuracy. For example, in some variations, a distal edge 521a of the electrode 520 may be located at least about 10 μm (e.g., between about 20 μm and about 30 μm) from the distal apex or tip of the microneedle, as measured along a longitudinal axis of the microneedle.
The body portion 512 of the microneedle 510 may further include an electrically conductive pathway extending between the electrode 520 and a backside electrode or other electrical contact (e.g., arranged on a backside of the substrate of the microneedle array). The backside electrode may be soldered to a circuit board, enabling electrical communication with the electrode 520 via the conductive pathway. For example, during use, the in-vivo sensing current (inside the dermis) measured at a working electrode is interrogated by the backside electrical contact, and the electrical connection between the backside electrical contact and the working electrode is facilitated by the conductive pathway. In some variations, this conductive pathway may be facilitated by a metal via running through the interior of the microneedle body portion (e.g., shaft) between the microneedle's proximal and distal ends. Alternatively, in some variations the conductive pathway may be provided by the entire body portion being formed of a conductive material (e.g., doped silicon). In some of these variations, the complete substrate on which the microneedle array 500 is built upon may be electrically conductive, and each microneedle 510 in 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 with an insulative barrier including electrically insulative material (e.g., dielectric material such as silicon dioxide) that surrounds the conductive pathway extending between the electrode 520 and backside electrical contact. For example, body portion 512 may include an insulative material that forms a sheath around the conductive pathway, thereby preventing electrical communication between the conductive pathway and the substrate. Other example variations of structures enabling electrical isolation among microneedles are described in further detail below.
Such electrical isolation among microneedles in the microneedle array permits the sensors to be individually addressable. This individual addressability advantageously enables independent and parallelized measurement among the sensors, as well as dynamic reconfiguration of sensor assignment (e.g., to different analytes). In some variations, the electrodes in 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 measurement values from different microneedles which reduces the effect of extreme high or low sensor signals on the determination of analyte levels) and/or improving reliability of the device by reducing the likelihood of total failure.
In some variations, as described in further detail below with respective different variations of the microneedle, the microneedle array may be formed at least in part with suitable semiconductor and/or MEMS fabrication techniques and/or mechanical cutting or dicing. Such processes may, for example, be advantageous for enabling large-scale, cost-efficient manufacturing of microneedle arrays.
Described herein are further example variations of microneedle structures incorporating one or more of the above-described microneedle features for a microneedle array in an analyte monitoring device.
In some variations, a microneedle may have a generally columnar body portion and a tapered distal portion with an electrode. For example,
Also as shown in
The electrode 720 may be in electrical communication with a conductive core 740 (e.g., conductive pathway) passing along the body portion 712 to a backside electrical contact 730 (e.g., made of 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., highly doped silicon). As shown in
The microneedle 700 may be formed at least in part by suitable MEMS fabrication techniques such as plasma etching, also called dry etching. For example, in some variations, the insulating moat 713 around the body portion 712 of the microneedle may be made by first forming a trench in a silicon substrate by deep reactive ion etching (DRIE) from the backside of the substrate, then filling that trench with a sandwich structure of SiO2/polycrystalline silicon (poly-Si)/SiO2 by low pressure chemical vapor deposition (LPCVD) or other suitable process. In other words, the insulating moat 713 may passivate the surface of the body portion 712 of the microneedle, and continue as a buried feature in the substrate 702 near the proximal portion of the microneedle. By including largely compounds of silicon, the insulating moat 713 may provide good fill and adhesion to the adjoining silicon walls (e.g., of the conductive core 740, substrate 702, etc.). The sandwich structure of the insulating moat 713 may further help provide excellent matching of coefficient of thermal expansion (CTE) with the adjacent silicon, thereby advantageously reducing faults, cracks, and/or other thermally-induced weaknesses in the insulating structure 713.
The tapered distal portion may be fashioned out by an isotropic dry etch from the frontside of the substrate, and the body portion 712 of the microneedle 700 may be formed from DRIE. The frontside metal electrode 720 may be deposited and patterned on the distal portion by specialized lithography (e.g., electron-beam evaporation) that permits metal deposition in the desired annular region for the electrode 720 without coating the distal apex 716. Furthermore, the backside electrical contact 730 of Ni/Au may be deposited by suitable MEMS manufacturing techniques (e.g., sputtering).
The microneedle 700 may have any suitable dimensions. By way of illustration, the microneedle 700 may, in some variations, have a height of between about 300 μm and about 500 μm. In some variations, the tapered distal portion 714 may have a tip angle between about 60 degrees and about 80 degrees, and an apex diameter of between about 1 μm and about 15 μm. In some variations, the surface area of the annular electrode 720 may include between about 9,000 μm2 and about 11,000 μm2, or about 10,000 μm2.
As can most easily be seen in
Details of example variations of microneedle array configurations are described in further detail below.
As described above, each microneedle in the microneedle array may include an electrode. In some variations, multiple distinct types of electrodes may be included among the microneedles in the microneedle array. For example, in some variations the microneedle array may function as an electrochemical cell operable in an electrolytic manner with 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 distinct electrode types, though one or more of each electrode type may form a complete system (e.g., the system might include multiple distinct working electrodes). Furthermore, multiple distinct 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 with working electrode sites). Each of these electrode types may include a metallization layer and may include one or more coatings or layers over the metallization layer that help facilitate the function of that electrode.
Generally, the working electrode is the electrode at which oxidation and/or reduction reaction of interest occurs for detection of an analyte of interest. The counter electrode functions to source (provide) or sink (accumulate) the electrons, via an electrical current, that are required to sustain the electrochemical reaction at the working electrode. The reference electrode functions to provide a reference potential for the system; that is, the electrical 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 sinked to the reference electrode. Additionally, to implement such a three-electrode system, the analyte monitoring device may include a suitable potentiostat or electrochemical analog front end to maintain a fixed potential relationship between the working electrode and reference electrode contingents within the electrochemical system (via an electronic feedback mechanism), while permitting the counter electrode to dynamically swing to potentials required to sustain the redox reaction of interest.
Multiple 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 of how to configure the microneedles include factors such as desired insertion force for penetrating skin with the microneedle array, optimization of electrode signal levels and other performance aspects, manufacturing costs and complexity, etc.
For example, the microneedle array may include multiple microneedles that are spaced apart at a predefined pitch (distance between the center of one microneedle to the center of its nearest neighboring microneedle). In some variations, the microneedles may be spaced apart with a sufficient pitch so as to distribute force (e.g., avoid a “bed of nails” effect) that is applied to the skin of the user to cause the microneedle array to penetrate the skin. As pitch increases, force required to insert the microneedle array tends to decrease and depth of penetration tends to increase. However, it has been found that pitch only begins to affect insertion force at low values (e.g., less than about 150 μm). Accordingly, in some variations the microneedles in a 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 between about 200 μm and about 800 μm, between about 300 μm and about 700 μm, or between about 400 μm and about 600 μm. In some variations, the microneedles may be arranged in a periodic grid, and the pitch may be uniform in all directions and across all regions of the microneedle array. Alternatively, the pitch may be different as measured along different axes (e.g., X, Y directions) and/or some regions of the microneedle array may include a smaller pitch while others may include a larger pitch.
Furthermore, for more consistent penetration, microneedles may be spaced equidistant from one another (e.g., same pitch in all directions). To that end, in some variations, the microneedles in a microneedle array may be arranged in a hexagonal configuration as shown in
Another consideration for determining configuration of a microneedle array is overall signal level provided by the microneedles. Generally, signal level at each microneedle is invariant of the total number of microneedle elements in an array. However, signal levels can be enhanced by electrically interconnecting multiple microneedles together in an array. For example, an array with a large number of electrically connected microneedles is expected to produce a greater signal intensity (and hence increased accuracy) than one with fewer microneedles. However, a higher number of microneedles on a die will increase die cost (given a constant pitch) and will also require greater force and/or velocity to insert into skin. In contrast, a lower number of microneedles on a die may reduce die cost and enable insertion into the skin with reduced application force and/or velocity. Furthermore, in some variations a lower number of microneedles on a die may reduce the overall footprint area of the die, which may lead to less unwanted localized edema and/or erythema. Accordingly, in some variations, a balance among these factors may be achieved with a microneedle array including 37 microneedles as shown in
Additionally, as described in further detail below, in some variations only a subset of the microneedles in a microneedle array may be active during operation of the analyte monitoring device. For example, a portion of the microneedles in a microneedle array may be inactive (e.g., no signals read from electrodes of inactive microneedles). In some variations, a portion of the microneedles in a microneedle array may be activated at a certain time during operation and remain active for the remainder of the operating lifetime of the device. Furthermore, in some variations, a portion of the microneedles in a microneedle array may additionally or alternatively be deactivated at a certain time during operation and remain inactive for the remainder of the operating lifetime of the device.
In considering characteristics of a die for a microneedle array, die size is a function of the number of microneedles in the microneedle array and the pitch of the microneedles. Manufacturing costs are also a consideration, as a smaller die size will contribute to lower cost since the number of dies that can be formed from a single wafer of a given area will increase. Furthermore, a smaller die size will also be less susceptible to brittle fracture due to the relative fragility of the substrate.
Furthermore, in some variations, microneedles at the periphery of the microneedle array (e.g., near the edge or boundary of the die, near the edge or boundary of the housing, near the edge or boundary of an adhesive layer on the housing, along the outer border 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. Accordingly, in some variations, working electrodes may be arranged largely or entirely on microneedles located at the periphery of the microneedle array, to obtain more accurate and/or precise analyte measurements.
Furthermore, the microneedle arrays described herein may have a high degree of configurability concerning where the working electrode(s), counter electrode(s), and reference electrode(s) are located within the microneedle array. This configurability may be facilitated by the electronics system.
In some variations, a microneedle array may include electrodes distributed in two or more groups in a symmetrical or non-symmetrical manner in the microneedle array, with each group featuring the same or differing number of electrode constituents depending on requirements for signal sensitivity and/or redundancy. For example, electrodes of the same type (e.g., working electrodes) may be distributed in a bilaterally or radially symmetrical manner in the microneedle array. For example,
As another example,
While
As described above, the analyte monitoring device (or various aspects thereof as described above) may be integrated with an applicator or application components configured to urge the microneedle array 140 toward the skin of the user such that the microneedle array 140 is inserted into the skin (e.g., to the desired target depth). In some variations, one or more adhesive layers are provided on a distal end of the housing of the analyte monitoring device and are adhered to the skin to securely hold the analyte monitoring device 110 in place during or prior to deployment of the microneedle array 140 into the skin.
In some variations, an actuation member 1430 is formed at a proximal surface of the housing cover 1410. The actuation member 1430 is a depressible or releasable (e.g., flexible) member that responds to user force. For example, when the user pushes downward on the actuation member 1430, the actuation member responds by depressing inward. After removal of the user force, the actuation member 1430 may assume its original shape. In some variations, the actuation member 1430 may be a deformable portion of the housing cover 1410. For example, the actuation member 1430 may be made of a material that responds to force and/or pressure. Surrounding portions of the housing cover 1410, in some variations, may be made of a stronger, more resilient material that maintains its shape and structure as the actuation member 1430 deforms upon a force applied by a user. In some variations, the actuation member 1430 may be a component separate from, but coupled with, the housing cover 1410. For example, the actuation member 1430 may be a releasable member such as a cap or button that is fitted within or mated with the surrounding portions of the housing cover 1410. In some variations, the actuation member 1430 may be a diaphragm.
In some variations, a printed circuit board assembly 1440, including a first assembly portion 1442 and a second assembly portion 1444, is arranged in the housing (e.g., in the 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 through, for example, a connection component 1422. The connection component 1422 may be analogous or similar to the secondary PCB component and/or secondary PCB connector described above (e.g., secondary PCB 420 and secondary PCB connector 430 depicted in
In some variations, the microneedle array 140 is provided as part of a microneedle array assembly, similar to the microneedle array assembly described above (e.g., microneedle array assembly 360 depicted in
The second assembly portion 1444 generally surrounds the first assembly portion 1442 and includes other components of the analyte monitoring device as described elsewhere herein (e.g., the electronic components for processing and communicating analyte signals). In some variations, the first assembly portion 1442 comprises a flexible PCB which provides an electrical connection between the microneedle array 140 and the second assembly portion 1444, thereby providing the microneedle array in electrical communication with the other components of the analyte monitoring device. In some variations, the first assembly portion 1442 comprises an elastic material and may be utilized as a biasing element without the need for an additional component. For example, the printed circuit board assembly 1440 may comprise an elastic substrate (e.g., a fiberglass reinforced PCB) which allows for the first assembly portion 1442 to be cut out and utilized as a biasing element while remaining integral with the second assembly portion 1444.
As shown in
The biasing element 1450 may be disengaged from the retention element 1460 upon actuation of the actuation member 1430. For example, by applying force or pressure to an outer surface of the actuation member 1430, the retention element 1460 is released from the biasing element 1450. The release or disengagement of the biasing element 1450 and the retention element 1460 causes an accelerating force on the microneedle array 140, causing insertion into the skin surface of the user. The biasing element 1450 moves from the first, loaded configuration to the second, deployed configuration in which the first biasing element 1450 is compressed into a stressed state and thus presses on the microneedle array 140 with a force (e.g., between about 15 to about 35 Newtons). Once the biasing element 1450 is released via actuation by the user, the first biasing element 1450 applies an accelerating force on the microneedle array 140 in the direction of application.
The biasing element, when loaded, is compressed and/or bent into a stressed state and thus provides potential energy when the microneedle array is in a first configuration. Once the biasing element is released from the retention element via actuation by the user, the biasing element applies an accelerating force on the microneedle array in the direction of application. Because the biasing element is only acting on the microneedle array, and not the entire monitoring device, the force accelerates the microneedle array to relatively high speeds in a very short displacement distance to impact the skin.
In some variations, the biasing element accelerates the microneedle array to a velocity of about 7 to about 14 meters per second (m/s) prior to penetration of the skin surface of the user. In some variations, the biasing element accelerates the microneedle array to a velocity of about 2.5 m/s to about 5 m/s, of about 2.5 m/s to about 7 m/s, of about 2.5 m/s to about 10 m/s, of about 2.5 m/s to about 12.5 m/s, of about 2.5 m/s to about 15 m/s, of about 2.5 m/s to about 20 m/s, of about 2.5 m/s to about 25 m/s, of about 5 m/s to about 7 m/s, of about 5 m/s to about 10 m/s, of about 5 m/s to about 12.5 m/s, of about 5 m/s to about 15 m/s, of about 5 m/s to about 20 m/s, of about 5 m/s to about 25 m/s, of about 7 m/s to about 10 m/s, of about 7 m/s to about 12.5 m/s, of about 7 m/s to about 15 m/s, of about 7 m/s to about 20 m/s, of about 7 m/s to about 25 m/s, of about 10 m/s to about 12.5 m/s, of about 10 m/s to about 15 m/s, of about 10 m/s to about 20 m/s, of about 10 m/s to about 25 m/s, of about 12.5 m/s to about 15 m/s, of about 12.5 m/s to about 20 m/s, of about 12.5 m/s to about 25 m/s, of about 15 m/s to about 20 m/s, of about 15 m/s to about 25 m/s, or of about 20 m/s to about 25 m/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.
In some variations, the microneedle array is translated about 1.5 to about 3 millimeters (mm) as it is 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, 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 at most about 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 5 mm, 7 mm, or 10 mm.
In variations, the retention element 1460 is integral with the actuation member 1430 and/or coupled thereto. The retention element 1460 may include an extension arm 1462 with a retention ledge 1464. The retention 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 retention ledge 1464 when loaded.
In response to actuation of the actuation member 1430 (e.g., pressure or force applied by the user), the biasing element 1450 and the retention element 1460 disengage. The retention element 1460 may flex and/or move in a downward direction in response to the actuation, allowing for the disengagement between the biasing element 1450 and the retention element 1460. In some variations, as depicted in
In some variations, a second biasing element may be arranged in the cavity of the housing body to provide additional compression of the microneedle array 140 once inserted into the skin of the user. For example, the second biasing element may be positioned in a volume defined between the housing body and the biasing element 1450. The second biasing element may be a spring, such as a coiled compression 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 an additional force on the biasing element 1450 while in the deployed configuration.
The analyte monitoring device 1500 includes a housing body comprising an internal cavity wherein various components of the analyte monitoring device 1500 are retained. In some variations, the housing includes a cover 1510 and a housing base 1515 that together form a housing body and define an internal cavity. An adhesive layer 1520 may be provided on a distal end of the housing body (e.g., a bottom, outer-facing region of the housing base 1515) to adhere the analyte monitoring device 1500 to the skin of the user.
In some variations, an actuation member 1530 is formed at a top surface of the housing cover 1510. The actuation member 1530 is a depressible or releasable (e.g., flexible) member that responds to user force. For example, when the user pushes downward on the actuation member 1530, the actuation member responds by depressing inward. After removal of the user force, the actuation member 1530 may assume its original shape. In some variations, the actuation member 1530 may be a deformable portion of the housing cover 1510. For example, the actuation member 1530 may be made of a material that responds to force and/or pressure. Surrounding portions of the housing cover 1510, in some variations, may be made of a stronger, more resilient material that maintains its shape and structure as the actuation member 1530 deforms upon a force applied by a user.
As shown in
The biasing element 1550 may be disengaged from the retention element 1560 upon actuation of the actuation member 1530. For example, by applying force or pressure to an outer surface of the actuation member 1530, the retention element 1560 is released from the biasing element 1550. The release or disengagement of the biasing element 1550 and the retention element 1560 causes an accelerating force on the microneedle array 140, causing insertion into the skin surface of the user. As the biasing element 1550 moves from a loaded configuration to a deployed configuration, the biasing element 1550 moves from a loaded, stressed state and thus presses the microneedle array 140 with a force (e.g., between about 15 to about 35 Newtons) into the skin surface when the device 1500 has been applied on a user.
In some variations, the biasing element 1550 has two opposing ends which are coupled, attached, or otherwise anchored to an inside surface of the housing cover 1510, a surface of the main PCB 1544, or a surface of the housing base 1515. During assembly, a middle portion of the biasing element 1550 (which may be configured for attachment to the microneedle array and/or connection component) is translated and engaged with the retention element 1560, thereby providing the biasing element 1550 in the loaded configuration. In the loaded configuration, the biasing element 1550 is provided in a bent, stressed state, such that the middle portion of the biasing element 1550 accelerates the attached microneedle array 140 toward a skin surface when the biasing element 1550 is disengaged from the retention element 1560.
In variations, the retention element 1560 is integral with the actuation member 1530 and/or coupled thereto. The retention element 1560 may include a retention ledge 1565. In some variations, the retention 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 retention ledge 1565 to retain the analyte monitoring device 1500 in the loaded configuration. In some variations, the retention ledge engages with connection component 1522 to retain the analyte monitoring device 1500 in the loaded configuration.
In some variations, a second biasing element (not shown) may be arranged in the cavity of the housing to provide additional compression of the microneedle array 140 once inserted into the skin of the user. For example, the second biasing element may be positioned in a volume defined between the housing and the biasing element 1550. The second biasing element may be a spring, such as a coiled compression 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 an additional compressive force on the microneedle array 140 while transitioning the microneedle array 140 from the first configuration to the second configuration.
In some variations, the analyte monitoring device 1500 comprises a printed circuit board (PCB) assembly, including a main PCB portion 1544 and a flexible PCB portion 1542, arranged in the housing (e.g., in a cavity defined by the housing cover 1510 and the housing base 1515). The flexible PCB 1542 may be configured to connect to the microneedle array 140 array 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. The main PCB portion 1544 and the flexible PCB portion 1542 may therefore be integrated and do not require a connection to be established between them. In some variations, the microneedle array 140 may be electrically connected to the flexible PCB 1542 through, for example, a connection component 1522. The connection component 1522 may be analogous to the secondary PCB component and/or secondary PCB connector described above (e.g., secondary PCB 420 and secondary PCB connector 430 depicted in
In some variations, the housing base 1515, adhesive layer 1520, and/or main PCB 1544 comprise an aperture forming 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 the first configuration to the 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 through a skin surface of a user. 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 the ingress of moisture into the internal cavity of the housing.
In some variations, the sealing element 1512 is integral with the housing base 1515. In some variations, the sealing element 1512 is adhered to or otherwise coupled to the housing base 1515. While the sealing element 1512 is depicted as substantially rectangular or square, the features of the sealing element 1512 may substantially correspond to the shape of the microneedle array 140 and/or connection component 1522. For example, if the microneedle array 140 and/or connection component 1522 are substantially circular, the inner wall 1516 and the ledge 1514 of the sealing element 1512 may also be substantially circular and dimensioned to create an interference fit.
In some variations, the components of the analyte monitoring device may have a conformal waterproof coating to prevent corrosion, disruption, or other negative effects resulting from exposure to liquids or moisture. A seal may also be provided by a flexible and/or bellowed membrane. For example, a bellowed membrane may be provided between the microneedle array and the base of the housing, such that moisture is not allowed to pass there between. Such a configuration may allow for 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 internal cavity of the housing.
In some variations, the biasing element applies a constant force on the microneedle array in the second configuration to retain the microneedles in the skin surface of the user. In some variations, a locking mechanism is utilized to maintain the position of the microneedle array once deployed. For example, the ledge 1514 of the sealing element 1512 may be coated with a contact adhesive such that an outer edge of the microneedle array 140 and/or the connection component 1522 adheres the ledge 1514 of the sealing element 1512 when the ledge 1514 is contacted during deployment. Additional or alternative lockout mechanisms may be utilized, such as detents, spring loaded slides, etc. For example, the retention element 1560 may have a bottom portion, extending beyond the retention ledge 1565, such that the bottom surface of the retention element 1560 abuts the top surface of the biasing element 1550 in the deployed configuration. In such an example, the retention element 1560 may move outwardly during actuation to allow the biasing element 1550 to transition into the deployed configuration, then move back into place after an actuation force has been removed, such that the bottom surface of the retention element abuts the top surface of the biasing element.
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 retains a shuttle 1640 when in the loaded configuration (as depicted in
In some variations, the shuttle 1640 is a substantially cylindrical member having one or more flexible arms 1642 extending from outer sidewalls thereof. The flexible arms 1642 enable retention of the shuttle 1640 as a distal surface (e.g., protrusions) of the flexible arms 1642 abuts a distal surface of corresponding apertures 1612 of the protrusion 1617 when the analyte monitoring device 1600 is in the loaded configuration (e.g., as shown in
In some variations, during deployment of the microneedle array 140, the protrusions of the flexible arms 1642 of the shuttle 1640 are depressed inward by an inner surface of the actuation member 1630, thereby releasing the flexible arms 1642 from engagement with apertures 1612 and allowing the shuttle 1640 and attached microneedle array 140 to be translated toward the base and to a skin surface of a user. In some variations, as described above, the base 1615 comprises an aperture which forms a distal opening of the housing body to allow a plurality of microneedles of the microneedle array 140 to pass through and extend from the device in the deployed configuration (as depicted in
In some variations, the actuation member 1630 is integrated with a top portion of the housing 1610. The actuation member 1630 may therefore be engaged by a user depressing a top portion of the housing. In some variations, the actuation member 1630 may be a separate component from the housing 1610. The biasing element 1650 may also serve to provide a bias against the actuation member 1630 to prevent accidental deployment of the microneedle array 140. In some variations, where the actuation member 1630 is engaged by deforming a portion of the housing 1610, the biasing element 1650 may serve to push the housing 1610 back to its original shape after deployment.
In some variations, the actuation member 1630 has one or more protrusions 1632 which snap into apertures 1612 upon actuation to ensure the flexible arms 1642 of the shuttle 1640 are fully retracted into an interior portion of the protrusion 1617 of the base. In some variations, the protrusions 1632 of the actuation member 1630 are provided on flexible arms 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 for guiding the actuation member 1630 and/or the shuttle 1640 as they are translated during actuation and deployment.
While
In some variations, the microneedle array 140 is coupled to the shuttle 1640 and the shuttle 1640 is coupled to the biasing element 1650 (e.g., a coil spring), thereby facilitating indirect coupling of the microneedle array 140 to the biasing element. In some variations, electronic components (e.g., a battery, wireless transceiver, microprocessor, etc.) of the wearable analyte monitoring device 1600 are coupled to and/or provided within the shuttle 1640. In some variations, the electronic components are provided elsewhere in the cavity formed by the housing or 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 1642 may correspond to a slot 1614 formed in the protrusion 1617 of the base 1615 to allow a flexible PCB or wire connection to be maintained during translation of the shuttle 1640 and microneedle array 140 from the first configuration to the second configuration.
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 an 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, an actuation member 1730 may have one or more protrusions 1732 which provide a retention element as a bottom surface of protrusions 1732 on a distal surface thereof that abut a proximal surface of the protrusions 1717 of the base 1715 in the loaded configuration (as depicted in
While
In some variations, the biasing element 1750 abuts an inner surface of a top portion of the housing 1710 at a first end. In some variations, the biasing element 1750 abuts a top surface of one or more of the protrusions 1732 of the actuation member 1730 at a second end, opposite of the first end. In some variations, the inner surface of the protrusions 1717 of the base 1715 form a guide for the actuation member 1730 during translation. In some variations, the biasing element 1750 is coiled around a portion of the actuation member 1730, and an outer circumference of the biasing element 1750 fits within the inner surface of the protrusions 1717 of the base 1715. In some variations, translation of the actuation member 1730 is stopped when the protrusions 1732 abut a portion of the base 1715, or when a bottom surface of a top portion of the actuation member abuts the housing 1710.
In some variations, the wearable analyte monitoring device 1800 has a base 1815 with 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, a retention 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 to, or anchored at, the first end. The second end of the biasing element 1850 may include a slot 1855 having a width slightly greater than the outer diameter of the protrusion 1817 of the base 1815. In the loaded configuration (as depicted in
While
In some variations, the actuation member 1830 includes a flexible portion of the housing 1810 which is depressed to abut the retention element 1840. In some variations, the actuation member 1830 has a protrusion to abut the retention element 1840. The protrusion may be coupled to or integrated to a flexible portion of the housing 1810 which is depressed by a user. In some variations, the retention element 1840 is coupled to or integrated with the actuation member 1830. As described above, the base 1815 may comprise an aperture, which forms a distal opening of the housing body, to allow a 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.
In some variations, the wearable analyte monitoring device 1900 has a base 1915 having one or more protrusions 1917. The protrusions 1917 extend from a proximal surface of a base 1915 into a cavity formed by the base 1915 and a housing 1910. In some variations, the protrusions 1917 form a retaining element to hold a shuttle 1940 when in a loaded configuration (as depicted in
In some variations, a user engages the actuation member 1930 such that one or more surfaces of the actuation member 1930 abut the shuttle 1940. The depression applied to the actuation member 1930 is translated to the shuttle 1940 to force a portion of shuttle 1940 into an opening created by the protrusions 1917. In some variations, the shuttle 1940 is tapered to facilitate unidirectional passing of the shuttle 1940 through the protrusions 1917. After the distal end of the shuttle 1940 passes through opening created by the protrusions 1917, the biasing element 1950 translates the microneedle array 140 to the second configuration (as depicted in
In some variations, the protrusions 1917 are flexible (e.g., formed from a flexible material) and are deflected outward by the shuttle 1940 upon depression of the actuation member 1930, allowing the shuttle 1940 to pass through into the opening. In some variations, the shuttle 1940 has one or more flexible members which are deflected inward by the protrusions 1917 upon depression of the actuation member 1930, allowing the shuttle 1940 to pass through. The abutting surfaces of the shuttle 1940 and/or protrusions 1917 may be beveled (e.g., ramped, tapered, etc.) to facilitate translation of the shuttle 1940 past the protrusions 1917. While
In some variations, the actuation member 1930 is integrated with a top portion of the housing 1910. The actuation member 1930 may therefore be engaged by a user depressing a top portion of the housing. In some variations, the actuation member 1930 may be a separate component from the housing 1910. The biasing element 1950 may also serve to provide a bias against the actuation member 1930 to prevent accidental deployment of the microneedle array 140. In some variations, where the actuation member 1930 is engaged by deforming a portion of the housing 1910, the biasing element 1950 may serve to push the housing 1910 back to its original shape after deployment. In some variations, protrusions 1917 define distal opening in the base 1915 to allow a plurality of microneedles of the microneedle array 140 to pass through and extend from the analyte monitoring device 1900 when in the deployed configuration. As described 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 an inner surface formed by the protrusions 1917.
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., a flexible PCB connection) may allow the microneedle array to maintain an electrical connection with a main PCB as it moves from the first configuration to the second configuration. Further, 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 on the components of the analyte monitoring device, establish a connection to a 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.
In some variations, some or all components of the analyte monitoring system may be provided in a kit (e.g., to a user, to a clinician, etc.). For example, a kit may include at least one analyte monitoring device. In some variations, a kit may include multiple analyte monitoring devices, which may form a supply of analyte monitoring devices sufficient that is for a predetermined period of time (e.g., a week, two weeks, three weeks, a month, two months, three months, six months, a year, etc.).
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 the applicator, instructions for pairing the analyte monitoring device with one or more peripheral devices (e.g., computing devices such as a mobile phone), etc.).
Described below is an overview of various aspects of a method of use and operation of the analyte monitoring system, including the analyte monitoring device and peripheral devices, etc.
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 microneedle array's electrodes 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, bore through the epidermis, and come to rest within the papillary or upper reticular dermis. The sensing region, confined to the electrode at the distal extent of each microneedle constituent of the array (as described above) may be configured to rest and remain seated in the papillary or upper reticular dermis following application in order to ensure adequate exposure to circulating dermal interstitial fluid (ISF) without the risk of bleeding or undue influence with nerve endings.
In some variations, the analyte monitoring device may include a wearable housing or patch with an adhesive layer provided at a distal end of the housing and configured to adhere to the skin and fix the microneedle array in position.
The analyte monitoring device may be applied in any suitable location, though in some variations it may be desirable to avoid anatomical areas of thick or calloused skin (e.g., palmar and plantar regions), or areas undergoing significant flexion (e.g., olecranon or patella). Suitable wear sites may include, for example, on the arm (e.g., upper arm, lower arm, forearm, or volar forearm), shoulder (e.g., over the deltoid), back of hands, neck, face, scalp, torso (e.g., on the back such as in the thoracic region, lumbar region, sacral region, etc. or on the chest or abdomen), buttocks, legs (e.g., upper legs, lower legs, etc.), and/or top of feet, etc.
Once the analyte monitoring device is inserted and warm-up and any calibration has completed, the analyte monitoring device may be ready for providing sensor measurements of a target analyte. The target analyte (and any requisite co-factor(s)) diffuses from the biological milieu, through the biocompatible and diffusion-limiting layers on the working electrode, and to the biorecognition layer including the biorecognition element. In the presence of a co-factor (if present), the biorecognition element may convert the target analyte to an electroactive product.
A bias potential may be applied between the working and reference electrodes of the analyte monitoring device, and an electrical current may flow from the counter electrode to maintain the fixed potential relationship between the working and reference electrodes. This causes the oxidation or reduction of the electroactive product, causing a current to flow between the working electrodes and counter electrodes. The current value 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 Cottrell relation as described in further detail above.
The electrical current may be converted to a voltage signal by a transimpedance amplifier and quantized to a digital bitstream by means of an analog-to-digital converter (ADC). Alternatively, the electrical current may be directly quantized to a digital bitstream by means of a current-mode ADC. The digital representation of the electrical current may be processed in the embedded microcontroller(s) in the analyte monitoring device and relayed to the wireless communication module for broadcast or transmission (e.g., to one or more peripheral devices). In some variations, the microcontroller may perform additional algorithmic treatment to the data to improve the signal fidelity, accuracy, and/or calibration, etc.
In some variations, the digital representation of the electrical current, or sensor signal, may be correlated to an analyte measurement (e.g., glucose measurement) by the analyte monitoring device. For example, the microcontroller may execute a programmed routine in firmware to interpret the digital signal and perform any relevant algorithms and/or other analysis. Keeping the analysis on-board the analyte monitoring device may, for example, enable the analyte monitoring device to broadcast analyte measurement(s) to multiple devices in parallel, while ensuring that each connected device has the same information. Thus, generally, the user's target analyte (e.g., glucose) values may be estimated and stored in the analyte monitoring device and communicated to one or more peripheral devices.
The foregoing description, for purposes of explanation, used specific nomenclature 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 in order to practice the invention. Thus, the foregoing descriptions of specific embodiments of the invention are 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 view of the above teachings. The embodiments were chosen and described in order to explain the principles of the invention and its practical applications, they thereby enable others skilled in the art to utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention.
Notwithstanding the appended claims, the disclosure sets forth the following numbered embodiments:
Embodiment I-1. A wearable analyte monitoring device, comprising: a housing comprising a body defining a cavity therein, wherein the housing body comprises 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 the user; a biasing element contained within the cavity; a microneedle array coupled to the biasing element and comprising a plurality of microneedles; a retention element contained within the cavity and configured to releasably retain the biasing element, and an actuation member coupled to the retention element, wherein engagement of the actuation member moves the microneedle array between a first configuration and a second configuration, and 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 the distal opening of the housing body.
Embodiment I-2. The wearable analyte monitoring device of Embodiment I-1, wherein in the second configuration, the plurality of microneedles is inserted through the skin surface of the user.
Embodiment I-3. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the microneedle array achieves a velocity of at least 10 meters per second moving from the first configuration to the second configuration.
Embodiment I-4. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the microneedle array travels 1.5 millimeters or less moving from the first configuration to the second configuration.
Embodiment I-5. The wearable analyte monitoring device of any one of the preceding embodiments, wherein a seal is formed between an outer perimeter of the microneedle array and the distal opening when the microneedle array is in the second configuration.
Embodiment I-6. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the cavity is watertight when the microneedle array is in the second configuration.
Embodiment I-7. The wearable analyte monitoring device of Embodiment any one of the preceding embodiments, wherein the actuation member is integrated with a portion of the housing body.
Embodiment I-8. The wearable analyte monitoring device of any one of the preceding embodiments, 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.
Embodiment I-9. The wearable analyte monitoring device of Embodiment I-8, wherein the retention element is integrated with the housing body.
Embodiment I-10. The wearable analyte monitoring device of Embodiment I-8 or Embodiment I-9, wherein the housing body comprises one or more tapered portions to facilitate flexing of the portion of the housing body upon depression.
Embodiment I-11. The wearable analyte monitoring device of Embodiment I-1, wherein engagement of the actuation member comprises rotating the actuation member.
Embodiment I-12. The wearable analyte monitoring device of any one of Embodiment I-1 through Embodiment I-6, wherein a portion of the biasing element is coupled proximal to an internal distal end of the housing body within the cavity.
Embodiment I-13. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the biasing element comprises a leaf spring, a coil spring, a compression spring, a flexible member, or a combination thereof.
Embodiment I-14. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the biasing element comprises a first end and a second end, wherein the first end of the biasing element couples to the microneedle array, and wherein the second end of the biasing element is coupled proximal to an internal distal end of the housing body within the cavity.
Embodiment I-15. The wearable analyte monitoring device of Embodiment I-14, wherein the first end of the biasing element is releasably retained by the retention element.
Embodiment I-16. The wearable analyte monitoring device of Embodiment I-15, wherein the retention element is proximal to an internal proximal end of the housing body within the cavity.
Embodiment I-17. The wearable analyte monitoring device of any one of the preceding embodiments, further comprising a printed circuit board contained within the cavity of the housing body.
Embodiment I-18. The wearable analyte monitoring device of Embodiment I-17, wherein the printed circuit board is in electrical communication with the microneedle array via a flexible printed circuit board, wherein the microneedle array is mounted on the flexible printed circuit board.
Embodiment I-19. The wearable analyte monitoring device of Embodiment I-17, wherein the flexible printed circuit board comprises an actuation contact, wherein the actuation contact makes contact with a corresponding contact provided on the printed circuit board when the microneedle array is in the second configuration.
Embodiment I-20. The wearable analyte monitoring device of any one of the preceding embodiments, wherein the wearable analyte monitoring device activates when the microneedle array is in the second configuration.
Embodiment I-21. The wearable analyte monitoring device of Embodiment I-17, wherein the printed circuit board moves with the microneedle array.
Embodiment I-22. The wearable analyte monitoring device of any one of the preceding embodiments, wherein a first microneedle of the plurality of microneedles of the microneedle array comprises a working electrode having an electrochemical sensing coating.
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.
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.
Embodiment I-25. The wearable analyte monitoring device of any one of the preceding embodiments, further comprising a shuttle configured to couple the microneedle array to the biasing element.
Embodiment I-26. The wearable analyte monitoring device of Embodiment I-25, further comprising a tubular protrusion extending within the cavity from a distal end of the housing body, the tubular protrusion configured to guide the shuttle as the microneedle array moves between the first configuration and the second configuration.
Embodiment I-27. The wearable analyte monitoring device of Embodiment I-26, wherein the tubular protrusion comprises an aperture configured to engage a flexible arm of the shuttle, thereby retaining the microneedle array in the first configuration.
Embodiment I-28. The wearable analyte monitoring device of Embodiment I-27, wherein depression of the actuation member deflects the flexible arm of the shuttle inward, thereby releasing the shuttle and moving the microneedle array from the first configuration to the second configuration.
Embodiment I-29. The wearable analyte monitoring device of any one of Embodiment I-26 through Embodiment I-28, wherein internal sidewalls of the tubular protrusion define the distal opening of the housing body
Embodiment I-30. The wearable analyte monitoring device of Embodiment I-25, further comprising a protrusion extending within the cavity from a distal end of the housing body, the protrusion configured to abut the shuttle when the microneedle array is in the first configuration.
Embodiment I-31. The wearable analyte monitoring device of Embodiment I-30, wherein depression of the actuation member deflects the protrusion outward, thereby releasing the shuttle and moving the microneedle array from the first configuration to the second configuration.
Embodiment I-32. The wearable analyte monitoring device of Embodiment I-30 or Embodiment I-31, wherein internal sidewalls of the protrusion define the distal opening of the housing body.
Embodiment I-33. The wearable analyte monitoring device of any one of the preceding embodiments, further comprising a second biasing element.
Embodiment I-34. The wearable analyte monitoring device of Embodiment I-33, wherein the second biasing element is deployed after the microneedle array reaches the second configuration.
Embodiment I-35. A method of inserting a microneedle array into a skin surface of a user, the method comprising: providing a wearable analyte monitoring device comprising the microneedle array in a first configuration, the microneedle array comprising a plurality of microneedles, the microneedle array coupled to a biasing element contained within a cavity of a housing, the housing comprising a body defining the cavity therein, the biasing element releasably retained by a retention element contained within the cavity, and the retention element coupled to an actuation member; and transitioning the microneedle array from the first configuration to a second configuration, and 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.
Embodiment I-36. The method of Embodiment I-35, further comprising adhering the wearable analyte monitoring device to the skin surface of the user.
Embodiment I-37. The method of Embodiment I-36, wherein the wearable analyte monitoring device is adhered to the skin surface of the user prior to the transitioning the microneedle array from the first configuration to the second configuration.
Embodiment I-38. An analyte monitoring device, comprising: a housing comprising a body defining a cavity therein, wherein the housing body comprises a distal opening; a biasing element contained within the cavity; a microneedle array coupled to the biasing element; and an actuation member, wherein engagement of the actuation member moves the microneedle array from a first configuration to a second configuration under influence of the biasing element, and wherein in the first configuration, the microneedle array is held 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.
Embodiment I-39. The analyte monitoring device of Embodiment I-38, wherein the microneedle array is configured to penetrate a skin surface of a subject and detect a target analyte present in dermal interstitial fluid of the subject.
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.
Embodiment I-41. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-40, wherein the microneedle array comprises a second microneedle comprising a reference electrode.
Embodiment I-42. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-41, wherein the microneedle array comprises a third microneedle comprising a counter electrode.
Embodiment I-43. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-42, further comprising a retention element configured to hold the microneedle array in the first configuration, wherein engagement of the actuation member deflects a portion of the retention element to allow the microneedle array to move from the first configuration to the second configuration under the influence of the biasing element.
Embodiment I-44. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-43, wherein in the second configuration, the plurality of microneedles is inserted through the skin surface of the user.
Embodiment I-45. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-44, wherein the microneedle array achieves a velocity of at least 7 meters per second moving from the first configuration to the second configuration.
Embodiment I-46. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-45, wherein the microneedle array travels 1.5 millimeters or less moving from the first configuration to the second configuration.
Embodiment I-47. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-46, wherein a seal is formed between an outer perimeter of the microneedle array and the distal opening when the microneedle array is in the second configuration.
Embodiment I-48. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-47, wherein the cavity is watertight when the microneedle array is in the second configuration.
Embodiment I-49. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-48, wherein the actuation member is integrated with a portion of the housing body.
Embodiment I-50. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-49, 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.
Embodiment I-51. The analyte monitoring device of Embodiment I-43, wherein the retention element is integrated with the housing body.
Embodiment I-52. The analyte monitoring device of Embodiment I-50 or Embodiment I-51, wherein the housing body comprises one or more tapered portions to facilitate flexing of the portion of the housing body upon depression.
Embodiment I-53. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-42 and Embodiment I-45 through I-48, wherein engagement of the actuation member comprises rotating the actuation member.
Embodiment I-54. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-53, wherein a portion of the biasing element is coupled proximal to an internal distal end of the housing body within the cavity.
Embodiment I-55. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-54, wherein the biasing element comprises a leaf spring, a coil spring, a compression spring, a flexible member, or a combination thereof.
Embodiment I-56. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-55, wherein the biasing element comprises a first end and a second end, wherein the first end of the biasing element couples to the microneedle array, and wherein the second end of the biasing element is coupled proximal to an internal distal end of the housing body within the cavity.
Embodiment I-57. The analyte monitoring device of Embodiment I-56, wherein the first end of the biasing element is releasably retained by a retention element.
Embodiment I-58. The analyte monitoring device of Embodiment I-57, wherein the retention element is proximal to an internal proximal end of the housing body within the cavity.
Embodiment I-59. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-58, further comprising a printed circuit board contained within the cavity of the housing body.
Embodiment I-60. The analyte monitoring device of Embodiment I-59, wherein the printed circuit board is in electrical communication with the microneedle array via a flexible printed circuit board, wherein the microneedle array is mounted on the flexible printed circuit board.
Embodiment I-61. The analyte monitoring device of Embodiment I-59 or Embodiment I-60, wherein the flexible printed circuit board comprises an actuation contact, wherein the actuation contact makes contact with a corresponding contact provided on the printed circuit board when the microneedle array is in the second configuration.
Embodiment I-62. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-61, wherein the analyte monitoring device activates when the microneedle array is in the second configuration.
Embodiment I-63. The analyte monitoring device of Embodiment I-59, wherein the printed circuit board moves with the microneedle array.
Embodiment I-64. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-63, wherein a first microneedle of the plurality of microneedles of the microneedle array comprises a working electrode having an electrochemical sensing coating.
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.
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.
Embodiment I-67. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-66, further comprising a shuttle configured to couple the microneedle array to the biasing element.
Embodiment I-68. The analyte monitoring device of Embodiment I-67, further comprising a tubular protrusion extending within the cavity from a distal end of the housing body, the tubular protrusion configured to guide the shuttle as the microneedle array moves between the first configuration and the second configuration.
Embodiment I-69. The analyte monitoring device of Embodiment I-68, wherein the tubular protrusion comprises an aperture configured to engage a flexible arm of the shuttle, thereby retaining the microneedle array in the first configuration.
Embodiment I-70. The analyte monitoring device of Embodiment I-69, wherein depression of the actuation member deflects the flexible arm of the shuttle inward, thereby releasing the shuttle and moving the microneedle array from the first configuration to the second configuration.
Embodiment I-71. The analyte monitoring device of any one of Embodiment I-68 through Embodiment I-70, wherein internal sidewalls of the tubular protrusion define the distal opening of the housing body
Embodiment I-72. The analyte monitoring device of Embodiment I-67, further comprising a protrusion extending within the cavity from a distal end of the housing body, the protrusion configured to abut the shuttle when the microneedle array is in the first configuration.
Embodiment I-73. The analyte monitoring device of Embodiment I-72, wherein depression of the actuation member deflects the protrusion outward, thereby releasing the shuttle and moving the microneedle array from the first configuration to the second configuration.
Embodiment I-74. The analyte monitoring device of Embodiment I-72 or Embodiment I-73, wherein internal sidewalls of the protrusion define the distal opening of the housing body.
Embodiment I-75. The analyte monitoring device of any one of Embodiment I-38 through Embodiment I-74, further comprising a second biasing element.
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.
Embodiment I-77. A method of monitoring a user using a wearable analyte monitoring device, the method comprising: providing the wearable analyte monitoring device comprising the microneedle array in a first configuration, the microneedle array comprising a plurality of microneedles, the microneedle array coupled to a biasing element contained within a cavity of a housing, the housing comprising a body defining the cavity therein, the biasing element releasably retained by a retention element contained within the cavity, and the retention 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, and 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 dermal interstitial fluid of the subject with the microneedle array.
Embodiment I-78. The method of Embodiment I-77, further comprising communicating information indicative of the measurement of the target analyte level.
Embodiment I-79. The method of Embodiment I-77 or Embodiment I-78, further comprising displaying the measurement of the target analyte level.
Embodiment I-80. The method of Embodiment I-78, wherein communicating information indicative of the measurement of the target analyte level comprises transmitting the information to an external device.
Embodiment I-81. The method of Embodiment I-80, wherein transmitting the information comprises wirelessly transmitting the measurement of the target analyte level.
Embodiment I-82. The method of Embodiment I-81, wherein wirelessly transmitting the measurement of the target analyte level comprises transmitting via near-field communication, Bluetooth communication, or both.
Embodiment I-83. The method of any one of Embodiment I-77 through Embodiment I-82, wherein measuring the target analyte level further comprises processing a signal received from the microneedle array.
Embodiment I-84. The method of Embodiment I-83, wherein processing the signal received from the microneedle array is carried out by a microprocessor provided within the housing of the wearable analyte monitoring device.
Embodiment I-85. The method of Embodiment I-83 or Embodiment I-84, wherein the processing comprises applying an algorithm to the signal received from the microneedle array.
Embodiment I-86. A method of inserting a microneedle array into a skin surface, the method comprising: providing the microneedle array within a cavity of a housing, the housing comprising a body defining the cavity therein, wherein the microneedle array is coupled to a biasing element within the cavity; loading the microneedle array in first configuration in which the microneedle array is biased by the biasing element toward a distal end of the housing body; and providing an actuation member, wherein the actuation member is 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 the transition from the first configuration to the second configuration, the microneedle array travels within the cavity toward the distal end of the housing body under influence of the biasing element.
Embodiment I-87. The method of Embodiment I-86, wherein loading the microneedle array in the first configuration further comprises locking the biasing element into a retention element, wherein the retention element is provided at a predetermined distance away from the distal end of the housing body.
Embodiment I-88. The method of Embodiment I-86 or Embodiment I-87, wherein the actuation member comprises a portion of the housing body.
This application claims priority to U.S. Provisional Patent Application No. 63/296,830, filed Jan. 5, 2022, the contents of which is hereby incorporated in its entirety by this reference.
| Number | Date | Country | |
|---|---|---|---|
| 63296830 | Jan 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2023/060177 | Jan 2023 | WO |
| Child | 18763798 | US |
