Continuous analyte monitoring system with microneedle array

Abstract

Described herein are variations of an analyte monitoring system, including an analyte monitoring device. For example, an analyte monitoring device may include an implantable microneedle array for use in measuring one or more analytes (e.g., glucose), such as in a continuous manner. The microneedle array may include, for example, at least one microneedle including a tapered distal portion having an insulated distal apex, and an electrode on a surface of the tapered distal portion located proximal to the insulated distal apex. At least some of the microneedles may be electrically isolated such that one or more electrodes is individually addressable.

Description

(19) *EP004647772A2* (11) EP 4 647 772 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: 12.11.2025 Bulletin 2025 / 46 (21) Application number: 25191106.1 (22) Date of filing: 29.07.2021 (51) International Patent Classification (IPC): G01N 33 / 66 (2006.01) (52) Cooperative Patent Classification (CPC): A61B 5 / 14514; A61B 5 / 14532; A61B 5 / 14865; A61B 5 / 685; A61B 5 / 0022; A61B 5 / 6833; A61B 5 / 742 (84) Designated Contracting States: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (30) Priority: 29.07.2020 US 202063058275 P (62) Document number(s) of the earlier application(s) in accordance with Art. 76 EPC: 23218205.5 / 4 365 593 21850331.6 / 4 048 152 (71) Applicant: Biolinq, Inc. San Diego, CA 92121 (US) (72) Inventors: • WINDMILLER, Joshua Ray San Diego, 92121 (US) • TANGNEY, Jared Rylan Encinitas, 92024 (US) • PEYSER, Thomas Arnold Menlo Park, 94025 (US) • SATTAYASAMITSATHIT, Sirilak San Diego, 92122 (US) • CHAUDHURI, Buddhadev Paul Walnut Creek, 94596 (US) • CAMPBELL, Alan San Diego, 92109 (US) • SAMANT, Pradnya Prakash San Diego, 92122 (US) • YANG, Richard Chien Carlsbad, 92009 (US) • MORELOCK, David Michael Escondido, 92029 (US) • HSU, William C. Chestnut Hill, 02467 (US) • HSU, Evan L. Chestnut Hill, 02467 (US) (74) Representative: Cooley (UK) LLP 22 Bishopsgate London EC2N 4BQ (GB) Remarks: •This application was filed on 22.07.2025 as a divisional application to the application mentioned under INID code 62. •Claims filed after the date of filing of the application (Rule 68(4) EPC). (54) CONTINUOUS ANALYTE MONITORING SYSTEM WITH MICRONEEDLE ARRAY (57) Described herein are variations of an analyte monitoring system, including an analyte monitoring de- vice. For example, an analyte monitoring device may include an implantable microneedle array for use in measuring one or more analytes (e.g., glucose), such as in a continuous manner. The microneedle array may include, for example, at least onemicroneedle includinga tapered distal portion having an insulated distal apex, andanelectrodeonasurfaceof the tapereddistal portion located proximal to the insulated distal apex. At least some of the microneedles may be electrically isolated such that one or more electrodes is individually addres- sable. EP 4 64 7 77 2 A 2 Processed by Luminess, 75001 PARIS (FR) Description CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S Patent App. No. 63 / 058,275 filed July 29, 2020, the contents of which are hereby incorporated in their entirety by this reference. TECHNICAL FIELD

[0002] This invention relates generally to the field of analyte monitoring, such as continuous glucose monitoring. BACKGROUND

[0003] 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).

[0004] Blood glucosemonitors 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 onlymeasure his or her glucose levels at discrete instances in time, whichmay 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). Theseweaknesses 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. SUMMARY

[0005] In some variations, a microneedle array for use in sensing an analyte may include a plurality of microneedles (e.g., solid microneedles). Eachmicroneedle may include a tapered distal portion having an insulated distal apex, and an electrode on a surface of the tapered distal portion, where the electrode is located proximal to the insulated distal apex.

[0006] In some variations, a method for monitoring a user may include accessing a body fluid of a user with an analyte monitoring device, and quantifying one or more analytes in the body fluid using the analyte monitoring device, where the analytemonitoringdevicemay includeaplurality of solidmicroneedles In somevariations, at least oneof themicroneedles may include a tapered distal portion having an insulated distal apex, and an electrode on a surface of the tapered distal portion, where the electrode is located proximal to the insulated distal apex.

[0007] In some variations, a microneedle array for use in sensing an analyte may include a plurality of solid micro- needles,whereat least onemicroneedle includesa tapereddistal portionhavingan insulateddistal apex, andanelectrode on a surface of the tapered distal portion, where a distal end of the electrode is offset from the distal apex.

[0008] In some variations, a method of sterilizing an analyte monitoring device may include exposing the analyte monitoring device to a sterilant gas, where the analyte monitoring device comprises a wearable housing, a microneedle array extending from the housing and comprising an analyte sensor, and an electronics system arranged in the housing and electrically coupled to themicroneedle array. The analytemonitoring devicemay be exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device.

[0009] In some variations, a microneedle array for an analyte monitoring device may include a plurality of sensing microneedles (e.g., solid microneedles), where each sensing microneedle includes a tapered distal portion comprising a working electrode configured to sense an analyte, and a body portion providing a conductive connection to the working electrode.Thebodyportionof each sensingmicroneedlemaybe insulatedsuch that eachworkingelectrode is individually addressable and electrically isolated from every other working electrode in the microneedle array.

[0010] In some variations, a microneedle array for a body-worn analyte monitoring device may include at least one microneedle including a pyramidal body portion having anon-circular (e.g., octagonal base), and a tapered distal portion extending from the body portion and comprising an electrode, where the distal portion comprises a planar surface that is 2 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 offset from a distal apex of the at least one microneedle.

[0011] In somevariations, amethod formonitoring ausermay include accessingadermal interstitial fluid of the user at a plurality of sensor locations with an integrated analyte monitoring device comprising a single microneedle array, and quantifying one or more analytes in the dermal interstitial fluid using a plurality of working electrodes in the microneedle array, where each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device.

[0012] In some variations, a body-worn analyte monitoring device may include a wearable housing and a microneedle array. Themicroneedle array may extend outwardly from the housing and include at least one microneedle configured to measure one or more analytes in a user wearing the housing, and the housing may include a user interface configured to communicate information indicative of the measurement of the one or more analytes.

[0013] In some variations, amethod formonitoring ausermay includemeasuring oneormore analytes in the user using a body-worn analyte monitoring device comprising a wearable housing and one or more analyte sensors, and commu- nicating information indicative of the measurement of the one or more analytes through a user interface on the housing. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 depicts an illustrative schematic of an analyte monitoring system with a microneedle array. FIG. 2A depicts an illustrative schematic of an analyte monitoring device. FIG. 2B depicts an illustrative schematic of microneedle insertion depth in an analyte monitoring device. FIGS 3A‑3C depict an upper perspective view, a side view, and a lower perspective view, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A including an adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A. FIGS 3F‑3I depict an upper perspective view, a lower perspective view, a side view, and an exploded view, respectively, of a sensor assembly in an analyte monitoring device. FIG. 3J depicts a transparent side view of a sensor assembly in an analyte monitoring device. FIGS. 4A‑4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and an upper perspective transparent view, respectively, of an analyte monitoring device. FIG. 5A depicts an illustrative schematic of a microneedle array. FIG. 5B depicts an illustrative schematic of a microneedle in the microneedle array depicted in FIG. 5A. FIG 6 depicts an illustrative schematic of a microneedle array used for sensing multiple analytes. FIG 7A depicts a cross-sectional side view of a columnar microneedle having a tapered distal end, FIGS. 7B and 7C are images depicting perspective and detailed views, respectively, of an embodiment of the microneedle shown in FIG. 7A. FIG. 8 depicts an illustrative schematic of a columnar microneedle having a tapered distal end. FIG 9 depicts a cross-sectional side view of a columnar microneedle having a tapered distal end. FIG. 10 depicts an illustrative schematic of a columnar microneedle having a tapered distal end. FIG. 11A depicts a cross-sectional side view of a pyramidal microneedle having a tapered distal end, FIG. 11B is an image depicting a perspective view of an embodiment of the microneedle shown in FIG. 11A FIG. 11C is an image depicting an illustrative variation of a microneedle array including microneedles similar to that shown in FIG. 11B. FIG. 12 depicts an illustrative schematic of a pyramidal microneedle having a tapered distal end FIG 13A depicts an illustrative schematic of a pyramidal microneedle having a tapered distal end and asymmetric cut 3 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 surface. FIG. 13B is an image depicting an illustrative variation of the microneedle shown in FIG. 13A. FIGS 13C‑13E illustrate a process for forming the pyramidal microneedle shown in FIG. 13A. FIG. 14A depicts an illustrative schematic of a columnar-pyramidal microneedle having a tapered distal end FIG. 14B depicts a detailed view of the distal portion of the microneedle depicted in FIG. 14A. FIGS 15A‑15D depict illustrative schematics of formation of conductive pathways within a microneedle array. FIGS 16A‑16C depict illustrative schematics of layered structures of a working electrode, a counter electrode, and a reference electrode, respectively. FIGS 16D‑16F depict illustrative schematics of layered structures of a working electrode, a counter electrode, and a reference electrode, respectively. FIGS. 16G‑16I depict illustrative schematics of layered structures of a working electrode, a counter electrode, and a reference electrode, respectively. FIG 17 depicts an illustrative schematic of a microneedle array configuration. FIGS. 18A and 18Bdepict perspective and orthogonal views, respectively, of an illustrative variation of a die including a microneedle array. FIGS 19A‑19J depict illustrative schematics of different variations of microneedle array configurations. FIG 20 depicts an illustrative schematic of a low profile battery holder. FIG. 21 depicts an illustrative flowchart of a method for sterilizing an analyte monitoring device. FIG 22 depicts an illustrative schematic of a sterilization setup usable for ethylene oxide sterilization. FIG. 23 depicts an illustrative variation of an ethylene oxide sterilization protocol. FIGS. 24A‑24C depict exemplary data suggesting feasibility of ethylene oxide sterilization for an analyte monitoring device. FIG 25 is an illustrative schematic of electronic circuitry enabling activation of an analyte monitoring device upon insertion of the microneedle array in skin. FIG. 26 is an illustrative schematic of pairing between an analyte monitoring device and a mobile computing device executing a mobile application. FIGS. 27A and 27B depict illustrative schematics of a microneedle array and a microneedle, respectively, FIGS. 27C‑27F depict detailed partial views of an illustrative variation of a microneedle. FIGS 28A and 28B depict an illustrative variation of a microneedle. FIGS 29A and 29B depict illustrative schematics of a microneedle array configuration. FIGS 30A and 30B depict illustrative schematics of a microneedle array configuration. FIGS. 31A and 31B depict illustrative schematics of a housing of an analyte monitoring device including a user interface with indicator light elements. FIGS 32A‑32C depict illustrative schematics of illumination modes in an analyte monitoring device for indicating analyte measurement data. FIGS 33A‑33D depict illustrative schematics of illumination modes in an analyte monitoring device for indicating 4 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 analyte measurement data. FIGS 34A‑34C depict illustrative schematics of illumination modes in an analyte monitoring device for indicating analyte measurement data. FIGS. 35A and 35B depict illustrative schematics of illumination modes in an analyte monitoring device for indicating device information (e.g., operational status, and / or fault modes). DETAILED DESCRIPTION

[0015] Non-limiting examples of various aspects and variations of the invention are described herein and illustrated in the accompanying drawings.

[0016] 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 FIG. 1, an analyte monitoring system 100 may include an analyte monitoring device 110 that is worn by a user, and the analyte monitoring device 110 may be a continuous analyte monitoring device (e.g., continuous glucose monitoring device). The analyte monitoring device 110 may include, for example, amicroneedle array comprising at least one electrochemical sensor for detecting and / ormeasuring one ormore analytes in body fluid of a user. In some variations, the analytemonitoring devicemay be applied to the user using suitable applicator 160, or may be applied manually. The analyte monitoring device 110 may include one or more processors for performinganalysis on sensordata, and / or a communicationmodule (e.g.,wireless communicationmodule) configured to communicate sensor data to a mobile computing device 102 (e.g., smartphone) or other suitable computing device. In some variations, themobile computing device 102may include one or more processors executing amobile application to handle sensor data (e.g., displaying data, analyzing data for trends, etc.) and / or provide suitable alerts or other notifications related to the sensor data and / or analysis thereof. It should be understood that while in some variations themobile computing device 102mayperformsensor data analysis locally, other computingdevice(s)mayalternatively or additionally remotely analyze sensor data and / or communicate information related to such analysis with the mobile computing device 102 (or other suitable user interface) for display to the user. Furthermore, in some variations themobile computing device 102 may be configured to communicate sensor data and / or analysis of the sensor data over a network 104 tooneormore storagedevices106 (eg., server) for archivingdata and / or other suitable information related to theuser of the analyte monitoring device.

[0017] The analyte monitoring devices described herein have characteristics that improve a number of properties that are advantageous for a continuous analytemonitoring device such as a continuous glucosemonitoring (CGM) device For example, theanalytemonitoringdevicedescribedhereinhave improvedsensitivity (amount of sensor signal producedper given concentration of target analyte), improved selectivity (rejection of endogenous and exogenous circulating com- pounds that can interferewith the detection of the target analyte), and improved stability to helpminimize change in sensor response over time through storage and operation of the analyte monitoring device. Additionally, compared to conven- tional 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, aswell as a short response time that enables the sensors(s) to quickly providea stable sensor signal followinga change in analyte concentration in the user. Furthermore, as described in further detail below, the analytemonitoring devices described hereinmaybe 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.

[0018] Although the analyte monitoring systems described herein may be described with reference to monitoring of glucose (e.g., in userswith Type 2 diabetes, Type 1 diabetes), it should be understood that such systemsmay 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 analytesmay be simultaneouslymonitored (e.g., in the same analytemonitoring 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).

[0019] Various aspects of example variations of the analyte monitoring systems, and methods of use thereof, are described in further detail below. 5 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 Analyte monitoring device

[0020] As shown in FIG. 2A, in some variations, an analyte monitoring device 110may generally include a housing 112 and a microneedle array 140 extending outwardly from the housing. The housing 112, may, for example, be a wearable housing configured to be worn on the skin of a user such that the microneedle array 140 extends at least partially into the skin of the user. For example, the housing 112 may include an adhesive such that the analyte monitoring device 110 is a skin-adhered patch that is simple and straightforward for application to a user. The microneedle array 140 may be configured to puncture the skin of the user and include one ormore electrochemical sensors (e.g., electrodes) configured for measuring one or more target analytes that are accessible after the microneedle array 140 punctures the skin of the user. In somevariations, theanalytemonitoringdevice110maybe integratedor self-containedasasingleunit, and theunit may be disposable (e.g., used for a period of time and replaced with another instance of the analyte monitoring device 1 10).

[0021] 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 system120may also include at least onemicrocontroller 122 for controlling the analytemonitoring device 110, at least onecommunicationmodule126, at least onepowersource130.and / or other varioussuitablepassivecircuitry127. 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 transforma- tions (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 For example, the communicationmodule 126may be configured to provide uni-directional and / or bi-directional communication of data with anexternal computingdevice102 that is pairedwith theanalytemonitoringdevice110.Thepower source130mayprovide power for theanalytemonitoringdevice110, suchas for theelectronics system.Thepower source130may includebattery 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.

[0022] In some variations, the analyte monitoring device 110may 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.

[0023] In somevariations, themicroneedlearray140 in theanalytemonitoringdevice110maybeconfigured topuncture skin of a user. As shown inFIG. 2B,when thedevice110 iswornby theuser, themicroneedle array140mayextend into the skin of the user such that electrodes on distal regions of the microneedles rest in the dermis. Specifically, in some variations, the microneedles may be designed to penetrate the skin and access the upper dermal region (e.g., papillary dermis and upper reticular dermis layers) of the skin, in order to enable the electrodes to access interstitial fluid that surrounds thecells in these layers.Forexample, in somevariations, themicroneedlesmayhaveaheightgenerally ranging between at least 350 µmand about 515 µm. In some variations, one or more microneedles may extend from the housing such that a distal endof the electrode on themicroneedle is located less thanabout 5mm fromaskin-interfacing surface of thehousing, less thanabout 4mm from thehousing, less thanabout 3mm from thehousing, less thanabout 2mm from the housing, or less than about 1 mm from the housing.

[0024] In contrast to traditional continuous analyte monitoring devices (e.g., CGM devices), which include sensors typically implanted between about 8mmand about 10mmbeneath 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 thoseof bloodFor example, it has beendiscovered that glucosemeasurements performedusing 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.

[0025] Additionally, because of the shallower microneedle insertion depth of the analyte monitoring device 110, a reduced timedelay in analyte detection is obtained compared to traditional continuous analytemonitoring devices. Such a 6 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 shallower insertion depth positions the sensor surfaces in close proximity (e.g., within a few hundredmicrometers 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 t 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 - 20minutes). 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.

[0026] 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

[0027] Thus, the analyte monitoring devices and methods described herein enable improved continuous monitoring of one ormore target analytes of a user. For example, as described above, the analytemonitoring devicemay be simple and straightforward to apply,which improvesease-of-use anduser compliance.Additionally, analytemeasurements of dermal interstitial fluidmayprovide for highly accurateanalytedetection. Furthermore, compared to traditional continuousanalyte 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. Housing

[0028] As described above, an analyte monitoring device may include a housing. The housing may at least partially surround or enclose other components of the analyte monitoring device (e.g., electronic components), 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 In some variations, an adhesive layer may attach the housing to a surface (e.g., skin) of a user, while permitting a microneedle array to extend outwardly from the housing and into the skin of the user. Furthermore, in somevariations thehousingmaygenerally include roundededgesor cornersand / orbe low-profilesoas to be atraumatic and reduce interference with clothing, etc. worn by the user.

[0029] For example, as shown in FIGS. 3A‑3E, an example variation of an analytemonitoring device 300may include a housing 310 configured to at least partially surround other various internal components of the device 300, and a microneedle array 330 that extends outwardly from a skin-facing surface (e.g., underside) of the housing 310.

[0030] The housing 310may, for example, include one ormore 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. For example, as shown in FIG. 3E, the housing may include a housing cover 310a and a housing base 310b, where the cover 310a and the base 310b may be secured together with one or more threaded fasteners (e.g., fasteners that engage threaded holes in the upper and / or lower housing portions). The cover 310a and the base 310bmay include radiused edges and corners, and / or other atraumatic features. When coupled together, the cover 310a and the base 310bmay form an internal volume that houses other internal components such as a device printed circuit board 350 (PCB), a sensor assembly 320, and / or other components such as a gasket 312. For example, the internal components arranged in the internal volume may be arranged in a compact, low profile stack-up as shown in FIG. 3E. While FIG. 3E illustrates a housing 310 include multiple housing components, in some variations the housing 310 may include a single component defining the internal volume for housing internal device components In some embodiments, the housing 310 may be filled with a suitable potting compound (e.g., epoxy) to reduce deleterious environmental effects such as temperature, humidity, pressure, and light.

[0031] Furthermore, the analyte monitoring device 300 may include an adhesive layer 340 configured to attach the housing310 toa surface (e.g., skin) of a user. Theadhesive layer 340may, for example, beattached toaskin-facing sideof the housing 310 via a double-sided adhesive liner 344 as shown in in the variation depicted in FIG. 3D. Alternatively, the adhesive layer 340may be coupled directly to the skin-facing side of the housing 310 with one or more suitable fasteners (e.g., adhesive, mechanical fasteners, etc.). The adhesive layer 340 may be protected by a release liner that the user removes prior to skin application, in order to expose the adhesive. In some variations, the analyte monitoring device may include3MR1504XL™double-sidedadhesive and3MR4076™skin-facing adhesive, available from3MR.Thesematerials are selected for their: breathability, wearability, mean water vapor transmission rate (MWVTR), biocompatibility, compat- ibility with sensor sterilization method / strategy, appearance, durability, tackiness, and ability to retain said tackiness for 7 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 the duration of sensor wear

[0032] The adhesive layer 340 may, in some variations, have a perimeter that extends farther than the perimeter or periphery of the housing 310 (e.g., which may increase surface area for attachment and increase stability of retention, or the attachment to the skin of a user). Furthermore, in some variations, the adhesive layer 340may include an opening 342 that permits passage of the outwardly extending microneedle array 330. The opening 342 may closely circumscribe the shapeof themicroneedlearray330asshown inFIG.3C (e.g., squareopeningclosely corresponding insizeandshape toa squaremicroneedlearray), or haveanother suitable sizeand shape that is larger than the footprint areaof themicroneedle array (e.g., circular opening larger than a square microneedle array).

[0033] Although the housing 310 depicted in FIGS. 3A‑3E is hexagonal shaped and generally prismatic, it should be understood that in other variations, the housing 310 may have any suitable shape. For example, in other variations the housing may be generally prismatic and have a base that has an elliptical (e.g., circular), triangular, rectangular, pentagonal, or other suitable shape. As another example, FIGS. 4A‑4C illustrate an example variation of an analyte monitoring device 400 including a dome-shaped housing 410. While the dome-shaped housing 410 depicted in FIGS. 4A‑4C is generally circular, in other variations the dome-shaped housing may have a base that has another suitable elliptical shape or polygonal shape.

[0034] Similar to the housing 310, the housing 4 10 may include an internal volume configured to at least partially surround other components of the analyte monitoring device 400. For example, as shown in the cross-sectional view of FIG. 4D, the housing 410may include a domed cover 410a coupled to a base 410b, so as to forman internal volumewithin which a device PCB450 and a sensor assemblywith amicroneedle array 430may be arranged . Additionally, the housing 410 may be configured to couple to a surface via an adhesive layer 440, and the microneedle array 430 may extend outwardly from the housing and beyond the adhesive layer 440. Furthermore, as shown in FIGS. 4D and 4E, the adhesive layer 440 may extend beyond the perimeter of the housing 410. User interface

[0035] In some variations, an analyte monitoring system may provide user status, analyte monitoring device status, and / or other suitable information directly via a user interface (e.g., display, indicator lights, etc. as described below) on the analyte monitoring device. Thus, in contrast to analyte monitoring systems that may solely communicate information to a separateperipheral device (eg.,mobilephone, etc.) that in turn communicates the information toauser. in somevariations such information may be directly provided by the analyte monitoring device. Advantageously, in some variations, such a user interface on the analyte monitoring device may reduce the need for a user to constantly maintain a separate peripheral device in order tomonitor user status and / or analytemonitoring device status (whichmay be impractical due to cost, inconvenience, etc.). Additionally, the user interface on the analyte monitoring device may reduce risks associated with lossof communicationbetween theanalytemonitoringdeviceandaseparateperipheral device, suchasauserhaving an inaccurate understanding of their current analyte levels (e.g., leading the user to assume their analyte levels are high when they are actually low, which could, for example, result in the user self-administering an inaccurate dose of drug or withholding a therapeutic intervention when it is medically necessary)

[0036] Additionally, the ability to communicate information to a user via the analyte monitoring device itself, indepen- dently of a separate peripheral device, may reduce or eliminate the need to maintain compatibility between the analyte monitoring device and separate peripheral devices as such peripheral devices are upgraded (e.g., replaced with new device models or other hardware, run new versions of operating systems or other software, etc.).

[0037] Accordingly, in some variations, the housing may include a user interface, such as an interface to provide information in a visual, audible, and / or tactile manner to provide information regarding user status and / or status of the analyte monitoring device, and / or other suitable information. Examples of user status that may be communicated via the user interface include information representative of analyte measurement in the user (e.g., below a predetermined target analyte measurement threshold or range, within a predetermined target analyte measurement range, above a pre- determined target analytemeasurement threshold or range, increase or decrease of analytemeasurement over time, rate of change of analyte measurement, other information relating to trend of analyte measurements, other suitable alerts associatedwith analytemeasurement, etc.). Examples of analytemonitoring device status thatmaybe communicated via the user interface include device operation mode (e.g., associated with device warm-up state, analyte monitoring state, battery power status such as low battery, etc.), a device error state (e.g.. operational error, pressure-induced sensing attenuation, fault, failuremode, etc), device power status, device life status (e.g., anticipated sensor end-of-life), status of connectivity between device and a mobile computing device, and / or the like.

[0038] In some variations, the user interface may by default be in an enabled or "on" state to communicate such information at least whenever the analyte monitoring device is performing analyte measurements) or whenever the analyte monitoring device is powered on, thereby helping to ensure that information is continuously available to the user. For example, user interface elements may communicate through a display or indicator light(s) (e.g, as described below) not only alerts to flag user attention or recommend remedial action, but also when user status and / or device status are 8 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 normal. Accordingly, in some variations, a user is not required to perform an action to initiate a scan to learn their current analyte measurement level(s), and such information may always readily be available to the user. In some variations, however, a usermay performan action to disable the user interface temporarily (e.g., similar to a "snooze" button) such as for a predetermined amount of time (e.g., 30 minutes, 1 hour, 2 hours, etc.) after which the user interface is automatically reenabled, or until a second action is performed to reenable the user interface

[0039] In some variations, the user interface of the housing may include a display configured to visually communicate information. The display may, for example, include a display screen (e.g., LCD screen, OLED display, electrophoretic display, electrochromic display, etc.) configured todisplay alphanumeric text (e.g., numbers, letters, etc.), symbols, and / or suitable graphics to communicate information to the user. For example, the display screen may include a numerical information, textual information, and / or a graphics (e.g., sloped line, arrows, etc.) of information suchasuser status and / or status of the analyte monitoring device. For example, the display screen may include text or graphical representations of analyte measurement levels, trends, and / or recommendations (e.g., physical activity, reduced dietary intake, etc.).

[0040] As another example, the display on the housing may include one or more indicator lights (e.g., including LEDs, OLEDs, lasers, electroluminescentmaterial, or other suitable light source,waveguides, etc.) thatmaybe controlled in one or more predetermined illumination modes to communicate different statuses and / or other suitable information. An indicator lightmaybecontrolled to illuminatewithmultiple colors (e.g., red, orange, yellow, green, blue, and / or purple, etc.) or in only one color. For example, an indicator lightmay include amulticolored LED. As another example, an indicator light may include a transparent or semitransparent material (e g., acrylic) positioned over one or more different-colored light sources (e.g., LED)such that different-colored light sourcesmaybeselectivelyactivated to illuminate the indicator light in a selected color. The activation of light sources can either occur simultaneously or in sequence. An indicator light may have any suitable form (e.g., raised, flush, recessed, etc. from housing body) and / or shape (e.g., circle or other polygon, ring, elongated strip, etc.). In some variations, an indicator light may have a pinhole size and / or shape to present the same intensity of the light as a larger light source, but with significantly less power requirements, which may help conserve onboard power in the analyte monitoring device

[0041] Indicator light(s) on the display may be illuminated in one or more various manners to communicate different kinds of information. For example, an indicator light may be selectively illuminated on or off to communicate information (e.g., illumination "on" indicates one status, while illumination "off" indicates another status). Additionally or alternatively, an indicator light may be illuminated in a selected color or intensity to communicate information (e.g., illumination in a first color or intensity indicates a first status, while illumination in a second color or intensity indicates a second status) Additionally or alternatively, an indicator light may be illuminated in a selected temporal pattern to communicate information (e.g., illumination in a first temporal pattern indicates a first status, while illumination in a second temporal pattern indicates a second status). For example, an indicator light may be selectively illuminated in one of a plurality of predetermined temporal patterns that differ in illumination frequency (e.g., repeated illumination at a rapid or slow frequency), regularity (e.g., periodic repeated illumination vs. intermittent illumination), duration of illumination "on" time, duration of illumination "off" time, rate of change in illumination intensity, duty cycle (e.g., ratio of illumination "on" time to illumination "off" time), and / or the like, where each predetermined temporal pattern may indicate a respective status.

[0042] Additionally or alternatively, in some variations, a display may include multiple indicator lights that may be collectively illuminated in one or more predetermined illumination modes or sequences in accordance with one or more predetermined spatial and / or temporal patterns. For example, in some variations, some or all of the indicator lights arranged on a display may be illuminated in synchrony or in sequence to indicate a particular status. Accordingly, the selected subset of indicator lights (e.g., the spatial arrangement of the indicator lights that are illuminated) and / or the manner in which they are illuminated (e.g., illumination order, illumination rate, etc ) may indicate a particular status Additionally or alternatively, a plurality of indicator lights may illuminate simultaneously or in sequence to increase the diversity of the color palette. For example, in some variations, red, green, and blue LEDs may be illuminated in rapid succession to create the impression of white light to a user.

[0043] It should furthermore be understood that one or more of the above-described illumination modes may be combined in any suitable manner (e.g., combination of varying color, intensity, brightness, luminosity, contrast, timing, location, etc.) to communicate information Additionally or alternatively, an ambient light sensor may be incorporated into the device body to enable dynamic adjustment light levels in the indicator light(s) to compensate for environmental light conditions to help conserve power. The ambient light sensormay, in some variations, be used in conjunction with a kinetic sensor (e.g., asdescribed in furtherdetail below) to further determineappropriateperiods for theanalytemonitoringdevice toenter intoapower savingmodeor reducedpower state. For example, detectionof darknessandnomotionof theanalyte monitoring device may indicate that the wearer of the analyte monitoring device is asleep, which may trigger the analyte monitoring device to enter into a power saving mode or reduced power state.

[0044] FIG. 31A illustrates an example variation of an analyte monitoring device 3100 including a user interface 3120 with multiple indicator lights (3122, 3 124a‑3124c). Indicator light 3120 may, for example, be selectively illuminated to indicate a device state (e g., operation mode, error state, power status, life status, etc.) Although indicator light 3122 is in the shape of a symbol (e.g., logo), it should be understood that in other variations, the indicator light 3122 may have any 9 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 suitable shape (e.g., text, other geometric shape, etc.). Indicator lights 3124a‑3124c may be selectively illuminated to indicate a user status (e.g., information representative of analyte measurement). Although indicator lights 3124a‑3 124c are linear elementsextendingacross theuser interface (e.g., chordsacrossacircular display), it shouldbeunderstood that in other variations, the indicator lights 3124a‑3124c have other suitable shapes (e.g., wavy lines, circular, etc.). In some variations, a I-dimensional array of indicator lights of any suitable shapemaybearrangedon thehousing (e.g., arranged in a row, a column, an arc, etc.). Alternatively, the housing may include a multi-dimensional array of indicator lights of any suitable shape

[0045] Furthermore, in some variations, an indicator light may include an icon (e.g., symbol) that may be indicative of analyte information (e.g., up arrow to indicate rising analyte measurement level trend, down arrow to indicate falling analyte measurement level trend), analyte monitoring device status (e.g., exclamation point to indicate a device error state), and / or other suitable information. Additionally or alternatively, iconography in the indicator light(s) may be used to communicate recommendations for the user such as behavioral recommendations. Iconographymay, for example, have the advantage of communicating recommendations to a user in a more universal or language-agnostic manner (e.g., without the need for language translations to tailor the device to different geographical regions or user preferences, etc.). For example, as shown inFIG. 31B, in some variations, in the context of glucosemonitoring, a user interface for ananalyte monitoring device 3100’ may include a running person icon 3126 to indicate a recommendation that the user engage in physical activity. As another example, a food icon 3128may indicate a recommendation that the user consume food (or in combination with an "X" icon 3130, to indicate a recommendation that the user restrict food). As another example, a drink icon 3132 may indicate a recommendation that the user consume fluid such as water (or in combination with an "X" icon 3134, to indicate a recommendation that the user restrict fluid) As another example, a star icon 3136may indicate positive reinforcement (e.g., indicating success in analyte measurement levels staying within a normal or target range for a predeterminedperiodof time).However, it shouldbeunderstood that behavioral recommendationsmayvarybasedon the indication relating to the analyte(s) being monitored. For example, in some variations in which the analyte monitoring device is additionally or alternatively used to monitor cortisol, rising cortisol levels (and / or rising glucose levels) may be correlated to an increase inuser stress.Accordingly, in someof thesevariations theanalytemonitoringdevicemay include a suitable icon to indicate a recommendation to the user to reduce exposure to stressors, to meditate, etc. to avoid implicating adverse health efrects due to stress.

[0046] In the variations shown in FIGS. 31A and 31B, each of the indicator lights 3124a‑3124c may be exclusively illuminated to indicate a different analytemeasurement (e.g., in target range, below target range, significantly below target range, above target range, significantly above target range, etc.). Furthermore, the indicator lights 3124a‑3124c may be arranged adjacent to each other, such that theymay be selectively illuminated in a progressive sequence to communicate trend information of analytemeasurements (e.g., progressive sequence of illumination in a first direction that corresponds to an increase in measured quantity of an analyte, progressive sequence of illumination in a second direction that corresponds to a decrease inmeasured quantity of an analyte, pace of illumination progression in the first direction or the seconddirection that corresponds toa rateof increaseordecrease inmeasuredquantityof ananalyte, etc.).Anexampleof such progressive sequence of illumination is further described below with reference to FIGS. 33A‑33D.While one device status indicator light 3120and threeuser status indicator lights 3124a‑3124care shown inFIGS. 31Aand31B, it shouldbe understood that in other variations, an analytemonitoring devicemay include any suitable number of indicator lights, such as one, two, three, four, five or more device status indicator lights, and one, two, three, four, five or more user status indicator lights. Further details regarding an example operation of the user interface 3120 to communicate device status and / or user status are described below (e.g., with reference to FIGS. 32A‑32C, 33A‑33D, 34A‑34C, and 35A‑35B). Microneedle array

[0047] Asshown in the schematic of FIG. 5A, in somevariations, amicroneedle array 510 for use in sensing oneormore analytes may include one or more microneedles 510 projecting from a substrate surface 502 The substrate surface 502 may, for example, begenerally planar andoneormoremicroneedles510mayproject orthogonally from theplanar surface Generally, as shown inFIG. 5B, amicroneedle 510may includeabodyportion 512 (e.g., shaft) and a tapereddistal portion 514 configured to puncture skin of a user. In some variations, the tapered distal portion 514may terminate in an insulated distal apex 516. The microneedle 510 may further include an electrode 520 on a surface of the tapered distal portion. In some variations, electrode-based measurements may be performed at the interface of the electrode and interstitial fluid locatedwithin the body (e g , on an outer surface of the overall microneedle). In some variations, themicroneedle 510may 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.

[0048] 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 10 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 may be retlow-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 electro- chemical sensing coating (including a biorecognition element such as an enzyme) that enables detection of a target analyte, a referenceelectrode, andacounter electrode. Inotherwords, themicroneedlearray500may includeat 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.

[0049] In somevariations, themicroneedle array500may includeaplurality ofmicroneedles that are insulatedsuch that theelectrodeoneachmicroneedle in theplurality ofmicroneedles is individually addressable andelectrically 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 target 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 amore comprehensive assessment of physiological status. For example, as shown in the schematic of FIG. 6, a microneedle array may include a portion of microneedles to detect a first Analyte A, a second portion of microneedles to detect a second Analyte B, and a third portion of microneedles to detect a third Analyte C. It should be understood that the microneedle array may be configured to detect any suitable number of analytes (e.g , 1, 2, 3, 4, 5 or more, etc.). Suitable target analytes for detection may, for example, include glucose, ketones, lactate, and cortisol. For example, in some variations, ketones may be detected in a manner similar to that described in U.S. Patent App. No. 16 / 701,784. which is incorporated herein in its entirety by this reference Thus, individual electrical addressability of the microneedle array 500 provides greater control and flexibility over the sensing function of the analyte monitoring device.

[0050] 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 doesnot cover theapexof themicroneedle,Rather, theelectrode520maybeoffset from theapexor tipof themicroneedle. The electrode 520 being proximal to or offset from the insulated distal apex 516 of the microneedle advantageously providesmore accurate sensormeasurements. For example, this arrangement prevents concentration of the electric field at themicroneedle apex 516 duringmanufacturing, thereby avoiding non-uniformelectro-deposition of sensing chemistry on the electrode surface 520 that would result in faulty sensing.

[0051] 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 uponmicroneedle 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 surfacewhen themicroneedle 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 apexmay improve sensing accuracy. For example, in somevariations, a distal edgeof the electrode 520may be locatedat least about10µm(e.g., betweenabout20µmandabout 30µm) from thedistal apexor tip of themicroneedle, as measured along a longitudinal axis of the microneedle

[0052] 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 pathwaymay be facilitated by ametal via running through the interior of themicroneedle body portion (e.g., shaft) between the microneedle’s proximal and distal ends. Alternatively, in some variations the conductivepathwaymaybeprovidedby theentire bodyportionbeing formedof a conductivematerial (e.g., dopedsilicon). 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 micro- needles 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 electrode520andbacksideelectrical contact. For example, bodyportion512may includean insulativematerial 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 amongmicroneedles are described in further detail below. 11 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0053] Such electrical isolation among microneedles in the microneedle array permits the sensors to be individually addressable.This individually addressability advantageouslyenables independent andparallelizedmeasurement among the sensors, as well as dynamic reconfiguration of sensor assignment (e.g., to different analytes). In some variations, the electrodes in themicroneedlearraycanbeconfigured toprovide redundantanalytemeasurements,which isanadvantage over conventional analytemonitoringdevices.Forexample, redundancycan improveperformanceby improvingaccuracy (e.g., averagingmultiple analytemeasurement values for the sameanalytewhich reduces theeffect of extremehighor low sensor signals on thedetermination of analyte levels) and / or improving reliability of the device by reducing the likelihood of total failure.

[0054] In somevariations, as described in further detail belowwith respectivedifferent variationsof themicroneedle, the microneedle arraymay be formed at least in part with suitable semiconductor and / orMEMS 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. For example, in some variations, the microneedle array may be formed at least in part using techniques described in U.S. Patent App. No. 15 / 913,709, which is incorporated herein in its entirety by this reference. Microneedle structures

[0055] Described herein are multiple example variations of microneedle structure incorporating one or more of the above-described microneedle features for a microneedle array in an analyte monitoring device.

[0056] In some variations, amicroneedle may have a generally columnar body portion and a tapered distal portion with an electrode. For example, FIGS. 7A‑7C illustrate an example variation of a microneedle 700 extending from a substrate 702. FIG. 7A is a side cross-sectional view of a schematic of microneedle 700, while FIG. 7B is a perspective view of the microneedle 700 and FIG. 7C is a detailed perspective view of a distal portion of the microneedle 700. As shown in FIGS. 7B and 7C, the microneedle 700 may include a columnar body portion 712, a tapered distal portion 714 terminating in an insulated distal apex 716, and an annular electrode 720 that includes a conductivematerial (e.g., Pt, Ir, Au, Ti, Cr, Ni, etc.) and is arranged on the tapered distal portion 714. As shown in FIG. 7A, the annular electrode 720 may be proximal to (or offset or spaced apart from) the distal apex 716. For example, the electrode 720may be electrically isolated from the distal apex 716 by a distal insulating surface 715a including an insulatingmaterial (e.g., SiO2). In some variations, the electrode 720 may also be electrically isolated from the columnar body portion 712 by a second distal insulating surface 715b The electrode720maybe inelectrical communicationwith a conductive core740 (e.g., conductive pathway) passingalong the bodyportion712 toabacksideelectrical contact 730 (e.g.,madeofNi / Aualloy) 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 FIG. 7A, in some variations, an insulating moat 713 including an insulating material (e.g., SiO2) may be arranged around (e.g., around theperimeter) of thebodyportion712andextendat least partially through thesubstrate702.Accordingly, the insulating moat 713 may, for example, help prevent electrical contact between the conductive core 740 and the surrounding substrate 702. The insulating moat 713 may further extend over the surface of the body portion 712. Upper and / or lower surfacesof thesubstrate702mayalso includea layerof substrate insulation704 (e.g.,SiO2).Accordingly, the insulation provided by the insulating moat 713 and / or substrate insulation 704 may contribute at least in part to the electrical isolation of the microneedle 700 that enables individual addressability of the microncedle 700 within a microneedle array. Furthermore, in some variations the insulating moat 713 extending over the surface of the body portion 712 may function to increase the mechanical strength of the microneedle 700 structure.

[0057] 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 bemade by first forming a trench in a silicon substrate by deep reactive ion etching (DRIE) from the backsideof thesubstrate, thenfilling that trenchwithasandwichstructureofSiO2 / polycrystallinesilicon (poly-Si) / SiO2by low pressure chemical vapor deposition (LPCVD) or other suitable process. In other words, the insulating moat 713 may passivate thesurfaceof thebodyportion712of themicroneedle, andcontinueasaburied feature in the substrate702near 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 insulatingmoat 713may further help provide excellentmatching 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.

[0058] 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 / Aumay be deposited by suitableMEMSmanufacturing techniques (e.g., sputtering).

[0059] The microneedle 700 may have any suitable dimensions. By way of illustration, the microneedle 700 may, in 12 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 some variations, have a height of between about 300µmand about 500µm. In some variations, the tapered distal portion 714may have a tip angle between about 60 degrees and about 80 degrees, and an apex diameter of between about 1µm andabout 15µm. In somevariations, the surface area of the annular electrode 720may include between about 9,000µm2 and about 11.000 µm2, or about 10,000 µm2. FIG. 8 illustrates various dimensions of an example variation of a columnar microneedle with a tapered distal portion and annular electrode, similar to microneedle 700 described above.

[0060] FIG. 9 illustrates another example variation of amicroneedle 900 having a generally columnar body portion. The microneedle 900may be similar tomicroneedle 700as described above, except as described below. For example, like the microneedle 700, the microneedle 900 may include a columnar body portion 912, and a tapered distal portion 914 terminating in an insulated distal apex 916. The microneedle 900 may further include an annular electrode 920 that includes a conductivematerial and is arranged on the tapered distal portion 914 at a location proximal to (or offset from or spaced apart from) the distal apex 916. Other elements of microneedle 900 have numbering similar to corresponding elements of microneedle 700.

[0061] However, compared to the microneedle 700, the microneedle 900 may have a sharper tip at the distal apex 916 andamodified insulatingmoat 913. For example, thedistal apex916mayhaveasharper tip angle, suchasbetweenabout 25 degrees and about 45 degrees, and an apex radius of less than about 100 nm, which provides a sharper microneedle profile that may penetrate skin with greater ease, lower velocity, less energy, and / or less trauma. Furthermore, in contrast to the insulatingmoat 713 (which extends through the substrate 702 and along the height of themicroneedle body portion 712 as shown in FIG. 7A), the modified insulating moat 913 may extend only through the substrate 902 such that the sandwich structure filling the trench (e.g., created by DRIE as described above) forms only the buried feature in the substrate. Although the sidewall of the microneedle 900 is shown in FIG. 9 as extending generally orthogonal to the substrate surface, it shouldbeunderstood that because themodified insulatingmoat 913neednot extend theentire height of the microneedle body portion 712, in some variations the sidewall of the microneedle 900 may be angled at non- orthogonal angles relative to the substrate (e.g., the sidewallmayhave a slight positive taper of betweenabout 1 degree to about 10 degrees, or between about 5 degrees and about 10 degrees).

[0062] In somevariations, the rest of themicroneedle surface900 (aside from theannular electrode920)may includean insulatingmaterial extending from substrate insulation 904. For example, a layer of an insulatingmaterial (e.g., SiO2)may extend from a frontside surface of the substrate 902 to provide a body portion insulation 918, and may further extend up over a proximal edge of the electrode 920 as shown in FIG. 9. Another region of insulating material may similarly cover a distal edge of the electrode 920 and insulate the distal apex 916. Such region of insulating material and / or modified insulating moat 913 may help prevent electrical contact between the conductive core 940 and the surrounding substrate 902. Accordingly, like the microneedle 700, the microneedle 900 may maintain electrical isolation for individual addres- sability within a microneedle array. In some variations, the process to form microneedle 900 may result in higher yield and / or provide lower production cost compared to the process to form microneedle 700.

[0063] Themicroneedle900mayhaveanysuitabledimensionsBywayof illustration, themicroneedle900may, in some variations, include a height of between about 400µmandabout 600µm, or about 500µm. In some variations, the tapered distal portion 914 may have a tip angle of between about 25 degrees and about 45 degrees, with a tip radius of less than about 100nm.Furthermore, themicroneedlemayhaveashaft diameter of betweenabout 160µmandabout 200µm.FIG. 10 illustratesadditional variousdimensionsof anexamplevariationof a columnarmicroneedlewitha tapereddistal portion and annular electrode, similar to microneedle 900 described above.

[0064] FIGS 27A‑27F illustrate another example variation of a microneedle 2700 having a generally columnar body portion. The microneedle 2700 may be similar to microneedle 700 as described above, except as described below. For example, as shown in FIG. 27B. like the microneedle 700, the microneedle 2700 may include a columnar body portion 2712. and a tapered distal portion arranged on a cylinder 2713 and terminating in an insulated distal apex 2716. The cylinder 2613may be insulated and have a smaller diameter than the columnar body portion 2712. Themicroneedle 2700 may further include an annular electrode 2720 that includes a conductive material and is arranged on the tapered distal portion at a location proximal to (or offset or spaced apart from) the distal apex 2916. Other elements ofmicroneedle 2700 as shown in FIGS. 27A‑27F have numbering similar to corresponding elements of microneedle 700.

[0065] However, the electrode 2720 on themicroneedle 2700may include a tip contact trench 2722 This contact trench maybeconfigured tohelpestablishohmic contact between theelectrode2720and theunderlyingconductive core2740of themicroneedle. In some variations, the shape of the tip contact trench 2722may include an annular recess formed in the surface of the conductive core 2740 (e.g., into the body portion of the microneedle, or otherwise in contact with a conductive pathway in the body portion) such that when the electrode 2720material is deposited onto the conductive core 2740, the electrode 2720 with the tip contact trench 2722 may have a stepped profile when viewed from the side. The tip contact trench2722mayadvantageously help provideamargin of error to ensure contact between theelectrode2720and the underlying conductive core 2740. Any of the othermicroneedle variations described hereinmay also have a similar tip contact trench to help ensure contact between the electrode (which may be, for example, a working electrode, reference electrode, counter electrode, etc.) with a conductive pathway within the microneedle.

[0066] FIGS. 28A and 28B illustrate additional various dimensions of an example variation of a columnar microneedle 13 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 with a tapered distal portion and annular electrode, similar to microneedle 2700 described above For example, the variation of themicroneedle shown in FIGS. 28Aand28Bmayhave a tapered distal portion generally having a taper angle of about 80 degrees (or between about 78 degrees and about 82 degrees, or between about 75 degrees and about 85 degrees), and a cone diameter of about 140µm (or between about 133µmand about 147µm, or between about 130µm and about 150 µm). The cone of the tapered distal portion may be arranged on a cylinder such that the overall combined height of the cone and cylinder is about 110µm (or between about 99µmand about 116µm, or between about 95µmand about120µm).Theannularelectrodeon the tapereddistal portionmayhaveanouter orbasediameterof about106µm(or betweenabout 95µmandabout 117µm,or betweenabout 90µmandabout 120µm), andan inner diameter of about 33.2 µm (or between about 30 µm and about 36 µm, or between about 25 µm and about 40 µm). The length of the annular electrode, as measured along the slope of the tapered distal portion, may be about 57 µm (or between about 55 µm and about 65µm), and the overall surface area of the electrodemay be about 12,700µm2 (or between about 12,500µm2 and about 12,900 µm2, or between about 12,000 µm2 and about 13,000 µm2). As shown in FIG. 28B, the electrode may furthermore have a tip contact trench extending around a central region of the cone of the tapered distal portion, where the contact may have a width of about 11 µm (or between about 5 µmand about 50 µm , between about 10 µmand about 12 µm,orbetweenabout 8µmandabout14µm)asmeasuredalong theslopeof the tapereddistal portion, anda trenchdepth of about 1.5µm(or betweenabout 0.1µmandabout 5µm,or between about 0.5µmandabout 1.5µm,or betweenabout 1.4µmandabout 1.6µm,or betweenabout 1µmandabout 2µm). Themicroneedle has an insulated distal apex having a diameter of about 5.5 µm (or between about 5.3 µm and about 5.8 µm, or between about 5 µm and about 6 µm).

[0067] In some variations, amicroneedlemay have a generally pyramidal body portion and a tapered distal portion with an electrode. For example, FIG. 11A illustrates an example variation of a microneedle 1100 having a generally pyramidal body portion 1112 and a tapered distal portion 1114 extending from the body portion 1112. Themicroneedle 1100may also include an annular electrode 1120 arranged on the tapered distal portion 1114 and proximal to an insulated distal apex 1116. The electrode 1120may be conductively coupled via a conductive pathway through the conductive core 1140 of the microneedle to a backside electrical contact 1130. Like the microneedle 900 described above with respect to FIG. 9, the microneedle 1100 may include an insulating moat 1113 that is arranged around the base of the body portion 1112 and extends through the substrate 1102 to provide electrical insulation around the microneedle 1100 (e.g., for individual addressability) and help prevent electrical contact between the conductive core 1140and the surrounding substrate 1102. However, in contrast to the insulatingmoat 913shown inFIG. 9, the insulatingmoat 1113maybeoffset from thebaseof the microneedle 1100. Themoat may, for example, be offset between about 10µmand about 400µm, between about 10µm and about 300µm, between about 10 µmand about 200 µm, or between about 10µmand about 100 µm fromwhere the baseof themicroneedle 1100meets the substrate 1102 towhich it is attached. In somevariations, the insulatingmoatmay include a filler material including parylene, Si3N4, and SiO2, which may provide for low thermal stress and an insulating material that is chemical‑ andwater-resistant Additional body portion insulation 1118may extend from a frontside surface of the substrate 1102 up to the proximal edge of the electrode 1120. Another region of insulatingmaterial may extend from the distal edge of the electrode 1120 and insulate the distal apex 1116.

[0068] Asshown inFIG.11B, in somevariationsamicroneedle1100havingapyramidal bodyportion1112may includea polygonal base, though the base may have any suitable shape (e.g., circular). The pyramidal body portion 1112 may include a plurality of planar facets each extending from a respective of the polygonal base of the microneedle. In some variations, the planar facets may include anisotropically etched <311> planar facets for increased mechanical strength (e.g., compressive strength and shear strength) of themicroneedle 1110 and / or increased electrode surface area relative to a circular conewith a non-planar faceted surface. For example, themicroneedle 1110may have an octagonal basewith anisotropically etched<311>planar facets that increase themechanical strength and increase themetallization surfaceof the microneedle 110 for the electrode surface.

[0069] Themicroneedle 1100may be formed at least in part by suitableMEMS fabrication techniques. For example, the microneedle pyramidal structure may be formed by a timed anisotropic wet etch of a silicon wafer substrate. To form the annular electrode surface, metal deposition on the tapered distal portion of the microneedle may be performed, such as usingspecialized lithographic techniquesasdescribedabovewith respect toelectrode720,without coating thedistal apex 1116. However, compared to the process described above to form microneedle 700, much of the process to form microneedle 1100 does not involve expensive RIE techniques, which may thereby substantially reduce manufacturing costs. Furthermore, in some variations, instead of utilizing dry etch processes as described above with respect to microneedle 700, a process of forming the microneedle 1100 may include mechanical dicing, bulk micromachining, or other cutting techniques to shape themicroneedle 1100 into having a pyramidal body. Furthermore, such techniquesmay beperformedat a largescale, soas to form, for example,multiplemicroneedles1110arranged in anarrayasshown inFIG. 11C.

[0070] The microneedle 1100 may have any suitable dimensions. By way of illustration, the microneedle 1100 may, in some variations, have a height of between about 400 µm and about 600 µm, or about 500 µm. In some variations, the tapered distal portion 714 may have a tip angle between about 30 degrees and about 50 degrees, or about 40 degrees, which may provide a good balance between sharpness for skin penetration and lithography processability on the sloped 14 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 surface on which the electrode 1120 is to be disposed.

[0071] FIG. 12 illustrates various dimensions of an example variation of a pyramidal microneedle with a tapered distal portion having planar facets and an electrode arranged on at least a portion of the planar facets. While in some variations the electrode may be annular or annular-like in that all of the planar facets on the pyramidal microneedle may include a metallization surface for the electrode, it should be understood that alternatively, in some variations only a portion of the planar facets on the pyramidal microneedle may include a metallization surface (e.g., one, two, three, four, five, six, or seven planar facets of a pyramidal microneedle having an octagonal base and eight planar facets extending distally from the octagonal base)

[0072] In some variations, a pyramidal microneedle may be similar to that described above with respect to FIG. 11A, except that the microneedle may have an asymmetrical shape as shown in FIGS. 13A and 13B For example, in some variations as shown in FIG. 13A. amicroneedle 1300mayhave anon-circular or polygonal (e.g., square, octagonal) base, but may taper in a radially asymmetric manner. For example, the microneedle 1300 may include at least one cut surface 1350 (e.g., planar surface) that is offset from the distal apex 1316 of the microneedle (that is, not extending through a central z-axis defined as passing from the base of themicroneedle 1300 to the distal apex 1316. The insulated distal apex 1316maybekept intact soas tonot compromisesurfacearea formetallization for theelectrode. In somevariations, thecut surface 1350 may be angled at a non-orthogonal angle relative to the base of the microneedle (and / or surface of the substrate 1302), as shown in FIG. 13A. For example, in some variations the cut surface may configured to produce a sharpened asymmetrical distal tip at distal apex 1316 that is less than about 50 degrees, less than 40 degrees, less than about 30 degrees, or less than about 20 degrees. Alternatively, in some variations the cut surface 1350 may be angled normal to or orthogonal to the base of the microneedle (and / or surface of the substrate 1302).

[0073] Additionally or alternatively, as shown inFIG. 13A, anexample variationof anasymmetricmicroneedle1300may haveapolygonal (e.g., octagonal)base,but includevariousslopedsurfaces that taperat differentangles.Asshown inFIG. 13A, a body portion 1316 of themicroneedle 1300may have a first taper angle (A) and a second taper angle (B)measured relative to a base of the body portion (and / or surface of the substrate 1302). The second taper angle (B) may be greater than the first taper angle (A) such that themicroneedle has a sharper penetrating tip extending fromastable,mechanically strong base. For example, in some variations, the first taper angle (A) may be between about 10 degrees and about 30 degrees, between about 15 degrees and about 25 degrees, or about 20 degrees Additionally, in some variations, the second taper angle (B)maybebetweenabout 60degrees andabout 80degrees, betweenabout 65degreesandabout 75 degrees, or about 70 degrees.

[0074] FIGS. 13C‑13E depict a series of steps in an example variation of forming a pyramidal microneedle with an asymmetric cut surface. As shown in FIG. 13C, a symmetric pyramidal microneedle with two taper anglesmay be formed through an anisotropic wet etch process. The two taper angles of the microneedle may include, for example, a first taper angle of about 20degrees locatednear thebaseof themicroneedle, andasecond taper angle of about 70degrees located distal to the first tape angle, thereby forming progressively sloping surfaces (e.g., along planar facets of the pyramidal microneedle). As shown in FIG. 13D, a dicing blade may be applied at an angle offset from the distal apex of the microneedle, so as to forma cut surface similar to cut surface1350 described above. The cut surfacemay leavea reduced microneedle base diameter (e.g., between about 150µmand about 190µm, or about 170µm) so as to result in low tissue trauma. As shown in FIG. 13E, the resultingmicroneedle (with its offset cut surface) is asymmetric but has an intact, sharp distal apex.

[0075] Like thepyramidalmicroneedle1100describedabovewith respect toFIG.11A, themicroneedle1300mayderive its mechanical strength at least in part from anisotropically etched <311> planes and the pyramidal shape However, an asymmetric pyramidal microneedle with a asymmetric cut surface may be advantageous in that it may reduce the longitudinal shear forces compared to a symmetricmicroneedle having similar dimensionsbut lacking theasymmetric cut. Furthermore, a sharper (e.g., more acute angle) distal microneedle tip may be achieved with such an asymmetric cut surface. Although the cut surface 1350 is shown in FIG. 13Aas positioned at a non-orthogonal angle relative to the base of themicroneedle, alternatively as describedabove, in somevariations the cut surface1350maybegenerally orthogonal or normal to the base of the microneedle (and / or surface of the substrate 1302), which may further reduce the longitudinal shear forces in the microneedle.

[0076] In some variations, a microneedle may be similar to those described above, except that the microneedle may include a columnar body portion anda pyramidal distal portion. For example, as shown in FIG. 14A, a columnar-pyramidal microneedle 1400may include a columnar body portion 1412 thatmay extend froma polygonal (e.g., octagonal) base out of a non-clectrically conductive substrate 1402 such as intrinsic (undoped) silicon. Additionally, the columnar-pyramidal microneedle 1400may include a tapered distal portion 1414 having a pyramidal shapewith a plurality of planar facets. For example, the columnar-pyramidal microneedle 1400may include a tapered distal portion 1414 having a pyramidal shape with eight facets extending from the octagonal columnar body portion 1412. However, the pyramidal shapemay have any suitable number of planar facets (e.g., one, two, three, four, five, six, seven, nine, ormore). Anannular electrode 1420may be formedonall the planar facets of the pyramidal distal portion 1414, or ononly a portion of the planar facets (e.g., on one, two, three, four, five, six, seven facets) may include a metallization surface for the electrode. Similar to that described 15 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 above, the columnar body portion 1412 may include a conductive core including an electrically conductive material functioningasaconductivepathway for signals toand from theelectrode142.Thecolumnarbodyportion1412may further include an insulationmaterial 1418may extend along the body portion 1412 and up to (or slightly overlapping) a proximal edge of the electrode 1420 The distal apex 1416 may or may not be covered by similar insulation material

[0077] In some variations, the tapered distal portion 1414may be similar to that described above with respect to FIGS. 11A‑11C, 12, and / or 13A‑13E. For example, the tapered distal portion 1414may be formed using anisotropic wet etching techniques. The electrode 1420 may be formed on the tapered distal portion 1414 by lithography, electrodeposition or other suitable techniqueThe tapereddistal portion1414may thenbeprotectedbyanetch resistantmaterialwhile thebody portion 1412 is formed out of the substrate by dry etching (e.g., DRIE or other suitable process(es).

[0078] The combination of columnar and pyramidal aspects of the microneedle 1400 has a number of advantages. Similar to that described above, the tapered distal portion 1414 and apex 1416 have high mechanical strength due to the <311> wet etched planes and the pyramidal shape. Additionally, because the substrate is formed from a non-conductive material, an insulation "moat" as described above may not be required to electrically isolate the microneedle, thereby simplifying and reducing cost of fabrication. The absence of the insulation moat also permits material continuity in the substrate, which may lead to better mechanical integrity of the overall microneedle array structure.

[0079] Although the columnar-pyramidal microneedle 1400 is described above as including a non-conductive sub- strate, it should be understood alternatively, in some variations a columnar-pyramidal microneedle may include a conductive core extending from a conductive substrate (e.g., doped silicon). For example, in some variations the columnar body portion 1412 may be similar to that described above with respect to FIGS. 7A‑7C, and 8‑10 (e.g., may include an insulation moat to electrically isolate the microneedle, etc.).

[0080] In somevariationsofmicroneedlearrays includingoneormoremicroneedles1400, conductivepathwaysmaybe formed in the non-conductive substrate to facilitate communicationwith the electrode(s) 1420. For example, as described above, the body portion 1412 of each microneedle may include a conductive core including a conductive material Such conductivematerialmayextendbetween theelectrode1420 to thesubstrate1402.Asshown inFIG.15D, themicroneedle array may include one or more connectors 1510 made of a conductive material (e.g., gold, aluminum) that is each in turn coupled to a backside electrical contact 1530 for further sensor communication. In some variations, as shown FIGS. 15A‑15D, theoneormore connectors 1510mayextend laterally along the surfaceof the substrate and then connect to the backside electrical contact 1530 with a conductive via 1520 within the substrate.

[0081] Additional details of example variations ofmicroneedle array configurations are described in further detail below. Electrodes

[0082] 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, themicroneedle 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 typesmay include ametallization layer andmay include one or more coatings or layers over the metallization layer that help facilitate the function of that electrode.

[0083] 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 theworking and reference electrodes, andwithin practical limits no current is sourced fromor sinked to the referenceelectrode.Additionally, to implement sucha three-electrodesystem, theanalytemonitoring 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. Working electrode

[0084] As described above, the working electrode is the electrode at which the oxidation and / or reduction reaction of interest occurs. In some variations, sensingmay beperformed at the interface of theworking electrode and interstitial fluid 16 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 locatedwithin the body (e.g., on an outer surface of the overall microneedle). In some variations, a working electrodemay includeanelectrodematerial andabiorecognition layer inwhichabiorecognitionelement (e.g., enzyme) is immobilizedon the working electrode to facilitate selective analyte quantification. In some variations, the biorecognition layer may also function as an interference-blocking layer and may help prevent endogenous and / or exogenous species from directly oxidizing (or reducing) at the electrode.

[0085] A redox current detected at the working electrodemay be correlated to a detected concentration of an analyte of interest. This is because assuming a steady-state, diffusion-limited system, the redox current detected at the working electrode follows the Cottrell relation below: where n is the stoichiometric number of electrons mitigating a redox reaction, F is Faraday’s constant, A is electrode surface area, D is the diffusion coefficient of the analyte of interest. C is the concentration of the analyte of interest, and t is thedurationof time that thesystem isbiasedwithanelectrical potential. Thus, thedetectedcurrent at theworkingelectrode scales linearly with the analyte concentration.

[0086] Moreover, because the detected current is a direct function of electrode surface area A, the surface area of the electrode may be increased to enhance the sensitivity (e.g., amperes per molar of analyte) of the sensor. For example, multiple singular working electrodes may be grouped into arrays of two or more constituents to increase total effective sensing surface area. Additionally or alternatively, to obtain redundancy, multiple working electrodesmay be operated as parallelized sensors to obtain a plurality of independent measures of the concentration of an analyte of interest. The working electrode can either be operated as the anode (such that an analyte is oxidized at its surface), or as the cathode (such that an analyte is reduced at its surface).

[0087] FIG. 16A depicts a schematic of an exemplary set of layers for a working electrode 1610. For example, as described above, in some variations the working electrode 1610 may include an electrode material 1612 and a biorecognition layer including a biorecognition element. The electrode material 1612 functions to encourage the electrocatalytic detection of an analyte or the product of the reaction of the analyte and the biorecognition element. The electrodematerial 1612 also provides ohmic contact and routes an electrical signal from the electrocatalytic reaction to processing circuitry In some variations, the electrode material 1612 may include platinum as shown in FIG. 16A. However, theelectrodematerial 1612mayalternatively include, for example, palladium, iridium, rhodium,gold, ruthenium, titanium, nickel, carbon, doped diamond, or other suitable catalytic and inert material.

[0088] In somevariations, theelectrodematerial 1612maybecoatedwith ahighly porouselectrocatalytic layer, suchas a platinum black layer 1613, which may augment the electrode surface area for enhanced sensitivity. Additionally or alternatively, the platinum black layer 1613 may enable the electrocatalytic oxidation or reduction of the product of the biorecognition reaction facilitated by the biorecognition layer 1614. However, in some variations the platinum black layer 1613 may be omitted (as shown in FIGS. 16D and 16G, for example). The electrode may enable the electrocatalytic oxidation or reduction of the product of the biorecognition reaction if the platinum black layer 1613 is not present.

[0089] Thebiorecognition layer 1614maybearrangedover theelectrodematerial 1612 (or platinumblack layer 1613 if it is present) and functions to immobilize and stabilize the biorecognition element which facilitates selective analyte quantification for extended time periods. In some variations, the biorecognition element may include an enzyme, such as an oxidase. As an exemplary variation for use in a glucosemonitoring system, the biorecognition element may include glucose oxidase, which converts glucose, in the presence of oxygen, to an electroactive product (i.e., hydrogen peroxide) that can be detected at the electrode surface. Specifically, the redox equation associated with this exemplary variation is Glucose +Oxygen→Hydrogen Peroxide - Gluconolactone (mediated by glucose oxidase). Hydrogen Peroxide→Water + Oxygen (mediated by applying an oxidizing potential at the working electrode).

[0090] However, in other variations the biorecognition element may additionally or alternatively comprise another suitable oxidase or oxidoreductase enzyme such as lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydro- genase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and / or xanthine oxidase.

[0091] In somevariations, thebiorecognitionelementmaybecross-linkedwithanamine-condensingcarbonyl chemical species thatmayhelpstabilize thebiorecognitionelementwithin thebiorecognition layer1614.As further describedbelow, in some variations, the cross-linking of the biorecognition element may result in the microneedle array being compatible with ethylene oxide (EO) sterilization, which permits exposure of the entire analyte monitoring device (including sensing elements and electronics) to the same sterilization cycle, thereby simplifying the sterilization process and lowering manufacture costs. For example, the biorecognition element may be cross-linked with glutaraldehyde, formaldehyde, glyoxal, malonaldehyde, succinaldehyde, and / or other suitable species. In some variations, the biorecognition element may be cross-linked with such an amine-condensing carbonyl chemical species to form cross-linked biorecognition 17 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 element aggregatesCross-linked biorecognition element aggregates that have at least a thresholdmolecular weightmay then be embedded in a conducting polymer. By embedding only those aggregates that havea thresholdmolecular weight, any uncross-linked enzymes may be screened out and not incorporated into the biorecogntion layer. Accordingly, only aggregates having a desiredmolecular weightmay be selected for use in the conducting polymer, to help ensure that only sufficiently stabilized, cross-linked enzyme entities are included in the biorecognition layer, thereby contributing to a biorecognition layer that is overall better suited forEOsterilizationwithout loss in sensingperformance. In somevariations, only cross-linked aggregates that have amolecular weight that is at least twice that of glucose oxidasemay be embedded in the conducting polymer.

[0092] In some variations, the conducting polymer may be permselective to contribute to the biorecognition layer’s robustness against circulating androgynous electroactive species (e.g., ascorbic acid, vitamin C, etc.), fluctuations of which may adversely affect the sensitivity of the sensor. Such a permselective conducting polymer in the biorecognition layer may further be more robust against pharmacological interferences (e.g., acetaminophen) in the interstitial fluid that may affect sensor accuracy. Conducting polymersmay bemade permselective by, for example, removing excess charge carriers by an oxidative electropolymerization process or by neutralizing these charge carriers with a counter-ion dopant, thereby transforming the conducting polymer into a non-conducting form. These oxidatively-polymerized conducting polymersexhibit permselectivity andarehenceable to reject ionsof similar chargepolarity to thedopant ion (net positiveor negative) or by via size exclusion due to the dense and compact form of the conducting polymers.

[0093] Furthermore, in some variations the conducting polymer may exhibit self-sealing and / or self-healing properties. For example, the conducting polymermay undergo oxidative electropolymerization, duringwhich the conducting polymer may lose its conductivity as the thickness of the deposited conducting polymer on the electrode increases, until the lack of sufficient conductivity causes the deposition of additional conducting polymer to diminish. In the event that the conducting polymer has succumbed to minor physical damage (e.g., during use), the polymeric backbone may re-assemble to neutralize free charge and thereby lower overall surface energy of the molecular structure, which may manifest as self- sealing and / or self-healing properties.

[0094] In some variations, the working electrode may further include a diffusion-limiting layer 1615 arranged over the biorecognition layer 1614. The diffusion-limiting layer 1615may function to limit the flux of the analyte of interest in order to reduce the sensitivity of the sensor to endogenous oxygen fluctuations. For example, the diffusion-limiting layer 1615may attenuate the concentration of the analyte of interest so that it becomes the limiting reactant to an aerobic enzyme. However, in some variation (e.g., if the biorecognition element is not aerobic), the diffusion-limiting layer 1615 may be omitted.

[0095] The working electrode may further include, in some variations, a hydrophilic layer 1616 that provides for a biocompatible interface to, for example, reduce the foreign body response. However, in some variations the hydrophilic layer 1616 may be omitted (e.g., if the diffusion-limiting layer expresses hydrophilic moieties to serve this purpose), as shown in FIGS 16D and 16G, for example. Counter electrode

[0096] As described above, the counter electrode is the electrode that is sourcing or sinking electrons (via an electrical current) required to sustain the electrochemical reaction at the working electrode. The number of counter electrode constituents can be augmented in the form of a counter electrode array to enhance surface area such that the current- carrying capacity of the counter electrode does not limit the redox reaction of the working electrode. It thus may be desirable tohaveanexcessof counterelectrodeareaversus theworkingelectrodearea tocircumvent thecurrent-carrying capacity limitation If theworkingelectrode isoperatedasananode, thecounterelectrodewill serveas thecathodeandvice versa. Similarly, if an oxidation reaction occurs at the working electrode, a reduction reaction occurs at the counter electrode and vice versa. Unlike the working or reference electrodes, the counter electrode is permitted to dynamically swing to electrical potentials required to sustain the redox reaction of interest on the working electrode.

[0097] As shown in FIG. 16B, a counter electrode 1620 may include an electrode material 1622, similar to electrode material 1612. For example, like the electrode material 1612, the electrode material 1622 in the counter electrode 1620 may include a noble metal such as gold. platinum, palladium, iridium, carbon, doped diamond, and / or other suitable catalytic and inert material

[0098] In some variations, the counter electrode 1620may have few or no additional layers over the electrodematerial 1632. However, in some variations the counter electrode 1620 may benefit from increase surface area to increase the amount of current it can support. For example, the counter electrode material 1632 may be textured or otherwise roughened in such a way to augment the surface area of the electrode material 1632 for enhanced current sourcing or sinking ability. Additionally or alternatively, the counter electrode 1620 may include a layer of platinum black 1624, which may augment electrode surface as described abovewith respect to some variations of the working electrode. However, in some variations of the counter electrode, the layer of platinum blackmay be omitted (e.g., as shown in FIG. 16E). In some variations, the counter electrodemay further include, a hydrophilic layer that provides for a biocompatible interface to, for 18 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 example, reduce the foreign body response.

[0099] Additionally or alternatively, in some variations as shown in FIG. 16H, the counter electrode 1620may include a diffusion-limiting layer 1625 (e.g , arranged over the electrode) The diffusion-limiting layer 1625 may, for example, be similar to the diffusion-limiting layer 1615 described above with respect to FIG. 16A. Reference electrode.

[0100] As described above, 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 or at least controlled potential relationship may be established between the working and reference electrodes, and within practical limits no current is sourced from or sinked to the reference electrode.

[0101] As shown in FIG. 16C, a reference electrode 1630 may include an electrode material 1632, similar to electrode material 1612. In some variations, like the electrodematerial 1612, the electrodematerial 1632 in the reference electrode 1630may includeametal salt ormetal oxide,whichservesasastable redoxcoupledwithawell-knownelectrodepotential. For example, the metal salt may, for example, include silver-silver chloride (Ag / AgCl) and the metal oxide may include iridium oxide (IrOx / Ir2O3 / IrO2). In other variations, noble and inert metal surfaces may function as quasi-reference electrodes and include gold, platinum, palladium, iridium, carbon, dopeddiamond, and / or other suitable catalytic and inert material Furthermore, in some variations the reference electrode 1630may be textured or otherwise roughened in such a way to enhance adhesion with any subsequent layers. Such subsequent layers on the electrode material 1632 may includeaplatinumblack layer1634.However, in somevariations, theplatinumblack layermaybeomitted (e.g, asshown in FIGS. 16F and 16I).

[0102] The reference electrode 1630 may, in some variations, further include a redox-couple layer 1636, which main contain a surface-immobilized, solid-state redox couple with a stable thermodynamic potential. For example, the reference electrode may operate at a stable standard thermodynamic potential with respect to a standard hydrogen electrode (SHE). The high stability of the electrode potential may be attained by employing a redox system with constant (e.g. buffered or saturated) concentrations of each participant of the redox reaction. For example, the reference electrode may includesaturatedAg / AgCl (E -+0.197Vvs.SHE)or IrOx (E - ‑0.177vs.SHE,pH-7.00) in the redox-couple layer1636. Other examples of redox-couple layers 1636 may include a suitable conducting polymer with a dopant molecule such as that described inU.S.PatentPub.No. 2019 / 0309433.which is incorporated in its entirety herein by this reference. In some variations, the reference electrode may be used as a half-cell to construct a complete electrochemical cell

[0103] Additionally or alternatively, in some variations as shown in FIG. 16I, the reference electrode 1630may include a diffusion-limiting layer 1635 (e.g , arranged over the electrode and / or the redox-couple layer). The diffusion-limiting layer 1635 may, for example, be similar to the diffusion-limiting layer 1615 described above with respect to FIG. 16A. Exemplary electrode layer formation

[0104] Various layers of the working electrode, counter electrode, and reference electrode may be applied to the microneedle array and / or functionalized, etc. using suitable processes such as those described below.

[0105] In a pre-processing step for themicroneedle array, themicroneedle arraymay be plasma cleaned in an inert gas (e.g., RF-generated inert gas such as argon) plasma environment to render the surface of the material, including the electrode material (e.g., electrode material 1612, 1622, and 1632 as described above), to be more hydrophilic and chemically reactive.Thispre-processing functions tonot onlyphysically removeorganicdebrisandcontaminants, but also to clean and prepare the electrode surface to enhance adhesion of subsequently deposited films on its surface. Working electrode

[0106] Anodization: To configure the working electrode after the pre-processing step, the electrode material 1612 may undergo an anodization treatment using an amperometry approach in which the electrode constituent(s) assigned for the working electrode function is (are) subject to a fixed high anodic potential (e.g., between 1.0 - 1.3 V vs. Ag / AgCl reference electrode) for a suitableamount of time (e.g., betweenabout 30secandabout 10min) in amoderate-strengthacid solution (e.g., 0.1 - 3M H2SO4). In this process, a thin, yet stable native oxide layer may be generated on the electrode surface. Owing to the low pH arising at the electrode surface, any trace contaminants may be removed as well.

[0107] In an alternative embodiment using a coulometry approach, anodization can proceed until a specified amount of charge has passed (measured in Coulombs). The anodic potential may be applied as described above; however, the duration of this might vary until the specified amount of charge has passed.

[0108] Activation Following the anodization process, the working electrode constituents may be subjected to a cyclically-scanned potential waveform in an activation process using cyclic voltammetry In the activation process, which may occur in amoderate-strength acid solution (e.g. 0.1 - 3MH2SO4), the potential appliedmay time-varying in a suitable 19 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 function (e.g, sawtooth function). For example, the voltage may be linearly scanned between a cathodic value (e.g., between ‑0.3 - ‑02Vvs.Ag / AgCl referenceelectrode)andananodic value (eg , between+1.0 ‑1.3Vvs.Ag / AgCl reference electrode) in an alternating function (e.g., 15‑50 linear sweep segments). The scan rate of this waveform can take on a value between 1 - 1000mV / sec. It should be noted that a current peak arising during the anodic sweep (sweep to positive extreme) corresponds to the oxidation of a chemical species, while the current peak arising during the ensuing cathodic sweep (sweep to negative extreme) corresponds to the reduction of said chemical species

[0109] Functionalization of the biorecognition layer: Following the activation process, the working electrode constitu- ents may be functionalized with the biorecognition layer 1614 such as that described above. Assuming that the working electrodecontingentof themicroneedlearrayhasundergone theaforementionedsteps, thepotential appliedmaybe time- varying inasawtooth functionForexample, avoltagemaybe linearly scannedbetweenacathodic value (e.g., between0.0 V vs. Ag / AgCl reference electrode) and an anodic value (e.g., between +1.0 V vs Ag / AgCl reference electrode) in an alternating function (e.g., 10 linear sweepsegments). In anexample variation, the scan rate of thiswaveformcan take ona value between about 1 mV / sec and about 10 mV / sec in an aqueous solution comprised of a monomeric precursor to the entrapment conducting polymer and a cross-linked biorecognition element (e.g., enzyme, such as glucose oxidase). In this process, a thin film (e.g., between about 10 nmand about 1000 nm) of biorecognition layer comprising of polymer with a dispersed cross-linked biorecognition element may be generated (e.g., electrodeposited or electropolymerized) on the working electrode surface. In some variations, the conducting polymer may include one or more of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylene diamine, thiophene, 3,4-ethylenedioxythiophene, and aminophe- nylboronic acid. The biorecognition layer imparts a selective sensing capability towards an analyte of interest, as described above.

[0110] In some variations, the working electrode surface may be electrochemically roughened in order to enhance adhesion of the biorecognition layer to theelectrodematerial 1612 surface (and / orPt black layer) The roughening process may involve a cathodization treatment (e.g., cathodic deposition, a subset of amperometry) wherein the electrode is subject to a fixed cathodic potential (e g., between ‑0.4 - 0.2Vvs.Ag / AgCl referenceelectrode) for a certain amount of time (e.g., 5 sec - 10min) in anacid solution containing thedesiredmetal cation dissolved therein (e.g., 0.01 - 100mMH2PtCl6). Alternatively, the electrode is subject to a fixed cathodic potential (e.g , between about ‑0.4 to about +0.2 V vs. Ag / AgCl reference electrode) until a certain amount of charge has passed (e.g., 0.1 mC 100mC) in an acid solution containing the desired metal cation dissolved therein (e.g., 0.01 - 100 mMH2PtCl6). In this process, a thin, yet highly porous layer of the metal may be generated on the electrode surface, thereby augmenting the electrode surface area dramatically. Additionally or alternatively, in some variations as described above, elemental platinum metal may deposited on the electrode to form or deposit a platinum black layer 1613.

[0111] Functionalization of the diffusion-limiting layer: Following the functionalization of the biorecognition layer, the working electrode constituents may, in some variations, be functionalized with the diffusion-limiting layer. Assuming that the working electrode contingent of the microneedle array has undergone the aforementioned steps, one or more of the following methods may be employed to apply the diffusion-limiting layer, which may be a thin film of thickness between about 100 nm to about 10,000 nm.

[0112] In some variations, a diffusion-limiting layer may applied by a spray coating method in which an aerosolized polymer formulation (dispersed in water or a solvent) is applied to the microneedle array device with a specified spray pattern and duration in a controlled-environment setting. This creates a thin film with the desired thickness and porosity required to restrict the diffusion of an analyte of interest to the biorecognition layer.

[0113] In somevariations, a diffusion-limiting layermaybeapplied byaplasma-inducedpolymerizationmethod inwhich a plasma source generates a gas discharge that provides energy to activate a cross-linking reaction within a gaseous, aerosolized, or liquid monomeric precursor (e.g., vinylpyridine). This converts the monomeric precursor to a polymeric coating that may be deposited on the microneedle array to a specified thickness, thereby creating a thin film with the desired thickness and porosity required to restrict the diffusion of an analyte of interest to the biorecognition layer 1614.

[0114] Furthermore, in some variations, a diffusion-limiting layer may applied by electrophoretic or dielectrophoretic deposition, such as example techniques described in U.S. Patent No. 10,092,207. which is incorporated herein in its entirety by this reference. Counter electrode

[0115] Anodization: In some variations, the counter electrodematerial may undergo an anodization treatment using an amperometry approach in which the electrode constituent(s) assigned for the counter electrode function is subject to a fixed high anodic potential or a suitable amount of time in a moderate-strength acid solution. Exemplary parameters and other specifics of the anodization process for the counter electrodemay be similar to that described above for the working electrode. Similarly, anodization for the counter electrode may alternatively use a coulometry approach as described above.

[0116] Activation: In some variations, following the anodization process, the counter electrode constituents may be 20 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 subjected toacyclically-scannedpotentialwaveform inanactivationprocessusingcyclic voltammetry. In somevariations, the activation process may be similar to that described above for the working electrode.

[0117] Roughening: Furthermore, in some variations, the counter electrode surface may be electrochemically rough- ened inorder toenhance thecurrent-sinkingor current-sourcingcapacityof thiselectrodecontingent. Theelectrochemical roughening processmay be similar to that described above for theworking electrode. Additionally or alternatively, in some variations as described above, elemental platinum metal may deposited on the electrode to form or deposit a platinum black layer 1623. Reference electrode

[0118] Anodization: Like theworking and counter electrodes as described above, the reference electrodemay undergo an anodization treatment using an amperometry approach in which the electrode constituent(s) assigned for the counter electrode function is subject to a fixed high anodic potential or a suitable amount of time in a moderate-strength acid solution. Exemplary parameters and other specifics of the anodization process for the counter electrodemay be similar to that described above for the working electrode. Similarly, anodization for the counter electrode may

[0119] Activation Following the anodization process, the reference electrode constituents may be subjected to a cyclically-scannedpotentialwaveform in anactivation processusing cyclic voltammetry. In somevariations, the activation process may be similar to that described above for the working electrode.

[0120] Functionalization Following the activation process, the reference electrode constituents may be functionalized Assuming that the reference electrode contingent of the microneedle array has undergone the aforementioned steps, a fixed anodic potential (e.g., between 0.4 - 1.0 V vs. Ag / AgCl reference electrode) may be applied for a certain suitable duration (e.g., between about 10 sec and about 10 min) in an aqueous solution. Alternatively, the reference electrode is subject to a fixedanodic potential (e.g., betweenabout ‑0.4 to about ‑1.0Vvs.Ag / AgC1 reference electrode) until a certain amount of chargehas passed (e.g., 0.01mC10mC) in an aqueous solution. In somevariations, the aqueous solutionmay include a monomeric precursor to a conducting polymer and a charged dopant counter ion or material (e.g., poly(styrene sulfonate)) carrying an opposing charge. In this process, a thin film (e.g., between about 10 nmand about 10,000 nm) of a conducting polymer with a dispersed counter ion or material may be generated on the reference electrode surface. This creates a surface-immobilized, solid-state redox couplewith a stable thermodynamic potential In some variations, the conducting polymer may include one or more of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylene diamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid

[0121] In somealternative embodiments, a native iridiumoxide film (e.g., IrO2 or Ir2O3 or IrO4)maybeelectrochemically grownonan iridiumelectrode surface in anoxidativeprocess. This also createsa stable redox couple, asdiscussedabove

[0122] Furthermore, in somevariations the referenceelectrode surfacemaybeelectrochemically roughened in order to enhance adhesion of the surface-immobilized redox couple. The electrochemical roughening process may be similar to that described above for the working electrode. Additionally or alternatively, in some variations as described above, elemental platinum metal may deposited on the electrode to form or deposit a platinum black layer 1633.

[0123] Other features and techniques for forming the reference electrode may be similar to that described in, for example, U.S Patent Pub. No. 2019 / 0309433, which was incorporated above by reference. Microneedle array configurations

[0124] Multiple microneedles (e.g., any of the microneedle variations described herein, each of which may have a workingelectrode, counter electrode, or referenceelectrodeasdescribedabove)maybearranged in amicroneedlearray. 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.

[0125] 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, themicroneedlesmaybe 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 themicroneedle 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 forceat lowvalues (e.g., less thanabout 150µm).Accordingly, in some variations themicroneedles in amicroneedlearraymayhaveapitchof at least 200µm,at least 300µm,at least 400µm,at least 500µm, at least 600µm, at least 700µm, or at least 750µm. For example, the pitchmay be between about 200µm and about 800 µm, between about 300 µm and about 700 µm, or between about 400 µm and about 600 µm. In some variations, themicroneedlesmaybearranged inaperiodic grid, and thepitchmaybeuniform inall directionsandacrossall regions of the microneedle array. Alternatively, the pitch may be different as measured along different axes (e.g., X, Y directions)and / or some regionsof themicroneedlearraymay includeasmaller pitchwhileothermay includea largerpitch. 21 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0126] Furthermore, for more consistent penetration, microneedles may be spaced equidistant from one another (e g., samepitch in all directions). To that end, in some variations, themicroneedles in amicroneedle arraymay be arranged in a hexagonal configuration as shown in FIG. 17. Alternatively, the microneedles in a microneedle array may arranged in a rectangular array (e.g., square array), or in another suitable symmetrical manner

[0127] Another consideration for determining configuration of amicroneedle 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 connectedmicroneedles is expected to produce a greater signal intensity (and hence increased accuracy) than one with fewer microneedles. However, a higher number of microneedles on adiewill increase die cost (given a constant pitch) andwill 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 forceand / or velocity. Furthermore, in somevariations a lower number ofmicroneedles onadiemay 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 factorsmaybe achievedwith amicroneedle array including 37microneedles as shown in FIG. 17 or amicroneedle array including 7microneedles are shown in FIGS. 29A and 29B. However, in other variations theremaybe fewermicroneedles in anarray (e.g., betweenabout 5andabout 35, betweenabout 5andabout 30, between about 5 and about 25, between about 5 and about 20, between about 5 and about 15, between about 5 and about 100, between about 10 and about 30, between about 15 and about 25, etc.) or more microneedles in an array (e.g., more than 37, more than 40, more than 45, etc.).

[0128] 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 lifetimeof the device. Furthermore, in somevariations, a portion of the microneedles in amicroneedle arraymayadditionally or alternatively bedeactivated at a certain timeduring operation and remain inactive for the remainder of the operating lifetime of the device

[0129] In considering characteristics of a die for amicroneedle array, die size is a function of the number ofmicroneedles in themicroneedle array and the pitch of themicroneedles. 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.

[0130] 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 themicroneedle 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.

[0131] FIG. 17 depicts an illustrative schematic of 37 microneedles arranged in an example variation of a microneedle array. The37microneedlesmay, for example, bearranged in ahexagonal arraywith an inter-needle center-to-center pitch of about 750µm (or between about 700µmandabout 800µm, or between about 725µmandabout 775µm) between the center of each microneedle and the center of its immediate neighbor in any direction. FIG. 18A depicts an illustrative schematic of an example variation of a die including themicroneedle arrangement shown in FIG. 17. Example dimensions of the die (e.g., about 4.4 mm by about 5.0 mm) and the microneedle array are shown in FIG. 18B.

[0132] FIGS29Aand 29Bdepict perspective views of an illustrative schematic of sevenmicroneedles 2910 arranged in an example variation of a microneedle array 2900. The sevenmicroneedles 2910 are arranged in a hexagonal array on a substrate 2902. As shown in FIG. 29A, the electrodes 2920 are arranged on distal portions of the microneedles 2910 extending froma first surface of the substrate 2902. As shown in FIG. 29B, proximal portions of themicroneedles 2910 are conductively connected to respective backside electrical contacts 2930 on a second surface of the substrate 2902 opposite the first surface of the substrate 2902. FIGS. 30A and 30B depict plan and side views of an illustrative schematic of a microneedle array similar to microneedle array 2900. As shown in FIGS. 30A and 30B, the seven microneedles are arranged in a hexagonal array with an inter-needle center-to-center pitch of about 750 µm between the center of each microneedle and the center of its immediate neighbor in any direction In other variations the inter-needle center-to-center pitch may be, for example, between about 700 µm and about 800 µm, or between about 725 µmand about 775 µm. The microneedles may have an approximate outer shaft diameter of about 170 µm (or between about 150 µmand about 190 µm, or between about 125µmand about 200µm)and a height of about 500µm (or between about 475µmand about 525 µm, or between about 450 µm and about 550 µm).

[0133] Furthermore, the microneedle arrays described herein may have a high degree of configurability concerning where theworkingelectrode(s), counter electrode(s), and referenceelectrode(s) are locatedwithin themicroneedle array. 22 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 This configurability may be facilitated by the electronics system.

[0134] In some variations, a microneedle array may include electrodes distributed in two or more groups in a symmetrical or non-symmetrical manner in themicroneedle array, with each group featuring the sameor 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, FIG. 19A depicts a variation of a microneedle array 1900A including two symmetrical groups of seven working electrodes (WE), with the two working electrode groups labeled "1" and "2". In this variation, the twoworkingelectrodegroupsaredistributed inabilaterally symmetricalmannerwithin themicroneedlearray. Theworking electrodes are generally arranged between a central region of three reference electrodes (RE) and an outer perimeter region of twenty counter electrodes (CE). In some variations, each of the twoworking electrode groupsmay include seven workingelectrodes that are electrically connectedamongst themselves (e.g, to enhance sensor signal). Alternatively, only a portion of one or both of the working electrode groups may include multiple electrodes that are electrically connected amongst themselves. As yet another alternative, the working electrode groups may include working electrodes that are standalone and not electrically connected to other working electrodes. Furthermore, in some variations the working electrode groups may be distributed in the microneedle array in a non-symmetrical or random configuration.

[0135] Asanother example,FIG19Bdepictsa variationofamicroneedlearray1900B including four symmetrical groups of three working electrodes (WE), with the four working electrode groups labeled "1", "2", "3", and "4." In this variation, the four working electrode groups are distributed in a radially symmetrical manner in the microneedle array. Each working electrode group is adjacent to one of two reference electrode (RE) constituents in themicroneedle array and arranged in a symmetrical manner. Themicroneedle array also includes counter electrodes (CE) arranged around the perimeter of the microneedle array, except for two electrodes on vertices of the hexagon that are inactive ormay be used for other features or modes of operation.

[0136] In some variations, only a portion of microneedle array may include active electrodes. For example. FIG. 19C depicts a variation of a microneedle array 1900C with 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1", "2", "3", and "4") in a bilaterally symmetrical arrangement, twenty-two counter electrodes, and three reference electrodes. The remaining eight electrodes in the microneedle array are inactive In themicroneedlearrayshown inFIG.19C,eachof theworkingelectrodes is surroundedbyagroupof counterelectrodes. Two groups of such clusters of working electrodes and counter electrodes are separated by a row of the three reference electrodes.

[0137] As another example, FIG. 19D depicts a variation of a microneedle array 1900D with 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1". "2", "3", and "4") in a bilaterally symmetrical arrangement, twenty counter electrodes, and three referenceelectrodes,where the remaining tenelectrodes in the microneedle array are inactive

[0138] As another example, FIG. 19E depicts a variation of a microneedle array 1900E with 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1". "2", "3", and "4"), eighteen counter electrodes, and two reference electrodes The remaining thirteen electrodes in the microneedle array are inactive. The inactive electrodes are along a partial perimeter of the overall microneedle array, thereby reducing the effective size and shape of the active microneedle arrangement to a smaller hexagonal array. Within the active microneedle arrangement, the four working electrodes are generally in a radially symmetrical arrangement, and each of the working electrodes is surrounded by a group of counter electrodes.

[0139] FIG. 19F depicts another example variation of a microneedle array 1900F with 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled " 1". "2", "3", and ’"4"), two counter electrodes, and one referenceelectrode. The remaining thirty electrodes in themicroneedle array are inactive. The inactive electrodes are arranged in two layersaround theperimeter of theoverallmicroneedlearray, thereby reducing theeffective sizeandshape of the active microneedle arrangement to a smaller hexagonal array centered around the reference electrode. Within the activemicroneedle arrangement, the fourworkingelectrodes are in abilaterally symmetrical arrangement and the counter electrodes are equidistant from the central reference electrode

[0140] FIG. 19G depicts another example variation of a microneedle array 1900Gwith 37microneedles and a reduced number of active electrodes. The active electrodes inmicroneedle array 1900Gare arranged in a similarmanner as that in microneedlearray1900Fshown inFIG. 19F, except that themicroneedlearray1900G includesonecounter electrodeand two reference electrodes, and the smaller hexagonal array of active microneedles is centered around the counter electrode Within the active microneedle arrangement, the four working electrodes are in a bilaterally symmetrical arrangement and the reference electrodes are equidistant from the central counter electrode.

[0141] FIG. 19Hdepicts another example variationof amicroneedlearray1900Hwith 7microneedles. Themicroneedle arrangement contains two microneedles assigned as independent working electrodes ( 1 and 2), a counter electrode contingent comprised of 4microneedles, and a single reference electrode There is bilateral symmetry in the arrangement of working and counter electrodes, which are equidistant from the central reference electrode Additionally, the working electrodesarearrangedas far as possible from thecenter of themicroneedlearray (e.g, at theperiphery of thedieor array) 23 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 to take advantage of a location where the working electrodes are expected to have greater sensitivity and overall performance.

[0142] FIG 19I depicts another example variation of a microneedle array 1900I with 7 microneedles. The microneedle arrangement contains four microneedles assigned as two independent groupings (1 and 2) of two working electrodes each, a counter electrode contingent comprised of 2 microneedles, and a single reference electrode. There is bilateral symmetry in the arrangement of working and counter electrodes, which are equidistant from the central reference electrode. Additionally, the working electrodes are arranged as far as possible from the center of the microneedle array (e.g., at theperiphery of thedieor array) to takeadvantageof a locationwhere theworkingelectrodesareexpected to have greater sensitivity and overall performance.

[0143] FIG. 19J depicts another example variation of amicroneedle array 1900Jwith 7microneedles. Themicroneedle arrangement contains fourmicroneedles assigned as independentworking electrodes (1, 2, 3, and4), a counter electrode contingent comprised of 2microneedles, and a single reference electrode. There is bilateral symmetry in the arrangement of working and counter electrodes, which are equidistant from the central reference electrode. Additionally, the working electrodesarearrangedas faraspossible from thecenterof themicroneedlearray (e.g., at theperipheryof thedieorarray) to take advantage of a location where the working electrodes are expected to have greater sensitivity and overall performance.

[0144] While FIGS. 19A‑19J illustrate example variations of microneedle array configurations, it should be understood that these figures are not limiting andothermicroneedle configurations (including different numbers and / or distributions of working electrodes, counter electrodes, and reference electrodes, and different numbers and / or distributions of active electrodes and inactive electrodes, etc .) may be suitable in other variations of microneedle arrays. Warm-up

[0145] Many implanted electrochemical sensors require a "warm-up" time, or time for the sensor to attain a stable signal value following implantation. This process has origins in both physiology and sensor dynamics. However, various aspects of analyte monitoring devices described herein are configured to mitigate factors contributing to warm-up time, thereby allowing the analyte monitoring devices described herein to have significantly shorter warm-up times compared to traditional CGM systems. For example, the analyte monitoring devices described herein may have a warm-up time of about 30 minutes or less (e.g. between about 10 minutes and about 30 minutes, between about 15 minutes and about 30 minutes, between about 20 minutes and about 30 minutes, between about 25 minutes and about 30 minutes), about 45 minutes or less, about 60 minutes or less, about 90 minutes or less, or about 120 minutes or less. In some variations, following a warm-up period, the analyte monitoring device may calibration during a calibration period.

[0146] Wound response: For example, the implantation of a sensor creates a wound response due to the localization disruption, displacement, and destruction of tissue. The larger the sensor, or the deeper the implant, the more prolific the wound response. Accordingly, there is a compelling rationale to miniaturize the sensor to elicit an attenuated wound response, which would result in more rapid warm-up.

[0147] Protein adsorption: Additionally, following implantation of a sensor, the foreign body response is immediately instigated. The foreign body response includes a complex biochemical cascade that aims to encapsulate the foreign material with cellular matter. Hydrophobic surfaces tend to be subject to adsorption of endogenous proteins very rapidly following implant, this is referred to as biofouling. Hydrophilic surfaces, on the other hand, resist biofouling due to high water content. Human serum albumin (HSA) is the predominant protein in the dermal interstitial fluid, constituting about 60% of total protein, and maintains a negative charge at physiological pH. When the sensor is polarized with a positive potential (as in some variation of the analyte monitoring device), endogenous HSA is subject to electric drift and charge attraction to the positive (working) electrode of the sensor. This can give rise to an increased propensity for the sensor surface to biofoul. This is the rationale behind the implementation of either a hydrophilic diffusion limiting layer or outer biocompatible layer toeffectively conceal thesensor frombeing recognizedasa foreignbody, asdescribed in further detail above.

[0148] As described herein, the analyte monitoring device reduces the influence of the above physiological factors on warm-up time due to, for example, the shallow nature of the implant, the minimal volume of tissue displaced (e.g., up to about two orders of magnitude lower than current CGM systems, such as between about 100 and about 1000 times less tissuedisplaced, or betweenabout 200andabout 600 times less tissuedisplacedcompared to currentCGMsystems), the minimal amount of trauma to said tissue during implantation, and the lack of permeation of the vasculature deeper in the reticular dermis, which, when perturbed, can instigate a more prolific wound response that will engender an accelerated effort to encapsulate the implant, as is the case with competing wire-implanted CGM systems.

[0149] Attainment of equilibrium: One example of the effect of sensor dynamics on warm-up time relates to the attainment of equilibrium. An electrochemical sensor requires a finite amount of time to achieve equilibrium when used inanewenvironment. This is typically associatedwith theestablishmentof thermodynamicequilibriumdue toanadsorbed surface layer of ions at the electrodes. As the reference electrode in most implantable electrochemical sensors does not 24 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 employ an internal filling solution with a redox couple that is sealed from the rest of the electrochemical cell, this reference electrode must attain equilibrium with its surroundings in order to establish a stable reference potential.

[0150] Hydration of sensor layers: The electrode sensor layers must be immersed in an aqueous environment to function properly. The resulting hydration process may activate the electrode’s polymer layer(s) and biorecognition element(s) and allows them to rearrange and return to their native active tertiary structure, which is primarily responsible for their activity or unique properties. This process is often known as sensor "wetting" and allows themedium in which the sensing operation occurs to intercalate the sensor layers to a sufficient extent

[0151] Decaying of the non-Faradaic response: The biasing (application of a voltage) of an electrochemical sensor will cause a double layer of ions to form at the electrode surface. This process requires a finite amount of time due to the chargingof theadsorbedspecieson theelectrodesurface.Thisgives rise toadouble layer capacitance.Thenon-Faradaic time constant is equal to the product of the said double layer capacitance and the solution resistanceOftentimes, the non- Faradic response (electrical current) decays tonegligible levelsmore rapidly thanother physical phenomenaand it is often not the rate-limiting step in the warm-up process. Once the non-Faradaic response decays to negligible levels, the Faradaic response ensues, which is reflective of the electrochemical / redox reaction of interest

[0152] As described herein, the analyte monitoring device may reduce the influence of sensor dynamics on warm-up time due to, for example, the implementation thin membrane layers (on the order of 10 nm - 5000 nm), which allow the layers to hydrate more rapidly than competing implantable CGM systems. Moreover and owing to the diminutive dimensions of the electrodes described herein (e.g., geometric surface area of the working electrode(s)), the non- Faradaic response transpires for shorter durations (due to reduced double layer capacitance and hence charging of the double layer). In somevariations, a high-potential (e.g., > 0.75V) bias for a limitedperiod of time followingapplication of the device to skin may further expedite burn-in or warm-up of the sensor to achieve equilibrium and stable signal levels. Signal latency

[0153] Typically, implanted electrochemical sensors also experience a delay, or signal latency, in attaining a stable signal value followingchanges inanalyte levels. This signal latency isa functionof various factors.At ahigh level, latency is a function of 3 distinct effects: (1) diffusional lag (amount of time that is required for amolecule of analyte to diffuse from the capillary (source) to the sensor surface, (2) diffusional limitation imposed by the sensor membrane / layer architecture on the sensors, and (3) algorithmic processing of data (averaging, filtering, signal denoising, and other signal processing measures), which often results in a group delay However, various aspects of the analyte monitoring devices described herein minimize these factors contributing to signal latency, thereby resulting in a faster response time for analyte measurements.

[0154] Asdescribedabove, onesignificant advantageof theanalytemonitoringdevicesdescribedherein is that location of sensor placement. Because the electrode surface is implanted at a location in such close proximity (e.g., within a few hundred micrometers or less) to the dense and well-perfused capillary bed of the reticular dermis, the diffusional lag is negligible. This is a significant advantage over conventional analyte sensors, which reside in the very poorly vascularized adipose tissuebeneath thedermis andhence thediffusion distance, and resulting diffusional latency, from the vasculature in the dermis is substantial (e.g., typically 5 - 20 minutes).

[0155] Additionally, as the films deposited on the electrode sensor surface use electrodeposition methods, the precise thicknessof said films canbe controlled to a highly precise degree. For example, the electrodepositionmethodsof forming the sensor surface enable consistent, controlled creation of thin film layers that may reduce diffusional lag Moreover, the spatial localization of the thin film layers to the sensing electrode allows the realization of thinner and less diffusionally resistive films, which further reduce latency due to diffusion of the analyte from the other film surface to the biorecognition layer.

[0156] Furthermore, the high level of redundancy (parallel channels of analyte measurement) afforded by the micro- needle array allows for higher fidelity measurement and less reliance on the algorithm to interpolate sensor readings, which imparts greater reduced delay or latency. Electronics system

[0157] As shown in the schematic of FIG. 2A of an analyte monitoring device 110, the electronics system 120 may be integrated within the housing 112, such that the electronics system 120 may be combined with sensing elements (e g., microneedle array) as part of a single unit, in contrast to traditional CGMsystems, which typically incorporate components in multiple physically distinct units. Further details of an example variation of an electronics system 120 are described below. 25 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 PCBs

[0158] In some variations, the analyte monitoring device may include one or more PCBs For example, the analyte monitoring device may include at least one PCB in the sensor assembly 320 that includes the microneedle array, and at least one device PCB 350 as shown in FIG. 3E.

[0159] For example, as shown in FIGS. 3F‑31, a sensor assembly 320may include a sensor standoff PCB 322 coupled to a connecting PCB 324. Themicroneedle array 330may be attached to the sensor standoffPCB 322 (e.g., FR‑4, PTFE, Rogers 4350B), such as through a soldering process combined with an epoxy underfill for mechanical strength. In some variations, anepoxy skirtmaybedepositedalong theedgesof the siliconmicroneedlearray 330 to relieve the sharpedges from the silicon dicing processes described above. The epoxy may also provide a transition from the edge of the silicon substrate of the microneedle array silicon to the edge of the PCB 322. Alternatively, this epoxy may be replaced or supplemented by a rubber gasket or the like.

[0160] As shown in FIG. 3J. the sensor standoff PCB 322may function as a standoff that at least in part determines the desired distance to which the microneedle array 330 protrudes from the housing 310. Accordingly, the standoff height of the sensor standoff PCB 322 may be selected to help ensure that the microneedle array 330 is inserted properly into a user’s skin. During needle insertion, the bottom surface of the housing 310 will act as a stop for needle insertion. If the sensor standoff PCB 322 has a reduced height and its lower surface is flush or nearly flush with the bottom surface of the housing, then the housing 310 may prevent the microneedle array 330 from being fully inserted into the skin. However, increasing the standoff height may lead to more pressure of the microneedle array on the skin during microneedle insertion, which can lead to dermatological irritation and / or erythema (redness of the skin).

[0161] The sensor standoff PCB 322 may be secured to the housing 310 and / or secured within the stack up inside the housing, such as with suitable fasteners or the like. For example, as shown in FIGS. 3H‑3J, the sensor standoff PCB 322 (with themicroneedle array 330)may be coupled to a first side of the connectingPCB324,while a second opposite side of the connecting PCB 324may in turn be coupled to an interposer PCB connector 326. As shown in FIG. 3J. the interposer PCB connector 326may be communicatively coupled to the device PCB 350, such as for signal processing as described below. Accordingly, signals from themicroneedle array 330 may be communicated through the sensor standoff PCB 322 and to the device PCB via the sensor standoff PCB 322, connecting PCB 324, and interposer PCB connector 326. However, in some variations the analytemonitoring devicemay include fewer PCBs. For example, in some variations. the sensor assembly 320 may omit the sensor standoff PCB 322, such that the microneedle array 330 may directly communicate electrically to the connecting PCB 324 (or directly to the device PCB 350).

[0162] Additionally or alternatively, in some variations at least one of the PCBs in the sensor assembly 320may include or be coupled to one or more additional sensors in combination with the microneedle array 330. For example, the sensor assembly 320 may include a temperature sensor (e.g., thermistor, resistance temperature detector, thermocouple, bandgap reference, noncontact temperature sensor, etc.). In some variations, temperature measurement may addition- ally or alternatively be performed by one or more analyte-insensitive electrodes in the microneedle array.

[0163] In some variations, the sensor standoff PCB 322 may be between about 0.05 inches and about 0.15 inches, or between about 0 093 inches and about 0.127 inches in thickness The sensor standoff PCB 322, in some variations, may includeoneoraplurality of conductive through-substrateviasconfigured to routeelectrical signals fromananterior surface of the PCB to a posterior surface of the PCB. In some variations, the sensor standoff PCB 322 may comprise a semiconductor (e.g., silicon) with conductive through-substrate vias configured to route electrical signals froman anterior surfaceof the semiconductor to aposterior surfaceof the semiconductor In yet other variations, themicroneedle array 330 may be mounted directly to the PCB 324, without the sensor standoff PCB 322. Analog front end

[0164] In some variations, the electronics systemof the analytemonitoring devicemay include an analog front end. The analog front endmay include sensor circuitry (e g., sensor circuitry 124 as shown in FIG. 2A) that converts analog current measurements to digital values that can be processed by the microcontroller. The analog front end may, for example, include a programmable analog front end that is suitable for use with electrochemical sensors. For example, the analog front endmay include aMAX30131,MAX30132, orMAX30134 component (which have 1. 2. and 4 channel, respectively), available fromMaxim Integrated (San Jose, CA). which are ultra-low power programmable analog front ends for use with electrochemical sensors. Theanalog front endmayalso includeanAD5940orAD5941component, available fromAnalog Devices (Norwood, MA), which are high precision, impedance and electrochemical front ends. Similarly, the analog front end may also include an LMP91000, available from Texas Instruments (Dallas, TX), which is a configurable analog front end potentiostat for low-power chemical sensing applications. The analog front end may provide biasing and a complete measurement path, including the analog to digital converters (ADCs). Ultra-low power may allow for the continuous biasingof the sensor tomaintain accuracyand fast responsewhenmeasurement is required for anextendedduration (e.g. 7 days) using a body-worn, battery-operated device. 26 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0165] In some variations, the analog front end device may be compatible with both two and three terminal electro- chemical 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.

[0166] In some variations, the analog front endmay include amulti-channel potentiostat to multiplex sensor inputs and handle multiple signal channels. For example, the analog front endmay include amulti-channel potentiostat such as that described in U.S. Patent No. 9,933,387, which is incorporated herein in its entirety by this reference.

[0167] In some variations, the analog front end and peripheral electronicsmay be integrated into an application-specific integrated circuit (ASIC), which may help reduce cost, for example. This integrated solution may include the microcon- troller described below, in some variations. Microcontroller

[0168] In some variations, the electronics system of the analyte monitoring device may include at least one micro- controller (e.g, controller 122 as shown in FIG. 2A). The microcontroller may include, for example, a processor with integrated flash memory. In some variations, the microcontroller in the analyte monitoring device may be configured to perform analysis to correlate sensor signals to an analyte measurement (e.g., glucose measurement) For example. the microcontroller may execute a programmed routine in firmware to interpret the digital signal (e.g., from the analog front end), perform any relevant algorithms and / or other analysis, and route processed data to and / or from the communication module. Keeping the analysis on-board the analyte monitoring device may, for example, enable the analyte monitoring device to broadcast analytemeasurement(s) tomultiple devices (e g.,mobile computing devices suchas a smartphone or smartwatch, therapeutic delivery systems such as insulin pens or pumps, etc.) in parallel, while ensuring that each connected device has the same information.

[0169] In some variations, the microcontroller may be configured to activate and / or inactivate the analyte monitoring device ononeormore detected conditions. For example, the devicemaybe configured topower on theanalytemonitoring deviceupon insertionof themicroneedlearray into skin. Thismay, for example, enable apower-saving feature inwhich the battery is disconnected until the microneedle array is placed in skin, 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.

[0170] FIG. 25 illustrates a schematic of an example variation of circuitry enabling the above-described activation of the analytemonitoringdeviceupon insertion.Generally, uponpenetrationof thestratumcorneumof theskinandpositioningof the electrode at the distal tip of themicroneedle constituents in the highly electrolytic dermal interstitial fluid, the resistance of "Sensor Detect" reduces to a significant extent, thereby activating the p-channel MOSFETQ401. Once Q401 is turned on, thebattery voltageVBATflows toVDD_INand that providespower for thedevice.When themicrocontroller powerson, the first routine it executes is to set "PwrEnable" high, hence keeping the device the device powered by pulling the gate of Q401 low through Q402. This is performed in order to mitigate a scenario wherein the microneedles are not keeping contactwith the skin. If thedevicehasbeensubject toa falsestart, a high resistanceon "Sensor_Detect" shouldbepresent and the microprocessor can take "PwrEnable" low, thereby removing power to the device (and inactivating the device). Other example variations of structures and methods for activating and / or inactivating an analyte monitoring device are described in further detail in U.S. Patent App. No. 16 / 051.398, which is incorporated herein in its entirety by this reference

[0171] Additionally or alternatively, the microcontroller may be configured to actively confirm the insertion of the microneedle array into skin based on sensor measurements performed with the microneedle array For example, after two or more microneedles in the microneedle array are presumed to have been inserted into skin, a fixed or time-varying electrical potential or current may be applied to those microneedles. A measurement result (e.g., electrical potential or current value) of a signal generatedbetween theelectrodesof the insertedmicroneedles ismeasured, and thencompared to a known reference value to corroborate successful insertion of themicroneedle array into the skin. The reference value may, for example. include a voltage, a current, a resistant, a conductance, a capacitance, an inductance and / or an impedance. Other example variations of structures and methods for activating and / or inactivating an analyte monitoring device are described in further detail in U.S. Patent App No. 16 / 051,398 which was incorporated above by reference.

[0172] In some variations, the microcontroller may utilize an 8-bit, 16-bit, 32-bit, or 64-bit data structure Suitable microcontroller architectures includeARM®andRISC® architectures, and flashmemorymay be embedded or external to the microcontroller for suitable data storage. In some variations the microcontroller may be a single core microcontroller, while in somevariations themicrocontrollermay beamulti-core (e.g., dual core)microcontrollerwhichmayenable flexible architectures foroptimizingpowerand / orperformancewithin thesystemForexample, thecores in themicrocontrollermay include similar or differing architectures. For example, in an example variation, the microcontroller may be a dual core microcontroller including a first core with a high performance and high power architecture, and a second core with a low performance and low power architecture. The first core may function as a "workhorse" in that it may be used to process 27 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 higher performance functions (e g., sensor measurements, algorithmic calculations, etc.), while the second core may be used to perform lower performance functions (e.g., background routines, data transmission, etc.). Accordingly, the different cores of the microcontroller may be run at different duty cycles (e.g., the second core for lower performance functions may be run at a higher duty cycles) optimized for their respective functions, thereby improving overall power efficiency.Additionally or alternatively, in somevariations themicrocontrollermay includeembeddedanalogcircuitry, such as for interfacing with additional sensor(s) and / or the microneedle array. In some variations, the microcontroller may be configured to operate using a 0.8V - 5V power source, such as a 1 2V - 3V power source. Communication module

[0173] In some variations, the electronics system of the analyte monitoring device may include at least one commu- nication module (e g., communication module 126 as shown in FIG. 2A), such as a wireless communication module to communicate with one ormore devices. For example, the communicationmodulemay include awireless transceiver that is integrated into the microcontroller device. However, the electronics system may additionally or alternatively include a communication module that is separate from the microcontroller device. In some variations, the communication module may communicate via wireless network (e.g., throughBluetooth, NFC,WiFi, RFID, or any type of data transmission that is not connected by cables). For example, devices may directly communicate with each other in pairwise connection (1:1 relationship, i.e. unicasting), or in a hub-spoke or broadcasting connection ("one to many" or 1:m relationship, i.e. multicasting). As another example, the devicesmay communicate with each other throughmesh networking connections (e.g , "many to many", or m:m relationships, or ad-hoc), such as through Bluetooth mesh networking. Wireless communication may use any of a plurality of communication standards, protocols, and technologies, including but not limited to, Global System for Mobile Communications (GSM), Enhanced Data GSM Environment (EDGE), high-speed downlink packet access (HSDPA), high-speed uplink packet access (HSUPA), Evolution, Data-Only (EV-DO), HSPA, HSPA‑, Dual-Cell HSPA (DC-HSPDA), long term evolution (LTE), near field communication (NFC), wideband code division multiple access (W-CDMA), code division multiple access (CDMA), time division multiple access (TDMA), Bluetooth,Wireless Fidelity (WiFi) (e.g.. IEEE 802.11a, IEEE 802. 11b, IEEE 802.11g, IEEE 802.11n, and the like), or any other suitable communicationprotocol. Somewirelessnetwork deploymentsmay combinenetworks frommultiple cellular networks or use amix of cellular, Wi-Fi, and satellite communication. In an example variation, the communicationmodule may include a wireless transceiver integrated into the microcontroller and including a Bluetooth Low Energy compatible radio that complies with the Bluetooth Special Interest Group 5.0 specification.

[0174] The communication module may further include or be coupled to one or more antennas (e.g., antenna 128 as shown in FIG. 2A). For example, the electronics systemmay include a chip antenna mounted on the PCB, or an antenna implemented directly onto the PCB, which may provide better range while reducing cost and complexity. In some variations, a user wearing the analyte monitoring device 110 may function as an antenna (e.g., antenna 128). For example, the antenna input / output 128 of the communication module 126 may be electrically connected to a single microneedle or plurality of microneedles, which are inserted into the wearer’s skin (e.g., similar to microneedle array 140 shown in FIG. 2B). This may increase the effective cross-sectional area of the antenna, provide for an adequate impedancematch between the antenna input / output of the communication module and free space, and / or help improve operational metrics such as antenna gain, antenna diversity, omni-directionality, and communication module receiver sensitivity / transmitter efficiency.

[0175] Devices can come in and out of range from the communicationmodule to connect and reconnect so that the user is able to seamlessly connect and transfer information between devices. In some variations, the microcontroller on each analytemonitoring devicemayhaveaunique serial number,which enables trackingof specific analytemonitoring devices during production and / or field use. Additional sensors

[0176] As described above, in some variations, the analyte monitoring device may include one or more sensors in addition themicroneedle array. For example, the analytemonitoring devicemay include oneormore temperature sensors configured to measure skin temperature, thereby enabling temperature compensation for the analyte sensor(s). For example, in some variations, a temperature sensor (e.g., thermistor, RTD, semiconductor junction, bimetallic sensor, thermopile sensor) may be coupled to the device PCB within the housing such that the temperature sensor is arranged near a skin-facing portion or bottom portion of the housing 112. The housingmay be thinned to reduce thermal resistance and improveheat transfer andhencemeasurement accuracy.Additionally or alternatively, a thermally conductivematerial may thermally coupleasurface-mount temperature sensor to theuser’s skin. In variations inwhich the temperature sensor is coupled to thedevicePCBnear themicroneedlearraydie substrate, the thermally conductivematerialmay, for example, bemolded as a skirt to relieve the sharp edges of the die and wrap along the edges of the die and along the surface of the main PCB. 28 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0177] In some variations, the temperature sensor may be employed to develop a glucose interpolation characteristic based on measured current and an a priori sensitivity (e.g., nA / mM or pA / mg / dL). In the temperature-invariant case, the electrical current characteristic can be modeled by the following relation: y mG[G] where y is the measured current, mG is the glucose sensitivity, and [G] is the interpolated glucose concentration. In some cases, such as the incorporation of an analyte insensitive channel b, the background signal may be incorporated into the equation above: y = mG[G] + b. Incorporating themeasurements froma temperaturesensor, theelectrical current characteristic canbe representedby the following relation: y -mG[G] ·mT[T] · bwheremT is the temperature sensitivity (eg., pA / °C), T is themeasured temperature, and b is the background signal (e.g., pA). In other operating scenarios, the electrical current characteristic is modeled by the following relation. y m1[G][T] + b where m1 is a weighting factor determined a priori. In other operating scenarios, the electrical current characteristic canbemodeledasa convolution of temperature andglucose: y= {m1[T] -m2}[G] + bwhere m2 isaweighting factor determinedapriori. In yet otheroperatingscenarios, theclectrical current characteristic is provided by the following relation: y {mG[G] + m2}[T][G] + b. In yet other operating scenarios, the electrical current characteristic is givenby the followingnonlinear relation: y = {mG2[G]2 -mg[G]}[T] + bwheremG2 is a nonlinearweighting factor. In yet other operating scenarios, the electrical current characteristic is given by the following Gaussian relation: y = mG[G]exp{‑([T] [TOPT])2 / (2σ2)} + b where TOPT is the optimal temperature for maximal catalytic turnover of the enzyme and a is the operating temperature range of the enzyme.

[0178] In some variations, the analyte monitoring device may include at least one microneedle with an electrode configured to function as an analyte insensitive channel (e g.. glucose insensitive channel) having a known temperature sensitivity, where such a known temperature sensitivity may be used to compensate for temperature. For example, one advantageof usingaglucose insensitive channel includesproximity to theglucose sensor (e.g., resulting in lesserror from thermal gradients) and cost (e.g., by reducing external components and specialized processes to thermally couple the sensor to theskin) In somevariations, theanalytemonitoringdevicemay includebothananalyte insensitive channel along with a thermistor, with an algorithm that utilizes information from both. Additionally or alternatively, the analyte monitoring device may include an additional sensor(s) that measures ambient temperature, which may also be useful in the temperature compensation algorithm.

[0179] In some variations, the analyte insensitive channel may be used to perform differential measurements and / or subtract background noise levels from the analyte-sensitive channel(s) to improve signal fidelity and / or signal-to-noise ratio. The analyte insensitive channel may be sensitive to common mode signals that also arise on the analyte-sensitive channel(s) (e.g., endogenous and pharmacologic interference, pressure attenuations, etc.).

[0180] Additionally or alternatively, in some variations, the analyte monitoring device may include at least one kinetic sensor. The kinetic sensor may, for example, comprise an accelerometer, gyroscope, and / or inertial measurement unit to capture positional, displacement, trajectory, velocity, acceleration, and / or device orientation values. For example, such measurements may be used to infer the wearer’s physical activity (e.g., steps, intense exercise) over a finite duration. Additionally or alternatively, in some variations, the kinetic sensor(s) may be employed to enable detection of wearer interactions with the analyte monitoring device such as touch or tapping. For example, touch or tap detection can be employed to silence or snooze notifications, alerts, and alarms, control a wirelessly connected mobile computing device, or to activate / deactivate a user interface on the analyte monitoring device (e.g., an embedded display or indicator light). Touchingor tappingmaybeperformed inadefinedsequenceand / or for apredeterminedduration (e.g., at least 3 seconds, at least 5 seconds) to elicit certain actions (e.g., display or indicator light deactivation / activation). Additionally or alternatively, in some variations, the analyte monitoring device may enter into a power saving mode upon detection of limited motion or activity (e.g., absence of significant acceleration) for at least a predetermined period of time (e.g, 15 minutes, 30 minutes, 45 minutes, 1 hour, or other suitable of time), as measured by the kinetic sensor(s).

[0181] Additionally, or alternatively, in some variations, the analytemonitoring devicemay include at least one real-time clock (RTC). The real-time clockmay be employed to track absolute time (e.g., CoordinatedUniversal Time,UTC, or local time) when the analytemonitoring device is in storage or during use. In some variations, synchronization to absolute time maybeperformed followingmanufacturing of theanalytemonitoringdevice. The real-timeclockmaybeemployed to time- stamp analytemeasurements (e.g., glucosemeasurements) during operation of the analytemonitoring device in order to createa time-seriesdataset that is communicated toaconnectedperipheral device (e.g.,mobile computingdevice), cloud storage, or other suitable data storage device, such as for later review by the user (e.g., wearer of the analyte monitoring device), their support network, or their healthcare provider, etc Power source(s)

[0182] As shown in FIG. 2A, the analytemonitoring devicemay include one ormore power sources 130 (e.g., battery) in the housing 112 configured to provide power to other components. For example, the analyte monitoring device may include an AgO battery, which has a high energy density and is more environmentally friendly than lithium batteries. In some variations, a primary (e.g., non-rechargeable) battery may be used Furthermore, in some variations, a secondary (e.g., rechargeable) battery may be used However, any suitable power source may be used, including a lithium-based 29 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 battery.

[0183] In some variations, the power source may be coupled to the device PCB using a low profile holder or mount that reduces the overall height of the electronics, therebyminimizing the height or profile of the analyte monitoring device. For example,whereas traditional batteryholders apply force to the topsideof thebattery usinga conductivemetalwitha spring force, in some variations a lateral mounted battery holder may contact the sides of the battery to complete the electrical circuit For example, as shown in FIG. 20, a lateral mounted battery holder 2020may include an arcuate clip that clamps or otherwisecontacts thesidesof thebatterywithout increasingvertical bulk.Thebatteryholder2020may further includeone or more mounting holes to couple to the device PCB via one or more suitable fasteners (and / or may couple to the device PCB inany suitablemanner). In somevariations, thehousingmaybe sizedand / or shapedwith suitable tolerances soas to apply vertical or downward forceon thebattery toward thedevicePCB, in order to keep thebattery in contactwith thePCB. Applicator

[0184] In some variations, the analyte monitoring device may be applied manually For example, a user may remove a protective filmon the adhesive layer, andmanually press thedevice onto his or her skin onadesiredwear site. Additionally or alternatively, as illustrated in FIG. 1, in some variations the analytemonitoring devicemay be applied to the skin using a suitable applicator 160. The applicator 160 may, for example, be configured to urge the analyte monitoring device 110 toward the skin of the user such that the microneedle array 140 of the analyte monitoring device 110may be inserted into the skin (e.g., to the desired target depth). Kits

[0185] In some variations, some or all components of the analyte monitoring systemmay 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 110 and / or at least one applicator 160. In some variations, a kit may includemultiple analytemonitoring devices. 110. whichmay 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, twomonths, three months, six months, a year, etc.) The kit may include any suitable ratio of applicators to analyte monitoring devices (e.g. , 1:1, lower than 1:1, greater than 1:1). For example, the kit may include the same number of applicators as analytemonitoringdevices, suchas if each applicator is single-useand is configured to bedisposedafter its use in applying a respective analyte monitoring device to the user. As another example, the kit may include a number of applicators that is lower than the number of analyte monitoring devices. in the kit (e.g., one applicator per two or three analyte monitoring devices), such as if an applicator is intended to be reused for applying multiple analyte monitoring devices or if multiple analyte monitoring devices are loaded into a single applicator for repeated applications As another example, the kit may include a number of applicators that is higher than the number of analytemonitoring devices in the kit (e.g., twoapplicatorsper analytemonitoringdevice), suchas toprovideextraor redundant applicators in caseof applicator loss or breakage, etc.

[0186] In somevariations, the kitmay further includeuser instructions for operating theanalytemonitoringdeviceand / 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.). Sterilization of analyte monitoring device

[0187] As described above, the analyte monitoring devices 110 such as those described herein are differentiated from other CGM devices at least in that the sensing elements (e.g, microneedle array) and electronics are integrated into one unit. One benefit to this integration is that the user is not required to performany assembly of the analytemonitoring device 110. However, there are sterilization-related challenges to enabling such integration

[0188] Traditional CGM devices and similar electrochemical sensors are typically sterilized through processes that are incompatible with electronics. For example, conventional electrochemical sensor sterilization use gamma radiation or electronbeamradiation tosterilize thesensingelementsHowever, thebosonicor termionicparticlesassociatedwith these sterilization processes interfere with electronics operation. Thus, typically the electronic component(s) must either be sterilized separately and require the end user to perform someassembly of the device, or the electronic component(s) are simply not sterilized, which may lead to contamination issues.

[0189] In contrast, the sensor technologies described above are configured to be compatible with a form of sterilization that is suitable for both the sensing elements and the electronics. In some variations, as described above, the working electrodes in the microneedle array may include a biorecognition layer including a cross-linked biorecognition element. For example, the biorecognition element may be cross-linked with an amine-condensing carbonyl chemical species, which helps to bridge amine groups and thus help stabilize the biorecognition element within the biorecognition layer. For 30 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 example, the biorecognition element may include an enzyme (e.g., glucose oxidase) that is cross-linked with glutar- aldehyde, formaldehyde, glyoxal,malonaldehyde, succinaldehyde, and / or other suitable species and thenembedded in a conducting polymer as described above.

[0190] A result of the above-described cross-linked structure is that the enzyme is sufficiently stabilized so that it may undergo gaseousmethods of sterilization, such as ethylene oxide (EO) sterilization, with surprisingly onlyminimal impact on sensing elements in terms of sensing performance. Thus, since electronics may undergo EO sterilization, in some variations the analyte monitoring devices 110 are uniquely and advantageously configured to survive an "all in one" sterilization procedurewith their electronics and sensing elements fully integratedand simultaneously sterilized in a single unit, without damaging either set of components.

[0191] Accordingly, in some variations, a method of sterilizing an analyte monitoring device may include exposing the analyte monitoring device to a sterilant gas, where the analyte monitoring device includes a housing (c.g., wearable housing), a microneedle array extending from the housing and including an analyte sensor, and an electronics system arranged in the housing and electrically coupled to themicroneedle array. The analytemonitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analytemonitoring device. In some variations, the analytemonitoring device may be sterilized to a Sterility Assurance Level (SAL) of 10‑6 (i.e., having a probability that not more than 1 viable microorganism among 1,000,000 sterilized devices).

[0192] FIG. 21 illustrates an example variation of a method 2100 for sterilizing an analyte monitoring device. Method 2100 may include, for example, inserting an analyte monitoring device into a chamber 2110 suitable for sterilization, preconditioning the analyte monitoring device 2120. exposing the analyte monitoring device to a sterilant gas 2130, and aerating the analyte monitoring device 2140.

[0193] FIG 22 depicts a schematic of an example variation of a sterilization system including a chamber (or series of chambers) suitable for use in sterilizing an analytemonitoring device. For example, the sterilization systemmay include at least one chamber for executing a preconditioning process, at least one chamber for a sterilizing process, and / or at least one chamber for an aerating process. In some variations, the same chamber may be utilized for two or more these processes of method 2100.

[0194] Thus, for example, an analyte monitoring device may be placed within a preconditioning chamber for the preconditioning process 2120. As described above, the analyte monitoring device may be placed in the chamber as an integrated device, including both electrochemical sensing elements and electronic components

[0195] Preconditioning may function to heat and humidify the analyte monitoring device to a stable temperature and moisture content prior to entering the sterilization chamber, which may help ensure consistency and reliability of the sterilization process, regardless of environmental conditions. As shown in FIG. 23, preconditioning the analytemonitoring device may include reducing the pressure in the chamber to a vacuum set point (e.g. 1.0 psia). The vacuum may be established gradually, such as at a rate of about 2 psia / minute or other suitable rate. Furthermore, preconditioning may includesetting other environmental conditions to various set points for a predetermineddwell time.For example, as shown in FIG. 23, after reducing the pressure to the vacuum set point, steammay be injected into the chamber so as to establish the temperature, relative humidity, and / or humidity at predetermined set points. For example in one implementation, temperature inside the chambermaybeset to betweenabout 35degreesCelsius to about 40degreesCelsius, or about 38 degrees Celsius, which may be suitable so as to avoid denaturing the biorecognition element (e.g., enzyme) from higher heat during preconditioning. As another example, relative humidity may be set to between about 45% to about 55% (or about 51%). The temperature, relativehumidity, andvacuumset pointsmaybemaintained for a predetermineddwell time, such as between about 90minutes and about 180minutes, between about 100minutes and about 100minutes and about 160 minutes, between about 110 minutes and about 140 minutes, or about 120 minutes, or other suitable period of time. After the dwell time has passed, the chambermay be evacuated and / or the conditioned analytemonitoring devicemay be removed and placed in a sterilization chamber.

[0196] As shown in FIG. 21, after preconditioning the analyte monitoring device, the method may include exposing the analyte monitoring device to a sterilant gas 2130, such as ethylene oxide (EO). In some variations, the EO) may be introduced into the sterilization chamber at a gas concentration of between about 425mg / L. and about 475mg / L, or about 450 mg / L. As shown in FIG. 23, during the sterilization process the pressure in the chamber may be set to a sterilant set point of between about 5 psia and about 6 psia, or about 5.3 psia. In some variations, at least about 97% of the air must be evacuated from the chamber prior to delivering EO gas into the chamber. Additionally or alternatively, a series of partial vacuumsmay be established in the chamber followed by a series of nitrogen (N2) injections to purge a sufficient amount of air from the chamber Similar to the temperature during preconditioning, temperature of the chamber during sterilization may be set to between about 35 degrees Celsius to about 40 degrees Celsius, or about 38 degrees Celsius. Temperature may be increased to the temperature set point as EO is introduced. After introducing EOgas into the chamber, the analyte monitoring devicemay remain exposed to theEOgas for a suitable sterilant dwell time or exposure time. Suitable sterilant dwell times may, for example, range between about 90 minutes and about 180 minutes, between about 100 minutes and about 100 minutes and about 160 minutes, between about 110 minutes and about 140 minutes, or about 120 minutes, or other suitable period of time sufficient for sterilizing the analyte monitoring device. It should be understood that in some 31 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 variations, an increase in temperatureduringEOexposurewill reduce thenecessaryEOdwell time (e.g., asa ruleof thumb every 10 degrees Celsius increase in temperature may reduce the EO dwell time by about half). Following the sterilant dwell time, the chamber may undergo a vacuum / air cycle to purge the EO from the chamber.

[0197] As shown in FIG. 21, themethod 2100may include aerating the analyte monitoring device 2140. Aeration of the analyte monitoring device may allow for the additional removal of any residual gases from the device (e.g., prior to packagingandstorage), asEO is flammable andany residualEOon thedevicepost-sterilization canbeextremely toxic. In some variations, aerationmay occur at room temperature. As shown in FIG. 23, the aerationmay last for a predetermined periodof timesufficient to permit thoroughoutgassingFor example, theaerationprocessmay last betweenat least about 4 hours and 24 hours. such as about 12 hours. In other variations, the aeration process may last at least about 12 hours, at least about 15 hours, or at least 24 hours, etc. Example

[0198] An FO sterilization cycle was evaluated for feasibility to sterilize an analyte monitoring device such as those described herein. Briefly, the preconditioning was done for two hours at a temperature of 38 degrees Celsius. This was followed by exposure toEOgas for two hours at 38 degreesCelsius. After EOexposure, the sampleswere aerated to vent out theEOgasat ambient temperatures for aminimumof 12hours.Details of theEOexposureprotocol are shown inTable I: Table 1. Example EO Exposure Protocol Sterilization Set Points EO Gas Concentration 450 mg / L (100% EO) Temperature 38°C Relative Humidity 51% Initial Vacuum 1.0 psia EO Gas Dwell Time 120 minutes Steam Dwell Time 120 minutes Aeration Set Points Temperature Ambient Time 12 hours (minimum) Post-Vacuum 3.5 psia DETOX A Initial Steam Flush 3.7 psia Initial Steam Flush Dwell Time 0 min Steam Pulse 3.7 psia Steam Pulse Dwell Time 5 min Vacuum 3.5 psia Steam Flush 3.7 psia Steam Flush Dwell Time 0 DETOX B Steam Pulse 3.7 psia Steam Pulse Dwell Time 5 minutes Vacuum 3.5 psia Steam Flush 3.7 psia Steam Flush Dwell Time 0 min Air Washes 11.0‑2.0 psia (5 total) 32 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0199] To test the stability of sensing chemistry following exposure to EO, six functionalized microneedle sensors were subject to an EO sterilization cycle In this example, sensor chemistry using amide cross-linking ofglucose oxidase was evaluated in this feasibility study. FIG. 24 shows the retained sensitivity for the six sensors after exposure to EO (EO), as well as for three sensors functioning as a negative control (do not process (DNP)). Overall. all six sensors that were exposed to EO remained sensitive to glucose post processing. The average percentage sensitivity retained was 75%.

[0200] Three of the sensors that were exposed to EOwere also subsequently tested for operational stability in PBSwith 6 mM glucose over seven days. Sensors were kept in solution and sensitivity was measured by calibrating the sensors once per day. The summary results from the operational stability testing are shown in FIG. 24B. It is seen that the sensors remained stable over the course of the test. Nodatawasobtained for days fiveand six due to instrument error. This trend is similar to that observed for sensors sterilized with gamma irradiation.

[0201] Additionally, three sensors exposed to EO were used to test the storage stability FIG. 24C shows the average sensitivity on Day 0 (Pre EO exposure), Day 14, and Day 28. The sensors were stored dry between day 14 and 28 at 37 degrees C. The average sensitivity retained fromDay 14 to Day 28 of dry storagewas 92%. This shows the potential to be able to sterilize using EO and store the sensors after exposure to EO.

[0202] Thus, the cross-linked sensor chemistry was found to be sufficiently stable to EO exposure, indicating that using EO process is feasible to sterilize an analyte monitoring device with sensing elements including the cross-linked sensor chemistry. Additionally, the chemistry after EO exposure was stable over seven days of active operation and also during dry storage.

[0203] In some variations, the sensor may be decoupled from the electronics and undergo other suitable methods of sterilization, including those based on irradiation bymeans of gamma rays / particles or with an electron beamof sufficient acceleration potential. Dosage of sterilization (e.g., duration and particle energy) may be controlled in to achieve a satisfactory level of sterility, including a sterility assurance level (SAL) of less than 1E‑6. In somevariations, the electronics do not require sterilization as they do not contact breached or compromised skin surfaces. In such variations, the electronics may be coupled to the sensor prior to the application of the entire system to the user’s skin. Use of analyte monitoring system

[0204] 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. Application of analyte monitoring device

[0205] Asdescribed above, the analytemonitoring device is applied to the skin of a user such that themicroneedle array in the device penetrates the skin and the microneedle arrays 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 theouter layer of the skin, the stratumcorneum,bore through theepidermis, andcome to restwithin thepapillary or upper reticular dermis. Thesensing region, confined to theelectrodeat the distal extent of eachmicroneedle 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.

[0206] In somevariations, theanalytemonitoringdevicemay includeawearablehousingorpatchwithanadhesive layer configured to adhere to the skin and fix the microneedle array in position While the analyte monitoring device may be appliedmanually (e.g., removingaprotectivefilmon theadhesive layer, andmanually pressing thepatchonto theskinona desired wear site), in some variations the analytemonitoring devicemay be applied to the skin using a suitable applicator.

[0207] 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, lowerarm), shoulder (e.g., over thedeltoid), backofhands,neck, face, scalp, torso (e.g., on thebacksuchas 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.

[0208] As described above, in some variations the analyte monitoring device may be configured to automatically activate upon insertion, and / or confirm correct insertion into skin Details of these features are described in further detail above. In some variations, methods for performing such activation and / or confirmationmay be similar to that described in U.S. Patent App. No. 16 / 051,398, which was incorporated by reference above Pairing to peripheral device

[0209] In some variations, the analyte monitoring device may be paired to at least one peripheral device such that the 33 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 peripheral device receives broadcasted or otherwise transmitted data from the analyte monitoring device, including measurement data. Suitable peripheral devices include, for example a mobile computing device (e.g., smartphone, smartwatch) which may be executing a mobile application.

[0210] Additionally alternatively, ananalytemonitoringdevicemaybepaired (or otherwise combined)with a therapeutic delivery device (e.g., insulin penor pump). For example, ananalytemonitoringdevicemaybecombinedwith a therapeutic delivery device in amanner similar to that described inU.S.Patent App.Nos. 62 / 823,628and62 / 862,658, eachofwhich is incorporated herein in its entirety by this reference. Studies have shown that users with insulin delivery devices. that have smart algorithms controlling dosing are in euglycemic range (i.e. healthy blood glucose levels) >95% of the time when CGM is available. The ability of the analytemonitoring device to communicate directly with insulin delivery devices (i.e. no intermediary smartphone required) allows users to achieve increased time in range significantly by eliminating the time whenCGM is not available (during warmup or swap in of analytemonitoring devices). This featuremay also enable users to wear multiple analyte monitoring devices that detect different analytes simultaneously and input data into the same mobile application

[0211] As described above, the pairing may be accomplished through suitable wireless communication modules (e.g., implementing Bluetooth). In some variations, the pairing may occur after the analyte monitoring device is applied and inserted into the skin of a user (e.g., after the analyte monitoring device is activated). Additionally or alternatively, the pairing may occur prior to the analyte monitoring device being applied and inserted into the skin of a user.

[0212] Thus, the paired mobile or other device may receive the broadcasted or transmitted data from the analyte monitoring device. The peripheral device may display, store, and / or transmit the measurement data to the user and / or healthcare provider and / or support network. Furthermore, in some variations, the said paired mobile or wearable device performs algorithmic treatment to the data to improve the signal fidelity, accuracy, and / or calibration, etc. In some variations, measurement data and / or other user info may additionally or alternatively be communicated and / or stored via network (e.g., cloud network).

[0213] By way of illustration, in some variations a mobile computing device or other computing device (e.g., smart- phones, smartwatches, tablets, etc ) may be configured to execute a mobile application that provides an interface to display estimated glucose values, trend information and historical data, etc. Although the below description refers specifically to glucose as a target analyte, it should be understood that the features and processes described below with respect to glucose may be similarly applied to applications relating to other kinds of analytes.

[0214] In some variations, the mobile application may use the mobile computing device’s Bluetooth framework to scan for the analytemonitoring device. As shown in FIG. 26, the analytemonitoring devicemay power on or initialize as soon as it is applied to the skin, and the analyte monitoring devicemay begin the advertising process. Themobile applicationmay then connect to the analyte monitoring device and begin priming the sensor for measurement. In case the mobile application detects multiple analyte monitoring devices, the mobile application may detect the analyte monitoring device that is closest in proximity to itself and / or may request the user (e.g, via the user interface on themobile device) to confirm disambiguation. In some variations, the mobile application may also be capable of connecting to multiple analyte monitoring devices simultaneously. This may be useful, for example, to replace sensors that are reaching the end of their lifetime.

[0215] In some variations, the Bluetooth® Low Energy™ (BLE) protocol may be used for connectivity. For example, the sensor implements a custom BLE peripheral profile for the analyte monitoring system. Data may be exchanged after establishing a standard secure BLE connection between the analytemonitoring device and the smartphone, smartwatch, or tablet running themobileapplication.TheBLEconnectionmaybemaintainedpermanently for the lifeof thesensor. If the connection is brokendue toany reasons (e.g.,weak signal) theanalytemonitoringdevicemaystart advertising itself again and the mobile application may re-establish the connection at the earliest opportunity (i e when in range / physical proximity).

[0216] In some variations, there may be one or more additional layers of security implemented on top of the BLE connection to ensure authorized access consisting of a combination of one or more techniques such as passcode- protection, shared-secrets, encryption and multi-factor authentication.

[0217] Themobile applicationmay guide the user through initiating a new analytemonitoring device. Once this process completes, themobileapplication isnotbe required for theanalytemonitoringdevice tooperateand recordmeasurements In some variations, a smart insulin delivery device that is connected to the analyte monitoring device can be authorized from themobile application to receive glucose readings from the sensor directly. Additionally or alternatively, a secondary displaydevice likeasmartwatchcanbeauthorized from themobileapplication to receiveglucose readings from thesensor directly.

[0218] Furthermore, in somevariations themobile applicationmayadditionally or alternatively help calibrate theanalyte monitoring device. For example, the analyte monitoring device may indicate a request for calibration to the mobile application, and the mobile application may request calibration input from the user to calibrate the sensor. 34 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 Sensor measurements

[0219] 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.

[0220] A bias potential may be applied between the working and reference electrodes of the analytemonitoring 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.

[0221] 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 toadigital bitstreambymeansofacurrent-modeADC.Thedigital representationof theelectrical currentmaybe processed in theembeddedmicrocontroller(s) in theanalytemonitoringdeviceand relayed to thewireless communication module for broadcast or transmission (e.g., to oneormoreperipheral devices). In somevariations, themicrocontrollermay perform additional algorithmic treatment to the data to improve the signal fidelity, accuracy, and / or calibration, etc.

[0222] 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 monitoringdevice tobroadcast analytemeasurement(s) tomultipledevices inparallel,whileensuring thateachconnected 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.

[0223] Data exchange canbe initiated byeither themobile application or by theanalytemonitoring device. For example, theanalytemonitoringdevicemaynotify themobileapplicationofnewanalytedataas it becomesavailable.The frequency of updates may vary, for example, between about 5 seconds and about 5 minutes, and may depend on the type of data Additionally or alternatively, themobile applicationmay request data from the analytemonitoring device (e.g., if themobile application identifies gaps in the data it has collected, such as due to disconnections).

[0224] If themobile application is not connected to theanalytemonitoringdevice, themobile applicationmaynot receive data from the sensor electronics. However, the electronics in the analyte monitoring device may store each actual and / or estimated analyte data point.When themobile application is reconnected to the analytemonitoring device, it may request data that it has missed during the period of disconnection and the electronics on the analyte monitoring device may transmit that set of data as well (e.g., backfill).

[0225] Generally, the mobile application may be contigured to provide display of real-time or near real-time analyte measurement data, such as on the display of the mobile computing device executing the mobile application In some variations, the mobile application may communicate through a user interface regarding analysis of the analyte measure- ment, suchasalerts, alarms, insights on trends, etc. suchas to notify the user of analytemeasurements requiring attention or follow-up action (e.g., high analyte values, low analyte values, high rates of change, analyte values outside of a pre-set range, etc.). In some variations, the mobile application may additionally or alternatively facilitate communication of the measurement data to the cloud for storage and / or archive for later retrieval Interpreting analyte monitoring device user interface

[0226] In some variations, information relating to analyte measurement data and / or the analyte monitoring device may be communicated via auser interfaceof the analytemonitoringdevice. In somevariations, theuser interfaceof the analyte monitoring devicemay be used to communicate information to a user in addition to, or as an alternative to, communicating such information via a peripheral device such as through amobile application on a computing device. Accordingly, a user and / or those around the user may easily and intuitively view the analyte monitoring device itself for an assessment of analyte measurement data (e.g., analyte measurement status such as current and / or trending analyte measurement levels) and / or device status, without the need to view a separate device (e.g., peripheral device or other device remote from, and in communication with, the analyte monitoring device) Availability of such information directly on the analyte monitoring device itself may also enable a user and / or those around the user tomore promptly be alerted of any concerns (e.g., analyte measurements that are above or below target range, and / or analyte measurements that are increasing or decreasing at an alarming rate), thereby enabling a user to take appropriate corrective action more quickly.

[0227] For example, FIGS. 32A‑32C depict an example variation of an analyte measurement device 3200 including a 35 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 user interface 3220 with multiple indicator lights, including indicator lights 3224a‑3224c, which may be selectively illuminated to communicate a user status (e.g., information relating to analyte measurement in the user). The user interface 3220 may be similar, for example, to user interface 3120 described above with respect to FIG. 31A and / or FIG. 31B. Although the user interface 3220 includes three indicator lights 3224a‑3224c, it should be understood that in some variations, the user interface 3220may include any suitable number of lights, including fewer than three (e.g., one, two) or more than three (e.g., four, five, six, or more).

[0228] The indicator lights 3224a‑3224cmaybearranged in a sequentialmanner such that their relativepositions help a user to intuitively understand information communicated collectively by theuser interface. For example, the three indicator lights3224a‑3224cmaybe illuminated togenerally indicate threeprogressive levels (or ranges)of analytemeasurements: the lowest indicator light 3224amaybe illuminated to generally indicate ananalytemeasurement that is lowest of the three levels, the middle indicator light 3224b may be illuminated to generally indicate an analyte measurement that is in the middle of the three levels, and the highest indicator light 3224c may be illuminated to generally indicate an analyte measurement that is highest of the three levels. In one example variation, the lowest indicator light 3224a may be illuminated to indicate an analytemeasurement that is in a target range (FIG 32A), themiddle indicator light 3224bmay be illuminated to indicate an analyte measurement that is above a target range (FIG. 32B), and the highest indicator light 3224c may be illuminated to indicate an analyte measurement that is significantly above a target range (FIG. 32C). In another example variation, the lowest indicator light 3224amay be illuminated to indicate an analytemeasurement that is belowa target range, themiddle indicator light 3224bmay be illuminated to indicate an analytemeasurement that iswithin the target range, and thehighest indicator light 3224cmaybe illuminated to indicateananalytemeasurement that is above a target range

[0229] The threshold values for a target range may be any suitable values. For example, in some variations in which glucose monitoring is being performed, analyte measurements may be considered within a target range if they are between about 70 mg / dL and about 180 ng / dL (or between about 80 mg / dL or about 60 mg / dL and about 170 mg / dL or about 190mg / dL, etc. ), andmay be considered below a target range if they are below about 70mg / dL (or below about 80 mg / dL, or belowabout 60mg / dL, etc.). Thedifferent thresholds for "above" a target rangeand "significantly" abovea target rangemayhaveanysuitable value. For example, in somevariations, analytemeasurementsmaybeconsidered "above"a target range if it is above a first predetermined threshold (e.g., above a threshold value of about 180 mg / dL for hyperglycemia determination in glucose monitoring, or above a threshold value that is between about 170 mg / dL and about 200 mg / dL for hyperglycemia determination in glucose monitoring) and analyte measurement may be considered "significantly above" a target range if it is a predetermined amount (e.g., percentage) above the first predetermined threshold, such as at least 33% above the first predetermined threshold (e.g., >240 mg / dL for extreme hyperglycemia determination in glucose monitoring), or at least about 25% above the first predetermined threshold, at least about 30% above the first predetermined threshold, at least 35% above the first predetermined threshold, or at least 40% above the first predetermined threshold, or other suitable second predetermined threshold.

[0230] Furthermore, the thresholds for considering analytemeasurementswithin target range, or below target range, or "above" target range or "significantly above" target range (or other characterization of the analytemeasurements)may be static or dynamic, and / or may vary based on user information such as historical measurements and / or trends or other historical data (e.g., relative to an average or expected analytemeasurement for the user at particular times or average or expected rateof change)Furthermore, it shouldbeunderstood thatwhile theuser interface3220 includes threesequential indicator lights, in other variations a user interface on the housing of an analytemonitoring devicemay include fewer (e.g., two) ormore (e g., four, five, six, ormore) thatmay be similarly illuminated individually to indicate an analytemeasurement (e.g., each corresponding to a general relative level of analyte measurement).

[0231] In some variations, different illumination colors and / or timing for one or more of the indicator lights 3224a‑3224c may additionally or alternatively enable a user to easily distinguish between each analyte measurement level. For example, when an analytemeasurement is within a target range, the appropriate indicator light(s) may be illuminated in a first color (e.g., blue), while when the analyte measurement is outside the target range. the appropriate indicator light(s) maybe illuminated inanother color (e.g.,white for below target range,orange forabove target range).Asanotherexample, when the analyte measurement is within a target range, the appropriate indicator light(s) may be illuminated in a first temporal pattern (e.g., long, gentle pulse of illumination "on" time), while when the analyte measurement is outside the target range, theappropriate indicator light(s)maybe illuminated in another temporal pattern (e.g , short, flash-likepulseof illumination "on" time). Shorter pulses of illumination "on" timemay, for example, be helpful to better attract user attention and / ormore intuitively communicateanalertwhen theanalytemeasurement is belowa target range, abovea target range. or significantly above a target range Higher frequency illumination may, in some variations, correlate to greater alert level (e.g., significantly below the target range or significantly above the target range).

[0232] FIGS 33A‑33D and Table 2 illustrate different illuminating modes used in an example method of operating the user interface 3220 of an analyte monitoring device The exact parameter values of these illumination modes are non- limiting and are included for an example variation for illustrative purposes only. For example, in the "below target range" illuminationmode, the illumination colormaybe any suitable color, and / or the illumination "on" timemaybebetweenabout 36 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 0.1 secondsand1second, betweenabout 0.2 secondsand0.5 seconds, or about 0.3 seconds, and / or the illumination "off’ time may be between about 0.5 seconds and about 5 seconds, or between about 1 second and about 4 seconds, or between about 2 seconds and about 4 seconds, or about 3 seconds; and / or the ratio between the illumination "on" and illumination "off" times may be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, and / or other suitable illumination parameters. As another example, in the "in target range" illumination mode and / or the "above target range illumination mode, the illumination colormay be any suitable color, and / or the illumination "on" timemay be between about .1 seconds andabout 3 seconds, betweenabout .5secondsandabout 2seconds, or about I second, and / or the illumination "off"mode may be between about 0.5 seconds and about 5 seconds, or between about I second and about 4 seconds, or between about 2 seconds and about 4 seconds, or about 3 seconds, and / or the ratio between the illumination "on" and illumination "off’ times may be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, and / or other suitable illumination parameters As another example, in the "significantly above target range", the illumination color may be any suitable color, and / or the illumination "on" time may be between about 0.2 seconds and 2 seconds, between about 0.5 seconds and about 1.5 seconds, or about 0.8 seconds, and / or the illumination "off" timemaybebetween about 0.5 seconds andabout 5 seconds, or between about I second and about 4 seconds, or between about 2 seconds and about 4 seconds, or about 3 seconds and / or other suitable illumination parameters. Furthermore, fewer or more illumination modes for indicating analyte measurement level may be possible in other variations Table 2. Example illumination modes for indicating analyte measurement Analyte measurement level Figure Indicator light illuminated Illumination color Illumination "on" time t(on) Illumination "off" time t(off) Below target range FIG. 33A Lowest White 0.3 sec 3 sec In target range FIG. 33B Lowest Blue 1 sec 3 sec Above target range FIG. 33C Middle Orange 1 sec 3 sec Significantly above target range FIG. 33D Highest Orange 0.8 sec 3 sec

[0233] Additionally or alternatively, in some variations, the indicator lights 3224a‑3224c may be illuminated in a progressive sequence to indicate trend information of analyte measurements over time. For example, as shown in FIG. 34A, a progressive sequence of illumination of the indicator lights 3224a‑3224c in a first direction from lower indicator light(s) to higher indicator light(s) (e.g., indicator light 3224a followed by indicator light 3244b, followed by indicator light 3224c)may intuitively indicate a trendof increasinganalytemeasurements. In somevariations, the progressive sequence of illumination could haveany suitable illumination color. In somevariations, such rising sequential illumination of indicator lightsmaybe inasuitable color to indicateeither that thecurrent analytemeasurement iswithina target rangeand rising, or that the current analyte measurement is above a target range and rising. For example, FIG. 34A illustrates rising progressive illumination in a first color (e.g., blue) to indicate that current analyte measurement is within the target range and rising, whereas FIG. 34B illustrates rising progressive illumination in a second color(e.g., orange) to indicate that the current analytemeasurement is above (or significantly above) the target rangeand rising. As yet another example, a rising progressive illumination in a third color (e.g., white) may indicate that the current analyte measurement is below (or significantly below) the target range and rising.

[0234] As another example, as shown in FIG. 34C, a progressive sequence of illumination of the indicator lights 3224a‑3224c in a second direction (e.g., opposite direction of the first direction) from higher indicator light(s) to lower indicator light(s) (e.g.. indicator light 3224c followed by indicator light 3244b, followed by indicator light 3224a) may intuitively indicate a trend of decreasing analytemeasurements. Similar to that described abovewith respect to FIGS. 34A and34B, sucha falling progressive sequenceof illumination of indicator lightsmaybea suitable color to indicate the status of the current analytemeasurement that is falling (e.g., falling progressive illumination in a first color (e.g., blue) to indicate that current analyte measurement is within the target range and falling, falling progressive illumination in a second color (e.g., orange) to indicate the current analytemeasurement is above (or significantly above) the target range and falling, or falling progressive illumination in a third color (e.g., white) may indicate that the current analytemeasurement is below (or significantly below) the target range and falling.

[0235] It should be understood that other variations of progressive sequences of illumination may be used to similarly indicate analyte measurement trends. For example, a I-dimensional array of indicator lights (e.g., arranged in a row, a column, an arc, etc.)may be illuminated in a progressive sequence froma first end of the array to a secondendof the array to indicate a rising analytemeasurement trend, and illuminated in a progressive sequence from a second end of the array to a tirst end of the array to indicate a falling analyte measurement trend. For example, progressive sequences of illuminationmaybecharacterizedas left-to-right, right-to-left, top-to-bottom, bottom-to-top, clockwise, counter-clockwise, 37 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 etc. Furthermore, it should be understood that while the user interface 3220 includes three sequential indicator lights, in other variations a user interface on the housing of an analytemonitoring devicemay include fewer (e.g., two) ormore (e g., four, five, six, or more) that may be similarly illuminated in a progressive sequence to indicate rising and / or falling analyte measurement trends.

[0236] In some variations, within each rising or falling sequence of illumination across the indicator lights, the illumination of adjacent indicator lights may be interspersed by an illumination "off" period. Furthermore, in some variations, the pace at which the illumination transitions between indicator lights may indicate rate of change of analyte measurements. For example, the faster the illumination transitions from lower to higher indicator lights, the faster the rate of change (and potentially the greater urgency or need for user attention to the trend) Additionally or alternatively, each rising or falling sequence of illumination across the indicator lights may be separated by a sequence end illumination "off" time in order to help distinguish between a rising sequence and a falling sequence. The sequence end illumination "off" timemaybe longer than the illumination "off" periodwithin eachsequence In somevariations, thestart or endof each rising or fallingsequenceof illuminationmayadditionally oralternativelybedemarcated inanysuitablemanner (e.g., illuminating all lights simultaneously at the start or end of a rising or falling sequence)

[0237] Table 3 illustrates different illuminationmodes used in anexamplemethodof operating theuser interface 3220 of an analyte monitoring device to indicate analyte measurement trends. The exact parameter values of these illumination modes are non-limiting and are included for an example variation for illustrative purposes only For example, in a progressive sequence of illumination (e.g., for any one of more suitable illumination modes), the illumination color may be any suitable color, and / or the illumination "on" time may be between about 0.1 seconds and 1 second, between about 0.2 seconds and 0.5 seconds, or about 0.3 seconds, and / or the illumination "off" time between illumination of adjacent indicator lightsmay be between about 0.05 seconds and about 1 second, between about 0.1 seconds and about 0.5 seconds, or about 0.18 seconds, and / or the ratio between the illumination "on" time and illumination "off" timemay be about 1, about 1.5, or about 2, and / or the sequence end may be designated by illumination "off" for between about 2 seconds and about 5 seconds, or about 3 seconds. Furthermore, fewer or more illumination modes for indicating analyte measurement trends may be possible in other variations. Table 3. Example illumination modes for indicating analyte measurement trends Analyte measurement trend Figure Indicator lights illumination sequence Illumination color Illumination "on" time Illumination "off" time Sequence end In target range, rising FIG 34A Lower → Higher Blue 0.3 sec 0.18 sec 3 sec illumi- nation "off" Above target range, rising FIG. 34B Lower → Higher Orange 0.3 sec 0.18 sec 3 sec illumi- nation "off" Above (and / or signifi- can tly above) target range, dropping FIG. 34C Higher → Lower Orange 0.3 sec 0.18 sec 3 sec illumi- nation "off"

[0238] Additionally or alternatively, an indicator light 3222 may be selectively illuminated to communicate a device status. Similar to that described above, color and / or timing of illumination may be varied in a predetermined manner to indicate different device statuses. Status may, for example, include a warm-up period notification, an end-of-life notification, a sensor fault state notification, a sensor failure mode (e.g., improper insertion) notification, a low battery notification, and / or a device error notification Furthermore, any suitable number of indicators lights may be illuminated individually and / or collectively (e.g., in sequence or simultaneously) to indicate different device statuses. For example, as shown inFIG.35A,auser interface includingan indicator light 3222maybe illuminated inafirst illuminationmode (e.g., first illumination color such as white and / or first temporal illumination pattern) to indicate a device "wait" mode. The wait mode may, for example, correspond to a device warmup period (as described elsewhere herein), detection of a temporary error (e.g., detection of pressure-induced sensor attenuation). As another example, as shown in FIG 35B, a user interface including an indicator light 3222may be illuminated in a second illuminationmode (e.g., second illumination color such as red and / or second temporal illumination pattern) to indicate a device "end of life" mode (e.g., determination of an end of a predetermined wear period such as that described below, detection of a permanent error, etc.).

[0239] Table 4 illustrates different illumination modes used in an example method of operating the user interface of an analyte monitoring device to indicate device status. The exact parameter values of these illumination modes are non- limiting and are included for an example variation for illustrative purposes only. For example, in the "wait" illumination mode, the illumination colormay be any suitable color, and / or the illumination "on" timemay be between about .1 seconds 38 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 and about 3 seconds, between about .5 seconds and about 2 seconds, or about 1 second, and / or the illumination "off" mode may be between about 0.5 seconds and about 5 seconds, or between about 1 second and about 4 seconds, or between about 2 seconds and about 4 seconds, or about 3 seconds, and / or the ratio between the illumination "on" and illumination "off" times may be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, and / or other suitable illumination parameters. As another example, in the "end of life" illumination mode, the illumination color may be any suitable color, and / or the illumination "on" time may be between about 0.01 seconds and about 1 second, between about 0.01 seconds and about 0.5 seconds, between about 0.01 seconds and about 0.3 seconds, between about 0.01 seconds and about 0.1 seconds, or about 0.04 seconds, and / or the illumination "off" timemay be between about 1 second and about 10 seconds, between about 3 seconds and about 8 seconds, or about 6 seconds, and / or the ratio between the illumination "on" and illumination "off" timesmaybeabout 0.3, about 0.2, about 0.1, about 0.05, about 0.01, or less than about 0.01, and / or other suitable illumination parameters. Although only two illumination modes are shown, in some variations an analyte monitoring device may have fewer or more illumination modes, such as for each of the above statuses (e.g., first illumination mode for a device warmup period, a second illumination mode for detection of a temporary error, a third illumination mode for determination of an end of device lifetime, a fourth illumination mode for detection of a permanent error, etc.). Table 4. Example illumination modes for indicating device status Device status Figure Illumination color Illumination "on" time t(on) Illumination "off" time t(off) Wait FIG. 35A White 1 sec 3 sec End of life FIG. 35B Red 0.04 sec 6 sec

[0240] In some variations, a photodiode, phototransistor, photodetector, or other suitable ambient light sensor may be employed to measure the illumination level in the device’s immediate environment. The ambient light measurement may, for example, be used to trigger an adjustment (e g , dimming) of the brightness of the user interface (e.g., display, indicator light(s), etc.) to conservebattery charge in a power savingmode, to improve contrast under various illumination scenarios, and / or to reduce device visibility to other individuals. For example, the analyte monitoring device may enter the power savingmode in response tomeasurements from theambient light sensor indicatinggeneral absenceof ambient light (e.g., sufficient darkness for at least a predetermined period of time) such as when the device is placed under the clothing of a wearer or when the wearer is asleep in a dark environment. In these scenarios, the power saving mode may be practical because the indicator lights may have limited utility when concealed and out of view of the wearer (e.g., under clothing) or otherwisemay be perceived as an annoyance (e.g., during slumber), etc. In response tomeasurements from the ambient light sensor indicating exposure to ambient light (e.g., sufficient brightness for at least a predetermined period of time), the analyte monitoring device may then exit the power saving mode and increase the brightness of the user interface accordingly. Additional system functions

[0241] In some variations, the mobile application may help a user manage the lifetimes and replacement of analyte monitoring devices. For example, the mobile application may terminate data display when the wear period of the analyte monitoringdevicehaselapsed. Insomevariations, theanalytemonitoringdevicemayhaveenhanced longevity compared to conventional CGM devices. For example, the analyte monitoring devices described herein may have a wear period (e.g., intended lifetime)of at least 3days, at least 5days, at least 6days, at least 7days, at least 10days, or at least 12days, between 5 days and between 10 days, between 10 days and 14 days, etc. without material loss in performance.

[0242] Additionally or alternatively,mobile applicationmay provide configurable alerts to the user that thewear period is about to elapse, which permits users to apply a newanalytemonitoring devicewhen the current analytemonitoring device is still active but close to expiry. Additionally, the new analyte monitoring device can warm up (typically between about 30 minutes and about 2 hours) while the old unit is still delivering analyte measurements. The old analyte monitoring device can then be removed upon expiry. The new analyte monitoring device may then become the primary sensor delivering analyte measurements to the mobile application This may provide for an uninterrupted coverage for analyte measure- ments. Additionally, the readings from the old analyte monitoring device may be used to calibrate or algorithmically improve the accuracy of the new analyte monitoring device.

[0243] In some variations, an analyte monitoring device may have a unique serial number contained within the microcontroller (e.g., located in the electronics system). This serial number may enable sensors to be tracked from manufacturing and throughout theuseof theproduct. For example, sensor device history records includingmanufacturing and customer usemay be transmitted and stored in the cloud database. This enables tracking and inferences to bemade on various parameters such as sensor performance metrics and improvement for individual users as well as sensor lots, 39 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 tracking defective sensor lots back from field data to manufacturing or supplier issues very rapidly, personalized health monitoring features for individual users, etc.

[0244] In some variations, the systemmay be able to track inventory of analytemonitoring devices fromwarehousing to purchasing transactions to product use, whichmay enable the system to assist users in fulfillment of timely orders (e.g., to ensure that users don’t run out of analyte monitoring devices). Additionally or alternatively, fulfillment can be executed automatically as monitoring device utilization is tracked, and timely delivery can be made to the user’s residence to help ensure that sensor supply never depletes (e.g. ’just-in-time’ delivery). This can interface with virtual or e-pharmacies, logistics centers, and / or web-based sales portals, such as Amazon™.

[0245] Through web portals, the cloud infrastructure may also allow users to view their real-time and historical glucose data / trends and share the said data with caregivers, their healthcare provider(s), support network, and / or other suitable persons. Enumerated embodiments

[0246] Embodiment I‑1. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, wherein at least one microneedle comprises. a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex.

[0247] Embodiment I‑2. The microneedle array of embodiment I‑1, wherein the electrode is a working electrode configured to sense at least one analyte and the at least onemicroneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises a biorecognition element.

[0248] Embodiment I‑3. The microneedle array of embodiment I‑2, wherein the biorecognition element comprises an enzyme.

[0249] Embodiment I‑4. The microneedle array of embodiment I‑3, wherein the enzyme is an oxidoreductase.

[0250] Embodiment I‑5. Themicroneedle array of embodiment I‑4, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

[0251] Embodiment I‑6. The microneedle array of embodiment I‑4, wherein the oxidoreductase is glucose oxidase.

[0252] Embodiment 1‑7. Themicroneedle array of embodiment I‑2, wherein the biorecognition element is cross-linked with an amine-condensing carbonyl chemical species.

[0253] Embodiment I‑8. The microneedle array of embodiment 1‑7, wherein the amine-condensing carbonyl chemical species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde.

[0254] Embodiment I‑ 9. Themicroneedle array of embodiment 1‑7, wherein the amine-condensing carbonyl chemical species is glutaraldehyde.

[0255] Embodiment I‑10. Themicroneedle array of embodiment I‑2, wherein the at least onemicroneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0256] Embodiment I‑11. Themicroneedle array of embodiment 1‑2, wherein themicroneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on the working electrode

[0257] Embodiment I‑12. The microneedle array of embodiment I‑2, wherein the microneedle array comprises at least one microneedle comprising a reference electrode configured to provide a reference potential for the working electrode.

[0258] Embodiment I‑13.Themicroneedlearrayofembodiment I‑12, further comprisingaconductingpolymerarranged over the reference electrode.

[0259] Embodiment I‑14. The microneedle array of embodiment I‑13, wherein the conducting polymer comprises a dopant.

[0260] Embodiment I‑15. The microneedle array of embodiment I‑13, wherein the reference electrode comprises a metal oxide with a stable electrode potential

[0261] Embodiment I‑16. Themicroneedle array of embodiment I‑15, wherein themetal oxide comprises iridium oxide.

[0262] Embodiment I‑17. The microneedle array of embodiment I‑13, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0263] Embodiment I‑18. The microneedle array of embodiment I‑17, wherein the metal salt comprises silver chloride.

[0264] Embodiment I‑19. The microneedle array of embodiment I‑1, wherein the entirety of the electrode is on the tapered distal portion of the at least one microneedle.

[0265] Embodiment I‑20. The microneedle array of embodiment I‑1, wherein the electrode comprises a catalytic surface. 40 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0266] Embodiment I‑21. The microneedle array of embodiment I‑20, wherein the catalytic surface comprises at least one of platinum, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, and doped diamond.

[0267] Embodiment I‑22. The microneedle array of embodiment I‑20, wherein the at least one microneedle comprises platinum black arranged over the electrode.

[0268] Embodiment I‑23. The microneedle array of embodiment I‑1, wherein a distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one microneedle.

[0269] Embodiment I‑24. The microneedle array of embodiment I‑1, wherein the electrode is annular

[0270] Embodiment I‑25. The microneedle array of embodiment I‑1, wherein a portion of the working electrode is recessed into the tapered distal portion.

[0271] Embodiment I‑26. The microneedle array of embodiment I‑1, wherein the electrode is on only a segment of the tapered distal portion

[0272] Embodiment I‑27. The microneedle array of embodiment I‑1, further comprising an electrical contact, wherein the at least onemicroneedle comprises a body portion providing a conductive pathway between the electrical contact and the electrode.

[0273] Embodiment I‑28. The microneedle array of embodiment I‑27, wherein the body portion is formed from a conductive material.

[0274] Embodiment I‑29.Themicroneedlearrayofembodiment I‑27,wherein thebodyportion comprisesanembedded pathway.

[0275] Embodiment I‑30. The microneedle array of embodiment I‑27, wherein the body portion is insulated

[0276] Embodiment I‑31. Themicroneedle array of embodiment I‑27,wherein thebody portion has a circular, square, or an octagonal base.

[0277] Embodiment I‑32. The microneedle array of embodiment I‑27, wherein at least a segment of the body portion is columnar.

[0278] Embodiment I‑33. The microneedle array of embodiment I‑27, wherein at least a segment of the body portion is pyramidal.

[0279] Embodiment I‑34. Themicroneedle array of embodiment I‑33,wherein at least a portionof the bodyportion has a first taper angle measured relative to a base of the body portion and the distal apex has a second taper angle measured relative to the base, wherein the second taper angle is greater than the first taper angle.

[0280] Embodiment I‑35. The microneedle array of embodiment I‑34, wherein at least one of the body portion and the distal portion of the microneedle is radially asymmetric.

[0281] Embodiment I‑36. The microneedle array of embodiment I‑35, wherein the tapered distal portion comprises a planar surface that is offset from the distal apex of the at least one microneedle

[0282] Embodiment 1‑37. Themicroneedle array of embodiment I‑1,wherein eachof themicroneedles in theplurality of microneedles comprises a a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex.

[0283] Embodiment I‑38. The microneedle array of embodiment I‑1, wherein the microneedles of the plurality of microneedles are electrically insulated from one another.

[0284] Embodiment 1‑39. The microneedle array of embodiment 1‑38, wherein the microncedle array is configured to detect multiple analytes.

[0285] Embodiment I‑40. The microneedle array of embodiment I‑1, wherein the microneedles of the plurality of microneedles are arranged in a periodic grid.

[0286] Embodiment I‑41. Themicroneedle array of embodiment I‑40, wherein the periodic grid comprises a rectangular array.

[0287] Embodiment I‑42. Themicroneedle array of embodiment I‑40, wherein the periodic grid comprises a hexagonal array.

[0288] Embodiment I‑43. Themicroneedle array of embodiment I‑40, wherein themicroneedles in the periodic grid are spaced apart by a distance between about 200 µm and about 800 µm.

[0289] Embodiment I‑44. Themicroneedle array of embodiment I‑40, wherein themicroneedles in the periodic grid are uniformly spaced apart

[0290] Embodiment I‑45. Themicroneedle array of embodiment I‑1, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen.

[0291] Embodiment I‑46. Themicroneedle array of embodiment I‑1, wherein the at least onemicroneedle is configured to puncture skin of a user and sense an analyte in interstitial fluid in a dermal layer of the user. 41 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0292] Embodiment 1‑47. An analyte monitoring system comprising the microneedle array of embodiment I‑1 and a wearable housing, wherein the microneedle array extends outwardly from the housing.

[0293] Embodiment I‑48. The system of embodiment I‑47, wherein the at least one microneedle extends from the housing such that a distal end of the electrode is located less than about 5 mm from the housing.

[0294] Embodiment I‑49. The system of embodiment I‑48, wherein the at least one microneedle extends from the housing such that the distal end of the electrode is located less than about 1 mm from the housing.

[0295] Embodiment I‑50. The system of embodiment I‑47, wherein the housing encloses an electronics system comprising at least one of a processor and a wireless communication module.

[0296] Embodiment I‑51. The system of embodiment I‑50, wherein the electronics system comprises a wireless communication module and the system further comprises a software application executable on a mobile computing device to be paired with the wireless communication module.

[0297] Embodiment I‑52. The system of embodiment I‑47, wherein the housing comprises one or more indicator lights configured to communicate status information.

[0298] Embodiment I‑53. The system of embodiment I‑52, wherein at least one of the indicator lights is configured to be selectively illuminated in accordance with an illumination mode corresponding to an analyte measurement status.

[0299] Embodiment I‑54. The system of embodiment I‑53, wherein at least one of the indicator lights is configured to be selectively illuminated to communicate a current analyte measurement level.

[0300] Embodiment I‑55. The system of embodiment I‑53, wherein the user interface comprises a plurality of indicator lights configured to be selectively illuminated in a progressive sequence to communicate an analyte measurement trend.

[0301] Embodiment I‑56. The system of embodiment I‑55, wherein the plurality of indicator lights is configured to be selectively illuminated in a first progressive sequence in a first direction to communicate a rising analyte measurement trend, and is further configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a falling analyte measurement trend.

[0302] Embodiment I‑57. The system of embodiment I‑52, wherein the user interface is further configured to commu- nicate information indicative of a status of the analyte monitoring device.

[0303] Embodiment I‑58. The system of embodiment I‑47, further comprising an adhesive configured to couple the housing to the skin of a user

[0304] Embodiment I‑59. The system of embodiment I‑47, further comprising an applicator configured to apply the at least a portion of the analyte monitoring system to the skin of a user.

[0305] Embodiment 1‑60. The system of embodiment I‑47, wherein the analyte monitoring system is a skin-adhered patch.

[0306] Embodiment I‑61. The system of embodiment I‑47, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen.

[0307] Embodiment I‑62. The system of embodiment I‑47, wherein the plurality of microneedles comprises at least one solid microneedle comprising a coating comprising a therapeutic substance.

[0308] Embodiment I‑63. The system of embodiment I‑62, wherein the therapeutic substance comprises at least one of insulin, glucagon, metformin, acetaminophen, acetylsalicylic acid, isobutylphenylpropionic acid, levodopa, a statin, a hydrocodone, an opioid, a non-steroidal antiinflammatory, an anesthetic, an analgesic, an anticonvulsant, an antide- pressant, an antipsychotic, a sedative, a relaxant, a hormonal agent, an antibacterial agent, and an antiviral agent.

[0309] Embodiment I‑64. A method for monitoring a user, comprising: accessing a body fluid of the user with an analyte monitoring device; and quantifying one or more analytes in the body fluid using the analyte monitoring device, wherein the analyte monitoring device comprises a plurality of solid microneedles, wherein at least one microneedle comprises: a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex.

[0310] Embodiment I‑65. Themethod of embodiment I‑64, wherein the body fluid comprises a dermal interstitial fluid of the user.

[0311] Embodiment 1‑66. The method of embodiment I‑64, wherein the one or more analytes comprises glucose.

[0312] Embodiment I‑67. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, wherein at least one microneedle comprises: a tapered distal portion having an insulated distal apex, and an electrode on a surface of the tapered distal portion, wherein a distal end of the electrode is offset from the distal 42 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 apex.

[0313] Embodiment I‑68. The microneedle array of embodiment 1‑67, wherein the electrode is a working electrode configured to sense at least one analyte and the at least onemicroneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises a biorecognition element.

[0314] Embodiment I‑69. The microneedle array of embodiment I‑68, wherein the biorecognition element comprises glucose oxidase.

[0315] Embodiment I‑70. The microneedle array of embodiment I‑67, wherein the distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one microneedle.

[0316] Embodiment I‑71. The microneedle array of embodiment I‑67, wherein the electrode is annular.

[0317] Embodiment I‑72. Themicroneedle array of embodiment 1‑67, wherein in at least onemicroneedle, a portion of the working electrode is recessed into the tapered distal portion

[0318] Embodiment I‑73. Themicroneedle array of embodiment I‑67, wherein the electrode is on only a segment of the tapered distal portion

[0319] Embodiment I‑74. The microneedle array of embodiment I‑67, further comprising an electrical contact, wherein the at least onemicroneedle comprises a body portion providing a conductive pathway between the electrical contact and the electrode.

[0320] Embodiment I‑75.Themicroneedlearrayofembodiment I‑67,whereineachof themicroneedles in theplurality of microneedles comprises a a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex.

[0321] Embodiment I‑76. The microneedle array of embodiment I‑67, wherein the microneedle array comprises a plurality of working electrodes, wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device.

[0322] Embodiment I‑77. The microneedle array of embodiment I‑76, wherein the microneedle array is configured to detect multiple analytes.

[0323] Embodiment I‑78. The microneedle array of embodiment I‑67, wherein the microneedles of the plurality of microneedles are arranged in a hexagonal array.

[0324] Embodiment 1‑79. The microneedle array of embodiment I‑67, wherein the at least one microneedle is configured to puncture skin of a user and sense an analyte in interstitial fluid in a dermal layer of the user.

[0325] Embodiment I‑80. An analyte monitoring system comprising the microneedle array of embodiment I‑67 and a wearable housing, wherein the microneedle array extends outwardly from the housing

[0326] Embodiment I‑81. The system of embodiment I‑80, wherein the at least one microneedle extends from the housing such that the distal end of the electrode is located less than about 5 mm from the housing.

[0327] Embodiment I‑82. The system of embodiment I‑80, wherein the housing encloses an electronics system comprising a wireless communication module and the system further comprises a software application executable on a mobile computing device to be paired with the wireless communication module.

[0328] Embodiment I‑83. The system of embodiment I‑80, wherein the housing comprises a user interface comprising one or more indicator lights configured to communicate status information.

[0329] Embodiment I‑84. The system of embodiment I‑83, wherein at least one of the indicator lights is configured to be selectively illuminated in accordance with an illumination mode corresponding to an analyte measurement status.

[0330] Embodiment I‑85. The system of embodiment I‑83, wherein the analyte monitoring system comprises a skin- adhered patch.

[0331] Embodiment 1‑86. A method of sterilizing an analyte monitoring device, the method comprising: exposing theanalytemonitoringdevice toasterilantgas,wherein theanalytemonitoringdevicecomprisesawearable housing, a microneedle array extending from the housing and comprising an analyte sensor, and an electronics system arranged in the housing and electrically coupled to the microneedle array, wherein the analyte monitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device.

[0332] Embodiment I‑87. Themethodof embodiment I‑86,wherein the sterilant gas is suitable for oxidative sterilization.

[0333] Embodiment I‑88. The method of embodiment I‑87, wherein the sterilant gas comprises ethylene oxide. 43 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0334] Embodiment I‑89. The method of embodiment 1‑86, wherein the analyte sensor comprises an electrode.

[0335] Embodiment I‑90. Themethod of embodiment I‑89,wherein the analyte sensor comprises a biorecognition layer arranged over the electrode, wherein the biorecognition layer comprises a biorecognition element.

[0336] Embodiment I‑91. The method of embodiment I‑90, wherein the biorecognition element comprises an enzyme.

[0337] Embodiment I‑92. The method of embodiment I‑91, wherein the enzyme is an oxidoreductase.

[0338] Embodiment I‑93.Themethodof embodiment I‑92,wherein theoxidoreductase is at least oneof lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

[0339] Embodiment I‑94. The method of embodiment I‑92, wherein the oxidoreductase is glucose oxidase.

[0340] Embodiment I‑95. The method of embodiment I‑90, wherein the biorecognition element is cross-linked with an amine-condensing carbonyl chemical species.

[0341] Embodiment I‑96. The method of embodiment 1‑95, wherein the amine-condensing carbonyl chemical species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde.

[0342] Embodiment I‑97. Themethodof embodiment I‑95,wherein theamine-condensing carbonyl chemical species is glutaraldehyde.

[0343] Embodiment 1‑98 Themethod of embodiment I‑90, wherein the biorecognition layer is formed at least in part by cross-linking the biorecognition element to form cross-linked biorecognition element aggregates, and embedding the cross-linked biorecognition element aggregates in a conducting polymer.

[0344] Embodiment I‑99.Themethodofembodiment 1‑98,whereinembedding thecross-linkedbiorecognitionelement aggregates comprises embedding only cross-linked biorecognition element aggregates having at least a threshold molecular weight.

[0345] Embodiment I‑100. The method of embodiment 1‑86, wherein exposing the analyte monitoring device to the sterilant gas comprises injecting the sterilant gas into a compartment containing the analyte monitoring device. and heating the compartment to a sterilization temperature

[0346] Embodiment I‑101. The method of embodiment I‑100, wherein the sterilization temperature is below about 45 degrees Celsius and the dwell time is at least about 2 hours

[0347] Embodiment I‑102. The method of embodiment I‑86, further comprising preconditioning the analyte monitoring device prior to exposing the analytemonitoring device to the sterilant gas, wherein preconditioning the analyte comprises exposing the analyte monitoring device to steam.

[0348] Embodiment I‑103. A microneedle array for an analyte monitoring device. the microneedle array comprising. a plurality of solid sensing microneedles, wherein each sensing microneedle comprises: a tapered distal portion comprising a working electrode configured to sense an analyte, and a body portion providing a conductive connection to the working electrode, wherein the body portion of each sensing microneedle is insulated such that each working electrode is individually addressable and electrically isolated from every other working electrode in the microneedle array.

[0349] Embodiment I‑104. The microneedle array of embodiment I‑103, wherein at least one sensing microneedle comprises a biorecognition layer arranged over the working electrode. wherein the biorecognition layer comprises a biorecognition element.

[0350] Embodiment I‑105. Themicroneedle array of embodiment I‑104, wherein the biorecognition element comprises an enzyme.

[0351] Embodiment I‑106. The microneedle array of embodiment I‑105, wherein the enzyme is an oxidoreductase.

[0352] Embodiment I‑107. The microneedle array of embodiment I‑100, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cho- lesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

[0353] Embodiment I‑108.Themicroneedlearrayofembodiment I‑106,wherein theoxidoreductase isglucoseoxidase.

[0354] Embodiment I‑109. The microneedle array of embodiment 1‑104, wherein the biorecognition element is cross- linked with an amine-condensing carbonyl chemical species

[0355] Embodiment I‑110. The microneedle array of embodiment I‑109, wherein the amine-condensing carbonyl chemical species is at least one of formaldehyde, glyoxal. malonaldehyde, and succinaldehyde.

[0356] Embodiment I‑111. The microneedle array of embodiment I‑109, wherein the amine-condensing carbonyl chemical species is glutaraldehyde

[0357] Embodiment I‑112. The microneedle array of embodiment I‑104, wherein the at least one sensing microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0358] Embodiment I‑113. The microneedle array of embodiment I‑103, wherein the microneedle array further comprises at least one microneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on the working electrode of at least one sensing microneedle 44 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0359] Embodiment I‑114.Themicroneedlearrayofembodiment I‑103,wherein theplurality ofmicroneedlescomprises at least one microneedle comprising a reference electrode configured to provide a reference potential for the working electrode

[0360] Embodiment I‑115. The microneedle array of embodiment I‑114, further comprising a conducting polymer arranged over the reference electrode.

[0361] Embodiment I‑116. The microneedle array of embodiment 1‑115, wherein the conducting polymer comprises a dopant.

[0362] Embodiment I‑117. The microneedle array of embodiment I‑114, wherein the reference electrode comprises a metal oxide with a stable electrode potential.

[0363] Embodiment I‑118. The microneedle array of embodiment I‑117, wherein the metal oxide comprises iridium oxide.

[0364] Embodiment I‑119. The microneedle array of embodiment I‑114, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0365] Embodiment I‑120.Themicroneedlearrayofembodiment I‑119,wherein themetal salt comprisessilver chloride.

[0366] Embodiment I‑121. The microneedle array of embodiment I‑103, wherein in at least one sensing microneedle, the tapered distal portion comprises an insulated distal apex and the working electrode is proximal to the insulated distal apex.

[0367] Embodiment I‑122. Themicroneedle array of embodiment I‑121, wherein a distal end of the working electrode is offset from the distal apex by an offset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one sensing microneedle.

[0368] Embodiment I‑123. Themicroneedle array of embodiment 1‑103,wherein in at least one sensingmicroneedle. a portion of the working electrode is recessed into the tapered distal portion.

[0369] Embodiment I‑124. An analyte monitoring device comprising themicroneedle array of embodiment 1‑103 and a wearable housing, wherein the microneedle array extends outwardly from the housing.

[0370] Embodiment 1‑125. The analytemonitoring device of embodiment I‑124, wherein the housing comprises one or more indicator lights configured to communicate status information

[0371] Embodiment I‑126. The analyte monitoring device of embodiment I‑124, wherein the housing encloses an electronics system comprising at least one of a processor and a wireless communication module.

[0372] Embodiment I‑127.Theanalytemonitoringdeviceofembodiment I‑126,wherein theanalytemonitoringdevice is a skin-adhered patch.

[0373] Embodiment I‑128. A microneedle array for a body-worn analyte monitoring device, wherein the microneedle array comprises: at least one microneedle comprising: a pyramidal body portion having a non-circular base; and a tapered distal portion extending from the body portion and comprising an electrode, wherein the distal portion comprises a planar surface that is offset from a distal apex of the at least one microneedle.

[0374] Embodiment I‑129. The microneedle array of embodiment I‑128, wherein at least a portion of the body portion has a first taper anglemeasured relative to the base and the distal apex has a second taper anglemeasured relative to the base, wherein the second taper angle is greater than the first taper angle.

[0375] Embodiment I‑130. Themicroneedle array of embodiment I‑128, wherein the second taper is between about 65 degrees and about 75 degrees.

[0376] Embodiment I‑131. The microneedle array of embodiment I‑130, wherein the first taper is between about 15 degrees and about 25 degrees.

[0377] Embodiment I‑132. The microneedle array of embodiment I‑128, wherein the planar surface is angled between about 75 degrees and 85 degrees measured relative to the base

[0378] Embodiment I‑133.Themicroneedlearrayof embodiment I‑128,wherein the tapereddistal portion comprisesan insulated distal apex.

[0379] Embodiment 1‑134. An analyte monitoring device comprising themicroneedle array of embodiment I‑128 and a wearable housing, wherein the microneedle array is configurable to extend outwardly from the housing.

[0380] Embodiment I‑135.Theanalytemonitoringdeviceofembodiment I‑134,wherein theanalytemonitoringdevice is a patch.

[0381] Embodiment I‑136. A method for monitoring a user, comprising: accessing a dermal interstitial fluid of the user at a plurality of sensor locations with an integrated analyte monitoring device comprising a single microneedle array; quantifying one or more analytes in the dermal interstitial fluid using a plurality of working electrodes in the 45 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 microneedle array, wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device.

[0382] Embodiment I‑137. The method of embodiment I‑136, wherein quantifying one or more analytes comprises quantifying a plurality of analytes in the dermal interstitial fluid using the plurality of working electrodes.

[0383] Embodiment I‑138. The method of embodiment 1‑136, wherein the microneedle array comprises a plurality of sensing microneedles, each sensing microneedle comprising a respective working electrode.

[0384] Embodiment I‑139. The method of embodiment 1‑138, wherein at least one sensing microneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises an enzyme.

[0385] Embodiment 1‑140. The method of embodiment I‑139, wherein the at least one microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0386] Embodiment I‑141 . The method of embodiment I‑136, wherein the microncedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on at least one working electrode.

[0387] Embodiment I‑142. The method of embodiment I‑136, wherein the plurality of microneedles comprises at least one microneedle comprising a reference electrode configured to provide a reference potential for at least one working electrode.

[0388] Embodiment I‑143. The method of embodiment 1‑142, further comprising a conducting polymer arranged over the reference electrode.

[0389] Embodiment I‑144. The method of embodiment I‑143, wherein the conducting polymer comprises a dopant.

[0390] Embodiment I‑145. Themethod of embodiment I‑142, wherein the reference electrode comprises ametal oxide with a stable electrode potential.

[0391] Embodiment I‑146. The method of embodiment I‑145, wherein the metal oxide comprises iridium oxide.

[0392] Embodiment I‑147. The method of embodiment I‑142, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0393] Embodiment I‑148. The method of embodiment I‑147, wherein the metal salt comprises silver chloride.

[0394] Embodiment I‑149, The method of embodiment 1‑136, further comprising communicating status information indicative of the quantification of the one or more analytes

[0395] Embodiment I‑150, Themethod of embodiment I‑149, wherein the microneedle array extends outwardly from a wearable housing and communicating status information comprises: communicating status information via a user interface on the housing.

[0396] Embodiment I‑151. The method of embodiment I‑150, wherein communicating status information comprises selectively illuminating one ormore indicator lights on the housing in accordancewith an illuminationmode corresponding to an analyte measurement status or a status of the integrated analyte monitoring device.

[0397] Embodiment I‑152. The method of embodiment 1‑150, wherein communicating status information comprises activating a display corresponding to an analyte measurement status or a status of the integrated analyte monitoring device.

[0398] Embodiment 1‑153. A body-worn analyte monitoring device, comprising a wearable housing, and a microneedle array extending outwardly from the housing and comprising at least one microneedle configured to measure one or more analytes in a user wearing the housing, wherein the housing comprises a user interface configured to communicate information indicative of the measure- ment of the one or more analytes.

[0399] Embodiment I‑154. Thedevice of embodiment I‑153,wherein the user interface comprises oneormore indicator lights configured to be selectively illuminated in accordance with an illumination mode corresponding to an analyte measurement status or a status of an integrated analyte monitoring device.

[0400] Embodiment I‑155. The device of embodiment 1‑154, wherein at least one of the indicator lights is configured to be selectively illuminated to communicate a current analyte measurement level.

[0401] Embodiment I‑156. Thedevice of embodiment I‑154,wherein the user interface comprises a plurality of indicator lights configured to be selectively illuminated in a progressive sequence to communicate an analyte measurement trend.

[0402] Embodiment I‑157. The device of embodiment I‑156, wherein the plurality of indicator lights is configured to be selectively illuminated in a first progressive sequence in a first direction to communicate a rising analyte measurement trend

[0403] Embodiment I‑158. The device of embodiment I‑156, wherein the plurality of indicator lights is configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a falling analyte measurement trend. 46 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55

[0404] Embodiment I‑159. The device of embodiment I‑153, wherein the user interface is further configured to communicate information indicative of a status of the analyte monitoring device.

[0405] Embodiment I‑160. The device of embodiment I‑153, wherein the user interface comprises a display screen.

[0406] Embodiment I‑161. The device of embodiment I‑153, wherein the analyte monitoring device is a skin-adhered patch.

[0407] Embodiment I‑162. The device of embodiment I‑153, wherein the at least onemicroneedle comprises a tapered distal portion with an insulated distal apex, and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex.

[0408] Embodiment I‑163. The device of embodiment I‑153, wherein the microneedle array comprises a plurality of working electrodes. wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device.

[0409] Embodiment I‑164. A method for monitoring a user, comprising: measuring one or more analytes in the user using a body-worn analyte monitoring device comprising a wearable housing and one or more analyte sensors; communicating information indicative of themeasurement of the one ormore analytes through a user interface on the housing.

[0410] Embodiment I‑165. Themethod of embodiment I‑164, wherein communicating information comprises illuminat- ing one or more indicator lights on the housing in accordance with an illumination mode corresponding to an analyte measurement status.

[0411] Embodiment I‑166. The method of embodiment 1‑165, wherein communicating information comprises selec- tively illuminating at least one of the indicator lights to communicate a current analyte measurement level.

[0412] Embodiment I‑167. The method of embodiment I‑166, wherein communicating information comprises commu- nicating the current analytemeasurement level based on color of the illuminated indicator light, location of the illuminated indicator light, or both.

[0413] Embodiment I‑168. The method of embodiment I‑165, wherein communicating information comprises selec- tively illuminating a plurality of indicator lights on the housing in a progressive sequence to communicate an analyte measurement trend

[0414] Embodiment I‑169. The method of embodiment 1‑168, wherein communicating information comprises selec- tively illuminating the plurality of indicator lights in a first progressive sequence in a first direction to communicate a rising analyte measurement trend.

[0415] Embodiment I‑170. The method of embodiment I‑108, wherein communicating information comprises selec- tively illuminating the plurality of indicator lights in a second progressive sequence in a second direction to communicate a falling analyte measurement trend.

[0416] Embodiment I‑171. Themethod of embodiment 1‑164, further comprising communicating information indicative of a status of the analyte monitoring device through the user interface.

[0417] Embodiment I‑172. The method of embodiment I‑164, further comprising accessing a dermal interstitial fluid of the user at a plurality of sensor locations with the analyte monitoring device, wherein quantifying one of more analytes comprises quantifying one or more analytes in the dermal interstitial fluid.

[0418] Embodiment I‑173. The method of embodiment 1‑164, wherein the analyte monitoring device comprises a microneedle array comprising a plurality of working electrodes, wherein each working electrode is individually addres- sable and electrically isolated from every other working electrode in the analyte monitoring device.

[0419] 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 anddescription. They are not intended to be exhaustive or to limit the invention to theprecise 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 variousmodifications as are suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention. Embodiments

[0420] Various emboiments of the invention are defined in the clauses below: 1. A microneedle array for use in sensing an analyte, comprising: 47 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 a plurality of solid microneedles, wherein at least one microneedle comprises: a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex. 2. The microneedle array of clause 1, wherein the electrode is a working electrode configured to sense at least one analyte and the at least one microneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises a biorecognition element. 3. The microneedle array of clause 2, wherein the biorecognition element comprises an enzyme. 4. The microneedle array of clause 3, wherein the enzyme is an oxidoreductase. 5. The microneedle array of clause 4, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxi- dase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase. 6. The microneedle array of clause 4, wherein the oxidoreductase is glucose oxidase. 7. The microneedle array of clause 2, wherein the biorecognition element is cross-linked with an amine-condensing carbonyl chemical species. 8. The microneedle array of clause 7, wherein the amine-condensing carbonyl chemical species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde. 9. The microneedle array of clause 7, wherein the amine-condensing carbonyl chemical species is glutaraldehyde. 10. The microneedle array of clause 2, wherein the at least one microneedle comprises at least one of a diffusion- limiting layer and a hydrophilic layer arranged over the biorecognition layer. 11. Themicroneedle array of clause 2,wherein themicroneedle array comprises at least onemicroneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on the working electrode. 12. Themicroneedle array of clause2,wherein themicroneedle array comprises at least onemicroneedle comprising a reference electrode configured to provide a reference potential for the working electrode. 13. The microneedle array of clause 12, further comprising a conducting polymer arranged over the reference electrode. 14. The microneedle array of clause 13, wherein the conducting polymer comprises a dopant. 15. The microneedle array of clause 13, wherein the reference electrode comprises a metal oxide with a stable electrode potential. 16. The microneedle array of clause 15, wherein the metal oxide comprises iridium oxide. 17.Themicroneedlearrayof clause13,wherein the referenceelectrodecomprisesametal saltwith astableelectrode potential. 18. The microneedle array of clause 17, wherein the metal salt comprises silver chloride. 19. The microneedle array of clause 1, wherein the entirety of the electrode is on the tapered distal portion of the at least one microneedle. 20. The microneedle array of clause 1, wherein the electrode comprises a catalytic surface. 48 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 21. The microneedle array of clause 20, wherein the catalytic surface comprises at least one of platinum, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, and doped diamond. 22. Themicroneedlearrayof clause20,wherein theat least onemicroneedle comprisesplatinumblackarrangedover the electrode. 23. The microneedle array of clause 1, wherein a distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one microneedle. 24. The microneedle array of clause 1, wherein the electrode is annular. 25. The microneedle array of clause 1, wherein a portion of the working electrode is recessed into the tapered distal portion. 26. The microneedle array of clause 1, wherein the electrode is on only a segment of the tapered distal portion. 27. Themicroneedle array of clause 1, further comprising an electrical contact, wherein the at least onemicroneedle comprises a body portion providing a conductive pathway between the electrical contact and the electrode. 28. The microneedle array of clause 27, wherein the body portion is formed from a conductive material. 29. The microneedle array of clause 27, wherein the body portion comprises an embedded pathway. 30. The microneedle array of clause 27, wherein the body portion is insulated. 31. The microneedle array of clause 27, wherein the body portion has a circular, square, or an octagonal base. 32. The microneedle array of clause 27, wherein at least a segment of the body portion is columnar. 33. The microneedle array of clause 27, wherein at least a segment of the body portion is pyrami dal. 34. Themicroneedle array of clause 33, wherein at least a portion of the body portion has a first taper anglemeasured relative to a base of the body portion and the distal apex has a second taper angle measured relative to the base, wherein the second taper angle is greater than the first taper angle. 35. The microneedle array of clause 34, wherein at least one of the body portion and the distal portion of the microneedle is radially asymmetric. 36. The microneedle array of clause 35, wherein the tapered distal portion comprises a planar surface that is offset from the distal apex of the at least one microneedle. 37. Themicroneedle array of clause 1, wherein each of themicroneedles in the plurality of microneedles comprises a a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex. 38. The microneedle array of clause 1, wherein the microneedles of the plurality of microneedles are electrically insulated from one another. 39. The microneedle array of clause 38, wherein the microneedle array is configured to detect multiple analytes. 40. The microneedle array of clause 1, wherein the microneedles of the plurality of microneedles are arranged in a periodic grid. 41. The microneedle array of clause 40, wherein the periodic grid comprises a rectangular array. 49 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 42. The microneedle array of clause 40, wherein the periodic grid comprises a hexagonal array. 43. Themicroneedle array of clause 40, wherein themicroneedles in the periodic grid are spaced apart by a distance between about 200 µm and about 800 µm. 44. The microneedle array of clause 40, wherein the microneedles in the periodic grid are uniformly spaced apart. 45. The microneedle array of clause 1, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen. 46. The microneedle array of clause 1, wherein the at least one microneedle is configured to puncture skin of a user and sense an analyte in interstitial fluid in a dermal layer of the user. 47. An analytemonitoring system comprising themicroneedle array of clause 1 and awearable housing, wherein the microneedle array extends outwardly from the housing. 48. The system of clause 47, wherein the at least onemicroneedle extends from the housing such that a distal end of the electrode is located less than about 5 mm from the housing. 49. The systemof clause48,wherein theat least onemicroneedle extends from thehousing such that the distal endof the electrode is located less than about 1 mm from the housing. 50. The system of clause 47, wherein the housing encloses an electronics system comprising at least one of a processor and a wireless communication module. 51. The system of clause 50, wherein the electronics system comprises a wireless communication module and the system further comprises a software application executable on a mobile computing device to be paired with the wireless communication module. 52. The system of clause 47, wherein the housing comprises one or more indicator lights configured to communicate status information. 53. The system of clause 52, wherein at least one of the indicator lights is configured to be selectively illuminated in accordance with an illumination mode corresponding to an analyte measurement status. 54. The system of clause 53, wherein at least one of the indicator lights is configured to be selectively illuminated to communicate a current analyte measurement level. 55. The system of clause 53, wherein the user interface comprises a plurality of indicator lights configured to be selectively illuminated in a progressive sequence to communicate an analyte measurement trend. 56. The system of clause 55, wherein the plurality of indicator lights is configured to be selectively illuminated in a first progressivesequence inafirst direction tocommunicatea risinganalytemeasurement trend, and is further configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a falling analyte measurement trend. 57. The systemof clause 52, wherein the user interface is further configured to communicate information indicative of a status of the analyte monitoring device. 58. The system of clause 47, further comprising an adhesive configured to couple the housing to the skin of a user. 59. The system of clause 47, further comprising an applicator configured to apply the at least a portion of the analyte monitoring system to the skin of a user. 60. The system of clause 47, wherein the analyte monitoring system is a skin-adhered patch. 61. The systemof clause 47, wherein the plurality ofmicroneedles comprises at least one deliverymicroneedle with a lumen. 50 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 62. The system of clause 47, wherein the plurality of microneedles comprises at least one solid microneedle comprising a coating comprising a therapeutic substance. 63. The system of clause 62, wherein the therapeutic substance comprises at least one of insulin, glucagon, metformin, acetaminophen, acetylsalicylic acid, isobutylphenylpropionic acid, levodopa, a statin, a hydrocodone, an opioid, a non-steroidal anti-inflammatory, an anesthetic, an analgesic, an anticonvulsant, an antidepressant, an antipsychotic, a sedative, a relaxant, a hormonal agent, an antibacterial agent, and an antiviral agent. 64. A method for monitoring a user, comprising: accessing a body fluid of the user with an analyte monitoring device; and quantifying one or more analytes in the body fluid using the analyte monitoring device, wherein the analyte monitoring device comprises a plurality of solid microneedles, wherein at least one microneedle comprises: a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex. 65. The method of clause 64, wherein the body fluid comprises a dermal interstitial fluid of the user. 66. The method of clause 64, wherein the one or more analytes comprises glucose. 67. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, wherein at least one microneedle comprises: a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion,wherein a distal end of the electrode is offset from the distal apex. 68. Themicroneedle array of clause 67, wherein the electrode is a working electrode configured to sense at least one analyte and the at least one microneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises a biorecognition element. 69. The microneedle array of clause 68, wherein the biorecognition element comprises glucose oxidase. 70.Themicroneedlearrayof clause67,wherein thedistal endof theelectrode isoffset from thedistal apexbyanoffset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one microneedle. 71. The microneedle array of clause 67, wherein the electrode is annular. 72. The microneedle array of clause 67, wherein in at least one microneedle, a portion of the working electrode is recessed into the tapered distal portion. 73. The microneedle array of clause 67, wherein the electrode is on only a segment of the tapered distal portion. 74. Themicroneedle array of clause 67, further comprising an electrical contact, wherein the at least onemicroneedle comprises a body portion providing a conductive pathway between the electrical contact and the electrode. 75. Themicroneedlearray of clause67,wherein eachof themicroneedles in theplurality ofmicroneedles comprisesa a tapered distal portion having an insulated distal apex; and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex. 76. The microneedle array of clause 67, wherein the microneedle array comprises a plurality of working electrodes, wherein each working electrode is individually addressable and electrically isolated from every other working 51 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 electrode in the analyte monitoring device. 77. The microneedle array of clause 76, wherein the microneedle array is configured to detect multiple analytes. 78. The microneedle array of clause 67, wherein the microneedles of the plurality of microneedles are arranged in a hexagonal array. 79. Themicroneedle array of clause 67, wherein the at least onemicroneedle is configured to puncture skin of a user and sense an analyte in interstitial fluid in a dermal layer of the user. 80. Ananalytemonitoring systemcomprising themicroneedle arrayof clause67andawearable housing,wherein the microneedle array extends outwardly from the housing. 81. The systemof clause80,wherein theat least onemicroneedle extends from thehousing such that the distal endof the electrode is located less than about 5 mm from the housing. 82. The system of clause 80, wherein the housing encloses an electronics system comprising a wireless commu- nicationmodule and the system further comprises a software application executable on amobile computing device to be paired with the wireless communication module. 83. The system of clause 80, wherein the housing comprises a user interface comprising one or more indicator lights configured to communicate status information. 84. The system of clause 83, wherein at least one of the indicator lights is configured to be selectively illuminated in accordance with an illumination mode corresponding to an analyte measurement status. 85. The system of clause 83, wherein the analyte monitoring system comprises a skin-adhered patch. 86. A method of sterilizing an analyte monitoring device, the method comprising: exposing the analyte monitoring device to a sterilant gas, wherein the analyte monitoring device comprises a wearable housing, a microneedle array extending from the housing and comprising an analyte sensor, and an electronics system arranged in the housing and electrically coupled to the microneedle array, wherein the analyte monitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device. 87. The method of clause 86, wherein the sterilant gas is suitable for oxidative sterilization. 88. The method of clause 87, wherein the sterilant gas comprises ethylene oxide. 89. The method of clause 86, wherein the analyte sensor comprises an electrode. 90. The method of clause 89, wherein the analyte sensor comprises a biorecognition layer arranged over the electrode, wherein the biorecognition layer comprises a biorecognition element. 91. The method of clause 90, wherein the biorecognition element comprises an enzyme. 92. The method of clause 91, wherein the enzyme is an oxidoreductase. 93. The method of clause 92, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxi- dase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase. 94. The method of clause 92, wherein the oxidoreductase is glucose oxidase. 95. Themethod of clause 90, wherein the biorecognition element is cross-linked with an amine-condensing carbonyl 52 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 chemical species. 96. The method of clause 95, wherein the amine-condensing carbonyl chemical species is at least one of formalde- hyde, glyoxal, malonaldehyde, and succinaldehyde. 97. The method of clause 95, wherein the amine-condensing carbonyl chemical species is glutaraldehyde. 98. The method of clause 90, wherein the biorecognition layer is formed at least in part by cross-linking the biorecognition element to form cross-linked biorecognition element aggregates, and embedding the cross-linked biorecognition element aggregates in a conducting polymer. 99. The method of clause 98, wherein embedding the cross-linked biorecognition element aggregates comprises embedding only cross-linked biorecognition element aggregates having at least a threshold molecular weight. 100. Themethodof clause86,wherein exposing theanalytemonitoringdevice to the sterilant gas comprises injecting the sterilant gas into a compartment containing the analyte monitoring device, and heating the compartment to a sterilization temperature. 101. Themethod of clause 100,wherein the sterilization temperature is belowabout 45 degreesCelsius and thedwell time is at least about 2 hours. 102. Themethod of clause 86, further comprising preconditioning the analyte monitoring device prior to exposing the analyte monitoring device to the sterilant gas, wherein preconditioning the analyte comprises exposing the analyte monitoring device to steam. 103. A microneedle array for an analyte monitoring device, the microneedle array comprising: a plurality of solid sensing microneedles, wherein each sensing microneedle comprises: a tapered distal portion comprising a working electrode configured to sense an analyte; and a body portion providing a conductive connection to the working electrode, wherein thebodyportionofeachsensingmicroneedle is insulatedsuch that eachworkingelectrode is individually addressable and electrically isolated from every other working electrode in the microneedle array. 104. Themicroneedle arrayof clause103,wherein at least one sensingmicroneedle comprisesabiorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises a biorecognition element. 105. The microneedle array of clause 104, wherein the biorecognition element comprises an enzyme. 106. The microneedle array of clause 105, wherein the enzyme is an oxidoreductase. 107. The microneedle array of clause 106, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, choles- terol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase. 108. The microneedle array of clause 106, wherein the oxidoreductase is glucose oxidase. 109. The microneedle array of clause 104, wherein the biorecognition element is cross-linked with an amine-condensing carbonyl chemical species. 110. Themicroneedle array of clause 109,wherein theamine-condensing carbonyl chemical species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde. 111. The microneedle array of clause 109, wherein the amine-condensing carbonyl chemical species is glutaralde- hyde. 53 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 112. The microneedle array of clause 104, wherein the at least one sensing microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer. 113. Themicroneedle array of clause 103, wherein themicroneedle array further comprises at least onemicroneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on the working electrode of at least one sensing microneedle. 114. Themicroneedle array of clause 103, wherein the plurality of microneedles comprises at least one microneedle comprising a reference electrode configured to provide a reference potential for the working electrode. 115. The microneedle array of clause 114, further comprising a conducting polymer arranged over the reference electrode. 116. The microneedle array of clause 15, wherein the conducting polymer comprises a dopant. 117. The microneedle array of clause 114, wherein the reference electrode comprises a metal oxide with a stable electrode potential. 118. The microneedle array of clause 117, wherein the metal oxide comprises iridium oxide. 119. The microneedle array of clause 114, wherein the reference electrode comprises a metal salt with a stable electrode potential. 120. The microneedle array of clause 119, wherein the metal salt comprises silver chloride. 121. The microneedle array of clause 103, wherein in at least one sensing microneedle, the tapered distal portion comprises an insulated distal apex and the working electrode is proximal to the insulated distal apex. 122.Themicroneedlearrayof clause121,whereinadistal endof theworkingelectrode isoffset from thedistal apexby an offset distance of at least about 10 µm, wherein the offset distance is measured along a longitudinal axis of the at least one sensing microneedle. 123. The microneedle array of clause 103, wherein in at least one sensing microneedle, a portion of the working electrode is recessed into the tapered distal portion. 124. An analyte monitoring device comprising the microneedle array of clause 103 and a wearable housing, wherein the microneedle array extends outwardly from the housing. 125. The analyte monitoring device of clause 124, wherein the housing comprises one or more indicator lights configured to communicate status information. 126. The analytemonitoring device of clause 124, wherein the housing encloses an electronics system comprising at least one of a processor and a wireless communication module. 127. The analyte monitoring device of clause 126, wherein the analyte monitoring device is a skin-adhered patch. 128. A microneedle array for a body-worn analyte monitoring device, wherein the microneedle array comprises: at least one microneedle comprising: a pyramidal body portion having a non-circular base; and a tapered distal portion extending from the body portion and comprising an electrode, wherein the distal portion comprises a planar surface that is offset from a distal apex of the at least one microneedle. 54 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 129. The microneedle array of clause 128, wherein at least a portion of the body portion has a first taper angle measured relative to thebaseand thedistal apexhasasecond taper anglemeasured relative to thebase,wherein the second taper angle is greater than the first taper angle 130. The microneedle array of clause 128, wherein the second taper is between about 65 degrees and about 75 degrees. 131. Themicroneedle array of clause 130, wherein the first taper is between about 15 degrees and about 25 degrees. 132. The microneedle array of clause 128, wherein the planar surface is angled between about 75 degrees and 85 degrees measured relative to the base. 133. The microneedle array of clause 128, wherein the tapered distal portion comprises an insulated distal apex. 134. An analyte monitoring device comprising the microneedle array of clause 128 and a wearable housing, wherein the microneedle array is configurable to extend outwardly from the housing. 135. The analyte monitoring device of clause 134, wherein the analyte monitoring device is a patch. 136. A method for monitoring a user, comprising: accessing a dermal interstitial fluid of the user at a plurality of sensor locations with an integrated analyte monitoring device comprising a single microneedle array; quantifying one or more analytes in the dermal interstitial fluid using a plurality of working electrodes in the microneedle array, wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device. 137.Themethodof clause136,wherein quantifyingoneormoreanalytes comprisesquantifyingaplurality of analytes in the dermal interstitial fluid using the plurality of working electrodes. 138. The method of clause 136, wherein the microneedle array comprises:a plurality of sensing microneedles, each sensing microneedle comprising a respective working electrode. 139. Themethod of clause 138, wherein at least one sensingmicroneedle comprises a biorecognition layer arranged over the working electrode, wherein the biorecognition layer comprises an enzyme. 140. The method of clause 139, wherein the at least one microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer. 141. The method of clause 136, wherein the microneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current to sustain an electrochemical reaction on at least one working electrode. 142. Themethod of clause 136, wherein the plurality ofmicroneedles comprises at least onemicroneedle comprising a reference electrode configured to provide a reference potential for at least one working electrode. 143. The method of clause 142, further comprising a conducting polymer arranged over the reference electrode. 144. The method of clause 143, wherein the conducting polymer comprises a dopant. 145. The method of clause 142, wherein the reference electrode comprises a metal oxide with a stable electrode potential. 146. The method of clause 145, wherein the metal oxide comprises iridium oxide. 147. The method of clause 142, wherein the reference electrode comprises a metal salt with a stable electrode potential. 55 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 148. The method of clause 147, wherein the metal salt comprises silver chloride. 149.Themethodof clause136, further comprisingcommunicating status information indicativeof thequantificationof the one or more analytes. 150. The method of clause 149, wherein the microneedle array extends outwardly from a wearable housing and communicating status information comprises communicating status information via a user interface on the housing. 151. Themethod of clause 150, wherein communicating status information comprises selectively illuminating one or more indicator lights on the housing in accordance with an illumination mode corresponding to an analyte measure- ment status or a status of the integrated analyte monitoring device. 152. The method of clause 150, wherein communicating status information comprises activating a display corre- sponding to an analyte measurement status or a status of the integrated analyte monitoring device. 153. A body-worn analyte monitoring device, comprising: a wearable housing; and amicroneedlearray extendingoutwardly from thehousingand comprisingat least onemicroneedle configured to measure one or more analytes in a user wearing the housing, wherein the housing comprises a user interface configured to communicate information indicative of the measurement of the one or more analytes. 154. The device of clause 153, wherein the user interface comprises one or more indicator lights configured to be selectively illuminated in accordancewith an illuminationmode corresponding to an analytemeasurement status or a status of an integrated analyte monitoring device. 155. The device of clause 154, wherein at least one of the indicator lights is configured to be selectively illuminated to communicate a current analyte measurement level. 156. The device of clause 154, wherein the user interface comprises a plurality of indicator lights configured to be selectively illuminated in a progressive sequence to communicate an analyte measurement trend. 157.Thedeviceof clause156,wherein thepluralityof indicator lights is configured tobeselectively illuminated inafirst progressive sequence in a first direction to communicate a rising analyte measurement trend. 158. The device of clause 156, wherein the plurality of indicator lights is configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a falling analyte measurement trend. 159. The device of clause 153, wherein the user interface is further configured to communicate information indicative of a status of the analyte monitoring device. 160. The device of clause 153, wherein the user interface comprises a display screen. 161. The device of clause 153, wherein the analyte monitoring device is a skin-adhered patch. 162. The device of clause 153, wherein the at least one microneedle comprises a tapered distal portionwith an insulated distal apex, and an electrode on a surface of the tapered distal portion, wherein the electrode is located proximal to the insulated distal apex. 163. The device of clause 153, wherein the microneedle array comprises a plurality of working electrodes, wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device. 164. A method for monitoring a user, comprising: measuring one ormore analytes in the user using a body-worn analytemonitoring device comprising awearable housing and one or more analyte sensors; 56 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 communicating information indicativeof themeasurement of theoneormoreanalytes throughauser interfaceon the housing. 165. The method of clause 164, wherein communicating information comprises illuminating one or more indicator lights on the housing in accordance with an illumination mode corresponding to an analyte measurement status. 166. Themethod of clause 165, wherein communicating information comprises selectively illuminating at least one of the indicator lights to communicate a current analyte measurement level. 167. The method of clause 166, wherein communicating information comprises communicating the current analyte measurement level based on color of the illuminated indicator light, location of the illuminated indicator light, or both. 168. The method of clause 165, wherein communicating information comprises selectively illuminating a plurality of indicator lights on the housing in a progressive sequence to communicate an analyte measurement trend. 169. Themethod of clause 168, wherein communicating information comprises selectively illuminating the plurality of indicator lights in a first progressive sequence in a first direction to communicate a rising analytemeasurement trend. 170. Themethod of clause 168, wherein communicating information comprises selectively illuminating the plurality of indicator lights inasecondprogressivesequence inaseconddirection tocommunicatea fallinganalytemeasurement trend. 171. The method of clause 164, further comprising communicating information indicative of a status of the analyte monitoring device through the user interface. 172. The method of clause 164, further comprising accessing a dermal interstitial fluid of the user at a plurality of sensor locations with the analytemonitoring device, wherein quantifying one ofmore analytes comprises quantifying one or more analytes in the dermal interstitial fluid. 173. The method of clause 164, wherein the analyte monitoring device comprises a microneedle array comprising a plurality of working electrodes, wherein each working electrode is individually addressable and electrically isolated from every other working electrode in the analyte monitoring device. Claims 1. A microneedle array for use in sensing an analyte, comprising: a semiconductor substrate; and a plurality of microneedles formed from the semiconductor substrate, the plurality of microneedles comprising: a first microneedle comprising a first working electrode comprising a first biorecognition element configured to react with the analyte; a second microneedle comprising a second working electrode comprising a second biorecognition element configured to react with the analyte; and a third microneedle comprising a counter electrode, wherein each of the first microneedle, the second microneedle, and the third microneedle are insulated from the semiconductor substrate and electrically isolated from one another such that a first redox reaction between the first working electrode and the counter electrode and a second redox reaction between the second working electrode and the counter electrode are independent of one another. 2. The microneedle array of claim 1, wherein the plurality of microneedles further comprises a fourth microneedle comprising a reference electrode. 3. Themicroneedle array of claim 1, wherein the first microneedle and the secondmicroneedle are solid microneedles. 4. The microneedle array of claim 1, wherein the first microneedle and the second microneedle each comprise an 57 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 insulated distal tip. 5. The microneedle array of claim 1, wherein the first microneedle and the second microneedle each comprise an insulative sheath that electrically isolates a respective one of the first microneedle and the second microneedle from the semiconductor substrate. 6. The microneedle array of claim 5, wherein respective insulative sheaths insulates the first microneedle and the second microneedle such that they are individually addressable and electrically isolated from one another. 7. Themicroneedle array of claim1,wherein oneormoreof the firstworking electrodeand the secondworking electrode comprises a material selected from the group consisting of: platinum, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, and doped diamond. 8. The microneedle array of claim 1, wherein the first biorecognition element is entrapped within a first biorecognition layer comprising a conducting polymer, andwherein the second biorecognition element is entrappedwithin a second biorecognition layer comprising a conducting polymer. 9. The microneedle array of claim 1, wherein the first redox reaction and the second redox reaction correspond to independent measurements of the analyte from the first working electrode and the second working electrode. 10. A method for sensing an analyte via a microneedle array, comprising: applying a first bias potential between a first working electrode on a first microneedle formed from a semi- conductor substrate and a reference electrode, wherein the first working electrode comprises a first biorecogni- tion element; applying a second bias potential between a second working electrode on a secondmicroneedle formed from the semiconductor substrateand the referenceelectrode,wherein thesecondworkingelectrodecomprisesasecond biorecognition element; measuring a first current value between the first working electrode and a counter electrode, the first current value being proportional to a concentration of the analyte; and measuring a second current value between the second working electrode and the counter electrode, the second current value being proportional to a concentration of the analyte, wherein each of the first microneedle and the second microneedle are insulated from the semiconductor substrate and electrically isolated from one another such that the first current value and the second current value are independent of one another. 11. Themethod of claim 10, wherein the first microneedle and the secondmicroneedle each comprise an insulated distal tip. 12. The method of claim 10, wherein the first microneedle and the second microneedle are solid microneedles. 13. The method of claim 10, wherein the first current value and the second current value correspond to independent measurements of the analyte from the first working electrode and the second working electrode, respectively. 14. Themethodof claim10,wherein the firstmicroneedle and the secondmicroneedle are each insulatedbyan insulative sheath. 15. The method of claim 14, wherein respective insulative sheaths insulate the first microneedle and the second microneedle such that the first microneedle and the second microneedle are individually addressable. 58 EP 4 647 772 A2 5 10 15 20 25 30 35 40 45 50 55 59 EP 4 647 772 A2 60 EP 4 647 772 A2 61 EP 4 647 772 A2 62 EP 4 647 772 A2 63 EP 4 647 772 A2 64 EP 4 647 772 A2 65 EP 4 647 772 A2 66 EP 4 647 772 A2 67 EP 4 647 772 A2 68 EP 4 647 772 A2 69 EP 4 647 772 A2 70 EP 4 647 772 A2 71 EP 4 647 772 A2 72 EP 4 647 772 A2 73 EP 4 647 772 A2 74 EP 4 647 772 A2 75 EP 4 647 772 A2 76 EP 4 647 772 A2 77 EP 4 647 772 A2 78 EP 4 647 772 A2 79 EP 4 647 772 A2 80 EP 4 647 772 A2 81 EP 4 647 772 A2 82 EP 4 647 772 A2 83 EP 4 647 772 A2 84 EP 4 647 772 A2 85 EP 4 647 772 A2 86 EP 4 647 772 A2 87 EP 4 647 772 A2 88 EP 4 647 772 A2 89 EP 4 647 772 A2 90 EP 4 647 772 A2 91 EP 4 647 772 A2 92 EP 4 647 772 A2 93 EP 4 647 772 A2 94 EP 4 647 772 A2 95 EP 4 647 772 A2 96 EP 4 647 772 A2 97 EP 4 647 772 A2 98 EP 4 647 772 A2 99 EP 4 647 772 A2 100 EP 4 647 772 A2 101 EP 4 647 772 A2 102 EP 4 647 772 A2 103 EP 4 647 772 A2 104 EP 4 647 772 A2 105 EP 4 647 772 A2 106 EP 4 647 772 A2 107 EP 4 647 772 A2 108 EP 4 647 772 A2 109 EP 4 647 772 A2 110 EP 4 647 772 A2 111 EP 4 647 772 A2 112 EP 4 647 772 A2 113 EP 4 647 772 A2 114 EP 4 647 772 A2 115 EP 4 647 772 A2 REFERENCES CITED IN THE DESCRIPTION This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard. Patent documents cited in the description • US 63058275

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[0210] (19) *EP004647772A3* (11) EP 4 647 772 A3 (12) EUROPEAN PATENT APPLICATION (88) Date of publication A3: 24.12.2025 Bulletin 2025 / 52 (43) Date of publication A2: 12.11.2025 Bulletin 2025 / 46 (21) Application number: 25191106.1 (22) Date of filin...

Claims

1. A microneedle array for use in sensing an analyte, comprising: a semiconductor substrate; and a plurality of microneedles formed from the semiconductor substrate, the plurality of microneedles comprising: a first microneedle comprising a first working electrode comprising a first biorecognition element configured to react with the analyte; a second microneedle comprising a second working electrode comprising a second biorecognition element configured to react with the analyte; and a third microneedle comprising a counter electrode, wherein each of the first microneedle, the second microneedle, and the third microneedle are insulated from the semiconductor substrate and electrically isolated from one another such that a first redox reaction between the first working electrode and the counter electrode and a second redox reaction between the second working electrode and the counter electrode are independent of one another.

2. The microneedle array of claim 1, wherein the plurality of microneedles further comprises a fourth microneedle comprising a reference electrode.

3. The microneedle array of claim 1, wherein the first microneedle and the second microneedle are solid microneedles.

4. The microneedle array of claim 1, wherein the first microneedle and the second microneedle each comprise an insulated distal tip.

5. The microneedle array of claim 1, wherein the first microneedle and the second microneedle each comprise an insulative sheath that electrically isolates a respective one of the first microneedle and the second microneedle from the semiconductor substrate.

6. The microneedle array of claim 5, wherein respective insulative sheaths insulates the first microneedle and the second microneedle such that they are individually addressable and electrically isolated from one another.

7. The microneedle array of claim 1, wherein one or more of the first working electrode and the second working electrode comprises a material selected from the group consisting of: platinum, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, and doped diamond.

8. The microneedle array of claim 1, wherein the first biorecognition element is entrapped within a first biorecognition layer comprising a conducting polymer, and wherein the second biorecognition element is entrapped within a second biorecognition layer comprising a conducting polymer.

9. The microneedle array of claim 1, wherein the first redox reaction and the second redox reaction correspond to independent measurements of the analyte from the first working electrode and the second working electrode.

10. A method for sensing an analyte via a microneedle array, comprising: applying a first bias potential between a first working electrode on a first microneedle formed from a semiconductor substrate and a reference electrode, wherein the first working electrode comprises a first biorecognition element; applying a second bias potential between a second working electrode on a second microneedle formed from the semiconductor substrate and the reference electrode, wherein the second working electrode comprises a second biorecognition element; measuring a first current value between the first working electrode and a counter electrode, the first current value being proportional to a concentration of the analyte; and measuring a second current value between the second working electrode and the counter electrode, the second current value being proportional to a concentration of the analyte, wherein each of the first microneedle and the second microneedle are insulated from the semiconductor substrate and electrically isolated from one another such that the first current value and the second current value are independent of one another.

11. The method of claim 10, wherein the first microneedle and the second microneedle each comprise an insulated distal tip.

12. The method of claim 10, wherein the first microneedle and the second microneedle are solid microneedles.

13. The method of claim 10, wherein the first current value and the second current value correspond to independent measurements of the analyte from the first working electrode and the second working electrode, respectively.

14. The method of claim 10, wherein the first microneedle and the second microneedle are each insulated by an insulative sheath.

15. The method of claim 14, wherein respective insulative sheaths insulate the first microneedle and the second microneedle such that the first microneedle and the second microneedle are individually addressable.

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