Continuous analyte monitoring system with microneedle arrays

Abstract

To provide a continuous analyte monitoring system with a microneedle array.SOLUTION: Described here are variations of an analyte monitoring system, including an analyte monitoring device. For example, the 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 are individually addressable.SELECTED DRAWING: Figure 2A

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Patent Application No. 63 / 058,275, filed July 29, 2020, the contents of which are incorporated herein by reference in their entirety.

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

[0003] Diabetes is a chronic disease in which the body does not produce or properly utilize insulin, a hormone that regulates blood sugar. Insulin can be administered to diabetic patients to help regulate blood sugar levels, but blood sugar levels must nevertheless be carefully monitored to help ensure that timing and dosage are appropriate. Without proper management of their condition, diabetic patients can suffer from a variety of complications resulting from hyperglycemia (high blood sugar levels) or hypoglycemia (low blood sugar levels).

[0004] Blood glucose monitors help diabetic patients manage their condition by measuring blood glucose levels from a sample of blood. For example, a diabetic patient may obtain a blood sample through a finger-prick sampling mechanism, transfer the blood sample to a test strip with a suitable reagent that reacts with the blood sample, and use the blood glucose monitor to analyze the test strip and measure the glucose level in the blood sample. However, patients using this process are typically only able to measure their glucose levels at discrete time points, which may not capture hyperglycemic or hypoglycemic conditions in a timely manner. Another more recent variety of glucose monitor is the continuous glucose monitor (CGM) device, which includes an implantable transcutaneous electrochemical sensor used to continuously detect and quantify blood glucose levels by surrogate measurement of glucose levels in 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 the capillary source to the sensor). These weaknesses also lead to several drawbacks, such as pain experienced by the patient when the electrochemical sensor is inserted and limited accuracy in measuring glucose, especially when blood glucose levels are changing rapidly. Therefore, a need exists for new and improved analyte monitoring systems. Summary of the Invention [Means for solving the problem]

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

[0006] In some variations, a method for monitoring a user may include accessing a bodily fluid of a user with an analyte monitoring device and quantifying one or more analytes in the bodily fluid using the analyte monitoring device, which may include a plurality of solid microneedles. In some variations, at least one of the microneedles may include a tapered distal portion having an insulated distal apex and an electrode on a surface of the tapered distal portion, the electrode 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 microneedles, at least one of which includes a tapered distal portion having an insulated distal apex and an electrode on a surface of the tapered distal portion, the distal end of the electrode being 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, the analyte monitoring device comprising a wearable housing, a microneedle array extending from the housing, the analyte sensor, and an electronics system disposed within the housing and electrically coupled to the microneedle array. The analyte monitoring device may 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 multiple sensing microneedles (e.g., solid microneedles), each including 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. The body portion of each sensing microneedle may be insulated such that each working electrode is individually addressable and electrically isolated from all other working electrodes 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 conical body portion having a non-circular shape (e.g., an octagonal base) and a tapered distal portion extending from the body portion and including an electrode, the distal portion including a planar surface offset from the distal apex of the at least one microneedle.

[0011] In some variations, a method for monitoring a user may include accessing the user's dermal interstitial fluid at multiple 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 multiple working electrodes in the microneedle array, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device.

[0012] In some variations, a body-worn analyte monitoring device may include a wearable housing and a microneedle array. The microneedle array may include at least one microneedle extending outward from the housing and 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, a method for monitoring a user may include measuring one or more analytes in a user using a body-worn analyte monitoring device comprising a wearable housing and one or more analyte sensors, and communicating information indicative of the measurement of the one or more analytes through a user interface on the housing. The present invention provides, for example, the following. (Item 1) 1. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, at least one of the microneedles comprising: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; a plurality of solid microneedles comprising: A microneedle array comprising: (Item 2) 2. The microneedle array of claim 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 across the working electrode, the biorecognition layer comprising a biorecognition element. (Item 3) 3. The microneedle array of claim 2, wherein the biorecognition element comprises an enzyme. (Item 4) Item 4. The microneedle array according to item 3, wherein the enzyme is an oxidoreductase. (Item 5) 5. The microneedle array of item 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. (Item 6) 5. The microneedle array according to item 4, wherein the oxidoreductase is glucose oxidase. (Item 7) 3. The microneedle array of claim 2, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species. (Item 8) 8. The microneedle array of claim 7, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde. (Item 9) 8. The microneedle array of claim 7, wherein the amine-fused carbonyl species is glutaraldehyde. (Item 10) 3. The microneedle array of claim 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. (Item 11) Item 3. The microneedle array of item 2, wherein the microneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction relative to the working electrode. (Item 12) Item 3. The microneedle array of item 2, wherein the microneedle array comprises at least one microneedle comprising a reference electrode configured to provide a reference potential relative to the working electrode. (Item 13) Item 13. The microneedle array of item 12, further comprising a conductive polymer arranged across the reference electrode. (Item 14) Item 14. The microneedle array of item 13, wherein the conductive polymer comprises a dopant. (Item 15) Item 14. The microneedle array of item 13, wherein the reference electrode comprises a metal oxide with a stable electrode potential. (Item 16) Item 16. The microneedle array of item 15, wherein the metal oxide comprises iridium oxide. (Item 17) Item 14. The microneedle array of item 13, wherein the reference electrode comprises a metal salt with a stable electrode potential. (Item 18) Item 18. The microneedle array according to item 17, wherein the metal salt comprises silver chloride. (Item 19) Item 10. The microneedle array of item 1, wherein the entire electrode is on a tapered distal portion of the at least one microneedle. (Item 20) Item 10. The microneedle array of item 1, wherein the electrode comprises a catalytic surface. (Item 21) 21. The microneedle array of item 20, wherein the catalytic surface comprises at least one of platinum, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, and doped diamond. (Item 22) 21. The microneedle array of claim 20, wherein the at least one microneedle comprises platinum black arranged across the electrode. (Item 23) Item 1, wherein the distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 μm, the offset distance being measured along the longitudinal axis of the at least one microneedle. (Item 24) Item 2. The microneedle array of item 1, wherein the electrode is annular. (Item 25) Item 10. The microneedle array of item 1, wherein a portion of the working electrode is recessed within the tapered distal portion. (Item 26) Item 2. The microneedle array of item 1, wherein the electrodes are located only on a section of the tapered distal portion. (Item 27) Item 10. The microneedle array of item 1, further comprising an electrical contact, wherein the at least one microneedle comprises a body portion that provides a conductive path between the electrical contact and the electrode. (Item 28) Item 28. The microneedle array of item 27, wherein the body portion is formed from a conductive material. (Item 29) Item 28. The microneedle array of item 27, wherein the body portion comprises an embedded pathway. (Item 30) Item 28. The microneedle array of item 27, wherein the body portion is insulated. (Item 31) Item 28. The microneedle array of item 27, wherein the body portion has a circular, square, or octagonal base. (Item 32) Item 33. The microneedle array according to Item 27, wherein at least a section of the body portion is cylindrical. Item 34. The microneedle array according to Item 27, wherein at least a section of the body portion is cone-shaped. Item 34. The microneedle array of item 33, wherein at least a portion of the body portion has a first taper angle measured relative to the base of the body portion, and the distal apex has a second taper angle measured relative to the base, the second taper angle being greater than the first taper angle. (Item 35) Item 35. The microneedle array of item 34, wherein at least one of the microneedle body portion and distal portion is radially asymmetric. (Item 36) Item 36. The microneedle array of item 35, wherein the tapered distal portion comprises a planar surface offset from the distal apex of the at least one microneedle. (Item 37) Each of the microneedles in the plurality of microneedles comprises: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; Item 2. The microneedle array of item 1, comprising: (Item 38) Item 1, wherein the microneedles of the plurality of microneedles are electrically isolated from each other. (Item 39) Item 39. The microneedle array of item 38, wherein the microneedle array is configured to detect multiple analytes. (Item 40) Item 1, wherein the microneedles of the plurality of microneedles are arranged in a periodic grid. (Item 41) Item 41. The microneedle array of item 40, wherein the periodic grid comprises a rectangular array. (Item 42) Item 41. The microneedle array of item 40, wherein the periodic grid comprises a hexagonal array. (Item 43) Item 41. The microneedle array of item 40, wherein the microneedles in the periodic grid are spaced apart by a distance of about 200 μm to about 800 μm. (Item 44) Item 41. The microneedle array of item 40, wherein the microneedles in the periodic grid are uniformly spaced. (Item 45) Item 1, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen. (Item 46) Item 10. The microneedle array of item 1, wherein the at least one microneedle is configured to pierce the skin of a user and sense an analyte in interstitial fluid within the dermis layer of the user. (Item 47) 10. An analyte monitoring system comprising the microneedle array of claim 1 and a wearable housing, the microneedle array extending outward from the housing. (Item 48) Item 48. The system of item 47, 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. (Item 49) Item 49. The system of item 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. (Item 50) Item 48. The system of item 47, wherein the housing encloses an electronics system including at least one of a processor and a wireless communication module. (Item 51) Item 51. The system of item 50, wherein the electronic device 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. (Item 52) Item 48. The system of item 47, wherein the housing comprises one or more indicator lights configured to communicate status information. (Item 53) Item 53. The system of item 52, wherein at least one of the indicator lights is configured to be selectively illuminated according to an illumination mode corresponding to an analyte measurement status. (Item 54) Item 54. The system of item 53, wherein at least one of the indicator lights is configured to be selectively illuminated to communicate a current analyte measurement level. (Item 55) Item 54. The system of item 53, wherein the user interface comprises a plurality of indicator lights selectively illuminated in a progressive sequence and configured to communicate analyte measurement trends. (Item 56) Item 56. The system of item 55, wherein the plurality of indicator lights are configured to be selectively illuminated in a first progressive sequence in a first direction to communicate an ascending analyte measurement trend and further configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a descending analyte measurement trend. (Item 57) 53. The system of claim 52, wherein the user interface is further configured to communicate information indicative of a status of the analyte monitoring device. (Item 58) Item 48. The system of item 47, further comprising an adhesive configured to couple the housing to the user's skin. (Item 59) Item 48. The system of item 47, further comprising an applicator configured to apply at least a portion of the analyte monitoring system to the skin of the user. (Item 60) 48. The system of claim 47, wherein the analyte monitoring system is a skin adhesive patch. (Item 61) Item 48. The system of item 47, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen. (Item 62) Item 48. The system of item 47, wherein the plurality of microneedles comprises at least one solid microneedle comprising a coating containing a therapeutic substance. (Item 63) 63. The system of claim 62, wherein the therapeutic agent comprises at least one of insulin, glucagon, metformin, acetaminophen, acetylsalicylic acid, isobutylphenylpropionic acid, levodopa, a statin, hydrocodone, an opioid, a nonsteroidal anti-inflammatory drug, an anesthetic, an analgesic, an anticonvulsant, an antidepressant, an antipsychotic, a sedative, a relaxant, a hormonal agent, an antibacterial agent, and an antiviral agent. (Item 64) 1. A method for monitoring a user, comprising: accessing a bodily fluid of the user with an analyte monitoring device; quantitating one or more analytes in the bodily fluid using the analyte monitoring device; Including, The analyte monitoring device comprises a plurality of solid microneedles, at least one of the microneedles comprising: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; A method comprising: (Item 65) Item 65. The method of item 64, wherein the bodily fluid comprises dermal interstitial fluid of the user. (Item 66) 65. The method of claim 64, wherein the one or more analytes comprises glucose. (Item 67) 1. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, at least one of the microneedles comprising: a tapered distal portion having an insulated distal apex; an electrode on the surface of the tapered distal portion, the distal end of the electrode being offset from the distal apex; a plurality of solid microneedles comprising: A microneedle array comprising: (Item 68) 68. The microneedle array of claim 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 across the working electrode, the biorecognition layer comprising a biorecognition element. (Item 69) Item 69. The microneedle array of item 68, wherein the biorecognition element comprises glucose oxidase. (Item 70) Item 68. The microneedle array of item 67, wherein the distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 μm, the offset distance being measured along the longitudinal axis of the at least one microneedle. (Item 71) Item 68. The microneedle array of item 67, wherein the electrodes are annular. (Item 72) Item 68. The microneedle array of item 67, wherein in at least one microneedle, a portion of the working electrode is recessed into the tapered distal portion. (Item 73) Item 68. The microneedle array of item 67, wherein the electrodes are on only a section of the tapered distal portion. (Item 74) Item 68. The microneedle array of item 67, further comprising an electrical contact, wherein the at least one microneedle comprises a body portion that provides a conductive path between the electrical contact and the electrode. (Item 75) Each of the microneedles in the plurality of microneedles comprises: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; Item 68. The microneedle array of item 67, comprising: (Item 76) Item 68. The microneedle array of item 67, wherein the microneedle array comprises a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device. (Item 77) Item 77. The microneedle array of item 76, wherein the microneedle array is configured to detect multiple analytes. (Item 78) Item 68. The microneedle array of item 67, wherein the microneedles of the plurality of microneedles are arranged in a hexagonal array. (Item 79) Item 68. The microneedle array of item 67, wherein the at least one microneedle is configured to pierce the skin of a user and sense an analyte in interstitial fluid within the dermis layer of the user. (Item 80) 68. An analyte monitoring system comprising the microneedle array of claim 67 and a wearable housing, the microneedle array extending outwardly from the housing. (Item 81) Item 81. The system of item 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. (Item 82) Item 81. The system of item 80, wherein the housing encloses an electronics system including a wireless communication module, the system further including a software application executable on a mobile computing device to be paired with the wireless communication module. (Item 83) Item 84. The system of item 80, wherein the housing includes a user interface including one or more indicator lights configured to communicate status information. Item 84. The system of item 83, wherein at least one of the indicator lights is configured to be selectively illuminated according to an illumination mode corresponding to an analyte measurement status. (Item 85) Item 84. The system of item 83, wherein the analyte monitoring system comprises a skin adhesive patch. (Item 86) 1. A method of sterilizing an analyte monitoring device, the method comprising: exposing the analyte monitoring device to a sterilant gas, the analyte monitoring device comprising a wearable housing, a microneedle array extending from the housing and comprising an analyte sensor, and an electronics system disposed within the housing and electrically coupled to the microneedle array; Including, A method wherein the analyte monitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device. (Item 87) 87. The method of claim 86, wherein the sterilant gas is suitable for oxidative sterilization. (Item 88) 88. The method of claim 87, wherein the sterilant gas comprises ethylene oxide. (Item 89) Item 87. The method of item 86, wherein the analyte sensor comprises an electrode. (Item 90) 90. The method of claim 89, wherein the analyte sensor comprises a biorecognition layer arranged over the electrodes, the biorecognition layer comprising a biorecognition element. (Item 91) 91. The method of claim 90, wherein the biorecognition element comprises an enzyme. (Item 92) 92. The method of claim 91, wherein the enzyme is an oxidoreductase. (Item 93) Item 93. The method of item 92, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, β-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase. (Item 94) Item 93. The method of item 92, wherein the oxidoreductase is glucose oxidase. (Item 95) 91. The method of claim 90, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species. (Item 96) Item 96. The method of item 95, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde. (Item 97) 96. The method of claim 95, wherein the amine-fused carbonyl species is glutaraldehyde. (Item 98) Item 91. The method of item 90, wherein the biorecognition layer is formed at least in part by crosslinking the biorecognition elements to form a crosslinked biorecognition element assembly, and embedding the crosslinked biorecognition element assembly in a conducting polymer. (Item 99) Item 99. The method of item 98, wherein embedding the cross-linked biorecognition element assemblies comprises embedding only cross-linked biorecognition element assemblies having at least a threshold molecular weight. (Item 100) 87. The method of claim 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. (Item 101) Item 101. The method of item 100, wherein the sterilization temperature is below about 45 degrees Celsius and the dwell time is at least about 2 hours. (Item 102) 87. The method of claim 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. (Item 103) 1. A microneedle array for an analyte monitoring device, the microneedle array comprising: a plurality of solid sensing microneedles, each sensing microneedle comprising: a tapered distal portion comprising a working electrode configured to sense an analyte; a body portion providing a conductive connection to said working electrode; Equipped with the body portion of each sensing microneedle is insulated so that each working electrode is individually addressable and electrically isolated from all other working electrodes in the microneedle array; Multiple solid sensing microneedles A microneedle array comprising: (Item 104) Item 104. The microneedle array of item 103, wherein at least one sensing microneedle comprises a biorecognition layer arranged across the working electrode, the biorecognition layer comprising a biorecognition element. (Item 105) Item 105. The microneedle array of item 104, wherein the biorecognition element comprises an enzyme. (Item 106) Item 106. The microneedle array according to item 105, wherein the enzyme is an oxidoreductase. (Item 107) Item 107. The microneedle array of item 106, 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. (Item 108) Item 109. The microneedle array according to Item 106, wherein the oxidoreductase is glucose oxidase. Item 105. The microneedle array of item 104, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species. (Item 110) Item 109. The microneedle array of item 109, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde. (Item 111) Item 109. The microneedle array of item 109, wherein the amine-fused carbonyl species is glutaraldehyde. (Item 112) Item 105. The microneedle array of item 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. (Item 113) Item 104. The microneedle array of item 103, further comprising at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction to the working electrode of the at least one sensing microneedle. (Item 114) Item 104. The microneedle array of item 103, wherein the plurality of microneedles comprises at least one microneedle comprising a reference electrode configured to provide a reference potential relative to the working electrode. (Item 115) Item 115. The microneedle array of item 114, further comprising a conductive polymer arranged across the reference electrode. (Item 116) Item 116. The microneedle array of item 115, wherein the conductive polymer comprises a dopant. (Item 117) Item 115. The microneedle array of item 114, wherein the reference electrode comprises a metal oxide with a stable electrode potential. (Item 118) Item 118. The microneedle array of item 117, wherein the metal oxide comprises iridium oxide. (Item 119) Item 115. The microneedle array of item 114, wherein the reference electrode comprises a metal salt with a stable electrode potential. (Item 120) Item 120. The microneedle array of item 119, wherein the metal salt comprises silver chloride. (Item 121) Item 104. The microneedle array of item 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. (Item 122) Item 122. The microneedle array of item 121, wherein the distal end of the working electrode is offset from the distal apex by an offset distance of at least about 10 μm, the offset distance being measured along the longitudinal axis of the at least one sensing microneedle. (Item 123) Item 104. The microneedle array of item 103, wherein in at least one sensing microneedle, a portion of the working electrode is recessed into the tapered distal portion. (Item 124) 104. An analyte monitoring device comprising the microneedle array of claim 103 and a wearable housing, the microneedle array extending outwardly from the housing. (Item 125) Item 125. The analyte monitoring device of item 124, wherein the housing comprises one or more indicator lights configured to communicate status information. (Item 126) Item 125. The analyte monitoring device of item 124, wherein the housing encloses an electronics system comprising at least one of a processor and a wireless communication module. (Item 127) Item 127. The analyte monitoring device of item 126, wherein the analyte monitoring device is a skin adhesive patch. (Item 128) 1. A microneedle array for a body-worn analyte monitoring device, the microneedle array comprising: at least one microneedle, a cone-shaped body portion having a non-circular base; a tapered distal portion extending from the body portion and including an electrode; and Equipped with the distal portion comprises a planar surface offset from a distal apex of the at least one microneedle. At least one microneedle A microneedle array comprising: (Item 129) Item 129. The microneedle array of item 128, wherein at least a portion of the body portion has a first taper angle measured relative to the base and the distal apex has a second taper angle measured relative to the base, the second taper angle being greater than the first taper angle. (Item 130) Item 131. The microneedle array according to Item 128, wherein the second taper is about 65 degrees to about 75 degrees. Item 132. The microneedle array according to Item 130, wherein the first taper is about 15 degrees to about 25 degrees. Item 129. The microneedle array of item 128, wherein the planar surface is angled at approximately 75 to 85 degrees measured relative to the base. (Item 133) Item 129. The microneedle array of item 128, wherein the tapered distal portion comprises an insulated distal apex. (Item 134) 129. An analyte monitoring device comprising the microneedle array of claim 128 and a wearable housing, wherein the microneedle array is configurable to extend outward from the housing. (Item 135) Item 136. The analyte monitoring device of Item 134, wherein the analyte monitoring device is a patch. 1. A method for monitoring a user, comprising: accessing the user's dermal interstitial fluid at multiple sensor locations with an integrated analyte monitoring device comprising a single microneedle array; quantitating one or more analytes in the dermal interstitial fluid using multiple working electrodes in the microneedle array, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device; A method comprising: (Item 137) 137. The method of claim 136, wherein quantifying one or more analytes comprises quantifying a plurality of analytes in the dermal interstitial fluid using the plurality of working electrodes. (Item 138) Item 137. The method of item 136, wherein the microneedle array comprises a plurality of sensing microneedles, each sensing microneedle comprising a respective working electrode. (Item 139) Item 139. The method of item 138, wherein at least one sensing microneedle comprises a biorecognition layer arranged over the working electrode, the biorecognition layer comprising an enzyme. (Item 140) Item 139. The method of item 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. (Item 141) Item 137. The method of item 136, wherein the microneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction to at least one working electrode. (Item 142) Item 143. The method of item 136, wherein the plurality of microneedles includes at least one microneedle including a reference electrode configured to provide a reference potential relative to at least one working electrode. Item 143. The method of item 142, further comprising a conducting polymer arranged across the reference electrode. (Item 144) Item 144. The method of item 143, wherein the conducting polymer comprises a dopant. (Item 145) Item 143. The method of item 142, wherein the reference electrode comprises a metal oxide with a stable electrode potential. (Item 146) Item 146. The method of item 145, wherein the metal oxide comprises iridium oxide. (Item 147) Item 143. The method of item 142, wherein the reference electrode comprises a metal salt with a stable electrode potential. (Item 148) Item 148. The method of item 147, wherein the metal salt comprises silver chloride. (Item 149) Item 137. The method of item 136, further comprising communicating status information indicative of the quantification of the one or more analytes. (Item 150) Item 149. The method of item 149, wherein the microneedle array extends outward from a wearable housing and communicating status information includes communicating status information via a user interface on the housing. (Item 151) 152. The method of claim 150, wherein communicating status information includes selectively illuminating one or more indicator lights on the housing according to an illumination mode corresponding to an analyte measurement status or a status of the integrated analyte monitoring device. Item 151. The method of Clause 150, wherein communicating status information includes activating a display corresponding to the analyte measurement status or the status of the integrated analyte monitoring device. (Item 153) 1. A body-worn analyte monitoring device comprising: a wearable housing; a microneedle array, the microneedle array extending outward from the housing and comprising at least one microneedle configured to measure one or more analytes in a user wearing the housing; Equipped with The device, wherein the housing comprises a user interface configured to communicate information indicative of the measurement of the one or more analytes. (Item 154) Item 155. The device of item 153, wherein the user interface comprises one or more indicator lights configured to be selectively illuminated according to an illumination mode corresponding to an analyte measurement status or a status of an integrated analyte monitoring device. Item 155. The device of item 154, wherein at least one of the indicator lights is configured to be selectively illuminated and to communicate a current analyte measurement level. (Item 156) Item 155. The device of item 154, wherein the user interface comprises a plurality of indicator lights selectively illuminated in a progressive sequence and configured to communicate analyte measurement trends. (Item 157) Item 157. The device of item 156, wherein the plurality of indicator lights are configured to be selectively illuminated in a first progressive sequence in a first direction to communicate an increasing analyte measurement trend. (Item 158) Item 157. The device of item 156, wherein the plurality of indicator lights are selectively illuminated in a second progressive sequence in a second direction to communicate a declining analyte measurement trend. (Item 159) Item 154. The device of item 153, wherein the user interface is further configured to communicate information indicative of a status of the analyte monitoring device. (Item 160) Item 154. The device of item 153, wherein the user interface comprises a display screen. (Item 161) Item 154. The device of item 153, wherein the analyte monitoring device is a skin adhesive patch. (Item 162) Item 154. The device of item 153, wherein the at least one microneedle comprises a tapered distal portion with an insulated distal apex and an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex. (Item 163) Item 154. The device of item 153, wherein the microneedle array comprises a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device. (Item 164) 1. 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 the measurement of the one or more analytes through a user interface on the housing; and A method comprising: (Item 165) Item 165. The method of item 164, wherein communicating information includes illuminating one or more indicator lights on the housing according to an illumination mode corresponding to the analyte measurement status. (Item 166) Item 166. The method of item 165, wherein communicating information includes selectively illuminating at least one of the indicator lights to communicate a current analyte measurement level. (Item 167) Item 167. The method of item 166, wherein communicating information includes communicating the current analyte measurement level based on a color of the illuminated indicator light, a location of the illuminated indicator light, or both. (Item 168) 166. The method of claim 165, wherein communicating information includes selectively illuminating a plurality of indicator lights on the housing in a progressive sequence to communicate an analyte measurement trend. (Item 169) Item 169. The method of item 168, wherein communicating information includes selectively illuminating the plurality of indicator lights in a first progressive sequence in a first direction to communicate an increasing analyte measurement trend. (Item 170) Item 169. The method of item 168, wherein communicating information includes selectively illuminating the plurality of indicator lights in a second progressive sequence in a second direction to communicate a declining analyte measurement trend. (Item 171) 165. The method of claim 164, further comprising communicating information indicative of a status of the analyte monitoring device through the user interface. (Item 172) Item 165. The method of item 164, further comprising accessing dermal interstitial fluid of the user at a plurality of sensor locations with the analyte monitoring device, wherein quantifying one or more analytes comprises quantifying one or more analytes in the dermal interstitial fluid. (Item 173) Item 165. The method of item 164, wherein the analyte monitoring device comprises a microneedle array comprising a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 depicts an illustrative schematic of an analyte monitoring system involving a microneedle array.

[0015] [Figure 2A] FIG. 2A depicts an illustrative schematic diagram of an analyte monitoring device.

[0016] [Figure 2B] FIG. 2B depicts an illustrative schematic of microneedle insertion depth in an analyte monitoring device.

[0017] [Figure 3A] 3A-3C depict top, side, and bottom perspective views, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A, including the adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A. [Figure 3B] 3A-3C depict top, side, and bottom perspective views, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A, including the adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A. [Figure 3C] 3A-3C depict top, side, and bottom perspective views, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A, including the adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A. [Figure 3D] 3A-3C depict top, side, and bottom perspective views, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A, including the adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A. [Figure 3E]3A-3C depict top, side, and bottom perspective views, respectively, of an analyte monitoring device. FIG. 3D depicts a partially exploded view of the analyte monitoring device shown in FIG. 3A, including the adhesive layer. FIG. 3E depicts an exploded view of the analyte monitoring device shown in FIG. 3A.

[0018] [Figure 3F] 3F-3I depict a top perspective view, a bottom perspective view, a side view, and an exploded view, respectively, of a sensor assembly in an analyte monitoring device. [Figure 3G] 3F-3I depict a top perspective view, a bottom perspective view, a side view, and an exploded view, respectively, of a sensor assembly in an analyte monitoring device. [Figure 3H] 3F-3I depict a top perspective view, a bottom perspective view, a side view, and an exploded view, respectively, of a sensor assembly in an analyte monitoring device. [Figure 3I] 3F-3I depict a top perspective view, a bottom perspective view, a side view, and an exploded view, respectively, of a sensor assembly in an analyte monitoring device.

[0019] [Figure 3J] FIG. 3J depicts a transparent side view of a sensor assembly in an analyte monitoring device.

[0020] [Figure 4A] 4A-4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and a top perspective transparent view, respectively, of an analyte monitoring device. [Figure 4B] 4A-4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and a top perspective transparent view, respectively, of an analyte monitoring device. [Figure 4C] 4A-4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and a top perspective transparent view, respectively, of an analyte monitoring device. [Figure 4D] 4A-4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and a top perspective transparent view, respectively, of an analyte monitoring device. [Figure 4E] 4A-4E depict a perspective view, a side view, a bottom view, a side cross-sectional view, and a top perspective transparent view, respectively, of an analyte monitoring device.

[0021] [Figure 5] Figure 5A depicts an illustrative schematic diagram of a microneedle array. Figure 5B depicts an illustrative schematic diagram of a microneedle in the microneedle array depicted in Figure 5A.

[0022] [Figure 6] FIG. 6 depicts an illustrative schematic of a microneedle array used to sense multiple analytes.

[0023] [Figure 7] Figure 7A depicts a cross-sectional side view of a pillar-shaped microneedle having a tapered distal end. Figures 7B and 7C are images depicting a perspective view and a detailed view, respectively, of the microneedle embodiment shown in Figure 7A.

[0024] [Figure 8] FIG. 8 depicts an illustrative schematic of a pillar-shaped microneedle with a tapered distal end.

[0025] [Figure 9] FIG. 9 depicts a cross-sectional side view of a pillar-shaped microneedle with a tapered distal end.

[0026] [Figure 10] FIG. 10 depicts an illustrative schematic of a pillar-shaped microneedle with a tapered distal end.

[0027] [Figure 11A] Figure 11A depicts a cross-sectional side view of a cone-shaped microneedle with a tapered distal end, Figure 11B is an image depicting a perspective view of the microneedle embodiment shown in Figure 11A, and Figure 11C is an image depicting an illustrative variation of a microneedle array including microneedles similar to those shown in Figure 11B. [Figure 11B]Figure 11A depicts a cross-sectional side view of a cone-shaped microneedle with a tapered distal end, Figure 11B is an image depicting a perspective view of the microneedle embodiment shown in Figure 11A, and Figure 11C is an image depicting an illustrative variation of a microneedle array including microneedles similar to those shown in Figure 11B. [Figure 11C] Figure 11A depicts a cross-sectional side view of a cone-shaped microneedle with a tapered distal end, Figure 11B is an image depicting a perspective view of the microneedle embodiment shown in Figure 11A, and Figure 11C is an image depicting an illustrative variation of a microneedle array including microneedles similar to those shown in Figure 11B.

[0028] [Figure 12] FIG. 12 depicts an illustrative schematic of a conical microneedle with a tapered distal end.

[0029] [Figure 13-1] Figure 13A depicts an illustrative schematic of a cone-shaped microneedle having a tapered distal end and an asymmetric cutting surface, and Figure 13B is an image depicting an illustrative variation of the microneedle shown in Figure 13A.

[0030] [Figure 13-2] 13C-13E illustrate a process for forming the conical microneedles shown in FIG. 13A.

[0031] [Figure 14] Figure 14A depicts an illustrative schematic of a pillar-cone microneedle with a tapered distal end, and Figure 14B depicts a detailed view of the distal portion of the microneedle depicted in Figure 14A.

[0032] [Figure 15] 15A-15D depict illustrative schematics of the formation of conductive pathways within a microneedle array.

[0033] [Figure 16-1] 16A-16C depict illustrative schematic diagrams of the layered structure of the working, counter, and reference electrodes, respectively.

[0034] [Figure 16-2] 16D-16F depict illustrative schematic diagrams of the layered structure of the working, counter, and reference electrodes, respectively.

[0035] [Figure 16-3] 16G-16I depict illustrative schematics of the layered structure of the working, counter, and reference electrodes, respectively.

[0036] [Figure 17] FIG. 17 depicts an illustrative schematic of a microneedle array configuration.

[0037] [Figure 18] 18A and 18B depict perspective and orthogonal views, respectively, of an illustrative variation of a die containing a microneedle array.

[0038] [Figure 19-1] 19A-19J depict illustrative schematics of different variations of microneedle array configurations. [Figure 19-2] 19A-19J depict illustrative schematics of different variations of microneedle array configurations. [Figure 19-3] 19A-19J depict illustrative schematics of different variations of microneedle array configurations. [Figure 19-4] 19A-19J depict illustrative schematics of different variations of microneedle array configurations.

[0039] [Figure 20] FIG. 20 depicts an illustrative schematic diagram of a low profile battery holder.

[0040] [Figure 21] FIG. 21 depicts an illustrative flow chart of a method for sterilizing an analyte monitoring device.

[0041] [Figure 22]FIG. 22 depicts an illustrative schematic of a sterilization setup that can be used for ethylene oxide sterilization.

[0042] [Figure 23] FIG. 23 depicts an illustrative variation of the ethylene oxide sterilization protocol.

[0043] [Figure 24A] 24A-24C depict exemplary data suggesting the feasibility of ethylene oxide sterilization for analyte monitoring devices. [Figure 24B] 24A-24C depict exemplary data suggesting the feasibility of ethylene oxide sterilization for analyte monitoring devices. [Figure 24C] 24A-24C depict exemplary data suggesting the feasibility of ethylene oxide sterilization for analyte monitoring devices.

[0044] [Figure 25] FIG. 25 is an illustrative schematic diagram of an electronic circuit that enables activation of an analyte monitoring device in response to insertion of a microneedle array into the skin.

[0045] [Figure 26] FIG. 26 is an illustrative schematic diagram of pairing between an analyte monitoring device and a mobile computing device running a mobile application.

[0046] [Figure 27-1] Figures 27A and 27B depict illustrative schematic diagrams of a microneedle array and microneedles, respectively. Figures 27C-27F depict detailed partial views of illustrative variations of microneedles. [Figure 27-2] Figures 27A and 27B depict illustrative schematic diagrams of a microneedle array and microneedles, respectively. Figures 27C-27F depict detailed partial views of illustrative variations of microneedles.

[0047] [Figure 28]28A and 28B depict illustrative variations of microneedles.

[0048] [Figure 29] 29A and 29B depict illustrative schematics of microneedle array configurations.

[0049] [Figure 30] 30A and 30B depict illustrative schematics of microneedle array configurations.

[0050] [Figure 31A] 31A and 31B depict illustrative schematic diagrams of a housing of an analyte monitoring device that includes a user interface with an indicator light element. [Figure 31B] 31A and 31B depict illustrative schematic diagrams of a housing of an analyte monitoring device that includes a user interface with an indicator light element.

[0051] [Figure 32] 32A-32C depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data.

[0052] [Figure 33A] 33A-33D depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data. [Figure 33B] 33A-33D depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data. [Figure 33C] 33A-33D depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data. [Figure 33D] 33A-33D depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data.

[0053] [Figure 34A]34A-34C depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data. [Figure 34B] 34A-34C depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data. [Figure 34C] 34A-34C depict illustrative schematics of illumination modes in an analyte monitoring device for displaying analyte measurement data.

[0054] [Figure 35A] 35A and 35B depict illustrative schematics of illumination modes in an analyte monitoring device for indicating device information (eg, operational status and / or failure modes). [Figure 35B] 35A and 35B depict illustrative schematics of illumination modes in an analyte monitoring device for indicating device information (eg, operational status and / or failure modes). DETAILED DESCRIPTION OF THE INVENTION

[0055] Detailed Description Non-limiting examples of various aspects and variations of the present invention are described herein and illustrated in the accompanying drawings.

[0056] Generally, as described herein, an analyte monitoring system may include an analyte monitoring device worn by a user and including one or more sensors for monitoring at least one analyte of the user. The sensor may include, for example, 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 the sensor data. For example, as shown in FIG. 1 , analyte monitoring system 100 may include analyte monitoring device 110 worn by a user, which may be a continuous analyte monitoring device (e.g., a continuous glucose monitoring device). Analyte monitoring device 110 may include, for example, a microneedle array with at least one electrochemical sensor for detecting and / or measuring one or more analytes in the user's bodily fluid. In some variations, the analyte monitoring device may be applied to the user using a suitable applicator 160 or may be applied manually. The analyte monitoring device 110 may include one or more processors for performing analyses on the sensor data and / or a communications module (e.g., a wireless communications module) configured to communicate the sensor data to the mobile computing device 102 (e.g., a smartphone) or other suitable computing device. In some variations, the mobile computing device 102 may include one or more processors that execute mobile applications to handle the sensor data (e.g., display the data, analyze the data for trends, etc.) and / or provide suitable alerts or other notifications related to the sensor data and / or its analyses.In some variations, the mobile computing device 102 may perform sensor data analysis locally, although it should be understood that other computing devices may alternatively or additionally analyze the sensor data remotely and / or communicate information related to such analysis with the mobile computing device 102 (or other suitable user interface) for display to a user. Further, in some variations, the mobile computing device 102 may be configured to communicate the sensor data and / or analysis of the sensor data to one or more storage devices 106 (e.g., servers) via the network 104 for archiving data and / or other suitable information related to a user of the analyte monitoring device.

[0057] The analyte monitoring devices described herein have characteristics that improve several properties that are advantageous relative to continuous analyte monitoring devices, such as continuous glucose monitoring (CGM) devices. For example, the analyte monitoring devices described herein have improved sensitivity (the amount of sensor signal generated per given concentration of target analyte), improved selectivity (rejection of endogenous and exogenous circulating compounds that may interfere with the detection of the target analyte), and improved stability, which helps minimize changes in sensor response over time throughout storage and operation of the analyte monitoring device. In addition, compared to conventional continuous analyte monitoring devices, the analyte monitoring devices described herein have a shorter warm-up time, which enables the sensor to quickly provide a stable sensor signal following implantation, and a shorter response time, which enables the sensor to quickly provide a stable sensor signal following changes in analyte concentration in the user. Furthermore, as described in more detail below, the analyte monitoring devices described herein may be adapted to and function at a variety of application sites, providing painless sensor insertion for the user. Other properties, such as biocompatibility, sterility, and mechanical integrity, are also optimized in the analyte monitoring devices described herein.

[0058] While the analyte monitoring systems described herein may be described with reference to monitoring glucose (e.g., in patients with type 2 diabetes, type 1 diabetes), it should be understood that such systems may be configured to sense and monitor other suitable analytes in addition to, or instead of, detecting other suitable analytes. As described in further detail below, target analytes suitable for detection may include, for example, glucose, ketones, lactate, and cortisol. A single target analyte may be monitored, or multiple target analytes may be monitored simultaneously (e.g., in the same analyte monitoring device). For example, monitoring other target analytes may enable monitoring of other indications such as stress (e.g., through detection of elevated cortisol and glucose) and ketoacidosis (e.g., through detection of elevated ketones).

[0059] Various aspects of exemplary variations of the analyte monitoring system and methods of use thereof are described in further detail below. Analyte Monitoring Devices

[0060] As shown in FIG. 2A , in some variations, analyte monitoring device 110 may generally include a housing 112 and a microneedle array 140 extending outwardly from the housing. Housing 112 may be a wearable housing configured to be worn on a user's skin, such that microneedle array 140 extends at least partially into the user's skin. For example, housing 112 may include an adhesive such that analyte monitoring device 110 is a skin-adhesive patch that is simple and easy to apply to a user. Microneedle array 140 may be configured to include one or more electrochemical sensors (e.g., electrodes) configured to pierce the user's skin and measure one or more target analytes accessible after microneedle array 140 pierces the user's skin. In some variations, analyte monitoring device 110 may be integrated or self-contained as a single unit, which may be disposable (e.g., used for a period of time and replaced with another instance of analyte monitoring device 110).

[0061] The electronics system 120 may include various electronic components, such as a sensor circuit 124, arranged at least in part within the housing 112 and configured to perform signal processing (e.g., biasing and readout of an electrochemical sensor, converting analog signals from the electrochemical sensor to a digital signal, etc.). The electronics system 120 may also include at least one microcontroller 122 for controlling the analyte monitoring device 110, at least one communications module 126, at least one power supply 130, and / or various other suitable passive circuitry 127. The microcontroller 122 may be configured, for example, to interpret digital signals output from the sensor circuit 124 (e.g., by executing programmed routines in firmware), perform various suitable algorithms or mathematical transformations (e.g., calibration, etc.), and / or route processed data to and / or from the communications module 124. In some variations, the communications module 126 may include a suitable wireless transceiver (e.g., a Bluetooth transceiver or equivalent) for communicating data with the external computing device 102 via one or more antennas 128. For example, communications module 126 may be configured to provide unidirectional and / or bidirectional communication of data with an external computing device 102 paired with analyte monitoring device 110. Power source 130 may provide power for analyte monitoring device 110, such as for the electronics system. Power source 130 may include a battery or other suitable source and, in some variations, may be rechargeable and / or replaceable. Passive circuitry 127 may include various unpowered electrical circuits (e.g., resistors, capacitors, inductors, etc.) that provide interconnections between other electronic components, etc. Passive circuitry 127 may be configured, for example, to perform noise reduction, biasing, and / or other purposes. In some variations, electronic components in electronics system 120 may be arranged on one or more printed circuit boards (PCBs), which may, for example, be rigid, semi-rigid, or flexible.Additional details of electronics system 120 are described further below.

[0062] In some variations, the analyte monitoring device 110 may further include one or more additional sensors 150 to provide additional information that may be relevant to user monitoring. For example, the analyte monitoring device 110 may further include at least one temperature sensor (e.g., a thermistor) configured to measure skin temperature, thereby enabling temperature compensation for sensor measurements obtained by the microneedle array electrochemical sensor.

[0063] In some variations, the microneedle array 140 in the analyte monitoring device 110 may be configured to pierce a user's skin. As shown in FIG. 2B, when the device 110 is worn by a user, the microneedle array 140 may extend into the user's skin such that electrodes on distal regions of the microneedles rest within the dermis. Specifically, in some variations, the microneedles may be designed to penetrate the skin and access the upper dermal regions of the skin (e.g., the papillary dermis and upper reticular dermis) to allow the electrodes to access the interstitial fluid surrounding cells in these layers. For example, in some variations, the microneedles may generally have a height ranging from at least 350 μm to about 515 μm. In some variations, one or more microneedles may extend from the housing such that the distal end of the electrode on the microneedle is located less than about 5 mm from the skin-interfacing surface of the housing, less than about 4 mm from the housing, less than about 3 mm from the housing, less than about 2 mm from the housing, or less than about 1 mm from the housing.

[0064] In contrast to conventional continuous analyte monitoring devices (e.g., CGM devices), which typically include sensors implanted about 8 mm to about 10 mm below the skin surface in the subcutaneous or adipose layer of the skin, the analyte monitoring device 110 has a shallower microneedle insertion depth of about 0.25 mm (such that the electrodes are implanted within the upper dermal region of the skin), providing numerous benefits. These benefits include access to dermal interstitial fluid, which contains one or more target analytes for detection, which is advantageous because at least some types of analyte measurements in dermal interstitial fluid have been found to correlate closely with those in blood. For example, glucose measurements performed using electrochemical sensors that access dermal interstitial fluid have been found to advantageously correlate highly linearly with blood glucose measurements. Thus, glucose measurements based on dermal interstitial fluid accurately represent blood glucose measurements.

[0065] Additionally, due to the shallower microneedle insertion depth of the analyte monitoring device 110, a reduced time delay in analyte detection is obtained compared to conventional continuous analyte monitoring devices. Such a shallower insertion depth positions the sensor surface in close proximity (e.g., within a few hundred micrometers or less) to the dense and well-perfused capillary bed of the reticular dermis, resulting in negligible diffusion delay from the capillaries to the sensor surface. The diffusion time is t=x 2The diffusion distance is related to the diffusion time according to ∂t / (2D), where t is the diffusion time, x is the diffusion distance, and D is the mass diffusion coefficient of the analyte of interest. Thus, positioning the analyte sensing element twice as far away from the source of the analyte in the capillaries would result in a diffusion delay time that is four times longer. Thus, conventional analyte sensors residing in the poorly vascularized adipose tissue below the dermis experience significantly longer diffusion distances from the vessels within the dermis, and thus substantial diffusion latencies (e.g., typically 5-20 minutes). In contrast, the shallower microneedle insertion depth of the analyte monitoring device 110 benefits from less diffusion latency from the capillaries to the sensor, thereby reducing the time delay in analyte detection and providing more accurate results in real time or near real time. For example, in some embodiments, the diffusion latency may be less than 10 minutes, less than 5 minutes, or less than 3 minutes.

[0066] Furthermore, when the microneedle array rests within the upper dermal region, the lower dermis beneath the microneedle array contains very high levels of vascularization and perfusion to support dermal metabolism, which allows for thermoregulation (via vasoconstriction and / or vasodilation) and provides a barrier function that helps stabilize the sensing environment around the microneedles. Another advantage of a shallower insertion depth is the lack of pain receptors in the upper dermal layer, thus resulting in reduced pain sensation when the microneedle array pierces the user's skin, providing a more comfortable, minimally invasive user experience.

[0067] Thus, the analyte monitoring devices and methods described herein enable improved continuous monitoring of one or more target analytes in a user. For example, as described above, the analyte monitoring devices can be simple and easy to apply, which improves ease of use and user compliance. In addition, analyte measurement in dermal interstitial fluid can provide highly accurate analyte detection. Furthermore, compared to conventional continuous analyte monitoring devices, insertion of the microneedle array and its sensors can be less invasive and less painful for the patient. Additional benefits of other aspects of the analyte monitoring devices and methods are further described below. chassis

[0068] As described above, the analyte monitoring device may include a housing. The housing may at least partially surround or enclose other components (e.g., electronic components) of the analyte monitoring device, 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 allowing the microneedle array to extend outward from the housing and into the user's skin. Furthermore, in some variations, the housing may include rounded edges or corners and / or have a low profile so as to be generally atraumatic and reduce interference with clothing and the like worn by the user.

[0069] For example, as shown in Figures 3A-3E, an exemplary variation of an analyte monitoring device 300 may include a housing 310 configured to at least partially enclose various other internal components of the device 300, and a microneedle array 330 extending outward from a skin-facing surface (e.g., an underside) of the housing 310.

[0070] The housing 310 may include one or more rigid or semi-rigid protective shell components that may be coupled together via, for example, suitable fasteners (e.g., mechanical fasteners), mechanical interlocking or interlocking features, and / or an engineering fit. For example, as shown in FIG. 3E , the housing may include a housing cover 310 a and a housing base 310 b, where the cover 310 a and base 310 b 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 310 a and base 310 b may include radiused edges and corners and / or other atraumatic features. When coupled together, the cover 310 a and base 310 b may form an interior volume that houses other internal components, such as the device printed circuit board 350 (PCB), the sensor assembly 320, and / or other components, such as a gasket 312. For example, the internal components arranged within the internal volume may be arranged in a compact, low-profile stack as shown in Figure 3E. While Figure 3E illustrates that the housing 310 includes multiple housing components, in some variations, the housing 310 may include a single component that defines the internal volume for storing the 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.

[0071] Additionally, analyte monitoring device 300 may include an adhesive layer 340 configured to attach housing 310 to a surface (e.g., skin) of a user. Adhesive layer 340 may be attached to the skin-facing side of housing 310 via, for example, a double-sided adhesive liner 344 as shown in the variation depicted in FIG. 3D . Alternatively, adhesive layer 340 may be bonded directly to the skin-facing side of housing 310 using one or more suitable fasteners (e.g., adhesive, mechanical fasteners, etc.). Adhesive layer 340 may be protected by a release liner that a user removes prior to skin application to expose the adhesive. In some variations, the analyte monitoring device may be attached to a 3M® 1504XL adhesive tape, available from 3M®. TM Double-sided adhesive and 3M® 4076 TM Skin-facing adhesives may also be included. These materials are selected for their breathability, wearability, mean moisture vapor transmission rate (MWVTR), biocompatibility, compatibility with sensor sterilization methods / strategies, appearance, durability, adhesion, and ability to retain said adhesion for the duration of sensor wear.

[0072] The adhesive layer 340, in some variations, may have an outer periphery that extends farther than the outer periphery or perimeter of the housing 310 (e.g., this may increase the surface area for attachment, increasing the stability of retention or attachment to the user's skin). Additionally, in some variations, the adhesive layer 340 may include an opening 342 that allows for the passage of the outwardly extending microneedle array 330. The opening 342 may closely surround the shape of the microneedle array 330, as shown in FIG. 3C (e.g., a square opening that closely corresponds in size and shape to a square microneedle array), or may have another suitable size and shape that is larger than the footprint of the microneedle array (e.g., a circular opening that is larger than a square microneedle array).

[0073] While the housing 310 depicted in Figures 3A-3E is hexagonal and generally prismatic, it should be understood that in other variations, the housing 310 can have any suitable shape. For example, in other variations, the housing may be generally prismatic and have a base having an oval (e.g., circular), triangular, rectangular, pentagonal, or other suitable shape. As another example, Figures 4A-4C illustrate an exemplary variation of an analyte monitoring device 400 that includes a dome-shaped housing 410. While the dome-shaped housing 410 depicted in Figures 4A-4C is generally circular, in other variations, the dome-shaped housing may have a base having another suitable oval or polygonal shape.

[0074] Similar to housing 310, housing 410 may include an interior volume configured to at least partially enclose other components of analyte monitoring device 400. For example, as shown in the cross-sectional view of FIG. 4D , housing 410 may include a dome-shaped cover 410 a coupled to a base 410 b to form an interior volume within which device PCB 450 and a sensor assembly with microneedle array 430 may be arranged. Additionally, housing 410 may be configured to be coupled to a surface via adhesive layer 440, and microneedle array 430 may extend outward from the housing and beyond adhesive layer 440. Furthermore, as shown in FIGS. 4D and 4E , adhesive layer 440 may extend beyond the perimeter of housing 410. User Interface

[0075] In some variations, the analyte monitoring system may provide user status, analyte monitoring device status, and / or other suitable information directly via a user interface on the analyte monitoring device (e.g., a display, indicator lights, etc., as described below). Thus, in contrast to analyte monitoring systems that may simply communicate information to a separate peripheral device (e.g., a mobile phone, etc.), which in turn communicates the information to the user, in some variations, such information may be provided directly by the analyte monitoring device. Advantageously, in some variations, such a user interface on the analyte monitoring device may reduce the need for a user to constantly maintain a separate peripheral device to monitor user status and / or analyte monitoring device status (which may be impractical due to cost, inconvenience, etc.). Additionally, the user interface on the analyte monitoring device may reduce risks associated with loss of communication between the analyte monitoring device and a separate peripheral device, such as the user having an inaccurate understanding of their current analyte levels (e.g., leading the user to believe their analyte levels are high when they are actually low, which may result in the user self-administering an incorrect dose of medication or withholding a therapeutic intervention when this is medically necessary).

[0076] Additionally, the ability to communicate information to a user via the analyte monitoring device itself, independent of a separate peripheral device, may reduce or eliminate the need to maintain compatibility between the analyte monitoring device and a separate peripheral device when such a peripheral device is upgraded (e.g., replaced with a new device model or other hardware, launched with a new version of an operating system or other software, etc.).

[0077] Thus, in some variations, the housing may include a user interface, such as an interface for providing information in a visual, auditory, and / or tactile manner, to provide information regarding the user status and / or the 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 indicative of an analyte measurement at the user (e.g., below a predetermined target analyte measurement threshold or range, within a predetermined target analyte measurement range, above a predetermined target analyte measurement threshold or range, an increase or decrease in the analyte measurement over time, a rate of change of the analyte measurement, other information regarding trends in the analyte measurement, other suitable alerts associated with the analyte measurement, etc.). Examples of analyte monitoring device status that may be communicated via the user interface include a device operating mode (e.g., associated with a device warm-up status, an analyte monitoring status, a battery power status such as low battery, etc.), a device error status (e.g., an operational error, pressure-induced sensing decay, a fault, a failure mode, etc.), a device power status, a device life status (e.g., an expected end of life for the sensor), a status of connectivity between the device and a mobile computing device, and / or the like.

[0078] In some variations, the user interface may be enabled or “on” by default 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 displays or indicator lights (e.g., as described below) not only as alerts to prompt the user's attention or recommend corrective action, but also when user status and / or device status are normal. Thus, in some variations, the user is not required to perform an action to initiate a scan to learn their current analyte measurement levels, and such information may be readily available to the user at all times. However, in some variations, the user may perform an action to temporarily disable the user interface (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 re-enabled, or until a second action is performed to re-enable the user interface.

[0079] In some variations, the user interface of the housing may include a display configured to visually communicate information. The display may include, for example, a display screen (e.g., an LCD screen, an OLED display, an electrophoretic display, an electrochromic display, etc.) configured to display alphanumeric text (e.g., numbers, letters, etc.), symbols, and / or suitable graphics for communicating information to a user. For example, the display screen may include numerical information, textual information, and / or informational graphics (e.g., sloping lines, arrows, etc.), such as user status and / or analyte monitoring device status. For example, the display screen may include textual or graphical representations of analyte measurement levels, trends, and / or recommendations (e.g., physical activity, reduced dietary intake, etc.).

[0080] As another example, a display on the housing may include one or more indicator lights (e.g., including LEDs, OLEDs, lasers, electroluminescent materials, or other suitable light sources, waveguides, etc.) that can be controlled in one or more predetermined illumination modes to communicate different status and / or other suitable information. The indicator lights may be controlled to illuminate using multiple colors (e.g., red, orange, yellow, green, blue, and / or purple, etc.) or in only one color. For example, the indicator lights may include multicolor LEDs. As another example, the indicator lights may include a transparent or translucent material (e.g., acrylic) positioned over one or more different colored light sources (e.g., LEDs) such that the different colored light sources can be selectively activated to illuminate the indicator light in a selected color. Activation of the light sources can occur either simultaneously or sequentially. The indicator lights may have any suitable form (e.g., raised, flush, recessed from the housing body, etc.) and / or shape (e.g., circular or other polygonal, ring, elongated strip, etc.). In some variations, the indicator light may have a pinhole size and / or shape that presents the same intensity of light as a larger light source but with significantly less power requirements, which may help to conserve on-board power in the analyte monitoring device.

[0081] Indicator lights on a display may be illuminated in one or more different ways to communicate different types of information. For example, indicator lights may be selectively illuminated on or off to communicate information (e.g., illuminated "on" indicates one status, while illuminated "off" indicates another status). Additionally or alternatively, indicator lights may be illuminated at a selected color or intensity to communicate information (e.g., illumination at a first color or intensity indicates a first status, while illumination at a second color or intensity indicates a second status). Additionally or alternatively, indicator lights may be illuminated in a selected temporal pattern to communicate information (e.g., illumination at a first temporal pattern indicates a first status, while illumination at a second temporal pattern indicates a second status). For example, the indicator light may be selectively illuminated in one of a plurality of predetermined temporal patterns that differ in illumination frequency (e.g., illumination repeated at a rapid or slow frequency), regularity (e.g., cyclically repeated illumination vs. intermittent illumination), duration of illumination "on" time, duration of illumination "off" time, rate of change of illumination intensity, duty cycle (e.g., ratio of illumination "on" time to illumination "off" time), and / or the like, and each predetermined temporal pattern may indicate a distinct status.

[0082] Additionally or alternatively, in some variations, a display may include multiple indicator lights that may be collectively illuminated in one or more predetermined lighting modes or sequences according to one or more predetermined spatial and / or temporal patterns. For example, in some variations, some or all of the indicator lights arranged on the display may be illuminated synchronously or sequentially to indicate a particular status. Thus, a selected subset of the indicator lights (e.g., the spatial arrangement of the illuminated indicator lights) and / or the manner in which they are illuminated (e.g., the illumination sequence, illumination rate, etc.) may indicate a particular status. Additionally or alternatively, multiple indicator lights may illuminate simultaneously or sequentially to increase the diversity of the color palette. For example, in some variations, red, green, and blue LEDs may be illuminated in quick succession to create the impression of white light to the user.

[0083] It should be further appreciated that one or more of the lighting modes described above may be combined in any suitable manner (e.g., combinations of various colors, intensities, 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 of the light level in the indicator light to compensate for ambient light conditions and help conserve power. The ambient light sensor may, in some variations, be used in conjunction with a motion sensor (e.g., as described in further detail below) to further determine appropriate periods for the analyte monitoring device to enter a power-saving mode or reduced power state. For example, detection of darkness and a lack of movement of the analyte monitoring device may indicate that the wearer of the analyte monitoring device is asleep, which may trigger the analyte monitoring device to enter a power-saving mode or reduced power state.

[0084] 31A illustrates an example variation of an analyte monitoring device 3100 that includes a user interface 3120 with multiple indicator lights (3122, 3124a-3124c). The indicator lights 3120 may be selectively illuminated to indicate, for example, a device status (e.g., an operating mode, an error state, a power status, a life status, etc.). The indicator lights 3122 are in the form of a symbol (e.g., a logo), although it should be understood that in other variations, the indicator lights 3122 may have any suitable shape (e.g., text, other geometric shapes, etc.). The indicator lights 3124a-3124c may be selectively illuminated to indicate a user status (e.g., information representative of an analyte measurement). It should be understood that while indicator lights 3124a-3124c are linear elements extending across the user interface (e.g., a cord across a circular display), in other variations indicator lights 3124a-3124c have other suitable shapes (e.g., wavy lines, circles, etc.). In some variations, a one-dimensional array of indicator lights of any suitable shape may be arranged on the housing (e.g., arranged in rows, columns, arcs, etc.). Alternatively, the housing may include a multi-dimensional array of indicator lights of any suitable shape.

[0085] Further, in some variations, the indicator light may include an icon (e.g., a symbol) that may indicate analyte information (e.g., an up arrow to indicate a rising analyte measurement level trend, a down arrow to indicate a falling analyte measurement level trend), analyte monitoring device status (e.g., an exclamation point to indicate a device error condition), and / or other suitable information. Additionally or alternatively, iconography in the indicator light may be used to communicate recommendations to the user, such as behavioral recommendations. Iconography may have the advantage, for example, of communicating recommendations to the user in a more universal or language-independent manner (e.g., without the need for language translation to tailor the device to different geographic regions or user preferences, etc.). For example, as shown in FIG. 31B , in some variations, in the context of glucose monitoring, a user interface for an analyte 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 3128 may indicate a recommendation that the user consume food (or in combination with an “X” icon 3130 to indicate a recommendation that the user limit food). As another example, the drink icon 3132 may indicate a recommendation that the user consume fluids, such as water (or in combination with the “X” icon 3134 to indicate a recommendation that the user limit fluids). As another example, the star icon 3136 may indicate positive reinforcement (e.g., indicating success in having an analyte measurement level remain within a normal or target range for a predetermined period of time). However, it should be understood that behavioral recommendations may vary based on indications regarding the analyte being monitored. For example, in some variations where the analyte monitoring device is additionally or alternatively used to monitor cortisol, rising cortisol levels (and / or rising glucose levels) may correlate with increased user stress. Thus, in some of these variations, the analyte monitoring device may include suitable icons to indicate recommendations to the user to reduce exposure to stressors, meditate, etc., to avoid adverse health effects resulting from stress.

[0086] In the variation shown in Figures 31A and 31B, indicator lights 3124a-3124c may each be exclusively illuminated to indicate a different analyte measurement (e.g., within the target range, below the target range, significantly below the target range, above the target range, significantly above the target range, etc.). Additionally, indicator lights 3124a-3124c may be arranged adjacent to one another such that they may be selectively illuminated in a progressive sequence to communicate trend information of the analyte measurement (e.g., a progressive sequence of illumination in a first direction corresponding to an increase in the measured quantity of the analyte, a progressive sequence of illumination in a second direction corresponding to a decrease in the measured quantity of the analyte, a pace of illumination progression in the first or second direction corresponding to a rate of increase or decrease in the measured quantity of the analyte, etc.). Examples of such progressive illumination sequences are further described below with reference to Figures 33A-33D. 31A and 31B, it should be understood that in other variations, the analyte monitoring device may 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 example operation of user interface 3120 for communicating 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

[0087] As shown in the schematic diagram of FIG. 5A, in some variations, a microneedle array 510 for use in sensing one or more analytes may include one or more microneedles 510 extending from a substrate surface 502. The substrate surface 502 may be, for example, generally planar, and the one or more microneedles 510 may extend orthogonally from the planar surface. Generally, as shown in FIG. 5B, the microneedle 510 may include a body portion 512 (e.g., a shaft) and a tapered distal portion 514 configured to pierce a user's skin. In some variations, the tapered distal portion 514 may terminate in an insulated distal apex 516. The microneedle 510 may further include an electrode 520 on the surface of the tapered distal portion. In some variations, electrode-based measurements may be performed at the interface of an electrode located within the body (e.g., on the outer surface of the entire microneedle) and interstitial fluid. In some variations, the microneedles 510 may have a solid core (e.g., a solid body portion), while in some variations, the microneedles 510 may include one or more lumens, which may be used, for example, for drug delivery or sampling of dermal interstitial fluid. Other microneedle variations, such as those described below, may similarly include either a solid core or one or more lumens.

[0088] The microneedle array 500 may be formed, at least in part, from a semiconductor (e.g., silicon) substrate and include various material layers applied and shaped using various suitable microelectromechanical systems (MEMS) fabrication techniques (e.g., deposition and etching techniques), as described further below. The microneedle array may be reflow soldered to the circuit board, similar to a typical integrated circuit. Furthermore, in some variations, the microneedle array 500 may include a three-electrode setup including a working (sensing) electrode having an electrochemical sensing coating (including a biorecognition element such as an enzyme) that enables detection of a target analyte, a reference electrode, and a counter electrode. In other words, the microneedle array 500 may include at least one microneedle 510 including 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 more detail below.

[0089] In some variations, the microneedle array 500 may include multiple insulated microneedles such that the electrodes on each microneedle in the multiple microneedles are individually addressable and electrically isolated from all other electrodes on the microneedle array. The resulting individual addressability of the microneedle array 500 may allow for greater control over the function of each electrode, since each electrode can be probed separately. For example, the microneedle array 500 may be used to provide multiple independent measurements of a given target analyte, improving the sensing reliability and accuracy of the device. Furthermore, in some variations, the electrodes of multiple microneedles may be electrically connected to generate enhanced signal levels. As another example, the same microneedle array 500 may additionally or alternatively measure multiple analytes simultaneously to provide a more comprehensive assessment of physiological status. For example, as shown in the schematic diagram of FIG. 6 , a microneedle array may include a portion of microneedles for detecting a first analyte A, a second portion of microneedles for detecting a second analyte B, and a third portion of microneedles for detecting a third analyte C. It should be understood that a microneedle array may be configured to detect any suitable number of analytes (e.g., one, two, three, four, five, or more, etc.). Suitable target analytes for detection may include, for example, glucose, ketones, lactate, and cortisol. For example, in some variations, ketones may be detected in a manner similar to that described in U.S. Patent Application No. 16 / 701,784 (herein incorporated by reference in its entirety). Thus, the individual electrical addressability of the microneedle array 500 provides additional control and flexibility over the sensing function of the analyte monitoring device.

[0090] In some variations of microneedles (e.g., microneedles with a working electrode), the electrode 520 may be located proximal to the insulated distal apex 516 of the microneedle. In other words, in some variations, the electrode 520 does not cover the apex of the microneedle. Rather, the electrode 520 may be offset from the apex or tip of the microneedle. An electrode 520 that is proximal to or offset from the insulated distal apex 516 of the microneedle advantageously provides more accurate sensor measurements. For example, this arrangement prevents concentration of the electric field at the microneedle apex 516 during manufacturing, thereby avoiding uneven deposition of the sensing chemistry on the electrode surface 520, which would result in erroneous sensing.

[0091] As another example, placing the electrode 520 offset from the microneedle apex further improves sensing accuracy by reducing undesirable signal artifacts and / or erroneous sensor readings caused by stresses upon microneedle insertion. The distal apex of the microneedle is the first area to penetrate into the skin and therefore experiences most of the stresses caused by the mechanical shearing phenomena associated with tearing or cutting the skin. If the electrode 520 is placed on the apex or tip of the microneedle, this mechanical stress may peel off the electrochemical sensing coating on the electrode surface as the microneedle is inserted and / or transport a small but interfering amount of tissue onto the active sensing portion of the electrode. Therefore, placing the electrode 520 sufficiently offset from the microneedle apex can improve sensing accuracy. For example, in some variations, the distal edge of the electrode 520 may be located at least about 10 μm (e.g., about 20 μm to about 30 μm) from the distal apex or tip of the microneedle, as measured along the longitudinal axis of the microneedle.

[0092] The body portion 512 of the microneedle 510 may further include a conductive pathway extending between the electrode 520 and a back electrode or other electrical contact (e.g., arranged on the back side of the microneedle array substrate). The back electrode may be soldered to a circuit board, allowing electrical communication with the electrode 520 via a conductive pathway. For example, during use, the in vivo sensing current measured at the working electrode (inside the dermis) is measured by the back electrical contact, and the electrical connection between the back electrical contact and the working electrode is facilitated by the conductive pathway. In some variations, this conductive pathway may be facilitated by a metal via extending through the interior of the microneedle body portion (e.g., shaft) between the proximal and distal ends of the microneedle. Alternatively, in some variations, the conductive pathway may be provided by forming the entire body portion from a conductive material (e.g., doped silicon). In some of these variations, the entire substrate on which the microneedle array 500 is constructed may be conductive, and each microneedle 510 in the microneedle array 500 may be electrically isolated from adjacent microneedles 510, as described below. For example, in some variations, each microneedle 510 in the microneedle array 500 may be electrically isolated from adjacent microneedles 510 using an insulating barrier comprising an electrically insulating material (e.g., a dielectric material such as silicon dioxide) surrounding the conductive pathway extending between the electrode 520 and the backside electrical contact. For example, the body portion 512 may include an insulating material that forms a sheath around the conductive pathway, thereby preventing electrical communication between the conductive pathway and the substrate. Other exemplary variations in structures that enable electrical isolation between microneedles are described in further detail below.

[0093] Such electrical isolation between microneedles in a microneedle array allows the sensors to be individually addressable. This individual addressability advantageously allows for independent, parallelized measurements between sensors and dynamic reconfiguration of sensor assignments (e.g., to different analytes). In some variations, the electrodes in a microneedle array can be configured to provide redundant analyte measurements, which is an advantage over conventional analyte monitoring devices. For example, redundancy can improve performance by improving accuracy (e.g., averaging multiple analyte measurements for the same analyte, reducing the effect of extremely high or low sensor signals on analyte level determinations) and / or improving the reliability of the device by reducing the likelihood of complete failure.

[0094] In some variations, as described in more detail below with individual different variations of microneedles, the microneedle array may be formed, at least in part, using suitable semiconductor and / or MEMS processing techniques and / or mechanical cutting or dicing. Such processes may be advantageous, for example, for enabling large-scale, cost-effective manufacturing of microneedle arrays. For example, in some variations, the microneedle array may be formed, at least in part, using the techniques described in U.S. Patent Application No. 15 / 913,709 (incorporated herein by reference in its entirety). Microneedle structure

[0095] Described herein are several exemplary variations of microneedle structures that incorporate one or more of the microneedle features described above with respect to microneedle arrays in analyte monitoring devices.

[0096] In some variations, the microneedle may have a generally cylindrical body portion and a tapered distal portion with an electrode. For example, Figures 7A-7C illustrate an exemplary variation of a microneedle 700 extending from a substrate 702. Figure 7A is a side cross-sectional schematic view of the microneedle 700, while Figure 7B is a perspective view of the microneedle 700, and Figure 7C is a detailed perspective view of the distal portion of the microneedle 700. As shown in Figures 7B and 7C, the microneedle 700 may include a cylindrical body portion 712, a tapered distal portion 714 that terminates in an insulated distal apex 716, and a ring electrode 720 comprising a conductive material (e.g., Pt, Ir, Au, Ti, Cr, Ni, etc.) and arranged on the tapered distal portion 714. As shown in Figure 7A, the ring electrode 720 may be proximal to (or offset or spaced from) the distal apex 716. For example, the electrode 720 may be electrically isolated from the distal apex 716 by a distal insulating surface 715a comprising an insulating material (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 electrode 720 may be in electrical communication with a conductive core 740 (e.g., a conductive pathway) that passes along the body portion 712 to a backside electrical contact 730 (e.g., made from a Ni / Au alloy) or other electrical pad in or on the substrate 702. For example, the body portion 712 may include a conductive core material (e.g., highly doped silicon). As shown in FIG. 7A, in some variations, an insulating moat 713 comprising an insulating material (e.g., SiO2) may be arranged around (e.g., around the periphery of) the body portion 712 and extend at least partially through the substrate 702. Thus, insulating moat 713 may help to prevent electrical contact between, for example, conductive core 740 and surrounding substrate 702. Insulating moat 713 may also extend across the surface of body portion 712. The upper and / or lower surfaces of substrate 702 may also include a layer of substrate insulator 704 (e.g., SiO2). Thus, the insulation provided by insulating moat 713 and / or substrate insulator 704 may contribute, at least in part, to electrical isolation of microneedles 700, enabling individual addressability of microneedles 700 within a microneedle array.Additionally, in some variations, insulating moats 713 extending across the surface of body portion 712 may function to increase the mechanical strength of the microneedle 700 structure.

[0097] The microneedle 700 may be formed, at least in part, by suitable MEMS processing techniques such as plasma etching, also known as dry etching. For example, in some variations, the insulating moat 713 around the microneedle body portion 712 may be fabricated by first forming a trench in a silicon substrate by deep reactive ion etching (DRIE) from the backside of the substrate and then filling the trench with a SiO2 / polycrystalline silicon (poly-Si) / SiO2 sandwich by low-pressure chemical vapor deposition (LPCVD) or other suitable process. In other words, the insulating moat 713 passivates the surface of the microneedle body portion 712 and may continue as a buried feature in the substrate 702 near the proximal portion of the microneedle. By comprising a primarily silicon compound, the insulating moat 713 may provide good filling and adhesion to adjacent silicon walls (e.g., of the conductive core 740, substrate 702, etc.). The sandwich structure of insulating moat 713 further helps to provide an excellent coefficient of thermal expansion (CTE) match with the adjacent silicon, which may advantageously reduce defects, cracks, and / or other thermally induced weaknesses in insulating structure 713.

[0098] The tapered distal portion may be shaped by isotropic dry etching from the front side of the substrate, and the body portion 712 of the microneedle 700 may be formed by DRIE. The front side metal electrode 720 may be deposited and patterned on the distal portion by specialized lithography (e.g., electron beam evaporation) that allows metal deposition in the desired annular region about the electrode 720 without coating the distal apex 716. Additionally, the Ni / Au backside electrical contact 730 may be deposited by a suitable MEMS fabrication technique (e.g., sputtering).

[0099] The microneedle 700 may have any suitable dimensions. By way of example, in some variations, the microneedle 700 may have a height of about 300 μm to about 500 μm. In some variations, the tapered distal portion 714 may have a tip angle of about 60 degrees to about 80 degrees and an apex diameter of about 1 μm to about 15 μm. In some variations, the surface area of ​​the ring electrode 720 may be about 9,000 μm. 2 ~approx. 11,000μm 2 or approximately 10,000 μm 2 Figure 8 illustrates various dimensions of an exemplary variation of a pillar-shaped microneedle with a tapered distal portion and a ring electrode, similar to microneedle 700 described above.

[0100] 9 illustrates another exemplary variation of a microneedle 900 having a generally cylindrical body portion. The microneedle 900 may be similar to the microneedle 700 described above, except as described below. For example, like the microneedle 700, the microneedle 900 may include a cylindrical body portion 912 and a tapered distal portion 914 that terminates in an insulated distal apex 916. The microneedle 900 may further include a ring electrode 920 comprising a conductive material and 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 the microneedle 900 have numbering similar to corresponding elements of the microneedle 700.

[0101] However, compared to microneedle 700, microneedle 900 may have a sharper tip at distal apex 916 and a modified insulating moat 913. For example, distal apex 916 may have a sharper tip angle, such as about 25 degrees to 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 insulating moat 713 (which extends through substrate 702 and along the height of microneedle body portion 712 as shown in FIG. 7A), modified insulating moat 913 may extend only through substrate 902, such that the sandwiching structure filling the trench (e.g., created by DRIE as described above) forms only a buried feature in the substrate. While the sidewalls of the microneedle 900 are shown in FIG. 9 as extending approximately perpendicular to the substrate plane, it should be understood that the modified insulating moat 913 does not need to extend the entire height of the microneedle body portion 712, and therefore in some variations the sidewalls of the microneedle 900 may be angled at a non-orthogonal angle relative to the substrate (e.g., the sidewalls may have a slight positive taper of about 1 degree to about 10 degrees or about 5 degrees to about 10 degrees).

[0102] In some variations, the remainder of the microneedle surface 900 (apart from the ring electrode 920) may include insulating material extending from the substrate insulator 904. For example, a layer of insulating material (e.g., SiO) may extend from the front side of the substrate 902 to provide body portion insulation 918 and may further extend up over the proximal edge of the electrode 920, as shown in FIG. 9 . Another region of insulating material may similarly cover the distal edge of the electrode 920 and insulate the distal apex 916. Such regions of insulating material and / or modified insulating moat 913 may help prevent electrical contact between the conductive core 940 and the surrounding substrate 902. Thus, like the microneedle 700, the microneedle 900 may maintain electrical isolation for individual addressability within a microneedle array. In some variations, the process for forming the microneedle 900 may result in higher yields and / or offer lower production costs compared to the process for forming the microneedle 700.

[0103] The microneedle 900 may have any suitable dimensions. By way of example, the microneedle 900 may, in some variations, include a height of about 400 μm to about 600 μm, or about 500 μm. In some variations, the tapered distal portion 914 may have a tip angle of about 25 degrees to about 45 degrees with a tip radius of less than about 100 nm. Additionally, the microneedle may have a shaft diameter of about 160 μm to about 200 μm. FIG. 10 illustrates additional various dimensions of an exemplary variation of a pillar-shaped microneedle with a tapered distal portion and a ring electrode, similar to the microneedle 900 described above.

[0104] 27A-27F illustrate another exemplary variation of a microneedle 2700 having a generally cylindrical body portion. The microneedle 2700 may be similar to the microneedle 700 described above, except as described below. For example, as shown in FIG. 27B, like the microneedle 700, the microneedle 2700 may include a cylindrical body portion 2712 and a tapered distal portion disposed on a cylinder 2713 and terminating in an insulated distal apex 2716. The cylinder 2713 may be insulated and have a smaller diameter than the cylindrical body portion 2712. The microneedle 2700 may further include a ring electrode 2720 comprising a conductive material and disposed on the tapered distal portion at a location proximal to (or offset or spaced from) the distal apex 2716. Other elements of the microneedle 2700 as shown in FIGS. 27A-27F have numbering similar to the corresponding elements of the microneedle 700.

[0105] However, the electrode 2720 on the microneedle 2700 may include a tip contact trench 2722. This contact trench may be configured to help establish ohmic contact between the electrode 2720 and the underlying conductive core 2740 of the microneedle. In some variations, the shape of the tip contact trench 2722 may include an annular recess formed in the surface of the conductive core 2740 (e.g., in the body portion of the microneedle or otherwise in contact with a conductive path within the body portion) such that when the electrode 2720 material is deposited on 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 trench 2722 may advantageously help to provide a margin of error to ensure contact between the electrode 2720 and the underlying conductive core 2740. Any of the other microneedle variations described herein may also have a similar tip contact trench to help ensure contact between an electrode (which may be, for example, a working electrode, a reference electrode, a counter electrode, etc.) and the conductive pathway within the microneedle.

[0106] 28A and 28B illustrate additional various dimensions of exemplary variations of a pillar-shaped microneedle with a tapered distal portion and a ring electrode, similar to microneedle 2700 described above. For example, the microneedle variations shown in FIGS. 28A and 28B may generally have a tapered distal portion with a taper angle of about 80 degrees (or about 78 degrees to about 82 degrees, or about 75 degrees to about 85 degrees) and a cone diameter of about 140 μm (or about 133 μm to about 147 μm, or about 130 μm to about 150 μm). The cone of the tapered distal portion may be arranged on the cylinder such that the overall combined height of the cone and cylinder is about 110 μm (or about 99 μm to about 116 μm, or about 95 μm to about 120 μm). The ring electrode on the tapered distal portion may have an outer or base diameter of about 106 μm (or about 95 μm to about 117 μm or about 90 μm to about 120 μm) and an inner diameter of about 33.2 μm (or about 30 μm to about 36 μm or about 25 μm to about 40 μm). The length of the ring electrode as measured along the slope of the tapered distal portion may be about 57 μm (or about 55 μm to about 65 μm), and the overall surface area of ​​the electrode may be about 12,700 μm. 2 (or approximately 12,500 μm 2 ~Approx. 12,900μm 2 or approximately 12,000 μm 2 ~Approx. 13,000μm 2 ). As shown in FIG. 28B, the electrode may further have a tip contact trench extending around the conical central region of the tapered distal portion, the contact having a width of about 11 μm (or about 5 μm to about 50 μm, about 10 μm to about 12 μm, or about 8 μm to about 14 μm) as measured along the slope of the tapered distal portion, and a trench depth of about 1.5 μm (or about 0.1 μm to about 5 μm, or about 0.5 μm to about 1.5 μm, or about 1.4 μm to about 1.6 μm, or about 1 μm to about 2 μm). The microneedle has an insulated distal apex with a diameter of about 5.5 μm (or about 5.3 μm to about 5.8 μm, or about 5 μm to about 6 μm).

[0107] In some variations, the microneedle may have a generally conical body portion and a tapered distal portion with an electrode. For example, Figure 11A illustrates an exemplary variation of a microneedle 1100 having a generally conical body portion 1112 and a tapered distal portion 1114 extending from the body portion 1112. The microneedle 1100 may also include a ring electrode 1120 arranged on the tapered distal portion 1114 and proximal to an insulated distal apex 1116. The electrode 1120 may be conductively coupled to a backside electrical contact 1130 via a conductive path through the microneedle's conductive core 1140. 9, the microneedle 1100 may include insulating moats 1113 arranged around the base of the body portion 1112, extending through the substrate 1102, and providing electrical insulation around the microneedle 1100 (e.g., for individual addressability) and helping to prevent electrical contact between the conductive core 1140 and the surrounding substrate 1102. However, in contrast to the insulating moat 913 shown in FIG. 9, the insulating moat 1113 may be offset from the base of the microneedle 1100. The moat may be offset, for example, by about 10 μm to about 400 μm, about 10 μm to about 300 μm, about 10 μm to about 200 μm, or about 10 μm to about 100 μm from where the base of the microneedle 1100 abuts the substrate 1102 to which it is attached. In some variations, the insulating moat may include filler materials including parylene, Si3N4, and SiO2, which may provide an insulating material that is low thermal stress and chemically and water resistant. Additional body portion insulator 1118 may extend from the front side of the substrate 1102 to the proximal edge of the electrode 1120. Another region of insulating material may extend from the distal edge of the electrode 1120 to insulate the distal apex 1116.

[0108] 11B, in some variations, a microneedle 1100 having a conical body portion 1112 may include a polygonal base, although the base may have any suitable shape (e.g., circular). The conical body portion 1112 may include multiple planar facets, each extending from the microneedle's respective polygonal base. In some variations, the planar facets are anisotropically etched for increased mechanical strength (e.g., compressive strength and shear strength) of the microneedle 1110 and / or increased electrode surface area relative to a circular cone with non-planar facet surfaces. <311> For example, the microneedles 1110 may include anisotropically etched surface areas, which increases the mechanical strength and increases the metallization surface of the microneedles 1110 relative to the electrode surface. <311> It may have an octagonal base with planar facets.

[0109] The microneedle 1100 may be formed, at least in part, by suitable MEMS processing techniques. For example, the microneedle cone-shaped structure may be formed by timed anisotropic wet etching 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 using specialized lithography techniques as described above with respect to the electrode 720, without coating the distal apex 1116. However, compared to the processes described above for forming the microneedle 700, many of the processes for forming the microneedle 1100 do not involve expensive RIE techniques, which may thereby substantially reduce manufacturing costs. Furthermore, in some variations, instead of utilizing a dry etching process as described above with respect to the microneedle 700, the process for forming the microneedle 1100 may include mechanical dicing, bulk micromachining, or other cutting techniques to shape the microneedle 1100 into a cone-shaped body. Moreover, such techniques may be implemented on a larger scale, for example to form multiple microneedles 1110 arranged in an array as shown in Figure 11C.

[0110] The microneedle 1100 may have any suitable dimensions. By way of example, the microneedle 1100 may have a height of about 400 μm to about 600 μm, or about 500 μm, in some variations. In some variations, the tapered distal portion 714 may have a tip angle of about 30 degrees to about 50 degrees, or about 40 degrees, which may provide a good balance between sharpness for skin penetration and lithographic processability on the beveled surface on which the electrode 1120 is to be placed.

[0111] 12 illustrates various dimensions of exemplary variations of conical microneedles with tapered distal portions having planar facets and electrodes arranged on at least some of the planar facets. It should be understood that in some variations, the electrodes may be annular or annular-like in that all of the planar facets on the conical microneedle may include a metallized surface for the electrode, although alternatively, in some variations, only a portion of the planar facets on the conical microneedle may include a metallized surface (e.g., one, two, three, four, five, six, or seven planar facets of a conical microneedle having an octagonal base and eight planar facets extending distally from the octagonal base).

[0112] In some variations, the conical microneedles may be similar to those described above with respect to FIG. 11A, except that the microneedles may have an asymmetric shape, as shown in FIGS. 13A and 13B. For example, in some variations, as shown in FIG. 13A, the microneedle 1300 may have a non-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 cutting surface 1350 (e.g., a planar surface) that is offset from the distal apex 1316 of the microneedle (i.e., does not extend through a central z-axis defined as passing from the base of the microneedle 1300 to the distal apex 1316). The insulated distal apex 1316 may be kept intact so as not to compromise the surface area for metallization for the electrode. In some variations, the cutting surface 1350 may be angled at a non-orthogonal angle relative to the base of the microneedle (and / or the surface of the substrate 1302), as shown in Figure 13A. For example, in some variations, the cutting surface may be configured to produce a sharpened, asymmetric distal tip at the 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 cutting surface 1350 may be angled normal to or orthogonal to the base of the microneedle (and / or the surface of the substrate 1302).

[0113] Additionally or alternatively, as shown in FIG. 13A, an exemplary variation of an asymmetric microneedle 1300 may have a polygonal (e.g., octagonal) base but include various beveled surfaces tapered at different angles. As shown in FIG. 13A, the body portion 1316 of the microneedle 1300 may have a first taper angle (A) and a second taper angle (B), measured relative to the base of the body portion (and / or the surface of the substrate 1302). The second taper angle (B) may exceed the first taper angle (A) so that the microneedle has a sharper piercing tip extending from a stable and mechanically strong base. For example, in some variations, the first taper angle (A) may be about 10 degrees to about 30 degrees, about 15 degrees to about 25 degrees, or about 20 degrees. Additionally, in some variations, the second taper angle (B) may be between about 60 degrees and about 80 degrees, between about 65 degrees and about 75 degrees, or about 70 degrees.

[0114] 13C-13E depict a series of steps in an exemplary variation for forming a conical microneedle with an asymmetric cut surface. As shown in FIG. 13C, a symmetric conical microneedle with two taper angles may be formed through an anisotropic wet etching process. The two taper angles of the microneedle may include, for example, a first taper angle of about 20 degrees located near the base of the microneedle and a second taper angle of about 70 degrees located distal to the first taper angle, thereby forming a gradually sloping surface (e.g., along the planar facet of the conical microneedle). As shown in FIG. 13D, a dicing blade may be applied at an angle offset from the distal apex of the microneedle to form a cut surface similar to the cut surface 1350 described above. The cut surface may leave a reduced microneedle base diameter (e.g., about 150 μm to about 190 μm, or about 170 μm) to cause less tissue trauma. As shown in Figure 13E, the resulting microneedle (with its offset cutting surface) is asymmetrical but has an intact sharp distal apex.

[0115] Like the conical microneedle 1100 described above with respect to FIG. 11A, the microneedle 1300 is, at least in part, anisotropically etched. <311> They may derive their mechanical strength from their flat and conical shapes. However, asymmetric conical microneedles with asymmetric cut surfaces may be advantageous in that they may reduce longitudinal shear forces compared to symmetric microneedles with similar dimensions but lacking the asymmetric cut. Furthermore, sharper (e.g., more acute) distal microneedle tips may be achieved with such asymmetric cut surfaces. While cut surface 1350 is shown in FIG. 13A as being positioned at a non-orthogonal angle relative to the base of the microneedle, alternatively, as described above, in some variations, cut surface 1350 may be approximately orthogonal or normal to the base of the microneedle (and / or the surface of substrate 1302), which may further reduce longitudinal shear forces in the microneedle.

[0116] In some variations, the microneedles may be similar to those described above, except that the microneedles may include a cylindrical body portion and a conical distal portion. For example, as shown in FIG. 14A, a pillar-conical microneedle 1400 may include a pillar-shaped body portion 1412, which may extend from a polygonal (e.g., octagonal) base from a non-conductive substrate 1402, such as intrinsic (undoped) silicon. In addition, the pillar-conical microneedle 1400 may include a tapered distal portion 1414 having a conical shape with multiple planar facets. For example, the pillar-conical microneedle 1400 may include a tapered distal portion 1414 having a conical shape with eight facets extending from the octagonal pillar-shaped body portion 1412. However, the conical shape may have any suitable number of planar facets (e.g., 1, 2, 3, 4, 5, 6, 7, 9, or more). An annular electrode 1420 may be formed on all planar facets of the conical distal portion 1414, or may include metallized surfaces for the electrode on only a portion of the planar facets (e.g., on one, two, three, four, five, six, or seven facets). Similar to that described above, the cylindrical body portion 1412 may include a conductive core including a conductive material that serves as a conductive path for signals to and from the electrode 142. The cylindrical body portion 1412 may further include an insulating material 1418 that may extend along the body portion 1412 to (or slightly overlap) the proximal edge of the electrode 1420. The distal apex 1416 may or may not be covered by a similar insulating material.

[0117] 11A-11C, 12, and / or 13A-13E. For example, tapered distal portion 1414 may be formed using an anisotropic wet etching technique. Electrode 1420 may be formed on tapered distal portion 1414 by lithography, electrodeposition, or other suitable technique. Tapered distal portion 1414 may then be protected by an etch-resistant material while body portion 1412 is formed from the substrate by dry etching (e.g., DRIE) or other suitable process.

[0118] The combination of cylindrical and conical sides of the microneedle 1400 has several advantages. Similar to those described above, the tapered distal portion 1414 and apex 1416: <311> Due to the wet-etched planar and conical shape, the substrate has high mechanical strength. In addition, because the substrate is formed from a non-conductive material, insulating "moats" as described above are not required to electrically isolate the microneedles, which may simplify and reduce the cost of fabrication. The absence of insulating moats also allows for material continuity in the substrate, which may lead to better mechanical integrity of the overall microneedle array structure.

[0119] While the pillar-cone microneedle 1400 is described above as including a non-conductive substrate, it should be understood that in some variations, the pillar-cone microneedle may alternatively include a conductive core extending from a conductive substrate (e.g., doped silicon). For example, in some variations, the pillar-cone body portion 1412 may be similar to that described above with respect to Figures 7A-7C and 8-10 (e.g., may include an insulating moat for electrically isolating the microneedle, etc.).

[0120] In some variations of microneedle arrays including one or more microneedles 1400, conductive pathways may be formed in a non-conductive substrate to facilitate communication with the electrode 1420. For example, as described above, the body portion 1412 of each microneedle may include a conductive core comprising a conductive material. Such conductive material may extend between the electrode 1420 and the substrate 1402. As shown in FIG. 15D , the microneedle array may include one or more connectors 1510 made from a conductive material (e.g., gold, aluminum), each of which is in turn coupled to a backside electrical contact 1530 for further sensor communication. In some variations, as shown in FIGS. 15A-15D , the one or more connectors 1510 may extend laterally along the surface of the substrate and then connect to the backside electrical contact 1530 using a conductive via 1520 in the substrate.

[0121] Additional details of exemplary variations of microneedle array configurations are described in greater detail below. electrode

[0122] As described above, each microneedle in the microneedle array may include an electrode. In some variations, multiple distinct types of electrodes may be included between the microneedles in the microneedle array. For example, in some variations, the microneedle array may function as an electrochemical cell capable of operating in an electrolytic mode with three types of electrodes. In other words, the microneedle array may include at least one working electrode, at least one counter electrode, and at least one reference electrode. Thus, the microneedle array may include three distinct electrode types, although one or more of each electrode type may form a complete system (e.g., the system may include multiple distinct working electrodes). Furthermore, multiple distinct microneedles may be electrically joined to form an effective electrode type (e.g., a single working electrode may be formed from two or more connected microneedles with working electrode sites). Each of these electrode types may include a metallization layer and one or more coatings or layers over the metallization layer that help facilitate the function of that electrode.

[0123] Generally, the working electrode is the electrode where the oxidation and / or reduction reaction of interest occurs for the detection of the analyte of interest. The counter electrode functions to source or sink (store) the electrons required to sustain the electrochemical reaction at the working electrode via current. The reference electrode functions to provide a reference potential for the system; i.e., the potential to which the working electrode is biased is referenced to the reference electrode. A fixed, time-varying, or at least controlled potential relationship is established between the working and reference electrodes, and, within practical limits, no current is sourced from or sunk to the reference electrode. In addition, to implement such a three-electrode system, the analyte monitoring device may include a suitable potentiostat or electrochemical analog front end to maintain a fixed potential relationship between the working and reference electrode components in the electrochemical system (via an electronic feedback mechanism) while allowing the counter electrode to dynamically swing to the potential required to sustain the redox reaction of interest. working electrode

[0124] As explained above, the working electrode is the electrode where the oxidation and / or reduction reaction of interest occurs. In some variations, sensing may be performed at the interface of a working electrode located within the body (e.g., on the outer surface of the entire microneedle) and interstitial fluid. In some variations, the working electrode may include an electrode material and a biorecognition layer, in which a biorecognition element (e.g., an enzyme) is immobilized on the working electrode to facilitate selective analyte quantification. In some variations, the biorecognition layer may also function as an interference blocking layer, helping to prevent endogenous and / or exogenous species from being directly oxidized (or reduced) at the electrode.

[0125] The redox current detected at the working electrode can be correlated to the detected concentration of the analyte of interest because, assuming a steady-state diffusion-limited system, the redox current detected at the working electrode obeys the Cottrell relationship: [ka] where n is the stoichiometric number of electrons mitigating the redox reaction, F is Faraday's constant, A is the 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 the duration the system is biased with a potential. Thus, the current detected at the working electrode is linearly proportional to the analyte concentration.

[0126] Also, because the detected current is a direct function of the electrode surface area A, the surface area of ​​the electrode may be increased to enhance the sensitivity of the sensor (e.g., amperes per mole of analyte). For example, multiple single working electrodes may be grouped into an array of two or more elements to increase the total effective sensing surface area. Additionally or alternatively, to obtain redundancy, multiple working electrodes may be operated as paralleled sensors to obtain multiple independent measurements of the concentration of an analyte of interest. The working electrode can be operated either as an anode (so that the analyte is oxidized at its surface) or as a cathode (so that the analyte is reduced at its surface).

[0127] FIG. 16A depicts a schematic diagram of an example 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 facilitate electrocatalytic detection of an analyte or a product of a reaction between the analyte and the biorecognition element. The electrode material 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, the electrode material 1612 may alternatively include, for example, palladium, iridium, rhodium, gold, ruthenium, titanium, nickel, carbon, doped diamond, or other suitable catalytic and inert materials.

[0128] In some variations, the electrode material 1612 may be coated with a highly porous electrocatalytic layer, such as a platinum black layer 1613, which may increase the electrode surface area for enhanced sensitivity. Additionally or alternatively, the platinum black layer 1613 may enable 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 (e.g., as shown in Figures 16D and 16G). The electrode may enable electrocatalytic oxidation or reduction of the product of the biorecognition reaction in the absence of the platinum black layer 1613.

[0129] A biorecognition layer 1614 may be disposed over the electrode material 1612 (or platinum-black layer 1613, if present) and serves to immobilize and stabilize the biorecognition element, which facilitates selective analyte quantification over 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 glucose monitoring system, the biorecognition element may include glucose oxidase, which, in the presence of oxygen, converts glucose 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).

[0130] However, in other variations, the biorecognition element may additionally or alternatively comprise another suitable oxidase or oxidoreductase, such as lactate oxidase, alcohol oxidase, β-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and / or xanthine oxidase.

[0131] In some variations, the biorecognition elements may be crosslinked with amine-condensed carbonyl species, which may help stabilize the biorecognition elements in the biorecognition layer 1614. As described further below, in some variations, crosslinking the biorecognition elements may render the microneedle array compatible with ethylene oxide (EO) sterilization, allowing the entire analyte monitoring device (including the sensing elements and electronics) to be subjected to the same sterilization cycle, thereby simplifying the sterilization process and reducing manufacturing costs. For example, the biorecognition elements may be crosslinked with glutaraldehyde, formaldehyde, glyoxal, malonaldehyde, succinaldehyde, and / or other suitable species. In some variations, the biorecognition elements may be crosslinked with such amine-condensed carbonyl species to form crosslinked biorecognition element assemblies. Crosslinked biorecognition element assemblies having at least a threshold molecular weight may then be embedded in a conducting polymer. By embedding only those assemblies having a threshold molecular weight, any uncrosslinked enzymes are screened out and cannot be incorporated into the biorecognition layer. Thus, only assemblies having the desired molecular weight can be selected for use in the conducting polymer, helping to ensure that only sufficiently stabilized cross-linked enzyme entities are included within the biorecognition layer, thereby contributing to a biorecognition layer that is overall more suitable for EO sterilization without loss of sensing performance. In some variations, only cross-linked assemblies having a molecular weight that is at least twice that of glucose oxidase may be embedded in the conducting polymer.

[0132] In some variations, the conducting polymer may be permselective to contribute to the robustness of the biorecognition layer against circulating neutral electroactive species (e.g., ascorbic acid, vitamin C, etc.), fluctuations of which can adversely affect sensor sensitivity. Such permselective conducting polymers in the biorecognition layer may also be more robust against pharmacological interferences in interstitial fluid (e.g., acetaminophen), which can affect sensor accuracy. Conducting polymers may be made permselective, for example, by removing excess charge carriers through an oxidative electropolymerization process or by neutralizing these charge carriers using a counterion dopant, thereby converting the conducting polymer to a non-conducting form. These oxidatively polymerized conducting polymers exhibit permselectivity and are therefore capable of rejecting ions of a charge polarity (net positive or negative) similar to that of the dopant ion or rejecting ions via size exclusion due to the dense and compact morphology of the conducting polymer.

[0133] Furthermore, in some variations, the conducting polymer may exhibit self-sealing and / or self-healing properties. For example, the conducting polymer may undergo oxidative electropolymerization, during which 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 reduces the deposition of additional conducting polymer. In the event that the conducting polymer suffers minor physical damage (e.g., during use), the polymer backbone may reassemble and neutralize free charges, thereby lowering the overall surface energy of the molecular structure, which may manifest as self-sealing and / or self-healing properties.

[0134] In some variations, the working electrode may further include a diffusion-limiting layer 1615 disposed over the biorecognition layer 1614. The diffusion-limiting layer 1615 may function to limit the flux of the analyte of interest to reduce the sensor's sensitivity to endogenous oxygen fluctuations. For example, the diffusion-limiting layer 1615 may attenuate the concentration of the analyte of interest so that it becomes the limiting reactant for an aerobic enzyme. However, in some variations (e.g., if the biorecognition element is not aerobic), the diffusion-limiting layer 1615 may be omitted.

[0135] The working electrode may further include a hydrophilic layer 1616 in some variations to provide a biocompatible interface, e.g., to reduce foreign body response. However, in some variations, the hydrophilic layer 1616 may be omitted (e.g., when the diffusion-limiting layer represents the hydrophilic portion for this purpose), as shown, for example, in Figures 16D and 16G. Counter electrode

[0136] As explained above, the counter electrode is the electrode that sources or sinks the electrons (via current) required to sustain the electrochemical reaction at the working electrode. The number of counter electrode components can be increased in the form of a counter electrode array to increase the surface area so that the current-carrying capacity of the counter electrode does not limit the redox reaction at the working electrode. Therefore, it may be desirable to have excess counter electrode area relative to the working electrode area to avoid current-carrying capacity limitations. When the working electrode is operated as an anode, the counter electrode will serve as a cathode, and vice versa. Similarly, when an oxidation reaction occurs at the working electrode, a reduction reaction occurs at the counter electrode, and vice versa. Unlike the working electrode or reference electrode, the counter electrode is allowed to dynamically swing to the potential required to sustain the redox reaction of interest on the working electrode.

[0137] 16B, counter electrode 1620 may include an electrode material 1622 similar to electrode material 1612. For example, like electrode material 1612, electrode material 1622 in counter electrode 1620 may include a precious metal such as gold, platinum, palladium, iridium, carbon, doped diamond, and / or other suitable catalytic and inert materials.

[0138] In some variations, the counter electrode 1620 may have little or no additional layer over the electrode material 1632. However, in some variations, the counter electrode 1620 may benefit from an increased 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 a manner that increases the surface area of ​​the electrode material 1632 for enhanced current sourcing or sinking capabilities. Additionally or alternatively, the counter electrode 1620 may include a layer of platinum black 1624, which may increase the electrode area, as described above with respect to some variations of the working electrode. However, in some variations of the counter electrode, the layer of platinum black may be omitted (e.g., as shown in FIG. 16E). In some variations, the counter electrode may further include a hydrophilic layer that provides a biocompatible interface, for example, to reduce foreign body response.

[0139] Additionally or alternatively, in some variations, such as that shown in Figure 16H, the counter electrode 1620 may include a diffusion-limiting layer 1625 (arranged across the electrode). The diffusion-limiting layer 1625 may be similar to the diffusion-limiting layer 1615 described above with respect to Figure 16A, for example. reference electrode

[0140] As explained above, the reference electrode functions to provide a reference potential for the system, i.e., the potential to 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 sunk to the reference electrode.

[0141] As shown in FIG. 16C , the reference electrode 1630 may include an electrode material 1632 similar to the electrode material 1612. In some variations, like the electrode material 1612, the electrode material 1632 in the reference electrode 1630 may include a metal salt or metal oxide, which serves as a stable redox couple with a known electrode potential. For example, the metal salt may 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, doped diamond, and / or other suitable catalytic and inert materials. Furthermore, in some variations, the reference electrode 1630 may be textured or otherwise roughened in a manner to enhance adhesion with any subsequent layers. Such subsequent layers on the electrode material 1632 may include a platinum-black layer 1634. However, in some variations, the platinum black layer may be omitted (eg, as shown in Figures 16F and 16I).

[0142] The reference electrode 1630 may further include, in some variations, a redox couple layer 1636, which primarily contains 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 relative to the standard hydrogen electrode (SHE). High stability of the electrode potential may be achieved by employing a redox system with a constant (e.g., buffered or saturated) concentration of each participant in the redox reaction. For example, the reference electrode may include saturated Ag / AgCl (E = +0.197 V vs. SHE) or IrOx (E = +0.177 V vs. SHE, pH = 7.00) in the redox couple layer 1636. Other examples of the redox couple layer 1636 may include a suitable conducting polymer with dopant molecules, such as those described in U.S. Patent Publication No. 2019 / 0309433 (herein incorporated by reference in its entirety). In some variations, the reference electrode may be used as a half-cell to construct a complete electrochemical cell.

[0143] Additionally or alternatively, in some variations, such as that shown in Figure 16I, the reference electrode 1630 may include a diffusion-limiting layer 1635 (e.g., arranged across the electrode and / or redox pair layer). The diffusion-limiting layer 1635 may be similar to the diffusion-limiting layer 1615 described above with respect to Figure 16A, for example. Exemplary Electrode Layer Formation

[0144] The various layers of working, counter, and reference electrodes may be applied and / or functionalized, etc. to the microneedle array using suitable processes such as those described below.

[0145] In a pretreatment step for the microneedle array, the microneedle array may be plasma cleaned in an inert gas (e.g., an RF-generated inert gas such as argon) plasma environment to make the surfaces of materials, including the electrode materials (e.g., electrode materials 1612, 1622, and 1632 as described above), more hydrophilic and chemically reactive. This pretreatment not only physically removes organic debris and contaminants, but also functions to clean and prepare the electrode surfaces to enhance adhesion of films subsequently deposited thereon. working electrode

[0146] Anodization: To configure the working electrode after the pretreatment step, the electrode material 1612 may undergo an anodization process using an amperometric approach, in which the electrode components assigned for working electrode function are subjected to a fixed high anodic potential (e.g., +1.0 to +1.3 V vs. an Ag / AgCl reference electrode) in a moderate strength acid solution (e.g., 0.1 to 3 M H2SO4) for a suitable amount of time (e.g., about 30 seconds to about 10 minutes). In this process, a thin but stable native oxide layer can be developed on the electrode surface. Due to the resulting low pH at the electrode surface, any trace contaminants can be removed as well.

[0147] In an alternative embodiment using a coulometric approach, anodization is allowed to proceed until a defined amount of charge (measured in coulombs) has passed. An anodic potential may be applied as described above, however, the duration of this may be varied until the defined amount of charge has passed.

[0148] Activation: Following the anodization process, the working electrode component may be subjected to a periodically scanned potential waveform in an activation process using cyclic voltammetry. In the activation process, which may be carried out in a moderate-strength acid solution (e.g., 0.1-3 M H2SO4), the applied potential may be varied over time in a suitable function (e.g., a sawtooth function). For example, the voltage may be scanned linearly in an alternating function (e.g., 15-50 linear sweep segments) between a cathodic value (e.g., -0.3 to -0.2 V vs. Ag / AgCl reference electrode) and an anodic value (e.g., +1.0 to +1.3 V vs. Ag / AgCl reference electrode). The scan rate of this waveform may range from 1 to 1,000 mV / s. Note that current peaks occurring during the anodic sweep (swirl to the positive electrode) correspond to the oxidation of the chemical species, while current peaks occurring during the subsequent cathodic sweep (swirl to the negative electrode) correspond to the reduction of the chemical species.

[0149] Biorecognition Layer Functionalization: Following the activation process, the working electrode component may be functionalized with a biorecognition layer 1614, such as that described above. Assuming that the working electrode configuration of the microneedle array has undergone the aforementioned steps, the applied potential may be time-varying in a sawtooth function. For example, the voltage may be scanned linearly in an alternating function (e.g., 10 linear sweep segments) between a cathodic value (e.g., 0.0 V vs. Ag / AgCl reference electrode) and an anodic value (e.g., +1.0 V vs. Ag / AgCl reference electrode). In an exemplary variation, the scan rate of this waveform may range from about 1 mV / sec to about 10 mV / sec in an aqueous solution consisting of a monomer precursor of a capture conducting polymer and a crosslinked biorecognition element (e.g., an enzyme such as glucose oxidase). In this process, a thin film (e.g., about 10 nm to about 1,000 nm) of a biorecognition layer consisting of a polymer with dispersed crosslinked biorecognition elements 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, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid. The biorecognition layer, as described above, confers selective sensing capability for an analyte of interest.

[0150] In some variations, the working electrode surface may be electrochemically roughened to enhance adhesion of the biorecognition layer to the electrode material 1612 surface (and / or platinum black layer). The roughening process may involve cathodic oxidation (e.g., cathodic deposition, a subset of amperometry), in which the electrode is subjected to a fixed cathodic potential (e.g., from -0.4 to +0.2 V vs. an Ag / AgCl reference electrode) for an amount of time (e.g., 5 seconds to 10 minutes) in an acid solution (e.g., 0.01 to 100 mM HPtCl) containing the desired metal cations dissolved therein. Alternatively, the electrode is subjected to a fixed cathodic potential (e.g., from about -0.4 to +0.2 V vs. an Ag / AgCl reference electrode) in an acid solution (e.g., 0.01 to 100 mM HPtCl) containing the desired metal cations dissolved therein until a certain amount of charge has passed (e.g., 0.1 mC to 100 mC). In this process, a thin but highly porous layer of metal may be generated on the electrode surface, thereby dramatically increasing the electrode surface area. Additionally or alternatively, in some variations as described above, elemental platinum metal may be deposited on the electrode to form or deposit a platinum black layer 1613.

[0151] Diffusion-Limiting Layer Functionalization: Following functionalization of the biorecognition layer, the working electrode component may, in some variations, be functionalized with a diffusion-limiting layer. Assuming the microneedle array working electrode component has undergone the steps described above, one or more of the following methods may be employed to apply the diffusion-limiting layer, which may be a thin film about 100 nm to about 10,000 nm thick.

[0152] In some variations, the diffusion-limiting layer may be 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 in a controlled environment using a defined spray pattern and duration, creating a thin film with the desired thickness and porosity required to limit the diffusion of the analyte of interest to the biorecognition layer.

[0153] In some variations, the diffusion-limiting layer may be applied by a plasma-induced polymerization method in which a plasma source generates a gas discharge that provides energy to activate a cross-linking reaction within a gaseous, aerosolized, or liquid monomer precursor (e.g., vinylpyridine), converting the monomer precursor into a polymer coating that can be deposited onto the microneedle array to a defined thickness, thereby creating a thin film with the desired thickness and porosity required to limit the diffusion of the analyte of interest into the biorecognition layer 1614.

[0154] Additionally, in some variations, the diffusion-limiting layer may be applied by electrophoretic or dielectrophoretic deposition, such as the exemplary techniques described in U.S. Pat. No. 10,092,207, which is incorporated herein by reference in its entirety. Counter electrode

[0155] Anodization: In some variations, the counter electrode material may undergo anodization using an amperometric approach, in which the electrode component assigned to the counter electrode function is subjected to a fixed high anodic potential in a moderate strength acid solution for a suitable amount of time. Exemplary parameters and other details of the anodization process for the counter electrode may be similar to those described above for the working electrode. Similarly, anodization for the counter electrode may alternatively use a coulometric approach as described above.

[0156] Activation: In some variations, following the anodization process, the counter electrode component may be subjected to a periodically scanned potential waveform in an activation process using cyclic voltammetry. In some variations, the activation process may be similar to that described above for the working electrode.

[0157] Roughening: Additionally, in some variations, the counter electrode surface may be electrochemically roughened to enhance the current sinking or current sourcing capabilities of the electrode configuration. 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 be deposited on the electrode to form or deposit a platinum black layer 1623. reference electrode

[0158] Anodization: Like the working and counter electrodes described above, the reference electrode may undergo an anodization process using an amperometric approach, in which the electrode component assigned to the counter electrode function is subjected to a fixed high anodic potential in a moderate strength acid solution for a suitable amount of time. Exemplary parameters and other details of the anodization process for the counter electrode may be similar to those described above for the working electrode. Similarly, anodization for the counter electrode may be performed ...

[0159] Activation: Following the anodization process, the reference electrode component may be subjected to a periodically scanned potential waveform in an activation process using cyclic voltammetry. In some variations, the activation process may be similar to that described above for the working electrode.

[0160] Functionalization: Following the activation process, the reference electrode component may be functionalized. Assuming the reference electrode component of the microneedle array has undergone the aforementioned steps, a fixed anodic potential (e.g., +0.4 to +1.0 V vs. Ag / AgCl reference electrode) may be applied in aqueous solution for a suitable duration (e.g., about 10 seconds to about 10 minutes). Alternatively, the reference electrode may be subjected to a fixed anodic potential (e.g., about +0.4 to about +1.0 V vs. Ag / AgCl reference electrode) until a certain amount of charge has passed in aqueous solution (e.g., 0.01 mC to 10 mC). In some variations, the aqueous solution may contain a monomer precursor of a conducting polymer and a charged dopant counterion or material (e.g., poly(styrene sulfonate)) that carries the opposite charge. In this process, a thin film (e.g., about 10 nm to about 10,000 nm) of conducting polymer with dispersed counterion or material may be generated on the reference electrode surface. This creates a surface-immobilized solid-state redox couple with a stable thermodynamic potential. In some variations, the conducting polymer may include one or more of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid.

[0161] In some alternative embodiments, a native iridium oxide film (e.g., IrO2 or Ir2O3 or IrO4) may be electrochemically grown on the iridium electrode surface in an oxidation process, which also creates a stable redox couple as described above.

[0162] Furthermore, in some variations, the reference electrode surface may be electrochemically roughened 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 be deposited on the electrode to form or deposit a platinum black layer 1633.

[0163] Other features and techniques for forming the reference electrode may be similar to those described, for example, in U.S. Patent Publication No. 2019 / 0309433 (incorporated by reference above). Microneedle array configuration

[0164] Multiple microneedles (e.g., any of the microneedle variations described herein, each of which may have a working electrode, a counter electrode, or a reference electrode as described above) may be arranged in a microneedle array. Considerations for how to configure the microneedles include factors such as the desired insertion force for penetrating the skin with the microneedle array, optimization of electrode signal levels and other performance aspects, and manufacturing cost and complexity.

[0165] For example, a microneedle array may include multiple microneedles spaced apart at a predetermined pitch (the distance between the center of one microneedle and the center of its nearest neighboring microneedle). In some variations, the microneedles may be spaced apart with sufficient pitch to distribute the force applied to a user's skin to cause the microneedle array to penetrate the skin (e.g., avoid a "bed of needles" effect). As the pitch increases, the force required to insert the microneedle array tends to decrease and the depth of penetration tends to increase. However, it has been found that the pitch begins to affect the insertion force only at low values ​​(e.g., less than about 150 μm). Thus, in some variations, the microneedles in the microneedle array may have a pitch of at least 200 μm, at least 300 μm, at least 400 μm, at least 500 μm, at least 600 μm, at least 700 μm, or at least 750 μm. For example, the pitch may be about 200 μm to about 800 μm, about 300 μm to about 700 μm, or about 400 μm to about 600 μm. In some variations, the microneedles may be arranged in a periodic grid, and the pitch may be uniform in all directions and across all regions of the microneedle array. Alternatively, the pitch may vary as measured along different axes (e.g., X, Y directions), and / or some regions of the microneedle array may include a smaller pitch while others include a larger pitch.

[0166] Additionally, for more consistent penetration, the microneedles may be spaced equal distances from one another (e.g., the same pitch in all directions). To that end, in some variations, the microneedles in the microneedle array may be arranged in a hexagonal configuration as shown in Figure 17. Alternatively, the microneedles in the microneedle array may be arranged in a rectangular array (e.g., a square array) or in another suitable symmetrical manner.

[0167] Another consideration for determining the configuration of a microneedle array is the overall signal level provided by the microneedles. Generally, the signal level at each microneedle is invariant to the total number of microneedle elements in the array. However, the signal level can be enhanced by electrically interconnecting multiple microneedles together in an array. For example, an array with a large number of electrically connected microneedles is expected to generate a signal strength (and therefore increased accuracy) greater than one with fewer microneedles. However, a larger number of microneedles on a die will increase the die cost (assuming a constant pitch) and require more force and / or speed to insert into the skin. In contrast, a smaller number of microneedles on a die may reduce die cost and enable insertion into the skin with reduced applied force and / or speed. Furthermore, in some variations, a smaller number of microneedles on a die may reduce the overall footprint of the die, which may lead to less unwanted localized edema and / or erythema. Thus, in some variations, a balance between these factors may be achieved using a microneedle array containing 37 microneedles as shown in Figure 17 or a microneedle array containing 7 microneedles as shown in Figures 29A and 29B. However, in other variations, there may be fewer microneedles in the array (e.g., about 5 to about 35, about 5 to about 30, about 5 to about 25, about 5 to about 20, about 5 to about 15, about 5 to about 100, about 10 to about 30, about 15 to about 25, etc.) or more microneedles in the array (e.g., more than 37, more than 40, more than 45, etc.).

[0168] Additionally, as described in more detail below, in some variations, only a subset of the microneedles in the microneedle array may be active during operation of the analyte monitoring device. For example, some of the microneedles in the microneedle array may be inactive (e.g., no signal is read from the electrodes of the inactive microneedles). In some variations, some of the microneedles in the microneedle array may be activated at some point during operation and remain active for the remainder of the operational life of the device. Furthermore, in some variations, some of the microneedles in the microneedle array may additionally or alternatively be deactivated at some point during operation and remain inactive for the remainder of the operational life of the device.

[0169] When considering die characteristics for a microneedle array, die size is a function of the number of microneedles in the microneedle array and the pitch of the microneedles. Manufacturing cost is also a consideration, as a smaller die size will increase the number of dies that can be formed from a single wafer of a given area, contributing to lower costs. Furthermore, a smaller die size will also be less susceptible to brittle fracture due to the relative fragility of the substrate.

[0170] 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 edge of the microneedle array, etc.) may be found to have better performance (e.g., sensitivity) due to better penetration compared to microneedles at the center of the microneedle array or die. Thus, in some variations, the working electrode may be arranged mostly or entirely on microneedles located at the periphery of the microneedle array to obtain more accurate and / or precise analyte measurements.

[0171] Figure 17 depicts an illustrative schematic diagram of 37 microneedles arranged in an exemplary variation of a microneedle array. The 37 microneedles may be arranged in a hexagonal array, for example, with a center-to-center pitch between needles of about 750 μm (or about 700 μm to about 800 μm, or about 725 μm to about 775 μm) between the center of each microneedle and the center of its immediate neighbor in any direction. Figure 18A depicts an illustrative schematic diagram of an exemplary variation of a die containing the microneedle array shown in Figure 17. Exemplary dimensions of the die (e.g., about 4.4 mm x about 5.0 mm) and microneedle array are shown in Figure 18B.

[0172] 29A and 29B depict perspective views of an illustrative schematic of seven microneedles 2910 arranged in an exemplary variation of microneedle array 2900. The seven microneedles 2910 are arranged in a hexagonal array on a substrate 2902. As shown in FIG. 29A, electrodes 2920 are arranged on distal portions of the microneedles 2910 extending from a first surface of the substrate 2902. As shown in FIG. 29B, proximal portions of the microneedles 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 top and side views of an illustrative schematic of a microneedle array similar to microneedle array 2900. As shown in Figures 30A and 30B, seven microneedles are arranged in a hexagonal array with a center-to-center pitch between each microneedle and its immediate neighbor in any direction of about 750 μm. In other variations, the center-to-center pitch between needles may be, for example, about 700 μm to about 800 μm or about 725 μm to about 775 μm. The microneedles may have an approximate outer shaft diameter of about 170 μm (or about 150 μm to about 190 μm or about 125 μm to about 200 μm) and a height of about 500 μm (or about 475 μm to about 525 μm or about 450 μm to about 550 μm).

[0173] Additionally, the microneedle arrays described herein may have a high degree of configurability regarding where the working, counter, and reference electrodes are located within the microneedle array, and this configurability may be facilitated by the electronics system.

[0174] In some variations, the microneedle array includes electrodes distributed symmetrically or asymmetrically into two or more groups in the microneedle array, with each group featuring the same or different numbers of electrode components, depending on requirements for signal sensitivity and / or redundancy. For example, the same type of electrodes (e.g., working electrodes) may be distributed bilaterally or in a radially symmetric manner in the microneedle array. For example, FIG. 19A depicts a variation of a microneedle array 1900A including two symmetric groups of seven working electrodes (WE), where the two working electrode groups are labeled "1" and "2." In this variation, the two working electrode groups are distributed bilaterally and symmetrically within the microneedle array. The working electrodes are generally arranged between a central region of three reference electrodes (RE) and an outer peripheral region of 20 counter electrodes (CE). In some variations, each of the two working electrode groups may include seven working electrodes electrically connected among themselves (e.g., to enhance the sensor signal). Alternatively, only a portion of one or both of the working electrode populations may include multiple electrodes that are electrically connected among themselves. As yet another alternative, the working electrode populations may include working electrodes that are stand-alone and not electrically connected to other working electrodes. Furthermore, in some variations, the working electrodes may be distributed in the microneedle array in an asymmetric or random configuration.

[0175] As another example, Figure 19B depicts a variation of microneedle array 1900B that includes four symmetric groups of three working electrodes (WE), labeled "1," "2," "3," and "4." In this variation, the four working electrode groups are distributed in a radially symmetric manner in the microneedle array. Each working electrode group is adjacent to one of two reference electrode (RE) components in the microneedle array, arranged in a symmetric manner. The microneedle array also includes counter electrodes (CE) arranged around the periphery of the microneedle array, except for two electrodes on the hexagonal vertices that may be inactive or used for other features or modes of operation.

[0176] In some variations, only a portion of the microneedle array may include active electrodes. For example, Figure 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, 22 counter electrodes, and three reference electrodes. The remaining eight electrodes in the microneedle array are inactive. In the microneedle array shown in Figure 19C, each working electrode is surrounded by a group of counter electrodes. The two groups of such clusters of working and counter electrodes are separated by a row of three reference electrodes.

[0177] As another example, Figure 19D depicts a variation of 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, 20 counter electrodes, and three reference electrodes; the remaining 10 electrodes in the microneedle array are inactive.

[0178] As another example, Figure 19E depicts a variation of microneedle array 1900E with 37 microneedles and a reduced number of active electrodes, including four working electrodes (labeled "1," "2," "3," and "4"), 18 counter electrodes, and two reference electrodes. The remaining 13 electrodes in the microneedle array are inactive. The inactive electrodes are along a partial perimeter of the entire microneedle array, thereby reducing the effective size and shape of the active microneedle array to a smaller hexagonal array. Within the active microneedle array, the four working electrodes are generally arranged in a radially symmetrical fashion, with each working electrode surrounded by a group of counter electrodes.

[0179] Figure 19F depicts another exemplary 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 reference electrode. The remaining 30 electrodes in the microneedle array are inactive. The inactive electrodes are arranged in two layers around the periphery of the entire microneedle array, thereby reducing the effective size and shape of the active microneedle array to a smaller hexagonal array centered around the reference electrode. Within the active microneedle array, the four working electrodes are arranged bilaterally symmetrically, and the counter electrodes are equidistant from the central reference electrode.

[0180] Figure 19G depicts another exemplary variation of a microneedle array 1900G with 37 microneedles and a reduced number of active electrodes. The active electrodes in microneedle array 1900G are arranged in a manner similar to that in microneedle array 1900F shown in Figure 19F, except that microneedle array 1900G includes one counter electrode and two reference electrodes, and the smaller hexagonal array of active microneedles is centered around the counter electrode. Within the active microneedle array, the four working electrodes are arranged bilaterally symmetrically, and the reference electrode is equidistant from the central counter electrode.

[0181] Figure 19H depicts another exemplary variation of a microneedle array 1900H with seven microneedles. The microneedle array contains two microneedles (1 and 2) assigned as independent working electrodes, a counter electrode configuration consisting of four 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. In addition, the working electrodes are arranged as far away from the center of the microneedle array as possible (e.g., on the periphery of the die or array) to take advantage of locations where the working electrodes are expected to have greater sensitivity and overall performance.

[0182] Figure 19I depicts another exemplary variation of a microneedle array 1900I with seven microneedles. The microneedle array contains four microneedles (1 and 2), each assigned as two independent groups of two working electrodes, a counter electrode configuration consisting of two microneedles, and a single reference electrode. There is bilateral symmetry in the arrangement of the working and counter electrodes, which are equidistant from the central reference electrode. In addition, the working electrodes are arranged as far away from the center of the microneedle array as possible (e.g., on the periphery of the die or array) to take advantage of locations where the working electrodes are expected to have greater sensitivity and overall performance.

[0183] Figure 19J depicts another exemplary variation of a microneedle array 1900J with seven microneedles. The microneedle array contains four microneedles (1, 2, 3, and 4) assigned as independent working electrodes, a counter electrode configuration consisting of two 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. In addition, the working electrodes are arranged as far away from the center of the microneedle array as possible (e.g., on the periphery of the die or array) to take advantage of locations where the working electrodes are expected to have greater sensitivity and overall performance.

[0184] While Figures 19A-19J illustrate exemplary variations of microneedle array configurations, it should be understood that these figures are not limiting and that other microneedle configurations (such as different numbers and / or distributions of working, counter, and reference electrodes, and different numbers and / or distributions of active and inactive electrodes) may be suitable in other variations of microneedle arrays. Warm-up

[0185] Many implanted electrochemical sensors require a "warm-up" period, or time for the sensor to achieve a stable signal value following implantation. This process stems from both physiology and sensor mechanics. However, various aspects of the analyte monitoring devices described herein are configured to mitigate factors that contribute 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 warm-up times of about 30 minutes or less (e.g., about 10 minutes to about 30 minutes, about 15 minutes to about 30 minutes, about 20 minutes to about 30 minutes, about 25 minutes to 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 the warm-up period, the analyte monitoring device may undergo calibration during a calibration period.

[0186] Wound response: For example, the implantation of a sensor creates a wound response due to localized disruption, displacement, and destruction of tissue. The larger the sensor or the deeper the implant, the greater the wound response. Therefore, there is a compelling rationale to miniaturize the sensor and elicit a damped wound response, which would result in a more rapid warm-up.

[0187] Protein adsorption: In addition, following sensor implantation, a foreign body response occurs immediately. The foreign body response involves a complex biochemical cascade aimed at encapsulating the foreign body with cellular material. Hydrophobic surfaces tend to undergo endogenous protein adsorption very rapidly following implantation, a process known as biofouling. Hydrophilic surfaces, on the other hand, resist biofouling due to their high water content. Human serum albumin (HSA) is the major protein in dermal interstitial fluid, comprising approximately 60% of the total protein and maintaining a negative charge at physiological pH. When the sensor is polarized at a positive potential (as in some variations of analyte monitoring devices), endogenous HSA undergoes electrical drift and charge attraction to the sensor's positive (working) electrode. This can increase the tendency of the sensor surface to biofoul. This is the rationale behind the implementation of either a hydrophilic diffusion-limiting layer or an outer biocompatible layer to effectively mask the sensor so that it is not recognized as a foreign body, as explained in further detail above.

[0188] As described herein, the analyte monitoring device reduces the impact 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 less than current CGM systems, such as about 100 to about 1,000 times less tissue displaced compared to current CGM systems, or about 200 to about 600 times less tissue displaced), the minimal amount of trauma to the tissue during implantation, and the lack of vascular penetration into the deeper portions of the reticular dermis, which, when disturbed, can cause a greater wound response that would result in an accelerated attempt to encapsulate the implant, as is the case with competing wire-implanted CGM systems.

[0189] Achieving Equilibrium: One example of the effect of sensor dynamics on warm-up time relates to achieving equilibrium. When used in a new environment, electrochemical sensors require a finite amount of time to achieve equilibrium. This is typically associated with the establishment of thermodynamic equilibrium due to an adsorbed surface layer of ions at the electrode. Because the reference electrode in most implantable electrochemical sensors does not employ an internal fill solution with a redox couple that is sealed from the rest of the electrochemical cell, the reference electrode must achieve equilibrium with its surroundings to establish a stable reference potential.

[0190] Hydration of the sensor layer: The electrode sensor layer must be immersed in an aqueous environment to function properly. The resulting hydration process can activate the electrode's polymer layer and biorecognition elements, allowing them to rearrange and return to their native active conformation, which is primarily responsible for their activity or unique properties. This process, often known as sensor "wetting," allows the medium in which sensing occurs to intercalate the sensor layer to a sufficient extent.

[0191] Decay of Non-Faradaic Response: Biasing (application of voltage) 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 charging of adsorbed species on the electrode surface. This gives rise to double-layer capacitance. The non-faradaic time constant is equal to the product of the double-layer capacitance and the solution resistance. In many cases, the non-faradaic response (current) decays to negligible levels more rapidly than other physical phenomena, and it is often not the rate-limiting step in the warm-up process. Once the non-faradaic response decays to negligible levels, a faradaic response follows, which reflects the electrochemical / redox reaction of interest.

[0192] As described herein, analyte monitoring devices may reduce the impact of sensor dynamics on warm-up time due, for example, to the implementation of thin-film layers (approximately 10 nm to 5,000 nm), which allow the layers to hydrate more rapidly than competing implantable CGM systems. Also, due to the small dimensions of the electrodes described herein (e.g., the geometric surface area of ​​the working electrode), non-faradaic responses occur over shorter durations (due to reduced double-layer capacitance and, therefore, double-layer charging). In some variations, a high-potential (e.g., >0.75 V) bias for a limited period of time following application of the device to the skin may further facilitate burn-in or warm-up of the sensor to achieve equilibrium and stable signal levels. Waiting time at traffic lights

[0193] Typically, implanted electrochemical sensors also suffer from a delay, or signal latency, in achieving a stable signal value following a change in analyte level. This signal latency is a function of a variety of factors. At a high level, latency is a function of three distinct effects: (1) diffusion delay (the amount of time required for analyte molecules to diffuse from the capillary (source) to the sensor surface); (2) diffusion limitations imposed by the sensor membrane / layer architecture on the sensor; and (3) algorithmic processing of the data (averaging, filtering, signal denoising, and other signal processing means), which often results in group delay. However, various aspects of the analyte monitoring devices described herein minimize these factors that contribute to signal latency, thereby resulting in faster response times for analyte measurements.

[0194] As explained above, one significant advantage of the analyte monitoring devices described herein is the location of sensor placement. Because the electrode surface is implanted in close proximity (e.g., within a few hundred micrometers or less) to the dense and well-perfused capillary bed of the reticular dermis, diffusion delays are negligible. This is a significant advantage over conventional analyte sensors, which reside in the very poorly vascularized adipose tissue below the dermis and therefore have substantial diffusion distances and resulting diffusion latencies from the vessels within the dermis (e.g., typically 5-20 minutes).

[0195] Additionally, because the film deposited on the electrode sensor surface uses an electrodeposition method, the precise thickness of the film can be controlled to a high degree of accuracy. For example, the electrodeposition method for forming the sensor surface allows for consistent and controlled creation of thin film layers, which can reduce diffusion delays. Furthermore, spatial localization of the thin film layer to the sensing electrode allows for thinner films with lower diffusion resistance, which further reduces latency due to the diffusion of analytes from other film surfaces to the biorecognition layer.

[0196] Furthermore, the high level of redundancy (parallel channels of analyte measurement) afforded by the microneedle array allows for higher fidelity measurements and less reliance on algorithms to interpolate sensor readings, which further confers reduced delay or latency. Electronic Equipment Systems

[0197] 2A schematic of analyte monitoring device 110, electronics system 120 may be integrated within housing 112 such that electronics system 120 may be combined with sensing elements (e.g., a microneedle array) as part of a single unit, in contrast to conventional CGM systems that typically incorporate components in multiple physically distinct units. Further details of exemplary variations of electronics system 120 are described below. PCB

[0198] 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 a sensor assembly 320 that includes a microneedle array and at least one device PCB 350, as shown in FIG. 3E.

[0199] For example, as shown in Figures 3F-3I, the sensor assembly 320 may include a sensor standoff PCB 322 coupled to a connection PCB 324. The microneedle array 330 may be attached to the sensor standoff PCB 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, an epoxy skirt may be deposited along the edge of the silicon microneedle array 330 to mitigate sharp edges from the silicon dicing process 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 equivalent.

[0200] As shown in FIG. 3J , the sensor standoff PCB 322 may function as a standoff that, at least in part, determines the desired distance the microneedle array 330 protrudes from the housing 310. Thus, the standoff height of the sensor standoff PCB 322 may be selected to help ensure that the microneedle array 330 is properly inserted into the 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, such that its underside is flush or nearly flush with the bottom surface of the housing, the housing 310 may prevent the microneedle array 330 from being fully inserted into the skin. However, increasing the standoff height may lead to greater pressure of the microneedle array against the skin during microneedle insertion, which may lead to skin irritation and / or erythema (skin redness).

[0201] The sensor standoff PCB 322 may be secured to the housing 310, such as with suitable fasteners or the like, and / or secured within a stack inside the housing. For example, as shown in FIGS. 3H-3J, the sensor standoff PCB 322 (with the microneedle array 330) may be coupled to a first side of the connection PCB 324, while a second, opposite side of the connection PCB 324 may in turn be coupled to the interposer PCB connector 326. As shown in FIG. 3J, the interposer PCB connector 326 may be communicatively coupled to the device PCB 350, such as for signal processing as described below. Thus, signals from the microneedle array 330 may be communicated through the sensor standoff PCB 322, via the sensor standoff PCB 322, the connection PCB 324, and the interposer PCB connector 326 to the device PCB. However, in some variations, the analyte monitoring device may 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 communicate electrically directly with the connection PCB 324 (or directly with the device PCB 350).

[0202] Additionally or alternatively, in some variations, at least one of the PCBs in the sensor assembly 320 may 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., a thermistor, a resistance temperature detector, a thermocouple, a bandgap reference, a non-contact temperature sensor, etc.). In some variations, temperature measurement may additionally or alternatively be performed by one or more analyte-insensitive electrodes in the microneedle array.

[0203] In some variations, the sensor standoff PCB 322 may be about 0.05 inches to about 0.15 inches or about 0.093 inches to about 0.127 inches in thickness. The sensor standoff PCB 322, in some variations, may include one or more conductive through-substrate vias configured to route electrical signals from the front side of the PCB to the rear side of the PCB. In some variations, the sensor standoff PCB 322 may be comprised of a semiconductor (e.g., silicon) with conductive through-substrate vias configured to route electrical signals from the front side of the semiconductor to the rear side of the semiconductor. In yet other variations, the microneedle array 330 may be mounted directly to the PCB 324 without the sensor standoff PCB 322. Analog Front End

[0204] In some variations, the electronics system of the analyte monitoring device may include an analog front end. The analog front end may include a sensor circuit (e.g., sensor circuit 124 as shown in FIG. 2A) that converts analog current measurements into digital values ​​that can be processed by a microcontroller. The analog front end may include a programmable analog front end, suitable for use with electrochemical sensors, for example. For example, the analog front end may include MAX30131, MAX30132, or MAX30134 components (having one, two, and four channels, respectively) available from Maxim Integrated (San Jose, CA), which are ultra-low-power programmable analog front ends for use with electrochemical sensors. The analog front end may also include AD5940 or AD5941 components available from Analog Devices (Norwood, MA), which are high-precision, impedance, and electrochemical front ends. Similarly, the analog front end may also include the LMP91000, available from Texas Instruments (Dallas, TX), a configurable analog front-end potentiostat for low-power chemical sensing applications. The analog front end may provide a complete measurement path, including bias and an analog-to-digital converter (ADC). Ultra-low power may enable continuous biasing of the sensor to maintain accuracy and fast response when measurements are required over long durations (e.g., 7 days) using a body-worn, battery-operated device.

[0205] In some variations, the analog front-end device may be compatible with both two- and three-terminal electrochemical sensors, such as to enable both DC and AC current measurements and electrochemical impedance spectroscopy (EIS) measurement capabilities. Additionally, the analog front-end may include an internal temperature sensor and programmable voltage reference, support external temperature monitoring and external reference sources, and integrate voltage monitoring of bias and supply voltages for safety and compliance.

[0206] In some variations, the analog front end may include a multi-channel potentiostat to multiplex sensor inputs and handle multiple signal channels. For example, the analog front end may include a multi-channel potentiostat such as that described in U.S. Pat. No. 9,933,387, which is incorporated herein by reference in its entirety.

[0207] In some variations, the analog front end and peripheral electronics may be integrated into an application specific integrated circuit (ASIC), which may help to reduce costs, for example. This integrated solution may, in some variations, include a microcontroller, as described below. Microcontroller

[0208] In some variations, the electronics system of the analyte monitoring device may include at least one microcontroller (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 analyses and correlate sensor signals to analyte measurements (e.g., glucose measurements). For example, the microcontroller may execute programmed routines in firmware, interpret digital signals (e.g., from the analog front end), perform any associated algorithms and / or other analyses, and route processed data to and / or from a communications module. Keeping the analyses onboard the analyte monitoring device may, for example, enable the analyte monitoring device to broadcast analyte measurements to multiple devices in parallel (e.g., mobile computing devices such as smartphones or smartwatches, therapy delivery systems such as insulin pens or pumps, etc.), while ensuring that each connected device has identical information.

[0209] In some variations, the microcontroller may be configured to activate and / or deactivate the analyte monitoring device in response to one or more detected conditions. For example, the device may be configured to power on the analyte monitoring device in response to insertion of the microneedle array into the skin. This may enable a power-saving feature, for example, where the battery is disconnected until the microneedle array is placed within the skin, at which point the device may begin broadcasting sensor data. Such a feature may help, for example, to improve the shelf life of the analyte monitoring device and / or simplify the analyte monitoring device-external device pairing process for the user.

[0210] FIG. 25 illustrates a schematic diagram of an exemplary variation of a circuit that enables the above-described activation of an analyte monitoring device upon insertion. Generally, upon penetration of the stratum corneum of the skin and positioning of the electrode at the distal tip of the microneedle component in the highly electrolytic dermal interstitial fluid, the resistance of “Sensor Detect” decreases to a significant extent, thereby activating p-channel MOSFET Q401. Once Q401 is turned on, battery voltage VBAT flows to VDD_IN, which provides power for the device. When the microcontroller is powered on, the first routine it executes is to set “PwrEnable” high, thus keeping the device powered by pulling the gate of Q401 low through Q402. This is done to mitigate scenarios where the microneedle does not maintain contact with the skin. If the device is experiencing a false activation, a high resistance to "Sensor_Detect" should be present, and the microprocessor can drive "PwrEnable" low, thereby removing power to the device (and deactivating the device). Other exemplary variations of structures and methods for activating and / or deactivating analyte monitoring devices are described in further detail in U.S. Patent Application No. 16 / 051,398, which is incorporated herein by reference in its entirety.

[0211] Additionally or alternatively, the microcontroller may be configured to actively confirm the insertion of the microneedle array into the skin based on sensor measurements performed with the microneedle array. For example, after two or more microneedles in the microneedle array are assumed to be inserted into the skin, a fixed or time-varying potential or current may be applied to the microneedles. Measurements (e.g., potential or current values) of signals generated between the electrodes of the inserted microneedles are measured and then compared with known reference values ​​to confirm successful insertion of the microneedle array into the skin. The reference values ​​may include, for example, voltage, current, resistance, conductance, capacitance, inductance, and / or impedance. Other exemplary variations of structures and methods for activating and / or deactivating analyte monitoring devices are described in further detail in U.S. Patent Application No. 16 / 051,398 (incorporated by reference above).

[0212] In some variations, the microcontroller may utilize 8-bit, 16-bit, 32-bit, or 64-bit data structures. Suitable microcontroller architectures include ARM® and RISC® architectures, and flash memory may be embedded in or external to the microcontroller for suitable data storage. In some variations, the microcontroller may be a single-core microcontroller, while in some variations, the microcontroller may be a multi-core (e.g., dual-core) microcontroller, which may allow for flexible architectures for optimizing power and / or performance within the system. For example, the cores in a microcontroller may include similar or different architectures. For example, in an exemplary 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 higher-performance functions (e.g., sensor measurements, algorithm calculations, etc.), while the second core may be used to perform lower-performance functions (e.g., background routines, data transmission, etc.). Thus, different cores of the microcontroller may run at different duty cycles optimized for their individual functions (e.g., a second core for a lower performance function may run at a higher duty cycle), thereby improving overall power efficiency. Additionally or alternatively, in some variations, the microcontroller may include embedded analog circuitry, such as for interfacing with additional sensors and / or microneedle arrays. In some variations, the microcontroller may be configured to operate using a 0.8V to 5V power supply, such as a 1.2V to 3V power supply. Communication Module

[0213] In some variations, the electronics system of the analyte monitoring device may include at least one communication module, such as a wireless communication module (e.g., communication module 126 as shown in FIG. 2A ), for communicating with one or more devices. For example, the communication module may include a wireless transceiver 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 a wireless network (e.g., through Bluetooth, NFC, WiFi, RFID, or any type of data transmission not connected by a cable). For example, devices may communicate with each other directly in a pairwise connection (a 1:1 relationship, i.e., unicast) or in a hub-spoke or broadcasting connection (a “1:many” or 1:m relationship, i.e., multicast). As another example, the devices may communicate with each other through a mesh networking connection (e.g., a “many-to-many,” or m:m relationship, or ad hoc), such as through Bluetooth mesh networking. The wireless communication may use any of a number of communication standards, protocols, and technologies, including, but not limited to, Global System for Mobile Communications (GSM), Enhanced Data Global 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-HSPA), 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 communication protocol.Some wireless network deployments may combine networks from multiple cellular networks or use a mixture of cellular, Wi-Fi, and satellite communications. In an exemplary variation, the communications module may include a wireless transceiver integrated into a microcontroller and including a Bluetooth Low Energy compatible radio that complies with the Bluetooth Special Interest Group 5.0 specification.

[0214] The communications 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 system may include a chip antenna mounted on a PCB or an antenna implemented directly on the PCB, which may provide better range while reducing cost and complexity. In some variations, the user wearing the analyte monitoring device 110 may function as the antenna (e.g., antenna 128). For example, the antenna input / output 128 of the communications module 126 may be electrically connected to a single microneedle or multiple microneedles that are inserted into the wearer's skin (e.g., similar to the microneedle array 140 shown in FIG. 2B). This may help to increase the effective cross-sectional area of ​​the antenna, provide a proper impedance match between the communications module's antenna input / output and free space, and / or improve operating metrics such as antenna gain, antenna diversity, omnidirectionality, and communications module receiver sensitivity / transmitter efficiency.

[0215] Devices can be moved in and out of range from the communications module, connected and reconnected so that users can seamlessly connect and transfer information between devices. In some variations, the microcontroller on each analyte monitoring device may have a unique serial number, which allows for tracking of specific analyte monitoring devices during production and / or field use. Additional Sensors

[0216] As described above, in some variations, the analyte monitoring device may include one or more sensors in addition to the microneedle array. For example, the analyte monitoring device may include one or more temperature sensors configured to measure skin temperature, thereby enabling temperature compensation for the analyte sensor. For example, in some variations, a temperature sensor (e.g., a thermistor, RTD, semiconductor junction, bimetallic sensor, thermopile sensor) may be coupled to a device PCB within the housing such that the temperature sensor is arranged near a skin-facing or bottom portion of the housing 112. The housing may be thinned to reduce thermal resistance and improve heat transfer and therefore measurement accuracy. Additionally or alternatively, a thermally conductive material may thermally couple the surface-mounted temperature sensor to the user's skin. In variations in which the temperature sensor is coupled to the device PCB near the microneedle array die substrate, the thermally conductive material may be molded as a skirt, for example, to cushion sharp edges of the die and to be deposited along the edges of the die and along the surface of the main PCB.

[0217] In some variations, a temperature sensor may be employed to develop a glucose interpolation profile based on the measured current and a priori sensitivity (e.g., nA / mM or pA / mg / dL). In the temperature-invariant case, the current profile follows the relationship: y=m G [G], where y is the measured current and m G is the glucose sensitivity and [G] is the interpolated glucose concentration. In some cases, such as the incorporation of an analyte-insensitive channel b, a background signal may be incorporated into the above equation, i.e., y=m G [G] + b. By incorporating measurements from the temperature sensor, the current characteristic is given by the following relationship: y = m G [G]+m T [T]+b, where m Tis the temperature sensitivity (e.g., pA / °C), T is the measured temperature, and b is the background signal (e.g., pA). In other operating scenarios, the current characteristic is modeled by the following relationship: y=m1[G][T]+b, where m1 is a weighting coefficient determined a priori. In other operating scenarios, the current characteristic is modeled by the convolution of temperature and glucose, i.e., y={m T [T]+m2}[G]+b, where m2 is a weighting factor determined a priori. In other operating scenarios, the current characteristic may be modeled as follows: y={m G [G]+m2}[T][G]+b. In other operating scenarios, the current characteristic follows the nonlinear relationship: y={m G2 [G] 2 +m G [G]}[T]+b, where m G2 is a nonlinear weighting coefficient. In other operating scenarios, the current characteristic follows the Gaussian relationship: y=m G [G]exp{-([T]-[T OPT ]) 2 / (2σ 2 )}+b, where T OPT is the optimum temperature for maximum catalytic turnover of the enzyme, and σ is the operating temperature range of the enzyme.

[0218] 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., a glucose-insensitive channel) with known temperature sensitivity, which may be used to compensate for temperature. For example, one advantage of using a glucose-insensitive channel includes proximity to the glucose sensor (e.g., resulting in fewer errors from thermal gradients) and cost (e.g., by reducing external components and specialized processes for thermally coupling the sensor to the skin). In some variations, the analyte monitoring device may include both an analyte-insensitive channel and a thermistor, along with an algorithm that utilizes information from both. Additionally or alternatively, the analyte monitoring device may include an additional sensor that measures ambient temperature, which may also be useful in the temperature compensation algorithm.

[0219] 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 to improve signal fidelity and / or signal-to-noise ratio. The analyte-insensitive channel may be sensitive to common-mode signals (e.g., endogenous and pharmacological interferences, pressure attenuation, etc.) that also occur on the analyte-sensitive channel.

[0220] Additionally or alternatively, in some variations, the analyte monitoring device may include at least one motion sensor. The motion sensor may comprise, for example, an accelerometer, gyroscope, and / or inertial measurement unit for capturing position, 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., walking, strenuous exercise) over a finite duration. Additionally or alternatively, in some variations, the motion sensor may be employed to enable detection of wearer interactions with the analyte monitoring device, such as touches or taps. 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 activate / deactivate a user interface (e.g., an embedded display or indicator light) on the analyte monitoring device. The touches or taps may be performed in a defined sequence and / or for a predetermined duration (e.g., at least 3 seconds, at least 5 seconds) to elicit an action (e.g., deactivate / activate a display or indicator light). Additionally or alternatively, in some variations, the analyte monitoring device may enter a power saving mode in response to detecting limited movement or activity (e.g., an 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 period) as measured by a motion sensor.

[0221] Additionally or alternatively, in some variations, the analyte monitoring device may include at least one real-time clock (RTC). The real-time clock may be employed to track absolute time (e.g., Coordinated Universal Time, UTC, or local time) when the analyte monitoring device is in storage or in use. In some variations, synchronization to absolute time may be performed subsequent to manufacture of the analyte monitoring device. The real-time clock may be employed to time-stamp analyte measurements (e.g., glucose measurements) during operation of the analyte monitoring device to create a time-series data set that is communicated to a connected peripheral device (e.g., a mobile computing device), cloud storage, or other suitable data storage device, such as for later review by a user (e.g., the wearer of the analyte monitoring device), their support network, or their healthcare provider. power supply

[0222] As shown in FIG. 2A , the analyte monitoring device may include one or more power sources 130 (e.g., batteries) within housing 112 configured to provide power to the 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. Additionally, in some variations, a secondary (e.g., rechargeable) battery may be used. However, any suitable power source may be used, including lithium-based batteries.

[0223] In some variations, the power source may be coupled to the device PCB using a low-profile retainer or mount that reduces the overall height of the electronics, thereby minimizing the height or profile of the analyte monitoring device. For example, while traditional battery retainers use conductive metal with a spring force to apply force to the top side of the battery, in some variations, a side-mounted battery retainer may contact the side of the battery to complete the electrical circuit. For example, as shown in FIG. 20 , the side-mounted battery retainer 2020 may include an arcuate clip that clamps or otherwise contacts the side of the battery without adding vertical bulk. The battery retainer 2020 may further include one or more mounting holes for coupling to the device PCB via one or more suitable fasteners (and / or may be coupled to the device PCB in any suitable manner). In some variations, the housing may be sized and / or shaped with suitable tolerances to apply a normal or downward force to the battery toward the device PCB to keep the battery in contact with the PCB. applicator

[0224] In some variations, the analyte monitoring device may be applied manually. For example, a user may remove a protective film over the adhesive layer and manually press the device onto their skin at the desired application site. Additionally or alternatively, as illustrated in FIG. 1 , in some variations, the analyte monitoring device may be applied to the skin using a suitable applicator 160. The applicator 160 may be configured, for example, to urge the analyte monitoring device 110 toward the user's skin so that the microneedle array 140 of the analyte monitoring device 110 may be inserted into the skin (e.g., to a desired target depth). kit

[0225] In some variations, some or all components of the analyte monitoring system may be provided (e.g., to a user, a clinician, etc.) in a kit. 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 include multiple analyte monitoring devices 110, which may form a supply of analyte monitoring devices sufficient for a predetermined period of time (e.g., 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, etc.). A kit may include any suitable ratio of applicators to analyte monitoring devices (e.g., 1:1, less than 1:1, greater than 1:1). For example, a kit may include the same number of applicators as there are analyte monitoring devices, such as where each applicator is single-use and configured to be disposed of after its use in applying an individual analyte monitoring device to a user. As another example, a kit may include fewer applicators than the number of analyte monitoring devices in the kit (e.g., one applicator per two or three analyte monitoring devices), such as when an applicator is intended to be reused to apply multiple analyte monitoring devices, or when multiple analyte monitoring devices are loaded into a single applicator for repeated applications. As another example, a kit may include more applicators than the number of analyte monitoring devices in the kit (e.g., two applicators per analyte monitoring device), such as to provide extra or redundant applicators in case an applicator is lost or damaged.

[0226] In some variations, the kit may further include user instructions for operating the analyte monitoring device and / or applicator (e.g., instructions for applying the analyte monitoring device manually or with an applicator, instructions for pairing the analyte monitoring device with one or more peripheral devices (e.g., computing devices such as mobile phones), etc.). Sterilization of Analyte Monitoring Devices

[0227] As explained above, analyte monitoring devices 110 such as those described herein are distinguished from other CGM devices in that at least the sensing element (e.g., a microneedle array) and electronics are integrated into one unit. One benefit of this integration is that the user is not required to perform any assembly of the analyte monitoring device 110. However, sterilization-related challenges exist to enabling such integration.

[0228] Conventional CGM devices and similar electrochemical sensors are typically sterilized through processes that are incompatible with electronics. For example, conventional electrochemical sensor sterilization uses gamma irradiation or electron beam irradiation to sterilize the sensing element. However, the bosons or fermions associated with these sterilization processes interfere with electronics operation. Therefore, typically, the electronic components must either be sterilized separately, requiring the end user to perform some degree of assembly of the device, or the electronic components are simply not sterilized, which can lead to contamination issues.

[0229] In contrast, the sensor technology described above is configured to be compatible with sterilization methods suitable for both the sensing element and the electronics. In some variations, as described above, the working electrode in the microneedle array may include a biorecognition layer containing a crosslinked biorecognition element. For example, the biorecognition element may be crosslinked with an amine-condensed carbonyl species, which serves to crosslink the amine groups and thus stabilize the biorecognition element within the biorecognition layer. For example, the biorecognition element may include an enzyme (e.g., glucose oxidase) crosslinked with glutaraldehyde, formaldehyde, glyoxal, malonaldehyde, succinaldehyde, and / or other suitable species, and then embedded in a conducting polymer as described above.

[0230] As a result of the cross-linked structure described above, the enzyme is sufficiently stabilized so that it can be subjected to gaseous sterilization methods, such as ethylene oxide (EO) sterilization, surprisingly with minimal impact on the sensing element in terms of sensing performance. Thus, because the electronics can be subjected to EO sterilization, in some variations, the analyte monitoring device 110 is uniquely and advantageously configured to withstand an "all-in-one" sterilization procedure in which the electronics and sensing element are fully integrated and sterilized simultaneously in a single unit without damaging either set of components.

[0231] Thus, in some variations, a method of sterilizing an analyte monitoring device may include exposing the analyte monitoring device to a sterilant gas, the analyte monitoring device including a housing (e.g., a wearable housing), a microneedle array extending from the housing and including an analyte sensor, and an electronics system arranged within the housing and electrically coupled to the microneedle array. The analyte monitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device. In some variations, the analyte monitoring device is exposed to the sterilant gas for a dwell time sufficient to sterilize the analyte monitoring device. -6 (i.e., have a probability of having no more than 1 viable microorganism in 1,000,000 sterilized devices).

[0232] 21 illustrates an exemplary variation of a method 2100 for sterilizing an analyte monitoring device. Method 2100 may include, for example, step 2110 of inserting the analyte monitoring device into a chamber suitable for sterilization, step 2120 of preconditioning the analyte monitoring device, step 2130 of exposing the analyte monitoring device to a sterilant gas, and step 2140 of aerating the analyte monitoring device.

[0233] 22 depicts a schematic diagram of an exemplary variation of a sterilization system including a chamber (or series of chambers) suitable for use in sterilizing an analyte monitoring device. For example, the sterilization system may include at least one chamber for performing a preconditioning process, at least one chamber for a sterilization process, and / or at least one chamber for an aeration process. In some variations, the same chamber may be utilized for two or more of these processes of method 2100.

[0234] Thus, for example, an analyte monitoring device may be placed within the preconditioning chamber for preconditioning process 2120. As explained above, the analyte monitoring device may be placed within the chamber as an integrated device that includes both electrochemical sensing elements and electronic components.

[0235] The preconditioning step may function to heat and humidify the analyte monitoring device to a stable temperature and moisture content prior to entry into the sterilization chamber, which may help ensure the consistency and reliability of the sterilization process regardless of environmental conditions. As shown in FIG. 23 , preconditioning the analyte monitoring device may include reducing the pressure within 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 / min or other suitable rate. Additionally, the preconditioning step may include setting other environmental conditions to various set points for a predetermined dwell time. For example, as shown in FIG. 23 , after reducing the pressure to the vacuum set point, steam may be injected into the chamber to establish the temperature, relative humidity, and / or humidity at the predetermined set points. For example, in one implementation, the temperature inside the chamber may be set to about 35 degrees Celsius to about 40 degrees Celsius, or about 38 degrees Celsius, which may be suitable to avoid denaturing biorecognition elements (e.g., enzymes) from higher heat during preconditioning. As another example, the relative humidity may be set at about 45% to about 55% (or about 51%). The temperature, relative humidity, and vacuum set points may be maintained for a predetermined dwell time, such as about 90 minutes to about 180 minutes, about 100 minutes to about 160 minutes, about 110 minutes to about 140 minutes, or about 120 minutes, or other suitable time period. After the dwell time has elapsed, the chamber may be evacuated and / or the conditioned analyte monitoring device may be removed and placed in a sterilization chamber.

[0236] As shown in FIG. 21 , after preconditioning the analyte monitoring device, the method may include step 2130 of exposing the analyte monitoring device to a sterilant gas, such as ethylene oxide (EO). In some variations, EO may be introduced into the sterilization chamber at a gas concentration of about 425 mg / L to about 475 mg / L, or about 450 mg / L. As shown in FIG. 23 , during the sterilization process, the pressure within the chamber may be set to a sterilant set point of about 5 psia to 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 vacuums may be established within the chamber, followed by a series of nitrogen (N) injections to purge a sufficient amount of air from the chamber. Similar to the temperature during preconditioning, the temperature of the chamber during sterilization may be set to about 35 degrees Celsius to about 40 degrees Celsius, or about 38 degrees Celsius. The temperature may be increased to the temperature set point as EO is introduced. After introducing EO gas into the chamber, the analyte monitoring device may remain exposed to the EO gas for a suitable sterilant dwell time or exposure time. Suitable sterilant dwell times may range, for example, from about 90 minutes to about 180 minutes, from about 100 minutes to about 160 minutes, from about 110 minutes to about 140 minutes, or about 120 minutes, or any other suitable time period sufficient to sterilize the analyte monitoring device. It should be understood that in some variations, increasing the temperature during EO exposure will reduce the required EO dwell time (e.g., as a rule of thumb, for every 10 degree Celsius increase in temperature, the EO dwell time may be reduced by about half). Following the sterilant dwell time, the chamber may be subjected to a vacuum / air cycle to purge the EO from the chamber.

[0237] As shown in FIG. 21 , method 2100 may include a step 2140 of aerating the analyte monitoring device. Because EO is flammable and any residual EO on the device after sterilization can be highly toxic, aeration of the analyte monitoring device may allow for additional removal of any residual gas from the device (e.g., prior to packaging and storage). In some variations, aeration may occur at room temperature. As shown in FIG. 23 , aeration may continue for a predetermined period of time sufficient to allow thorough outgassing. For example, the aeration process may continue for at least about 4 to 24 hours, such as about 12 hours. In other variations, the aeration process may continue for at least about 12 hours, at least about 15 hours, or at least 24 hours, etc. [Example]

[0238] An EO sterilization cycle was evaluated for its feasibility to sterilize analyte monitoring devices such as those described herein. Briefly, preconditioning was performed at a temperature of 38 degrees Celsius for 2 hours. Then, exposure to EO gas was performed at 38 degrees Celsius for 2 hours. After EO exposure, the samples were aerated to outgas the EO gas at ambient temperature for a minimum of 12 hours. Details of the EO exposure protocol are shown in Table 1. [Table 1-1] [Table 1-2]

[0239] To test the stability of the sensing chemistry following exposure to EO, six functionalized microneedle sensors were subjected to an EO sterilization cycle. In this example, a sensor chemistry using amide crosslinks of glucose oxidase was evaluated in this feasibility study. Figure 24 shows the retained sensitivity for six sensors (EO) after exposure to EO, and for three sensors (no treatment (DNP)) that served as negative controls. Overall, all six sensors exposed to EO remained sensitive to glucose after treatment. The average retained percentage sensitivity was 75%.

[0240] Three of the EO-exposed sensors were also subsequently tested for operational stability in PBS with 6 mM glucose over a seven-day period. The sensors were kept in solution, and sensitivity was measured by calibrating the sensors once a day. Summary results from the operational stability test are shown in FIG. 24B. It can be seen that the sensors remained stable over the course of the test. Due to instrument error, no data were obtained for days 5 and 6. This trend is similar to that observed for sensors sterilized using gamma irradiation.

[0241] In addition, three sensors exposed to EO were used to test storage stability. Figure 24C shows the average sensitivity on days 0 (before EO exposure), 14, and 28. The sensors were stored dry at 37 degrees Celsius between days 14 and 28. The average retained sensitivity from days 14 to 28 of dry storage was 92%. This demonstrates the potential for sterilization using EO and storage of sensors after exposure to EO.

[0242] Thus, the cross-linked sensor chemistry was found to be sufficiently stable to EO exposure, demonstrating that the EO process is feasible for sterilizing analyte monitoring devices with sensing elements containing cross-linked sensor chemistry. Additionally, the chemistry after EO exposure was stable over 7 days of active operation and during dry storage.

[0243] In some variations, the sensor may be decoupled from the electronics and subjected to other suitable methods of sterilization, including those based on irradiation with gamma rays / particles or with an electron beam of sufficient acceleration potential. The sterilization dose (e.g., duration and particle energy) may be controlled to achieve a satisfactory level of sterility, including a Sterility Assurance Level (SAL) of less than 1E-6. In some variations, the electronics do not require sterilization because they do not contact damaged or compromised skin surfaces. In such variations, the electronics may be coupled to the sensor prior to application of the entire system to the user's skin. Use of Analyte Monitoring Systems

[0244] Described below is an overview of various aspects of the use and method of operation of an analyte monitoring system, including the analyte monitoring device and peripheral devices. Applications of Analyte Monitoring Devices

[0245] As described above, analyte monitoring devices are applied to a user's skin such that the microneedle array in the device penetrates the skin and the electrodes of the microneedle array are positioned within the upper dermis for access to dermal interstitial fluid. For example, in some variations, the microneedle array may be geometrically configured to penetrate the stratum corneum, the outer layer of skin, puncture through the epidermis, and terminate within the papillary or upper reticular dermis. The sensing area, limited to the electrodes at the distal extent of each microneedle element of the array (as described above), may be configured to remain stationary and seated within the papillary or upper reticular dermis following application to ensure adequate exposure to circulating dermal interstitial fluid (ISF) without risk of bleeding or undue impact on nerve endings.

[0246] In some variations, the analyte monitoring device may include a wearable housing or patch with an adhesive layer configured to adhere to the skin and secure the microneedle array in place. The analyte monitoring device may be applied manually (e.g., by removing a protective film over the adhesive layer and manually pressing the patch onto the skin at the desired application site), although in some variations the analyte monitoring device may be applied to the skin using a suitable applicator.

[0247] The analyte monitoring device may be applied to any suitable location, although in some variations it may be desirable to avoid anatomical areas of thick or calloused skin (e.g., palmar and plantar regions) or areas subject to significant flexion (e.g., olecranon or kneecap). Suitable application sites may include, for example, on the arms (e.g., upper arms, forearms), shoulders (e.g., over the deltoid muscles), backs of the hands, neck, face, scalp, torso (e.g., on the back or on the chest or abdomen, such as in the thoracic region, lumbar region, sacral region), buttocks, legs (e.g., upper legs, lower legs, etc.), and / or tops of the feet, etc.

[0248] As described above, in some variations, the analyte monitoring device may be configured to automatically activate upon insertion and / or confirm proper insertion into the skin. Details of these features are described in further detail above. In some variations, methods for performing such activation and / or confirmation may be similar to those described in U.S. Patent Application No. 16 / 051,398 (incorporated by reference above). Pairing to peripheral devices

[0249] In some variations, the analyte monitoring device may be paired to at least one peripheral device such that the peripheral device receives broadcast or otherwise transmitted data, including measurement data, from the analyte monitoring device. Suitable peripheral devices include, for example, mobile computing devices (e.g., smartphones, smartwatches), which may be running mobile applications.

[0250] Additionally or alternatively, the analyte monitoring device may be paired (or otherwise combined) with a therapy delivery device (e.g., an insulin pen or pump). For example, the analyte monitoring device may be combined with a therapy delivery device in a manner similar to that described in U.S. Patent Application Nos. 62 / 823,628 and 62 / 862,658 (each of which is incorporated herein by reference in its entirety). Studies have shown that users using insulin delivery devices with smart algorithms that control dosing are within the euglycemic range (i.e., healthy blood glucose levels) more than 95% of the time when a CGM is available. The ability of the analyte monitoring device to communicate directly with the insulin delivery device (i.e., no intermediary smartphone is required) allows users to achieve significantly increased in-range time by eliminating time when a CGM is not available (during analyte monitoring device warm-up or swap-in). This feature may also allow users to wear multiple analyte monitoring devices that detect different analytes simultaneously and enter the data into the same mobile application.

[0251] As described above, pairing may be accomplished through a suitable wireless communication module (e.g., implementing Bluetooth®). In some variations, pairing may occur after the analyte monitoring device is applied and inserted into the user's skin (e.g., after the analyte monitoring device is activated). Additionally or alternatively, pairing may occur prior to the analyte monitoring device being applied and inserted into the user's skin.

[0252] Thus, a paired mobile or other device may receive data broadcast or transmitted 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. Additionally, in some variations, the paired mobile or wearable device may perform algorithmic processing on the data to improve signal fidelity, accuracy, calibration, etc. In some variations, the measurement data and / or other user information may additionally or alternatively be communicated and / or stored via a network (e.g., a cloud network).

[0253] By way of example, in some variations, a mobile computing device or other computing device (e.g., a smartphone, smartwatch, tablet, etc.) may be configured to run a mobile application that provides an interface for displaying estimated glucose values, trend information, historical data, etc. The description below specifically refers to glucose as the target analyte, but it should be understood that the features and processes described below with respect to glucose may be similarly applied to applications with other types of analytes.

[0254] In some variations, the mobile application may use the Bluetooth framework of the mobile computing device to scan for analyte monitoring devices. As shown in FIG. 26, the analyte monitoring device may be powered on or initialized as soon as it is applied to the skin, and the analyte monitoring device may begin the advertising process. The mobile application may then connect to the analyte monitoring device and begin priming the sensor for measurement. In cases where the mobile application detects multiple analyte monitoring devices, the mobile application may detect the nearest analyte monitoring device in its vicinity and / or may request that the user confirm the disambiguation (e.g., via a user interface on the mobile device). In some variations, the mobile application may also be able to connect to multiple analyte monitoring devices simultaneously. This may be useful, for example, to replace a sensor that is reaching the end of its life.

[0255] In some variants, Bluetooth® Low Energy TM 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 analyte monitoring device and a smartphone, smartwatch, or tablet running a mobile application. The BLE connection may be maintained permanently for the life of the sensor. If the connection is lost due to any reason (e.g., weak signal), the analyte monitoring device may begin advertising itself again, and the mobile application may re-establish the connection at the earliest opportunity (i.e., when in range / physical proximity).

[0256] 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.

[0257] The mobile application may guide the user through starting a new analyte monitoring device. Once this process is complete, the mobile application is not required for the analyte monitoring device to operate and record measurements. In some variations, a smart insulin delivery device connected to the analyte monitoring device can be authorized by the mobile application to receive glucose readings directly from the sensor. Additionally or alternatively, a secondary display device, such as a smartwatch, can be authorized by the mobile application to receive glucose readings directly from the sensor.

[0258] Further, in some variations, the mobile application may additionally or alternatively assist in calibrating the analyte 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. Sensor Measurement

[0259] Once the analyte monitoring device is inserted and warm-up and any calibration are complete, the analyte monitoring device may be ready to provide a sensor measurement of the target analyte. The target analyte (and any required cofactors) diffuse from the biological environment through the biocompatible and diffusion-limiting layer on the working electrode to the biorecognition layer containing the biorecognition element. In the presence of the cofactor (if present), the biorecognition element may convert the target analyte into an electroactive product.

[0260] A bias potential may be applied between the working and reference electrodes of the analyte monitoring device, and a current may flow from the counter electrode, maintaining a fixed potential relationship between the working and reference electrodes. This causes the oxidation or reduction of an electroactive product, causing a current to flow between the working and counter electrodes. The value of the current is proportional to the rate of the redox reaction at the working electrode, specifically, the concentration of the analyte of interest, according to the Cottrell relationship, as explained in more detail above.

[0261] The current may be converted to a voltage signal by a transimpedance amplifier and quantized into a digital bitstream using an analog-to-digital converter (ADC). Alternatively, the current may be quantized directly into a digital bitstream using a current-mode ADC. The digital representation of the current may be processed in an embedded microcontroller within the analyte monitoring device and relayed to a wireless communication module (e.g., to one or more peripheral devices) for broadcast or transmission. In some variations, the microcontroller may perform additional algorithmic processing on the data to improve signal fidelity, accuracy, and / or calibration, etc.

[0262] In some variations, the digital representation of the current or sensor signal may be correlated to an analyte measurement (e.g., a glucose measurement) by the analyte monitoring device. For example, a microcontroller may execute programmed routines in firmware to interpret the digital signal and perform any associated algorithms and / or other analyses. Keeping the analysis onboard the analyte monitoring device may, for example, allow the analyte monitoring device to broadcast analyte measurements to multiple devices in parallel, ensuring that each connected device has identical information. Thus, generally, a user's target analyte (e.g., glucose) value may be estimated, stored within the analyte monitoring device, and communicated to one or more peripheral devices.

[0263] Data exchange can be initiated either by the mobile application or by the analyte monitoring device. For example, the analyte monitoring device may notify the mobile application of new analyte data as it becomes available. 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, the mobile application may request data from the analyte monitoring device (e.g., if the mobile application identifies a gap in the data it has collected, such as due to a disconnection).

[0264] If the mobile application is not connected to the analyte monitoring device, the mobile application may not 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 the mobile application reconnects to the analyte monitoring device, it may request the data it 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).

[0265] Generally, the mobile application may be configured to provide real-time or near-real-time display of analyte measurement data, such as on a display of a mobile computing device executing the mobile application. In some variations, the mobile application may communicate through a user interface regarding analysis of the analyte measurements, such as alerts, alarms, trend insights, etc., to notify the user of analyte measurements that require attention or follow-up action (e.g., high analyte values, low analyte values, high rates of change, analyte values ​​outside of preset ranges, etc.). In some variations, the mobile application may additionally or alternatively facilitate communication of measurement data to the cloud for storage and / or archiving for later retrieval. Interpretation of the Analyte Monitoring Device User Interface

[0266] In some variations, analyte measurement data and / or information related to the analyte monitoring device may be communicated via a user interface of the analyte monitoring device. In some variations, the user interface of the analyte monitoring device may 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 a mobile application on a computing device. Thus, the user and / or those around the user may easily and intuitively view the analyte monitoring device itself to assess analyte measurement data (e.g., analyte measurement status, such as current and / or trending analyte measurement levels) and / or device status, without having to view a separate device (e.g., a peripheral device or other device remote from and in communication with the analyte monitoring device). Having such information available directly on the analyte monitoring device itself may also allow the user and / or those around the user to be more quickly alerted to any concerns (e.g., analyte measurements above or below target ranges and / or analyte measurements increasing or decreasing at a rapid rate), thereby allowing the user to take appropriate corrective action more quickly.

[0267] 32A-32C depict an example variation of an analyte measurement device 3200 that includes a user interface 3220 with multiple indicator lights, including indicator lights 3224a-3224c, that can be selectively illuminated to communicate user status (e.g., information regarding the analyte measurement at the user). The user interface 3220 can be similar to the user interface 3120 described above with respect to FIGS. 31A and / or 31B, for example. While the user interface 3220 includes three indicator lights 3224a-3224c, it should be understood that in some variations, the user interface 3220 can 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).

[0268] The indicator lights 3224a-3224c may be arranged in a sequential manner such that their relative positions help a user intuitively understand the information collectively communicated by the user interface. For example, three indicator lights 3224a-3224c may be illuminated to generally indicate three progressive levels (or ranges) of analyte measurement, with the lowest indicator light 3224a generally illuminated to indicate the lowest analyte measurement of the three levels, the middle indicator light 3224b generally illuminated to indicate the analyte measurement that is intermediate of the three levels, and the highest indicator light 3224c generally illuminated to indicate the highest analyte measurement of the three levels. In one exemplary variation, the lowest indicator light 3224a may be illuminated to indicate an analyte measurement that is within the target range (FIG. 32A), the middle indicator light 3224b may be illuminated to indicate an analyte measurement that is above the target range (FIG. 32B), and the highest indicator light 3224c may be illuminated to indicate an analyte measurement that is significantly above the target range (FIG. 32C). In another exemplary variation, the lowest indicator light 3224a may be illuminated to indicate an analyte measurement that is below the target range, the middle indicator light 3224b may be illuminated to indicate an analyte measurement that is within the target range, and the highest indicator light 3224c may be illuminated to indicate an analyte measurement that is above the target range.

[0269] The thresholds for the target ranges may be any suitable values. For example, in some variations where glucose monitoring is being performed, analyte measurements may be considered to be within the target range if they are between about 70 mg / dL and about 180 mg / dL (or about 80 mg / dL or about 60 mg / dL to about 170 mg / dL or about 190 mg / dL, etc.) and may be considered to be below the target range if they are below about 70 mg / dL (or below about 80 mg / dL, or below about 60 mg / dL, etc.). The different thresholds for "above" the target range and "significantly" above the target range may have any suitable values. For example, in some variations, an analyte measurement value may be considered to be "above" the target range if it is above a first predetermined threshold (e.g., above a threshold of about 180 mg / dL for a hyperglycemia determination in glucose monitoring, or above a threshold that is about 170 mg / dL to about 200 mg / dL for a hyperglycemia determination in glucose monitoring), and an analyte measurement value may be considered to be "significantly above" the target range if it is above the first predetermined threshold by a predetermined amount (e.g., percentage), such as at least 33% above the first predetermined threshold (e.g., >240 mg / dL for an 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.

[0270] Additionally, the thresholds (or other characterizations of the analyte measurements) for considering an analyte measurement to be within the target range, below the target range, or "above" or "significantly above" the target range 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 average or expected analyte measurements or average or expected rates of change for a user at a particular time). Additionally, while the user interface 3220 includes three sequential indicator lights, it should be understood that in other variations, the user interface on the housing of the analyte monitoring device may include fewer (e.g., two) or more (e.g., four, five, six, or more) that may also be individually illuminated to indicate the analyte measurements (e.g., each corresponding to a general relative level of the analyte measurement).

[0271] In some variations, different illumination colors and / or timing for one or more of the indicator lights 3224a-3224c may additionally or alternatively allow a user to easily distinguish between each analyte measurement level. For example, when an analyte measurement is within a target range, the appropriate indicator light may be illuminated in a first color (e.g., blue), while when an analyte measurement is outside the target range, the appropriate indicator light may be illuminated in another color (e.g., white for below the target range and amber for above the target range). As another example, when an analyte measurement is within the target range, the appropriate indicator light may be illuminated in a first temporal pattern (e.g., gentle pulses with long illumination "on" times), while when an analyte measurement is outside the target range, the appropriate indicator light may be illuminated in a different temporal pattern (e.g., flash-like pulses with short illumination "on" times). Shorter pulses of illumination "on" time may be useful, for example, to better attract the user's attention and / or more intuitively communicate an alert when an analyte measurement is below, above, or significantly above the target range. Higher frequency illumination may, in some variations, correlate to additional alert levels (e.g., significantly below or significantly above the target range).

[0272] 33A-33D and Table 2 illustrate different illumination modes used in an exemplary 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 with respect to exemplary variations for illustrative purposes only. For example, in a "below target range" illumination mode, the illumination color may be any suitable color, and / or the illumination "on" time may be about 0.1 seconds to 1 second, about 0.2 seconds to 0.5 seconds, or about 0.3 seconds, and / or the illumination "off" time may be about 0.5 seconds to about 5 seconds, or about 1 second to about 4 seconds, or about 2 seconds to about 4 seconds, or about 3 seconds, and / or the ratio between the illumination "on" time and the illumination "off" time 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 "within target range" and / or "above target range" lighting modes, the lighting color may be any suitable color, and / or the lighting "on" time may be from about 0.1 seconds to about 3 seconds, from about 0.5 seconds to about 2 seconds, or about 1 second, and / or the lighting "off" mode may be from about 0.5 seconds to about 5 seconds, or from about 1 second to about 4 seconds, or from about 2 seconds to about 4 seconds, or about 3 seconds, and / or the ratio between lighting "on" time and lighting "off" time may be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, and / or other suitable lighting parameters. As another example, for "significantly above the target range," the illumination color may be any suitable color, and / or the illumination "on" time may be about 0.2 seconds to about 2 seconds, about 0.5 seconds to about 1.5 seconds, or about 0.8 seconds, and / or the illumination "off" time may be about 0.5 seconds to about 5 seconds, or about 1 second to about 4 seconds, or about 2 seconds to about 4 seconds, or about 3 seconds, and / or other suitable illumination parameters. Additionally, fewer or more illumination modes to indicate the analyte measurement level may be possible in other variations. [Table 2]

[0273] Additionally or alternatively, in some variations, the indicator lights 3224a-3224c may be illuminated in a progressive sequence to indicate trend information of the 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 the lowest indicator light to the highest indicator light (e.g., indicator light 3224a, followed by indicator light 3224b, followed by indicator light 3224c) may intuitively indicate a trend of increasing analyte measurements. In some variations, the progressive sequence of illumination may have any suitable illumination color. In some variations, such ascending sequential illumination of the indicator lights may be a suitable color to indicate either that the current analyte measurement is within the target range and rising, or that the current analyte measurement is above the target range and rising. For example, Figure 34A illustrates increasing gradual illumination in a first color (e.g., blue) to indicate that the current analyte measurement is within the target range and rising, while Figure 34B illustrates increasing gradual illumination in a second color (e.g., orange) to indicate that the current analyte measurement is above (or significantly above) the target range and rising. As yet another example, increasing gradual 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.

[0274] As another example, as shown in FIG. 34C, a gradual sequence of illumination of indicator lights 3224a-3224c in a second direction (e.g., opposite the first direction) from the highest indicator light to the lowest indicator light (e.g., indicator light 3224c, followed by indicator light 3244b, followed by indicator light 3224a) may intuitively indicate a trend of decreasing analyte measurement values. Similar to that described above with respect to Figures 34A and 34B, such a descending gradual sequence of illumination of the indicator light may be in a suitable color to indicate the status of the current analyte measurement value that is declining (e.g., descending gradual illumination in a first color (e.g., blue) to indicate that the current analyte measurement value is within the target range and declining, descending gradual illumination in a second color (e.g., amber) to indicate that the current analyte measurement value is above (or significantly above) the target range and declining), or descending gradual illumination in a third color (e.g., white) to indicate that the current analyte measurement value is below (or significantly below) the target range and declining).

[0275] It should be understood that other variations in the progressive sequence of illumination can be used to similarly indicate analyte measurement trends. For example, a one-dimensional array of indicator lights (e.g., arranged in a row, column, arc, etc.) may be illuminated in a progressive sequence from a first end of the array to a second end of the array to indicate an ascending analyte measurement trend, and from the second end of the array to the first end of the array to indicate a descending analyte measurement trend. For example, the progressive sequence of illumination may be characterized as left to right, right to left, top to bottom, bottom to top, clockwise, counterclockwise, etc. Furthermore, while user interface 3220 includes three sequential indicator lights, it should be understood that in other variations, the user interface on the housing of the analyte monitoring device may include fewer (e.g., two) or more (e.g., four, five, six, or more) that may similarly be illuminated in a progressive sequence to indicate ascending and / or descending analyte measurement trends.

[0276] In some variations, within each ascending or descending sequence of illumination across the indicator lights, illumination of adjacent indicator lights may be interspersed with illumination “off” periods. Additionally, in some variations, the pace at which illumination transitions between indicator lights may indicate the rate of change of the analyte measurement. For example, the faster the illumination transitions from the lowest indicator light to the highest indicator light, the faster the rate of change (and potentially the greater the urgency or need for user attention to the trend). Additionally or alternatively, each ascending or descending sequence of illumination across the indicator lights may be separated by an end-of-sequence illumination “off” time to help distinguish between ascending and descending sequences. The end-of-sequence illumination “off” time may be longer than the illumination “off” period within each sequence. In some variations, the beginning or end of each ascending or descending sequence of illumination may additionally or alternatively be separated in any suitable manner (e.g., illuminating all lights simultaneously at the beginning or end of an ascending or descending sequence).

[0277] Table 3 illustrates different illumination modes used in an exemplary method of operating the user 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 with respect to exemplary variations for illustrative purposes only. For example, in the progressive illumination sequence (e.g., for any one or more preferred illumination modes), the illumination color may be any suitable color, and / or the illumination "on" time may be about 0.1 seconds to 1 second, about 0.2 seconds to 0.5 seconds, or about 0.3 seconds, and / or the illumination "off" time between illumination of adjacent indicator lights may be about 0.05 seconds to about 1 second, about 0.1 seconds to about 0.5 seconds, or about 0.18 seconds, and / or the ratio between illumination "on" time and illumination "off" time may be about 1, about 1.5, or about 2, and / or the end of the sequence may be designated by illumination "off" for about 2 seconds to about 5 seconds, or about 3 seconds. Additionally, fewer or more illumination modes to indicate analyte measurement trends may be possible in other variations. [Table 3-1] [Table 3-2]

[0278] Additionally or alternatively, indicator lights 3222 may be selectively illuminated to communicate device status. Similar to that described above, the color and / or timing of illumination may be varied in a predetermined manner to indicate different device statuses. The statuses may include, for example, a warm-up cycle notification, an end-of-life notification, a sensor bad condition 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 indicator lights may be illuminated individually and / or collectively (e.g., sequentially or simultaneously) to indicate different device statuses. For example, as shown in FIG. 35A , a user interface including indicator lights 3222 may be illuminated in a first illumination mode (e.g., a first illumination color, such as white, and / or a first temporal illumination pattern) to indicate a device “standby” mode. The standby mode may correspond, for example, to a device warm-up cycle (as described elsewhere herein), detection of a transient error (e.g., detection of pressure-induced sensor decay), etc. As another example, as shown in FIG. 35B, the user interface including indicator light 3222 may be illuminated in a second illumination mode (e.g., a second illumination color, such as red, and / or a second temporal illumination pattern) to indicate a device "end of life" mode (e.g., determining the end of a predetermined wearing cycle, such as those described below, detecting a permanent error, etc.).

[0279] Table 4 illustrates different illumination modes used in an exemplary 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 with respect to exemplary variations for illustrative purposes only. For example, in a "standby" illumination mode, the illumination color may be any suitable color, and / or the illumination "on" time may be about 0.1 seconds to about 3 seconds, about 0.5 seconds to about 2 seconds, or about 1 second, and / or the illumination "off" mode may be about 0.5 seconds to about 5 seconds, or about 1 second to about 4 seconds, or about 2 seconds to about 4 seconds, or about 3 seconds, and / or the ratio between the illumination "on" time and the illumination "off" time 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" lighting mode, the lighting color may be any suitable color, and / or the lighting "on" time may be from about 0.01 seconds to about 1 second, from about 0.01 seconds to about 0.5 seconds, from about 0.01 seconds to about 0.3 seconds, from about 0.01 seconds to about 0.1 seconds, or about 0.04 seconds, and / or the lighting "off" time may be from about 1 second to about 10 seconds, from about 3 seconds to about 8 seconds, or about 6 seconds, and / or the ratio between lighting "on" time and lighting "off" time may be about 0.3, about 0.2, about 0.1, about 0.05, about 0.01, or less than about 0.01, and / or other suitable lighting parameters. Although only two illumination modes are shown, in some variations, the analyte monitoring device may have fewer or more illumination modes, such as for each of the above statuses (e.g., a first illumination mode for a device warm-up period, a second illumination mode for detecting a temporary error, a third illumination mode for determining the end of device life, a fourth illumination mode for detecting a permanent error, etc.). [Table 4]

[0280] 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. Ambient light measurements may be used to trigger adjustments (e.g., dimming) of the brightness of a user interface (e.g., display, indicator light, etc.), for example, to conserve battery power in a power-saving mode, to improve contrast under various lighting scenarios, and / or to reduce device visibility to other individuals. For example, an analyte monitoring device may enter a power-saving mode in response to measurements from an ambient light sensor indicating a general absence of ambient light (e.g., sufficient darkness for at least a predetermined period of time), such as when the device is placed under the wearer's clothing or when the wearer is sleeping in a dark environment. In these scenarios, a power-saving mode may be practical because indicator lights may have limited usefulness when hidden (e.g., under clothing) and out of the wearer's field of view, or may otherwise be perceived as a nuisance (e.g., while sleeping). In response to measurements 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 Features

[0281] In some variations, the mobile application may help the user manage the lifespan and replacement of the analyte monitoring device. For example, the mobile application may terminate data display when the analyte monitoring device's wear cycle has expired. In some variations, the analyte monitoring device may have an enhanced longevity compared to conventional CGM devices. For example, the analyte monitoring devices described herein may have a wear cycle (e.g., intended lifespan) of at least 3 days, at least 5 days, at least 6 days, at least 7 days, at least 10 days, or at least 12 days, 5-10 days, 10-14 days, etc., without significant loss in performance.

[0282] Additionally or alternatively, the mobile application may provide a configurable alert to the user that the wearing period is about to expire, allowing the user to apply a new analyte monitoring device when the current analyte monitoring device is still active but is nearing expiration. In addition, the new analyte monitoring device can warm up (typically about 30 minutes to about 2 hours) while the old unit is still delivering analyte measurements. The old analyte monitoring device can then be removed upon expiration. The new analyte monitoring device can then become the primary sensor delivering analyte measurements to the mobile application. This can provide uninterrupted coverage for the analyte measurements. In addition, readings from the old analyte monitoring device may be used to calibrate or algorithmically improve the accuracy of the new analyte monitoring device.

[0283] In some variations, the analyte monitoring device may have a unique serial number contained within a microcontroller (e.g., located within the electronics system). This serial number may allow the sensor to be tracked from manufacture throughout the use of the product. For example, a sensor device history record, including manufacture and customer use, may be transmitted and stored in a cloud database. This allows tracking and inference to be made on various parameters, such as sensor performance metrics and improvements for individual users and sensor lots, very rapid tracing of defective sensor lots from field data back to manufacturing or supplier issues, personalized health monitoring features for individual users, etc.

[0284] In some variations, the system may be capable of tracking inventory of analyte monitoring devices from warehousing to purchase transactions to product use, which may allow the system to assist users in timely order fulfillment (e.g., to ensure that users do not run out of analyte monitoring devices). Additionally or alternatively, fulfillment can be performed automatically as monitoring device usage is tracked, and timely delivery can be made to the user's home (e.g., "just-in-time" delivery) to help ensure that sensor supplies are never depleted. This can be achieved through virtual or electronic pharmacies, distribution centers, and / or Amazon. TM It can interface with web-based sales portals such as

[0285] Through the web portal, the cloud infrastructure may also allow users to view their real-time and historical glucose data / trends and share the data with caregivers, their healthcare provider, support networks, and / or other suitable persons. Enumerated Embodiments

[0286] Embodiment I-1. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, at least one of the microneedles comprising: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; A microneedle array comprising a plurality of solid microneedles comprising:

[0287] 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 at least one microneedle comprises a biorecognition layer arranged across the working electrode, the biorecognition layer comprising a biorecognition element.

[0288] Embodiment I-3. The microneedle array of embodiment I-2, wherein the biorecognition element comprises an enzyme.

[0289] Embodiment I-4. The microneedle array of embodiment I-3, wherein the enzyme is an oxidoreductase.

[0290] Embodiment I-5. The microneedle array of embodiment I-4, wherein the oxidoreductase is at least one of lactate oxidase, alcohol oxidase, β-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

[0291] Embodiment I-6. The microneedle array of embodiment I-4, wherein the oxidoreductase is glucose oxidase.

[0292] Embodiment I-7. The microneedle array of embodiment I-2, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species.

[0293] Embodiment I-8. The microneedle array of embodiment I-7, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde.

[0294] Embodiment I-9. The microneedle array of embodiment I-7, wherein the amine-fused carbonyl species is glutaraldehyde.

[0295] Embodiment I-10. The microneedle array of embodiment I-2, wherein at least one microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0296] Embodiment I-11. The microneedle array of embodiment I-2, wherein the microneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction relative to the working electrode.

[0297] 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 relative to the working electrode.

[0298] Embodiment I-13. The microneedle array of embodiment I-12, further comprising a conducting polymer arranged over the reference electrode.

[0299] Embodiment I-14. The microneedle array of embodiment I-13, wherein the conducting polymer comprises a dopant.

[0300] Embodiment I-15. The microneedle array of embodiment I-13, wherein the reference electrode comprises a metal oxide with a stable electrode potential.

[0301] Embodiment I-16. The microneedle array of embodiment I-15, wherein the metal oxide comprises iridium oxide.

[0302] Embodiment I-17. The microneedle array of embodiment I-13, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0303] Embodiment I-18. The microneedle array of embodiment I-17, wherein the metal salt comprises silver chloride.

[0304] Embodiment I-19. The microneedle array of embodiment I-1, wherein the electrodes are entirely on the tapered distal portion of at least one microneedle.

[0305] Embodiment I-20. The microneedle array of embodiment I-1, wherein the electrode comprises a catalytic surface.

[0306] 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.

[0307] Embodiment I-22. The microneedle array of embodiment I-20, wherein at least one microneedle comprises platinum black, arranged across the electrode.

[0308] Embodiment I-23. A microneedle array according to embodiment I-1, wherein the distal end of the electrode is offset from the distal apex by an offset distance of at least about 10 μm, the offset distance being measured along the longitudinal axis of at least one microneedle.

[0309] Embodiment I-24. The microneedle array of embodiment I-1, wherein the electrode is annular.

[0310] Embodiment I-25. The microneedle array of embodiment I-1, wherein a portion of the working electrode is recessed within the tapered distal portion.

[0311] Embodiment I-26. The microneedle array of embodiment I-1, wherein the electrodes are on only one section of the tapered distal portion.

[0312] Embodiment I-27. The microneedle array of embodiment I-1, further comprising an electrical contact, wherein at least one microneedle comprises a body portion that provides a conductive path between the electrical contact and the electrode.

[0313] Embodiment I-28. The microneedle array of embodiment I-27, wherein the body portion is formed from a conductive material.

[0314] Embodiment I-29. The microneedle array of embodiment I-27, wherein the body portion comprises an embedded pathway.

[0315] Embodiment I-30. The microneedle array of embodiment I-27, wherein the body portion is insulated.

[0316] Embodiment I-31. The microneedle array of embodiment I-27, wherein the body portion has a circular, square, or octagonal base.

[0317] Embodiment I-32. The microneedle array of embodiment I-27, wherein at least a section of the body portion is cylindrical.

[0318] Embodiment I-33. The microneedle array of embodiment I-27, wherein at least a section of the body portion is cone-shaped.

[0319] Embodiment I-34. A microneedle array as described in embodiment I-33, wherein at least a portion of the body portion has a first taper angle measured relative to the base of the body portion, and the distal apex has a second taper angle measured relative to the base, the second taper angle being greater than the first taper angle.

[0320] Embodiment I-35. The microneedle array of embodiment I-34, wherein at least one of the body portion and distal portion of the microneedles is radially asymmetric.

[0321] Embodiment I-36. The microneedle array of embodiment I-35, wherein the tapered distal portion comprises a planar surface offset from the distal apex of at least one microneedle.

[0322] Embodiment I-37. Each of the microneedles in the plurality of microneedles comprises: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; The microneedle array of embodiment I-1, comprising:

[0323] Embodiment I-38. The microneedle array of embodiment I-1, wherein the microneedles of the plurality of microneedles are electrically isolated from one another.

[0324] Embodiment I-39. The microneedle array of embodiment I-38, wherein the microneedle array is configured to detect multiple analytes.

[0325] Embodiment I-40. The microneedle array of embodiment I-1, wherein the microneedles of the plurality of microneedles are arranged in a periodic grid.

[0326] Embodiment I-41. The microneedle array of embodiment I-40, wherein the periodic grid comprises a rectangular array.

[0327] Embodiment I-42. The microneedle array of embodiment I-40, wherein the periodic grid comprises a hexagonal array.

[0328] Embodiment I-43. The microneedle array of embodiment I-40, wherein the microneedles in the periodic grid are spaced apart by a distance of about 200 μm to about 800 μm.

[0329] Embodiment I-44. The microneedle array of embodiment I-40, wherein the microneedles in the periodic grid are uniformly spaced apart.

[0330] Embodiment I-45. The microneedle array of embodiment I-1, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen.

[0331] Embodiment I-46. The microneedle array of embodiment I-1, wherein at least one microneedle is configured to pierce the user's skin and sense an analyte in interstitial fluid within the user's dermis layer.

[0332] Embodiment I-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.

[0333] Embodiment I-48. The system of embodiment I-47, wherein 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.

[0334] Embodiment I-49. The system of embodiment I-48, wherein 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.

[0335] 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.

[0336] Embodiment I-51. A system as described in embodiment I-50, wherein the electronic equipment 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.

[0337] Embodiment I-52. The system described in embodiment I-47, wherein the housing comprises one or more indicator lights configured to communicate status information.

[0338] Embodiment I-53. The system of embodiment I-52, wherein at least one of the indicator lights is configured to be selectively illuminated according to an illumination mode corresponding to an analyte measurement status.

[0339] Embodiment I-54. The system of embodiment I-53, wherein at least one of the indicator lights is configured to be selectively illuminated and to communicate a current analyte measurement level.

[0340] Embodiment I-55. The system of embodiment I-53, wherein the user interface comprises a plurality of indicator lights selectively illuminated in a progressive sequence and configured to communicate analyte measurement trends.

[0341] Embodiment I-56. The system described in embodiment I-55, wherein the plurality of indicator lights are configured to be selectively illuminated in a first progressive sequence in a first direction to communicate an ascending analyte measurement trend, and further configured to be selectively illuminated in a second progressive sequence in a second direction to communicate a descending analyte measurement trend.

[0342] Embodiment I-57. The system of embodiment I-52, wherein the user interface is further configured to communicate information indicative of the status of the analyte monitoring device.

[0343] Embodiment I-58. The system of embodiment I-47, further comprising an adhesive configured to couple the housing to the user's skin.

[0344] Embodiment I-59. The system of embodiment I-47, further comprising an applicator configured to apply at least a portion of the analyte monitoring system to the skin of a user.

[0345] Embodiment I-60. The system of embodiment I-47, wherein the analyte monitoring system is a skin adhesive patch.

[0346] Embodiment I-61. The system of embodiment I-47, wherein the plurality of microneedles comprises at least one delivery microneedle with a lumen.

[0347] 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.

[0348] 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, hydrocodone, an opioid, a nonsteroidal anti-inflammatory drug, an anesthetic, an analgesic, an anticonvulsant, an antidepressant, an antipsychotic, a sedative, a relaxant, a hormonal agent, an antibacterial agent, and an antiviral agent.

[0349] Embodiment I-64. A method for monitoring a user, comprising: accessing a bodily fluid of a user with an analyte monitoring device; quantitating one or more analytes in the bodily fluid using an analyte monitoring device; the analyte monitoring device comprises a plurality of solid microneedles, at least one microneedle having a tapered distal portion with an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; A method comprising:

[0350] Embodiment I-65. The method of embodiment I-64, wherein the bodily fluid comprises the user's dermal interstitial fluid.

[0351] Embodiment I-66. The method of embodiment I-64, wherein the one or more analytes comprise glucose.

[0352] Embodiment I-67. A microneedle array for use in sensing an analyte, comprising: a plurality of solid microneedles, at least one of the microneedles comprising: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the distal end of the electrode being offset from the distal apex; A microneedle array comprising a plurality of solid microneedles comprising:

[0353] Embodiment I-68. The microneedle array of embodiment I-67, wherein the electrode is a working electrode configured to sense at least one analyte, and at least one microneedle comprises a biorecognition layer arranged across the working electrode, the biorecognition layer comprising a biorecognition element.

[0354] Embodiment I-69. The microneedle array of embodiment I-68, wherein the biorecognition element comprises glucose oxidase.

[0355] Embodiment I-70. A microneedle array according to 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, the offset distance being measured along the longitudinal axis of at least one microneedle.

[0356] Embodiment I-71. The microneedle array of embodiment I-67, wherein the electrode is annular.

[0357] Embodiment I-72. The microneedle array of embodiment I-67, wherein in at least one microneedle, a portion of the working electrode is recessed into the tapered distal portion.

[0358] Embodiment I-73. The microneedle array of embodiment I-67, wherein the electrodes are on only one section of the tapered distal portion.

[0359] Embodiment I-74. The microneedle array of embodiment I-67, further comprising an electrical contact, wherein at least one microneedle comprises a body portion that provides a conductive path between the electrical contact and the electrode.

[0360] Embodiment I-75. Each of the microneedles in the plurality of microneedles comprises: a tapered distal portion having an insulated distal apex; an electrode on a surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex; The microneedle array of embodiment I-67, comprising:

[0361] Embodiment I-76. The microneedle array of embodiment I-67, wherein the microneedle array comprises a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device.

[0362] Embodiment I-77. The microneedle array of embodiment I-76, wherein the microneedle array is configured to detect multiple analytes.

[0363] Embodiment I-78. The microneedle array of embodiment I-67, wherein the microneedles of the plurality of microneedles are arranged in a hexagonal array.

[0364] Embodiment I-79. The microneedle array of embodiment I-67, wherein at least one microneedle is configured to pierce the user's skin and sense an analyte in interstitial fluid within the user's dermis layer.

[0365] 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.

[0366] Embodiment I-81. The system of embodiment I-80, wherein 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.

[0367] Embodiment I-82. A system as described in embodiment I-80, wherein the housing encloses an electronic device system comprising a wireless communication module, the system further comprising a software application executable on a mobile computing device to be paired with the wireless communication module.

[0368] 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.

[0369] Embodiment I-84. The system described in embodiment I-83, wherein at least one of the indicator lights is configured to be selectively illuminated according to an illumination mode corresponding to an analyte measurement status.

[0370] Embodiment I-85. The system of embodiment I-83, wherein the analyte monitoring system comprises a skin-adhesive patch.

[0371] Embodiment I-86. A method of sterilizing an analyte monitoring device, comprising: 1. A method comprising: exposing an analyte monitoring device to a sterilant gas, the analyte monitoring device comprising a wearable housing, a microneedle array extending from the housing and comprising an analyte sensor, and an electronics system arranged within 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.

[0372] Embodiment I-87. The method of embodiment I-86, wherein the sterilant gas is suitable for oxidative sterilization.

[0373] Embodiment I-88. The method of embodiment I-87, wherein the sterilant gas comprises ethylene oxide.

[0374] Embodiment I-89. The method of embodiment I-86, wherein the analyte sensor comprises an electrode.

[0375] Embodiment I-90. The method of embodiment I-89, wherein the analyte sensor comprises a biorecognition layer arranged over the electrodes, the biorecognition layer comprising a biorecognition element.

[0376] Embodiment I-91. The method of embodiment I-90, wherein the biorecognition element comprises an enzyme.

[0377] Embodiment I-92. The method of embodiment I-91, wherein the enzyme is an oxidoreductase.

[0378] Embodiment I-93. The method of embodiment I-92, 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.

[0379] Embodiment I-94. The method of embodiment I-92, wherein the oxidoreductase is glucose oxidase.

[0380] Embodiment I-95. The method of embodiment I-90, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species.

[0381] Embodiment I-96. The method of embodiment I-95, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde.

[0382] Embodiment I-97. The method of embodiment I-95, wherein the amine-fused carbonyl species is glutaraldehyde.

[0383] Embodiment I-98. The method of embodiment I-90, wherein the biorecognition layer is formed, at least in part, by crosslinking the biorecognition elements to form a crosslinked biorecognition element assembly, and embedding the crosslinked biorecognition element assembly in a conducting polymer.

[0384] Embodiment I-99. The method of embodiment I-98, wherein embedding the crosslinked biorecognition element assemblies comprises embedding only crosslinked biorecognition element assemblies having at least a threshold molecular weight.

[0385] Embodiment I-100. The method of embodiment I-86, wherein exposing the analyte monitoring device to a sterilant gas comprises injecting the sterilant gas into a compartment containing the analyte monitoring device and heating the compartment to a sterilization temperature.

[0386] 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.

[0387] Embodiment I-102. The method of embodiment I-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 the vapor.

[0388] Embodiment I-103. A microneedle array for an analyte monitoring device, comprising: a plurality of solid sensing microneedles, each sensing microneedle comprising: a tapered distal portion comprising a working electrode configured to sense an analyte; a body portion providing a conductive connection to the working electrode; a microneedle array comprising a plurality of solid sensing microneedles, the body portion of each sensing microneedle being insulated such that each working electrode is individually addressable and electrically isolated from all other working electrodes in the microneedle array.

[0389] 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, the biorecognition layer comprising a biorecognition element.

[0390] Embodiment I-105. The microneedle array of embodiment I-104, wherein the biorecognition element comprises an enzyme.

[0391] Embodiment I-106. The microneedle array of embodiment I-105, wherein the enzyme is an oxidoreductase.

[0392] Embodiment I-107. The microneedle array of embodiment I-106, 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.

[0393] Embodiment I-108. The microneedle array of embodiment I-106, wherein the oxidoreductase is glucose oxidase.

[0394] Embodiment I-109. The microneedle array of embodiment I-104, wherein the biorecognition element is crosslinked with an amine-fused carbonyl species.

[0395] Embodiment I-110. The microneedle array of embodiment I-109, wherein the amine-fused carbonyl species is at least one of formaldehyde, glyoxal, malonaldehyde, and succinaldehyde.

[0396] Embodiment I-111. The microneedle array of embodiment I-109, wherein the amine-fused carbonyl species is glutaraldehyde.

[0397] Embodiment I-112. The microneedle array of embodiment I-104, wherein at least one sensing microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0398] Embodiment I-113. The microneedle array of embodiment I-103, further comprising at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction to the working electrode of the at least one sensing microneedle.

[0399] Embodiment I-114. The microneedle array of embodiment I-103, wherein the plurality of microneedles comprises at least one microneedle comprising a reference electrode configured to provide a reference potential relative to the working electrode.

[0400] Embodiment I-115. The microneedle array of embodiment I-114, further comprising a conducting polymer arranged over the reference electrode.

[0401] Embodiment I-116. The microneedle array of embodiment I-115, wherein the conducting polymer comprises a dopant.

[0402] Embodiment I-117. The microneedle array of embodiment I-114, wherein the reference electrode comprises a metal oxide with a stable electrode potential.

[0403] Embodiment I-118. The microneedle array of embodiment I-117, wherein the metal oxide comprises iridium oxide.

[0404] Embodiment I-119. The microneedle array of embodiment I-114, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0405] Embodiment I-120. The microneedle array of embodiment I-119, wherein the metal salt comprises silver chloride.

[0406] Embodiment I-121. A microneedle array according to 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.

[0407] Embodiment I-122. A microneedle array according to embodiment I-121, wherein the distal end of the working electrode is offset from the distal apex by an offset distance of at least about 10 μm, the offset distance being measured along the longitudinal axis of the at least one sensing microneedle.

[0408] Embodiment I-123. The microneedle array of embodiment I-103, wherein in at least one sensing microneedle, a portion of the working electrode is recessed into the tapered distal portion.

[0409] Embodiment I-124. An analyte monitoring device comprising the microneedle array of embodiment I-103 and a wearable housing, wherein the microneedle array extends outwardly from the housing.

[0410] Embodiment I-125. The analyte monitoring device of embodiment I-124, wherein the housing comprises one or more indicator lights configured to communicate status information.

[0411] 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.

[0412] Embodiment I-127. The analyte monitoring device of embodiment I-126, wherein the analyte monitoring device is a skin adhesive patch.

[0413] Embodiment I-128. A microneedle array for a body-worn analyte monitoring device, comprising: at least one microneedle, a cone-shaped body portion having a non-circular base; a tapered distal portion extending from the body portion and including an electrode; wherein the distal portion comprises a planar surface offset from the distal apex of the at least one microneedle; A microneedle array comprising at least one microneedle.

[0414] Embodiment I-129. A microneedle array as described in embodiment I-128, wherein at least a portion of the body portion has a first taper angle measured relative to the base and the distal apex has a second taper angle measured relative to the base, the second taper angle being greater than the first taper angle.

[0415] Embodiment I-130. The microneedle array of embodiment I-128, wherein the second taper is between about 65 degrees and about 75 degrees.

[0416] Embodiment I-131. The microneedle array of embodiment I-130, wherein the first taper is between about 15 degrees and about 25 degrees.

[0417] Embodiment I-132. The microneedle array of embodiment I-128, wherein the planar surface is angled at about 75 degrees to 85 degrees measured relative to the base.

[0418] Embodiment I-133. The microneedle array of embodiment I-128, wherein the tapered distal portion comprises an insulated distal apex.

[0419] Embodiment I-134. An analyte monitoring device comprising the microneedle array of embodiment I-128 and a wearable housing, wherein the microneedle array is configurable to extend outwardly from the housing.

[0420] Embodiment I-135. The analyte monitoring device of embodiment I-134, wherein the analyte monitoring device is a patch.

[0421] Embodiment I-136. A method for monitoring a user, comprising: accessing the user's dermal interstitial fluid at multiple sensor locations with an integrated analyte monitoring device comprising a single microneedle array; quantitating one or more analytes in dermal interstitial fluid using multiple working electrodes in a microneedle array, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device; A method comprising:

[0422] Embodiment I-137. The method of embodiment I-136, wherein quantifying the one or more analytes comprises quantifying multiple analytes in dermal interstitial fluid using multiple working electrodes.

[0423] Embodiment I-138. The method of embodiment I-136, wherein the microneedle array comprises a plurality of sensing microneedles, each sensing microneedle comprising a separate working electrode.

[0424] Embodiment I-139. The method of embodiment I-138, wherein at least one sensing microneedle comprises a biorecognition layer arranged over the working electrode, the biorecognition layer comprising an enzyme.

[0425] Embodiment I-140. The method of embodiment I-139, wherein at least one microneedle comprises at least one of a diffusion-limiting layer and a hydrophilic layer arranged over the biorecognition layer.

[0426] Embodiment I-141. The method of embodiment I-136, wherein the microneedle array comprises at least one microneedle comprising a counter electrode configured to source or sink current and sustain an electrochemical reaction to at least one working electrode.

[0427] 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 relative to at least one working electrode.

[0428] Embodiment I-143. The method of embodiment I-142, further comprising a conducting polymer arranged over the reference electrode.

[0429] Embodiment I-144. The method of embodiment I-143, wherein the conducting polymer comprises a dopant.

[0430] Embodiment I-145. The method of embodiment I-142, wherein the reference electrode comprises a metal oxide with a stable electrode potential.

[0431] Embodiment I-146. The method of embodiment I-145, wherein the metal oxide comprises iridium oxide.

[0432] Embodiment I-147. The method of embodiment I-142, wherein the reference electrode comprises a metal salt with a stable electrode potential.

[0433] Embodiment I-148. The method of embodiment I-147, wherein the metal salt comprises silver chloride.

[0434] Embodiment I-149. The method of embodiment I-136, further comprising communicating status information indicative of the quantification of one or more analytes.

[0435] Embodiment I-150. The method of embodiment I-149, wherein the microneedle array extends outward from the wearable housing and the step of communicating the status information includes the step of communicating the status information via a user interface on the housing.

[0436] Embodiment I-151. The method of embodiment I-150, wherein the step of communicating the status information includes selectively illuminating one or more indicator lights on the housing according to an illumination mode corresponding to the analyte measurement status or the status of the integrated analyte monitoring device.

[0437] Embodiment I-152. The method of embodiment I-150, wherein the step of communicating the status information includes the step of activating a display corresponding to the analyte measurement status or the status of the integrated analyte monitoring device.

[0438] Embodiment I-153. A body-worn analyte monitoring device, comprising: a wearable housing; a microneedle array including at least one microneedle extending outward from the housing and 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 one or more analytes.

[0439] Embodiment I-154. A device described in embodiment I-153, wherein the user interface comprises one or more indicator lights configured to be selectively illuminated according to an illumination mode corresponding to the analyte measurement status or the status of the integrated analyte monitoring device.

[0440] Embodiment I-155. The device of embodiment I-154, wherein at least one of the indicator lights is configured to be selectively illuminated and to communicate a current analyte measurement level.

[0441] Embodiment I-156. A device as described in embodiment I-154, wherein the user interface comprises a plurality of indicator lights selectively illuminated in a progressive sequence and configured to communicate analyte measurement trends.

[0442] Embodiment I-157. The device of embodiment I-156, wherein the plurality of indicator lights are selectively illuminated in a first progressive sequence in a first direction and configured to communicate an increasing analyte measurement trend.

[0443] Embodiment I-158. The device of embodiment I-156, wherein the plurality of indicator lights are selectively illuminated in a second progressive sequence in a second direction and configured to communicate a declining analyte measurement trend.

[0444] Embodiment I-159. The device of embodiment I-153, wherein the user interface is further configured to communicate information indicative of the status of the analyte monitoring device.

[0445] Embodiment I-160. A device as described in embodiment I-153, wherein the user interface comprises a display screen.

[0446] Embodiment I-161. The device of embodiment I-153, wherein the analyte monitoring device is a skin-adhesive patch.

[0447] Embodiment I-162. A device described in embodiment I-153, wherein at least one microneedle comprises a tapered distal portion with an insulated distal apex and an electrode on the surface of the tapered distal portion, the electrode being located proximal to the insulated distal apex.

[0448] Embodiment I-163. A device described in embodiment I-153, wherein the microneedle array comprises a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device.

[0449] Embodiment I-164. A method for monitoring a user, comprising: measuring one or more analytes in a user using a body-worn analyte monitoring device comprising a wearable housing and one or more analyte sensors; and communicating information indicative of the measurement of the one or more analytes through a user interface on the housing; A method comprising:

[0450] Embodiment I-165. The method of embodiment I-164, wherein the step of communicating information includes the step of illuminating one or more indicator lights on the housing according to an illumination mode corresponding to the analyte measurement status.

[0451] Embodiment I-166. The method of embodiment I-165, wherein the step of communicating information includes selectively illuminating at least one of the indicator lights to communicate the current analyte measurement level.

[0452] Embodiment I-167. The method of embodiment I-166, wherein the step of communicating information includes communicating the current analyte measurement level based on the color of the illuminated indicator light, the location of the illuminated indicator light, or both.

[0453] Embodiment I-168. The method of embodiment I-165, wherein the step of communicating information includes selectively illuminating a plurality of indicator lights on the housing in a progressive sequence to communicate the analyte measurement trend.

[0454] Embodiment I-169. The method of embodiment I-168, wherein the step of communicating information includes selectively illuminating a plurality of indicator lights in a first progressive sequence in a first direction to communicate an increasing analyte measurement trend.

[0455] Embodiment I-170. The method of embodiment I-168, wherein the step of communicating information includes selectively illuminating a plurality of indicator lights in a second progressive sequence in a second direction to communicate a declining analyte measurement trend.

[0456] Embodiment I-171. The method of embodiment I-164, further comprising communicating, through a user interface, information indicating the status of the analyte monitoring device.

[0457] Embodiment I-172. The method of embodiment I-164, further comprising accessing the user's dermal interstitial fluid at a plurality of sensor locations using an analyte monitoring device, and wherein quantifying one or more analytes comprises quantifying one or more analytes in the dermal interstitial fluid.

[0458] Embodiment I-173. The method of embodiment I-164, wherein the analyte monitoring device comprises a microneedle array comprising a plurality of working electrodes, each working electrode being individually addressable and electrically isolated from all other working electrodes in the analyte monitoring device.

[0459] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to those skilled in the art that specific details are not required to practice the invention. Thus, the foregoing descriptions of specific embodiments of the invention are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously, many modifications and variations are possible in light of the above teachings. The embodiments were chosen and described in order to explain the principles of the invention and its practical application, thereby enabling those skilled in the art to utilize the invention and its various embodiments with various modifications as suited to the particular use envisioned. It is intended that the following claims and their equivalents define the scope of the invention.

Claims

1. 1. A microneedle array for use in sensing an analyte, said microneedle array comprising: a first solid microneedle without lumen comprising a body portion and a tapered portion distal to the body portion, the first solid microneedle further comprising a working electrode on only a section of the tapered portion, the working electrode comprising a first electrode material and a biorecognition layer on the first electrode material, the biorecognition layer comprising a biorecognition element configured to react with the analyte, and the distal tip of the first solid microneedle is insulated; a second solid non-lumen microneedle comprising a counter electrode, the counter electrode comprising a second electrode material; a third solid microneedle without a lumen comprising a reference electrode, the reference electrode comprising a third electrode material and a redox pair layer on the third electrode material; wherein a redox reaction occurs between the working electrode on the first solid non-lumen microneedle and the counter electrode on the second solid non-lumen microneedle.

2. The microneedle array of claim 1 , wherein the working electrode further comprises an electrocatalytic layer between the first electrode material and the biorecognition layer.

3. The microneedle array of claim 1 , wherein the working electrode further comprises a diffusion-limiting layer on the biorecognition layer, the diffusion-limiting layer configured to limit the flux of the analyte to the biorecognition layer.

4. The microneedle array of claim 1 , wherein the working electrode further comprises a hydrophilic layer.

5. The microneedle array of claim 2 , wherein the electrocatalytic layer is a platinum black layer, the platinum black layer comprising elemental platinum metal.

6. The microneedle array of claim 2 , wherein the working electrode further comprises a diffusion-limiting layer on the biorecognition layer, the diffusion-limiting layer configured to limit the flux of the analyte to the biorecognition layer.

7. The microneedle array of claim 1, wherein the biorecognition layer is configured to both facilitate selective analyte quantification using the biorecognition element and prevent endogenous and / or exogenous species from being directly oxidized or reduced at the working electrode.

8. 2. The microneedle array of claim 1, wherein the biorecognition element comprises one or more enzymes selected from the group consisting of glucose oxidase, lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

9. 2. The microneedle array of claim 1, wherein the biorecognition layer comprises at least one polymer selected from the group consisting of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid.

10. The microneedle array of claim 1 , wherein the first electrode material and the second electrode material are different from the third electrode material.

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

12. The microneedle array of claim 1 , wherein the first electrode material and the second electrode material are the same material.

13. 2. The microneedle array of claim 1, wherein the third electrode material is a metal salt or metal oxide selected from the group consisting of silver-silver chloride and iridium oxide.

14. 2. The microneedle array of claim 1, wherein the working electrode is annular and the length of the working electrode measured along the length of the distal portion of the first solid non-lumen microneedle is shorter than the length of the distal portion of the first solid non-lumen microneedle.

15. 15. The microneedle array of claim 14, wherein a distal edge of the annular working electrode is offset from the insulated distal tip of the first solid non-lumen microneedle and is proximal to a proximal edge of the insulated distal tip, and a proximal edge of the annular working electrode is offset from a proximal edge of the distal portion of the first solid non-lumen microneedle.

16. 1. A microneedle array for use in glucose sensing, said microneedle array comprising: a first solid microneedle comprising a body portion and a tapered portion distal to the body portion, the first solid microneedle further comprising a working electrode on only a section of the tapered portion, the working electrode comprising a platinum layer and a biorecognition layer on the platinum layer, the biorecognition layer comprising a conducting polymer-entrapped glucose oxidase configured to react with the glucose, and the distal tip of the first solid microneedle being insulated; a second solid microneedle comprising a counter electrode, the counter electrode comprising a platinum layer; a third solid microneedle comprising a reference electrode, said reference electrode comprising silver-silver chloride; wherein a redox reaction occurs between the working electrode on the first solid microneedle and the counter electrode on the second solid microneedle.

17. 1. A method for controlling the operation of an analyte monitoring device, the analyte monitoring device comprising a microneedle array for sensing an analyte and an analog front end, the microneedle array comprising: a first solid microneedle without lumen comprising a body portion and a tapered portion distal to the body portion, the first solid microneedle further comprising a working electrode on only a section of the tapered portion, the working electrode comprising a first electrode material and a biorecognition layer on the first electrode material, the biorecognition layer comprising a biorecognition element configured to react with the analyte, and the distal tip of the first solid microneedle is insulated; a second solid non-lumen microneedle comprising a counter electrode, the counter electrode comprising a second electrode material; a third solid microneedle without a lumen comprising a reference electrode, the reference electrode comprising a third electrode material and a redox pair layer on the third electrode material; The method comprises: the analog front end applying a bias potential between the working electrode and the reference electrode; the analog front end measuring a current value between the working electrode and the counter electrode, the current value being proportional to the concentration of the analyte; wherein a redox reaction occurs between the working electrode and the counter electrode.

18. 20. The method of claim 17, wherein the working electrode further comprises an electrocatalytic layer between the first electrode material and the biorecognition layer.

19. 20. The method of claim 18, wherein the electrocatalytic layer is a platinum black layer, the platinum black layer comprising elemental platinum metal.

20. 18. The method of claim 17, wherein the biorecognition element comprises one or more enzymes selected from the group consisting of glucose oxidase, lactate oxidase, alcohol oxidase, beta-hydroxybutyrate dehydrogenase, tyrosinase, catalase, ascorbate oxidase, cholesterol oxidase, choline oxidase, pyruvate oxidase, urate oxidase, urease, and xanthine oxidase.

21. 18. The method of claim 17, wherein the biorecognition layer comprises at least one polymer selected from the group consisting of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid.

22. 18. The method of claim 17, wherein the working electrode is annular and the length of the working electrode measured along the length of the distal portion of the first solid non-lumen microneedle is less than the length of the distal portion of the first solid non-lumen microneedle.

23. The microneedle array of claim 1 , wherein the working electrode is disposed on the outer periphery of the first non-lumen solid microneedle.

24. The microneedle array of claim 1 , wherein the reference electrode further comprises an electrocatalytic layer on the third electrode material.

25. The microneedle array of claim 16 , wherein the working electrode further comprises an electrocatalytic layer between the platinum layer and the biorecognition layer.

26. 26. The microneedle array of claim 25, wherein the electrocatalytic layer is a platinum black layer, the platinum black layer comprising elemental platinum metal.

27. The microneedle array of claim 25, wherein the working electrode further comprises a diffusion-limiting layer on the biorecognition layer, the diffusion-limiting layer configured to limit the flux of the glucose to the biorecognition layer.

28. The microneedle array of claim 16, wherein the working electrode further comprises a diffusion-limiting layer on the biorecognition layer, the diffusion-limiting layer configured to limit the flux of the glucose to the biorecognition layer.

29. The microneedle array of claim 16 , wherein the working electrode further comprises a hydrophilic layer.

30. The microneedle array of claim 16, wherein the biorecognition layer is configured to both facilitate selective analyte quantification using biorecognition elements and prevent endogenous and / or exogenous species from being directly oxidized or reduced at the working electrode.

31. 17. The microneedle array of claim 16, wherein the biorecognition layer comprises at least one polymer selected from the group consisting of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid.

32. 17. The microneedle array of claim 16, wherein the working electrode is annular and the length of the working electrode measured along the length of the distal portion of the first solid microneedle is shorter than the length of the distal portion of the first solid microneedle.

33. 33. The microneedle array of claim 32, wherein a distal edge of the annular working electrode is offset from the insulated distal tip of the first solid microneedle and is proximal to a proximal edge of the insulated distal tip, and a proximal edge of the annular working electrode is offset from a proximal edge of the distal portion of the first solid microneedle.

34. The microneedle array of claim 16 , wherein the working electrode is disposed on the outer periphery of the first solid microneedle.

35. 1. A method for controlling the operation of a glucose monitoring device, the glucose monitoring device comprising a microneedle array for sensing glucose and an analog front end, the microneedle array comprising: a first solid microneedle comprising a body portion and a tapered portion distal to the body portion, the first solid microneedle further comprising a working electrode on only a section of the tapered portion, the working electrode comprising a platinum layer and a biorecognition layer on the platinum layer, the biorecognition layer comprising a conducting polymer-entrapped glucose oxidase configured to react with the glucose, and the distal tip of the first solid microneedle being insulated; a second solid microneedle comprising a counter electrode, the counter electrode comprising a platinum layer; a third solid microneedle comprising a reference electrode, said reference electrode comprising silver-silver chloride; The method comprises: the analog front end applying a bias potential between the working electrode and the reference electrode; the analog front end measuring a current value between the working electrode and the counter electrode, the current value being proportional to the glucose concentration; wherein a redox reaction occurs between the working electrode on the first solid microneedle and the counter electrode on the second solid microneedle.

36. 36. The method of claim 35, wherein the working electrode further comprises an electrocatalytic layer between the platinum layer and the biorecognition layer.

37. 37. The method of claim 36, wherein the electrocatalytic layer is a platinum black layer, the platinum black layer comprising elemental platinum metal.

38. 36. The method of claim 35, wherein the biorecognition layer comprises at least one polymer selected from the group consisting of aniline, pyrrole, acetylene, phenylene, phenylene vinylene, phenylenediamine, thiophene, 3,4-ethylenedioxythiophene, and aminophenylboronic acid.

39. 36. The method of claim 35, wherein the working electrode is annular and the length of the working electrode measured along the length of the distal portion of the first solid microneedle is less than the length of the distal portion of the first solid microneedle.

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