Wearable sensing device

Abstract

A wearable sensing device for detecting at least one analyte, comprising a device body comprising a first surface extending in a first plane and a second surface, wherein the first surface surrounds the second surface and the first surface is offset by an offset distance from the second surface along a longitudinal axis, the first surface being configured to receive adhesive means for affixing the device body to an application surface of a user, the device body further comprising a tapered surface extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface and the second surface such that the taper first end is adjacent to the second surface and the taper second end is adjacent to the first surface, and an array of microneedles each extending along a microneedle axis that is parallel to the longitudinal axis, each microneedle extending through apertures in the second surface and comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte. A taper first axis extends from the taper first end and is parallel to the longitudinal axis, and a first distance for each microneedle is defined as extending between the respective microneedle axis and the taper first axis in a direction perpendicular to the longitudinal axis, and wherein the first distance is 3.0 mm or less.

Description

WEARABLE SENSING DEVICETECHNICAL FIELD

[0001] The present disclosure relates to a wearable sensing device for detecting at least one analyte. Aspects of the invention relate to a wearable sensing device, to an intermediate assembly for use in the manufacture of a wearable sensing device, and to a method of manufacturing a wearable sensing device.BACKGROUND

[0002] Detecting and monitoring analyte concentrations in the human and animal body are widely recognized as critical metrics in various fields related to performance and disease management. For example, monitoring the concentration of analytes such as glucose and lactate, two key performance metrics, can allow a subject to predict exhaustion times, reduce the risk of injuries and maximise performance. In an alternative field, monitoring the concentration of an analyte such as glucose is of critical importance in the management of diseases such as diabetes mellitus. Diabetes results in an imbalance in glucose levels and can cause hyperglycemia or hypoglycemia. The imbalance in glucose levels typically arises from a lack of insulin production and / or insulin action, a hormone that regulates the level of glucose and is produced by the pancreas. A common practice in monitoring glucose concentration levels has been to employ devices such as blood glucose meters and continuous glucose monitors. Blood glucose meters are biosensors which are equipped with a needle, a lancet or the like and a measuring means in order to determine the glucose concentration in blood. This is typically achieved by acquiring a small drop of blood through pricking of the skin. The blood sample is subsequently placed onto a disposable test strip or similar measuring means in order to determine the glucose concentration in the blood of the subject. A continuous glucose monitor differs in a number of areas but most notably this technology measures glucose concentration in interstitial fluid, which is a thin layer of fluid surrounding cells in the body, as opposed to blood, as well as monitoring the glucose concentration continuously, rather than a one-off measurement.

[0003] In spite of the advances in the technology of continuous glucose monitors, there are a number of drawbacks associated with this technology. In particular, such devices are only capable of measuring a single analyte, thereby limiting their versatility. All require an assistive hypodermic needle to enable sensor insertion, which is problematic for users who have a needlephobia or dislike and provides a poor user experience. Commercially available devices are typically expensive, thereby prohibiting access for many who would benefit from such devices.

[0004] Many known devices have a large footprint in the skin. This can lead to trauma which gives rise to poor readings, especially in the first 6 to 48 hours of wear time.

[0005] The sensors of many known devices can contact the muscular layer or nerve cells of the wearer when inserted, leading to discomfort and pain. Similarly, certain devices are known to have sensors that can cause damage to blood vessels and lead to bleeding.

[0006] Many known devices sense in the subcutaneous region of the skin which gives rise to slower response times.

[0007] Certain analyte sensing devices that utilise microneedles have been proposed but no such device has been demonstrated that provides desired levels of robustness, accuracy and reliability. Consequently, no such device has yet reached market readiness.

[0008] In view of the above, there is a need for an analyte monitoring device which is minimally invasive, mechanically stable and biocompatible in a range of different physiological environments.

[0009] Aspects of the present invention were devised with the foregoing in mind.BRIEF SUMMARY

[0010] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body comprising a first surface extending in a first plane and a second surface, wherein the first surface surrounds the second surface and the first surface is offset by an offset distance from the second surface along a longitudinal axis, the first surface being configured to receive adhesive means for affixing the device body to an application surface of a user, the device body further comprising a tapered surface extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface and the second surface such that the taper first end is adjacent to the second surface and the taper second end is adjacent to the first surface; and an array of microneedles each extending along a microneedle axis that is parallel to the longitudinal axis, each microneedle extending through apertures in the second surface and comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte;wherein a taper first axis extends from the taper first end and is parallel to the longitudinal axis, and a first distance for each microneedle is defined as extending between the respective microneedle axis and the taper first axis in a direction perpendicular to the longitudinal axis; and wherein the first distance is 3.0 mm or less.In accordance with another aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body and an adhesive pad received on at least part of the device body, wherein an exposed one of the device body and the adhesive pad define a first surface extending in a first plane and a second surface, wherein the first surface surrounds the second surface and the first surface is offset by an offset distance from the second surface along a longitudinal axis, and an exposed one of the device body and the adhesive pad further defines a tapered surface extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface and the second surface such that the taper first end is adjacent to the second surface and the taper second end is adjacent to the first surface; and an array of microneedles each extending along a microneedle axis that is parallel to the longitudinal axis, each microneedle extending through apertures in the second surface and comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; wherein a taper first axis extends from the taper first end and is parallel to the longitudinal axis, and a first distance for each microneedle is defined as extending between the respective microneedle axis and the taper first axis in a direction perpendicular to the longitudinal axis; and wherein the first distance is 3.0 mm or less.

[0011] In certain embodiments, the first distance is about 0.5 mm.

[0012] In certain embodiments, a taper second axis extends from the taper second end and is parallel to the longitudinal axis, and a tapered surface length is defined as extending between the taper first axis and the taper second axis in a direction perpendicular to the longitudinal axis, wherein the tapered surface length is between 2.0 mm and 5.0 mm.

[0013] In certain embodiments, the tapered surface length is about 2.0 mm.

[0014] In certain embodiments, the offset distance is between 0.5 mm and 2.0 mm. In certain embodiments, the offset distance is about 1.3 mm.

[0015] In certain embodiments, a first angle is defined between the taper first end and the taper second end across the offset distance, wherein the first angle is between 5° and 60°. In certain embodiments, the first angle is between 20° and 40°. In certain embodiments, the first angle is about 32°.

[0016] In certain embodiments, each microneedle has an exposed portion that protrudes from the device body, wherein a substrate underlying the exposed portion has a length LI that is 2.0 mm or less.

[0017] In certain embodiments, each microneedle has an exposed portion that protrudes from the adhesive pad, wherein a substrate underlying the exposed portion has a length LI that is 2.0 mm or less.

[0018] In certain embodiments, LI is between 0.4 mm and 2.0 mm, or between 0.6 mm and 1.6 mm, and is optionally about 1.0 mm, 1.2 mm, or 1.4 mm.

[0019] In certain embodiments, each microneedle has an insertion tip, and a microneedle body disposed between the insertion tip and the device body, and wherein a susbtrate underlying each microneedle body has a width W1 that is between 0.05 mm and 0.4 mm, or between 0. 1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm, and is optionally about 0.2 mm, 0.25 mm or 0.3 mm. In certain embodiments, each microneedle comprises a shoulder disposed between the microneedle body and the device body. In certain embodiments, a substrate underlying the shoulder has a width W2 between 0.125 mm and 1.00 mm, or between 0.20 mm and 0.80 mm, or between 0.25 mm and 0.8 mm, and is optionally about 0.40 mm.

[0020] In certain embodiments, a substrate underlying each insertion tip has a length L2 that is between 0.15 mm and 0.5 mm, and is optionally about 0.3 mm.

[0021] In certain embodiments, the wearable sensing device comprises a plurality of channels recessed in the first surface. In certain embodiments, the plurality of channels have a width of between 0.25 mm and 1.5 mm, or between 0.5 mm and 1.0 mm, or about 0.8 mm. In certain embodiments, the plurality of channels have a depth of between 0.05 mm and 0.75 mm, or between 0.1 mm and 0.5 mm, or about 0.3 mm. In certain embodiments, wherein the plurality of channels extends into the tapered surface. In certain embodiments, the plurality of channels extends into the second surface.

[0022] In certain embodiments, the second surface extends in a second plane.

[0023] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; and at least one microneedle extending from the device body; wherein each of the at least one microneedle comprises a substrate underlying: an insertion tip; and a microneedle body disposed between the insertion tip and the device body; wherein the substrate underlying the microneedle body comprises a first planar surface and a second planar surface opposing the first planar surface, and wherein each of the first planar surface and the second planar surface comprises at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; wherein the distance between the first planar surface and the second planar surface of each microneedle defines a thickness T1 that may be 0.025 to 0.15 mm.

[0024] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; and an array of microneedles extending from the device body; wherein each of the microneedles comprises a substrate underlying: an insertion tip; and a microneedle body disposed between the insertion tip and the device body; wherein the substrate underlying the microneedle body comprises a first planar surface and a second planar surface opposing the first planar surface, and wherein each of the first planar surface and the second planar surface comprises at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; wherein the distance between the first planar surface and the second planar surface of each microneedle defines a thickness T1 that may be 0.025 to 0.15 mm.

[0025] In certain embodiments, the microneedle body comprises side walls extending between and perpendicularly relative to the first planar surface and the second planar surface.

[0026] In certain embodiments, edges of the first planar surface are parallel relative to one another.

[0027] In certain embodiments, the array has a pitch Pl defining a distance between adjacent microneedles of between 0.5 mm and 5.0 mm, or between 1.0 and 5.0 mm, and optionally about 3.0 mm or about 4.0 mm.

[0028] In certain embodiments, each microneedle has an exposed portion that protrudes from the device body, wherein the substrate underlying the exposed portion has a length LI that is 2.0 mm or less. In certain embodiments, LI is between 0.4 mm and 2.0 mm, or between 0.6 mm and 1.6 mm, and is optionally about 1.0 mm, 1.2 mm, or 1.4 mm.

[0029] In certain embodiments, the substrate underlying each microneedle body has a width W1 that is between 0.05 mm and 0.4 mm, or between 0.1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm, and is optionally about 0.2 mm, 0.25 mm or 0.3 mm.

[0030] In certain embodiments, the substrate underlying each microneedle comprises a shoulder disposed between the microneedle body and the device body. In certain embodiments, the shoulder has a width W2 between 0.125 mm and 1.00 mm, or between 0.20 mm and 0.80 mm, or between 0.25 mm and 0.8 mm, and is optionally about 0.40 mm.

[0031] In certain embodiments, the substrate underlying each insertion tip has a length L2 that is between 0.15 mm and 0.5 mm, and is optionally about 0.3 mm.

[0032] In certain embodiments, each insertion tip tapers, to a point, in the plane in which the first planar surface extends. Optionally, the insertion tip tapers symmetrically.

[0033] In certain embodiments, the distance between the first planar surface and the second planar surface of each microneedle defines a thickness T1 that is 0.2 mm or less.

[0034] In certain embodiments, the thickness T1 is between 0.025 mm and 0.5 mm, or between 0.025 mm and 0.4 mm, or between 0.05 mm and 0.15 mm, or between 0.05 mm and 0.20 mm, or between 0.075 mm and 0.100 mm, and is optionally about 0.025 mm, or about 0.05 mm, or about 0.075 mm, or about 0.10 mm.

[0035] In certain embodiments, the substrate underlying each insertion tip is bevelled such that a thickness of the respective insertion tip gradually reduces towards a distal end of the respective microneedle.

[0036] In certain embodiments, the wearable sensing device comprises two or three microneedles.

[0037] In certain embodiments, the substrate comprises a metal, a non-metal, or a combination thereof. In certain embodiments, the metal comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof. In certain embodiments, the non-metal comprises one or more of carbon, plastics, liquid crystal polymers, silicon or composites, wherein optionally the composites comprise glass-filled, mineral-filled, or carbon-filled composites. In certain embodiments, carbon comprises one or more of graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre.

[0038] In certain embodiments, the wearable sensing device comprises a non-conductive passivation layer, and a conductive electrode layer.

[0039] In certain embodiments, the at least one electrode comprises a composite material, wherein the composite material comprises: a semi-permeable outer layer; and a sensing layer positioned underneath the semi-permeable outer layer that is capable of generating an electrochemical response in the presence of the analyte(s).

[0040] In certain embodiments, the wearable sensing device comprises an optional non- conductive passivation layer, and a conductive electrode layer, a sensing layer, and a semi- permeable outer layer, wherein the substrate comprises metals (e.g., titanium, tungsten, silver, gold, copper, aluminium, steel (e.g., stainless steel), iron, platinum, tantalum, Nitinol, Eligoy, or alloys thereof), carbon (e.g., graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre), plastics, liquid crystal polymers, silicon or composites (e.g., glass-filled, mineral-filled, or carbon-filled composites); the non-conductive passivation layer comprises insulating polymers (e.g., parylene (e.g., parylene-C, parylene-F or parylene-N), polyimide, polyvinylchloride, benzocylcobutene or acrylate) or metal oxides (e.g., titanium dioxide, silicon dioxide or aluminium oxide); and the conductive electrode layer comprises carbon (e.g., graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre), platinum, gold, rhodium, palladium, silver, silversilver chloride, steel (e.g. stainless steel), copper, nickel, zinc, or aluminium, tantalum or chromium; the semi-permeable outer layer comprises a first polymeric material, whereinthe first polymeric material is a co-polymer (e.g., alternating, random or block copolymer) comprising monomers A, B, C and D, wherein A, B, C and D are each independently selected from a monomer comprising a zwitterionic portion, a monomer comprising a pyridine portion, a monomer comprising a phenyl portion and a monomer comprising a hydrophilic portion; the sensing layer comprises: i) an enzyme or an ionophore; and ii) a third polymeric material, wherein the third polymeric material is a co-polymer (e.g., alternating, random or block copolymer) comprising monomers X, Y and Z, wherein X, Y and Z are each independently selected from a monomer comprising a zwitterionic portion, a monomer comprising a pyridine portion and a monomer comprising a redox mediator.

[0041] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user, optionally including an adhesive pad received on the device body; and an array of microneedles extending from the device body; wherein each of the microneedles is formed on a common flat sheet comprising a substrate and has: an insertion tip; and a microneedle body disposed between the insertion tip and the device body and comprising a first planar surface and a second planar surface opposing the first planar surface, the distance between the first planar surface and the second planar surface defining a thickness T1 of the substrate of the respective microneedle; wherein each microneedle comprises at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte, and the substrate of each microneedle has a length LI that protrudes from the device body, or the adhesive pade, if present, by 2.0 mm or less and may have a thickness T1 of 0.5 mm or less or 0.025 to 0.15 mm.

[0042] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user, optionally including an adhesive pad received on the device body; andan array of microneedles extending from the device body; wherein each of the microneedles is formed on a common flat sheet comprising a metal substrate and has: an insertion tip; and a microneedle body disposed between the insertion tip and the device body and comprising a first planar surface and a second planar surface opposing the first planar surface, the distance between the first planar surface and the second planar surface defining a thickness T1 of the metal substrate of the respective microneedle; wherein each microneedle comprises at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte, and the metal substrate of each microneedle has a length LI that protrudes from the device body, or the adhesive pad, if present, by 2.0 mm or less and may have a thickness T1 of 0.5 mm or less or 0.025 to 0.15 mm.

[0043] In certain embodiments, the length LI is between 0.4 mm and 2.0 mm, or between 0.6 mm and 1.6 mm. In certain embodiments, the length LI is about 1.0 mm, 1.2 mm, or 1.4 mm.

[0044] In certain embodiments, the thickness T1 is 0.20 mm or less.

[0045] In certain embodiments, the thickness T1 is between 0.05 mm and 0.20 mm, or between 0.075 mm and 0.100 mm.

[0046] In certain embodiments, the thickness T1 is about 0.025 mm, or about 0.05 mm, or about 0.075 mm, or about 0.10 mm.

[0047] In certain embodiments, the array has a pitch Pl defining a distance between adjacent microneedles of between 0.5 mm and 5.0 mm, or between 1.0 to 5.0 mm, and optionally about 3.0 mm or about 4.0 mm.

[0048] In certain embodiments, the substrate of each microneedle body has a width W1 that is between 0.05 mm and 0.4 mm, or between 0.1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm, and is optionally about 0.2 mm, 0.25 mm or 0.3 mm.

[0049] In certain embodiments, each microneedle comprises a shoulder disposed between the microneedle body and the device body. In certain embodiments, the substrate of each shoulder has a width W2 between 0.125 mm and 1.00 mm, or between 0.20 mm and 0.80 mm, or between 0.25 mm and 0.8 mm, and is optionally about 0.40 mm.

[0050] In certain embodiments, the substrate of each insertion tip has a length L2 that is between 0.15 mm and 0.5 mm, and is optionally about 0.3 mm.

[0051] In certain embodiments, each insertion tip tapers, to a point, in the plane in which the first planar surface extends. In certain embodiments, the insertion tip tapers symmetrically.

[0052] In certain embodiments, each insertion tip is bevelled such that a thickness of the respective insertion tip gradually reduces towards a distal end of the respective microneedle.

[0053] In certain embodiments, the metal substrate comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof. In certain embodiments, the metal substrate comprises one or more of 304, 316, 316L, or 316 LVM stainless steel.

[0054] In certain embodiments, the wearable sensing device comprises a non-conductive passivation layer, and a conductive electrode layer.

[0055] In certain embodiments, the at least one electrode comprises a composite material, wherein the composite material comprises: a semi-permeable outer layer; and a sensing layer positioned underneath the semi-permeable outer layer that is capable of generating an electrochemical response in the presence of the analyte(s).

[0056] In certain embodiments, the wearable sensing device comprises an optional non- conductive passivation layer, a conductive electrode layer, a sensing layer, and a semi- permeable outer layer, wherein the substrate comprises metals (e.g., titanium, tungsten, silver, gold, copper, aluminium, steel (e.g., stainless steel), iron, platinum, tantalum, Nitinol, Elgiloy or alloys thereof); the non-conductive passivation layer comprises insulating polymers (e.g., parylene (e.g., parylene-C, parylene-F or parylene-N), polyimide, polyvinylchloride, benzocylcobutene or acrylate) or metal oxides (e.g., titanium dioxide, silicon dioxide or aluminium oxide); and the conductive electrode layer comprises carbon (e.g., graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre), platinum, gold or rhodium, palladium, silver, silver-silver chloride, steel (e.g. stainless steel), copper, nickel, zinc, aluminium, tantalum, or chromium; the semi-permeable outer layer comprises a first polymeric material, wherein the first polymeric material is a co-polymer (e.g., alternating, random or block copolymer) comprising monomers A, B, C and D, wherein A, B, C and D are each independently selected from a monomer comprising a zwitterionic portion, a monomer comprising a pyridineportion, a monomer comprising a phenyl portion and a monomer comprising a hydrophilic portion; the sensing layer comprises: i) an enzyme or an ionophore; and ii) a third polymeric material, wherein the third polymeric material is a co-polymer (e.g., alternating, random or block copolymer) comprising monomers X, Y and Z, wherein X, Y and Z are each independently selected from a monomer comprising a zwitterionic portion, a monomer comprising a pyridine portion and a monomer comprising a redox mediator.

[0057] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; a microneedle assembly connectable to the device body comprising: a plurality of microneedles each comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; and at least one rearward facing protrusion; wherein the device body further comprises at least one pogo pin and one or more electronic components in electrical connection therewith, wherein the at least pogo pin is electrically conductive and the at least one rearward facing protrusion is engageable with (e.g. by abutment) the at least one pogo pin so as to electrically connect the microneedle assembly bracket to the one or more electronic components.

[0058] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; a microneedle assembly connectable to the device body comprising: a plurality of microneedles each comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; and at least one connection piercing element; wherein the device body further comprises at least one elastomeric terminal and one or more electronic components in electrical connection therewith, wherein the at least one elastomeric terminal is electrically conductive and the at least one connection piercing element is insertableinto the at least one elastomeric terminal so as to electrically connect the microneedle assembly bracket to the one or more electronic components.

[0059] In certain embodiments, the microneedle assembly comprises a microneedle assembly bracket from which the plurality of microneedles and the at least one connection piercing element extend. In certain embodiments, the at least one connection piercing element is parallel to each of the plurality of microneedles and extends from the microneedle assembly bracket in an opposing direction relative to each of the plurality of microneedles.

[0060] In certain embodiments, the wearable sensing device comprises one or more electrical tracks that electrically connect each of the plurality of microneedles with at least one of the at least one connection piercing elements. In certain embodiments, each of the plurality of microneedles is connected to two or more of the at least one connection piercing elements by the one or more electrical tracks.

[0061] In certain embodiments, each of the plurality of microneedles comprises a substrate underlying: an insertion tip; and a microneedle body disposed between the insertion tip and the device body; wherein the substrate underlying the microneedle body comprises a first planar surface and a second planar surface opposing the first planar surface, and wherein at least one of the first planar surface and the second planar surface comprises at least one of the at least one electrodes.

[0062] In certain embodiments, each of the first planar surface and the second planar surface comprises at least one of the at least one electrodes.

[0063] In certain embodiments, the wearable sensing device comprises a plurality of electrical tracks, wherein each of the plurality of electrical tracks electrically connects one of the at least one electrodes to one of the connection piercing elements.

[0064] In certain embodiments, each of the plurality of electrical tracks is electrically isolated from the others of the plurality of electrical tracks.

[0065] In certain embodiments, the distance between the first planar surface and the second planar surface of each microneedle defines a thickness T1 that is 0.2 mm or less.

[0066] In certain embodiments, the distance between the first planar surface and the second planar surface of each microneedle defines a thickness T1 that is between 0.025 mm and 0.15mm, or between 0.025 mm and 0.5 mm, or between 0.025 mm and 0.4 mm, or between 0.05 mm and 0.20 mm, or between 0.075 mm and 0.100 mm, and is optionally about 0.025 mm, or about 0.05 mm, or about 0.075 mm, or about 0. 10 mm.

[0067] In certain embodiments, each of the at least one connection piercing elements comprises one or more barbs for engaging with the elastomeric terminal. In certain embodiments, each of the at least one connection piercing elements comprises a pair of barbs.

[0068] In certain embodiments, wherein the one or more electronic components comprises one or more processors and / or memory devices.

[0069] In certain embodiments, the device body comprises a gasket arranged to support the at least one elastomeric terminal and / or inhibit water ingress.

[0070] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; and at least one microneedle extending from the device body; wherein the at least one microneedle comprises: an insertion tip; a microneedle body disposed between the insertion tip and the device body; and a conductive layer extending over at least a portion of the microneedle body; a silver-silver chloride layer extending over at least a portion of microneedle body; a protective layer extending over the silver-silver chloride layer, the protective layer defining an aperture through which a portion of the silver-silver chloride layer is exposed, the protective layer inhibiting diffusion of silver chloride therethrough; and a semi-permeable outer layer external to the protective layer; wherein the at least one microneedle is capable of generating an electrochemical response in the presence of at least one analyte.

[0071] In accordance with an aspect of the present invention, there is provided a wearable sensing device for detecting at least one analyte, comprising: a device body that is fixable to an application surface of a user; and at least one microneedle extending from the device body; wherein the at least one microneedle comprises:an insertion tip; a microneedle body disposed between the insertion tip and the device body; and a conductive layer extending over at least a portion of the microneedle body; a silver-silver chloride layer extending over at least a portion of microneedle body; a protective layer extending over the silver-silver chloride layer, the protective layer being porous and inhibiting diffusion of silver chloride therethrough, but permitting limited exposure of the silver-silver chloride layer through pores of the porous protective layer; and a semi-permeable outer layer external to the protective layer; wherein the at least one microneedle is capable of generating an electrochemical response in the presence of at least one analyte.

[0072] In certain embodiments, the silver-silver chloride layer comprises the conductive layer.

[0073] In certain embodiments, the conductive layer comprises the protective layer.

[0074] In certain embodiments, the silver-silver chloride layer extends over at least a portion of the conductive layer.

[0075] In certain embodiments, the protective layer comprises a dielectric layer.

[0076] In certain embodiments, the aperture extends entirely across a width of the microneedle body.

[0077] In certain embodiments, the aperture has an aperture length between 0.1 mm and 0.5 mm, the aperture length being parallel to the length of each microneedle. In certain embodiments, the aperture length is about 0.15 mm.

[0078] In certain embodiments, the portion of the silver-silver chloride layer that is exposed through the aperture has an area between 0.005 mm2and 0.15 mm2.

[0079] In certain embodiments, the aperture has a minimum dimension that is between 0.1 mm and 0.5 mm.

[0080] In certain embodiments, the ratio of silver chloride to silver in the silver-silver chloride layer is between 1 :4 and 4: 1. In certain embodiments, the ratio of silver chloride to silver in the silver-silver chloride layer is about 2:3.

[0081] In certain embodiments, an ink solid content by weight of the silver-silver chloride layer is between 60% and 90%, or between 70% and 80%.

[0082] In certain embodiments, the conductive layer comprises one or more of carbon, platinum, gold, rhodium, palladium, silver, silver-silver chloride, steel (e.g. stainless steel),copper, nickel, zinc, aluminium, tantalum, or chromium. In certain embodiments, the carbon comprises one or more of graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre.

[0083] In certain embodiments, the dielectric layer comprises an insulating polymer or a metal oxide. In certain embodiments, the insulating polymer comprises one or more of parylene, polyimide, polyvinylchloride, benzocylcobutene or acrylate. In certain embodiments, the metal oxide comprises one or more of titanium dioxide, silicon dioxide or aluminium oxide.

[0084] In certain embodiments, an ink solid content by weight of the dielectric layer is 100%.

[0085] In certain embodiments, the at least one microneedle comprises a substrate, the substrate comprising a metal or a non-metal.

[0086] In certain embodiments, the metal comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof.

[0087] In certain embodiments, the non-metal comprises one or more of carbon, plastics, liquid crystal polymers, silicon or composites, wherein optionally the composites comprise glass-filled, mineral-filled, or carbon-filled composites.

[0088] In certain embodiments, the at least one microneedle comprises an array of microneedles.

[0089] In accordance with an aspect of the present invention, there is provided an intermediate assembly for use in the manufacture of a wearable sensing device, the intermediate assembly comprising: one or more handling tabs; a plurality of microneedle sub-assemblies, each of the microneedle sub-assemblies being frangibly connected to the one or more handling tabs; wherein the one or more handling tabs are configured to facilitate manoeuvring of the plurality of microneedle sub-assemblies such that a liquid may be applied on the plurality of microneedle sub-assemblies to provide a coating on the plurality of microneedle subassemblies.

[0090] In certain embodiments, adjacent ones of the one or more handling tabs are frangibly connected to one another.

[0091] In certain embodiments, each intermediate assembly comprises a substrate, wherein the substrate comprises a metal, a non-metal, or a combination thereof.

[0092] In certain embodiments, the metal comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof.

[0093] In certain embodiments, the non-metal comprises one or more of carbon, plastics, liquid crystal polymers, silicon or composites, wherein optionally the composites comprise glass-filled, mineral-filled, or carbon-filled composites.

[0094] In certain embodiments, each microneedle sub-assembly comprises at least one microneedle having at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte.

[0095] In certain embodiments, each microneedle sub-assembly comprises at least one microneedle having at least one of a passivation layer, dielectric layer, a conductive layer and / or a sensing layer.

[0096] In accordance with an aspect of the present invention, there is provided a method of manufacturing a wearable sensing device comprising: providing a first intermediate assembly and a second intermediate assembly, each of the first intermediate assembly and second intermediate assembly comprising: one or more handling tabs; and a plurality of microneedle sub-assemblies, wherein each of the microneedle subassemblies is frangibly connected to the one or more handling tabs; the method further comprising: manoeuvring the first intermediate assembly using the respective one or more handling tabs to apply a first liquid to the respective plurality of microneedle sub-assemblies to provide a first coating on the plurality of microneedle sub-assemblies; manoeuvring the second intermediate assembly using the respective one or more handling tabs to apply a second liquid to the respective plurality of microneedle sub-assemblies to provide a second coating on the plurality of microneedle sub-assemblies; on the first intermediate assembly separating the plurality of microneedle subassemblies from the one or more handling tabs by breaking the frangible connection therebetween;on the second intermediate assembly separating the plurality of microneedle subassemblies from the one or more handling tabs by breaking the frangible connection therebetween; and assembling in a wearable sensing device at least one of the separated plurality of microneedle sub-assemblies of the first intermediate assembly and at least one of the separated plurality of microneedle sub-assemblies of the second intermediate assembly.

[0097] In certain embodiments, the first liquid and / or the second liquid comprises a polymer.

[0098] In certain embodiments, the first liquid is different to the second liquid.

[0099] In certain embodiments, the first coating is different to the second coating.

[0100] In certain embodiments, the first coating and / or second coating comprises a semi- permeable membrane.

[0101] In certain embodiments, the first coating is an outermost layer of the plurality of microneedle sub-assemblies of the first intermediate assembly and / or the second coating is an outermost layer of the plurality of microneedle sub-assemblies of the second intermediate assembly.

[0102] In certain embodiments, each of the first intermediate assembly and the second intermediate assembly comprises a substrate, wherein the substrate comprises a metal, a non- metal, or a combination thereof.

[0103] In certain embodiments, the metal comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof.

[0104] In certain embodiments, the non-metal comprises one or more of carbon, plastics, liquid crystal polymers, silicon or composites, wherein optionally the composites comprise glass-filled, mineral-filled, or carbon-filled composites.

[0105] In certain embodiments, each of the plurality of microneedle sub-assemblies comprises at least one microneedle having at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte.

[0106] In certain embodiments, each of the plurality of microneedle sub-assemblies comprises at least one microneedle having at least one of a passivation layer, dielectric layer, a conductive layer and / or a sensing layer.

[0107] In accordance with an aspect of the present invention, there is provided a method of manufacturing a wearable sensing device comprising: providing an intermediate assembly comprising: a plurality of handling tabs frangibly connected to one another; and a plurality of microneedle sub-assemblies each connected to one of the plurality of handling tabs; the method further comprising: separating the plurality of handling tabs from one another by breaking the frangible connection therebetween; manoeuvring each of the plurality of microneedle sub-assemblies using the respective handling tab to apply a coating on the respective microneedle sub-assembly; assembling in a wearable sensing device at least one of the coated microneedle subassemblies.

[0108] In certain embodiments, each of the microneedle sub-assemblies is frangibly connected to one of the plurality of handling tabs, the method comprising separating at least one coated microneedle sub-assembly from the respective handling tab prior to assembling the coated microneedle sub-assembly in the wearable sensing device.

[0109] In certain embodiments, the coating comprises a semi-permeable membrane.

[0110] In certain embodiments, wherein the coating is an outermost layer of the plurality of microneedle sub-assemblies.

[0111] In certain embodiments, the intermediate assembly comprises a substrate, wherein the substrate comprises a metal, a non-metal, or a combination thereof.

[0112] In certain embodiments, the metal comprises one or more of titanium, tungsten, silver, gold, copper, aluminium, steel, stainless steel, iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof.

[0113] In certain embodiments, the non-metal comprises one or more of carbon, plastics, liquid crystal polymers, silicon or composites, wherein optionally the composites comprise glass-filled, mineral-filled, or carbon-filled composites.

[0114] In certain embodiments, each of the plurality of microneedle sub-assemblies comprises at least one microneedle having at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte.

[0115] In certain embodiments, each of the plurality of microneedle sub-assemblies comprises at least one microneedle having at least one of a passivation layer, dielectric layer, a conductive layer and / or a sensing layer.

[0116] In any aspect of the present invention, the microneedle may comprise a substrate, a non-conductive passivation layer and a conductive electrode layer, wherein the substrate comprises stainless steel, and optionally the conductive electrode layer comprises carbon ink; the semi-permeable outer layer comprises a first polymeric material, wherein the first polymeric material is a random co-polymer comprising the following monomers:a is 0 to 25 mol%; b is 50 to 90 mol%; c is 0.1 to 10 mol%; and d is 0 to 25 mol%, wherein the sum total of a, b, c and d is 100 mol; the sensing layer comprises: i) an enzyme; and ii) a third polymeric material, whereinthe enzyme is selected from the group consisting of glucose oxidase, lactate oxidase, glucose dehydrogenase, diamine oxidase, P-hydroxybutyrate dehydrogenase and alcohol oxidase; the third polymeric material is a random co-polymer comprising the following monomers:wherein: x1 is 5 to 25 mol%; y1 is 70 to 95 mol%; and z1 is 0 to 25 mol%, wherein the sum total of x1 , y1 and z1 is 100 mol%; wherein the microneedle electrode is substantially flat; and wherein the thickness of the microneedle electrode is 0.05 mm to 0.2 mm.BRIEF DESCRIPTION OF THE DRAWINGS

[0117] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which:

[0118] FIG. 1 shows a perspective view of a wearable sensing device in accordance with an embodiment of the present invention;

[0119] FIG. 2 shows an alternative perspective view of the wearable sensing device of FIG. 1;

[0120] FIG. 3 shows a top down view of the wearable sensing device of FIG. 1 ;

[0121] FIG. 4 shows an alternative perspective view of the wearable sensing device of FIG. 1;

[0122] FIG. 5 shows a side view of the wearable sensing device along direction A indicated on FIG. 3;

[0123] FIG. 6 shows an end view of the wearable sensing device along direction B indicated on FIG. 3;

[0124] FIG. 7 shows a microneedle assembly in accordance with an embodiment of the present invention;

[0125] FIG. 8 shows a side view of the microneedle assembly of FIG. 7;

[0126] FIG. 9 shows a microneedle assembly in accordance with another embodiment of the present invention;

[0127] FIG. 10 is an OCT image showing a cross section through a blunt, polymer microneedle during insertion in an application surface;

[0128] FIG. 11 is an OCT image showing a cross section through an array of microneedles with a pitch of 3 mm when inserted in an application surface for a dense array (top image) and a sparse array (bottom image);

[0129] FIG. 12 shows preliminary results showing insertion success with measured microneedle thickness;

[0130] FIG. 13 shows a microneedle comprising a working electrode in accordance with an embodiment of the present invention;

[0131] FIG. 14 shows a microneedle comprising a working electrode in accordance with another embodiment of the present invention;

[0132] FIG. 15 shows a cross-sectional view of a microneedle comprising a working electrode in accordance with an embodiment of the present invention;

[0133] FIG. 16 shows a microneedle comprising a counter electrode in accordance with an embodiment of the present invention;

[0134] FIG. 17 shows a cross-sectional view of a microneedle containing a counter electrode in accordance with an embodiment of the present invention;

[0135] FIG. 18 shows a microneedle comprising a reference electrode in accordance with an embodiment of the present invention;

[0136] FIG. 19 shows a cross-sectional view of a microneedle containing a reference electrode in accordance with an embodiment of the present invention;

[0137] FIG. 20 shows calibration curves for five working electrodes according to embodiments of the present invention;

[0138] FIG. 21 shows a graph demonstrating the effects of covering a portion of the silversilver chloride layer of a reference electrode in accordance with an embodiment of the present invention;

[0139] FIG. 22 shows further graphs demonstrating the effects of covering a portion of the silver-silver chloride layer of a reference electrode in accordance with an embodiment of the present invention;

[0140] FIG. 23 shows a cross-sectional view of a wearable sensing device in accordance with an embodiment of the present invention;

[0141] FIG. 24 shows the first body part of the wearable sensing device and the gasket to be inserted therein;

[0142] FIG. 25 shows a detailed cross-sectional view of a part of a wearable sensing device in accordance with an embodiment of the present invention;

[0143] FIG. 26 shows part of the cross-sectional view of FIG. 25;

[0144] FIG. 27 shows part of the cross-sectional view of FIG. 25;

[0145] FIG. 28 shows an intermediate assembly in accordance with an embodiment of the present invention;

[0146] FIG. 29 shows an intermediate assembly in accordance with another embodiment of the present invention;

[0147] FIG. 30 shows a method of manufacturing a wearable sensing device in accordance with an embodiment of the present invention;

[0148] FIG. 31 shows a method of manufacturing a wearable sensing device in accordance with another embodiment of the present invention;

[0149] FIG. 32 shows a wearable sensing device in accordance with another embodiment of the present invention; and

[0150] FIG. 33 shows a wearable sensing device in accordance with another embodiment of the present invention. 1DETAILED DESCRIPTION

[0151] FIGs. 1 to 6 show a wearable sensing device 100 in accordance with an embodiment of the present invention. The wearable sensing device 100 comprises a device body 102 that is fixable to an application surface of a user (i.e. skin) and an array of microneedles 108 (not visible in FIG. 1) that extend from the device body 102. FIG. 1 shows the a first perspective view of the wearable sensing device 100, FIG. 2 shows a second perspective view of the wearable sensing device 100, FIG. 3 shows a top-down view of the wearable sensing device 100, and FIG. 5 and FIG. 6 show side views of the 100 along directions A and B, respectively, shown in FIG. 3. Each of the array of microneedles 108 extends in a direction that is parallel to a longitudinal axis 124 of the wearable sensing device 100. One or more of the array of microneedles 108 may comprise one or more electrodes that are capable of generating an electrochemical response in the presence of at least one analyte.

[0152] As is described further below, the wearable sensing device 100 may be worn by a user such that the array of microneedles 108 penetrate the application surface of the user and extend into the interstitial fluid and detect at least one analyte. The wearable sensing device 100 may therefore provide the user with information (e.g. the concentration or another parameter) relating to an analyte of interest. Example analytes of interest include but are not limited to glucose, ketones and lactate.

[0153] The term analyte is known in the art as an analysable substance or chemical constituent in a biological fluid, such as blood, interstitial fluid, cerebral spinal fluid, lymph fluid, urine, sweat and saliva. Suitably, the analyte is present in blood, interstitial fluid, cerebral spinal fluid, lymph fluid, urine, sweat and / or saliva. More suitably, the analyte is present in interstitial fluid. The interstitial fluid may be in the dermis of the skin. The dermis of the skin is the layer of skin which lies beneath the epidermis and above the subcutaneous tissue layer. The analyte may alternatively be present in other layers of the skin, such as the stratum corneum, the epidermis and the subcutaneous tissue of the skin.

[0154] Interstitial fluid is the body fluid found in the spaces around cells and blood vessels and typically comprises, inter alia, a number of substances such as sugars, salts, fatty acids, amino acids and hormones. Therefore, the analyte may be a sugar, a salt, a fatty acid, an amino acid or a hormone. Suitably, the analyte is a sugar. More suitably, the analyte is selected from the groupconsisting of glucose, ketones (e.g., 0-hydroxybutyrate), histamine, alcohols, cholesterol, vitamins, iodine, potassium, sodium, magnesium, calcium, zinc, copper, iron, chloride, phosphate, ammonium, lithium, bicarbonate, thrombin, therapeutic drugs (e.g. aminoglycosides, doxorubicin, tetracyclines), hormones (e.g., testosterone, cortisol, oestrogen, serotonin and progesterone), pH (e.g., hydrogen ion), interleukin-6 (IL-6), creatinine, acarboxyprothrombin, acylcarnitine, adenine phosphoribosyl transferase, adenosine deaminase, albumin, a-fetoprotein, amino acid profiles (e.g., arginine, histidine / urocanic acid, homocysteine, phenylalanine / tyrosine, tryptophan), andrenostenedione, antipyrine, arabinitol enantiomers, arginase, benzoylecgonine (cocaine), biotinidase, biopterin, c-reactive protein, carnitine, carnosinase, CD4, ceruloplasmin, chenodeoxycholic acid, chloroquine, cholinesterase, conjugated 1-P hydroxy-cholic acid, cyclosporin A, d-penicillamine, de-ethylchloroquine, dehydroepiandrosterone sulphate, DNA (e.g., acetylator polymorphism, alcohol dehydrogenase, alpha 1 -antitrypsin, cystic fibrosis, Duchenne / Becker muscular dystrophy, haemoglobin A, haemoglobin S, haemoglobin C, haemoglobin D, haemoglobin E, haemoglobin F, D-Punjab, 0- thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexual differentiation, 21-deoxycortisol), desbutylhalofantrine, dihydropteridine reductase, diptheria / tetanus antitoxin, erythrocyte arginase, erythrocyte protoporphyrin, esterase D, fatty acids / acylglycines, free 0-human chorionic gonadotropin, free erythrocyte porphyrin, free thyroxine (FT4), free triiodothyronine (FT3), fumarylacetoacetase, galactose / gal-1 -phosphate, galactose- 1 -phosphate uridyltransferase, gentamicin, glucose-6-phosphate dehydrogenase, glycocholic acid, glycosylated haemoglobin, halofantrine, haemoglobin variants, hexosaminidase A, human erythrocyte carbonic anhydrase I, 17-a-hydroxyprogesterone, hypoxanthine phosphoribosyl transferase, immunoreactive trypsin, lactate, lead, lipoproteins ((a), B / A-l, 0), lysozyme, mefloquine, netilmicin, phenobarbitone, phenyloin, phytanic / pristanic acid, progesterone, prolactin, prolidase, purine nucleoside phosphorylase, quinine, reverse tri-iodothyronine (rT3), selenium, serum pancreatic lipase, sissomicin, somatomedin C, specific antibodies (e.g., adenovirus, anti-nuclear antibody, anti-zeta antibody), arbovirus, Aujeszky's disease virus, dengue virus, Dracunculus medinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus, Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpes virus, HIV-1, IgE (atopic disease), influenza virus, Leishmania donovani, leptospira, measles / mumps / rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenza virus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa, respiratory syncytial virus, rickettsia (scrub typhus), Schistosomamansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosoma cruzi / rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellow fever virus, specific antigens (e.g., hepatitis B virus, HIV-1), succinylacetone, sulfadoxine, theophylline, thyrotropin (TSH), thyroxine (T4), thyroxine-binding globulin, trace elements, transferrin, UDP-galactose-4-epimerase, urea, uroporphyrinogen I synthase, vitamin A, white blood cells, zinc protoporphyrin, salts, sugar, protein, fat, a metabolic product, a hormone, an antigen, an antibody, a radioisotope, a chemical agent, a fluorocarbon-based synthetic blood, or a drug or pharmaceutical composition, including: insulin; ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (e.g., nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (e.g., amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (e.g., barbituates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (e.g., phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (e.g., heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (e.g., analogs of fentanyl, meperidine, amphetamines, methamphetamines, and phencyclidine, for example, Ecstasy); anabolic steroids; and nicotine, and metabolic products of drugs and pharmaceutical compositions such as neurochemicals and other chemicals generated within the body such as, for example, noradrenaline, 3-methoxytyramine (3MT), 3,4- dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and 5- hydroxyindoleacetic acid (FHIAA). Even more suitably, the analyte is selected from the group consisting of glucose, ketones (e.g., P-hydroxybutyrate), lactate, histamine, urea, creatinine, alcohols, vitamins, hormones (e.g., testosterone, cortisol, serotonin, oestrogen and progesterone), pH (e.g., hydrogen ion), iodine, potassium, sodium, magnesium, calcium, zinc, copper, iron, chloride, phosphate, ammonium, lithium, bicarbonate, thrombin, IL-6 and therapeutic drugs (e.g. aminoglycosides, doxorubicin, tetracyclines). Yet even more suitably, the analyte is selected from the group consisting of glucose, ketones (e.g., P-hydroxybutyrate), lactate, histamine, urea, alcohols, cholesterol, vitamins, iodine, potassium, sodium, hormones (e.g., testosterone, cortisol, oestrogen and progesterone) and IL-6. Yet even more suitably, the analyte is selected from the group consisting of glucose, ketones and lactate. In some embodiments, the analyte is lactate. In other embodiments, the analyte is glucose.

[0155] The device body 102 of the wearable sensing device 100 comprises a first body part 104 that is fixable to the user and a second body part 106 that may be removably couplable tothe first body part 104. The first body part 104 comprises an upstanding wall 110 that defines a space into which the second body part 106 may be received. In certain embodiments (as exemplified below), the second body part 106 comprises a housing that houses one or more electronic components.

[0156] As shown in at least FIG. 1 and FIG. 2, the wearable sensing device 100 comprises an adhesive pad 122 for facilitating fixing of the device body 102 on the application surface. In the non-limiting embodiment shown in the Figures, the adhesive pad 122 extends beyond edges of the upstanding wall 110. The adhesive pad 122 may be removable and replaceable. In alternative embodiments, the wearable sensing device 100 may be fixable to the application surface by alternative means other than the adhesive pad 122. For example, an adhesive may be applied directly onto the device body 102.

[0157] In the non-limiting embodiment shown in the Figures, the array of microneedles 108 are arranged along a single axis. In other embodiments, the array of microneedles 108 may be otherwise arranged. Furthermore, in the non-limiting embodiment shown in the Figures, the array of microneedles 108 comprises three microneedles 108. In other embodiments, the array of microneedles 108 may comprise other numbers of microneedles 108.

[0158] FIG. 4 shows the wearable sensing device 100 without the adhesive pad 122 present. FIG. 5 shows that the first body part 104 comprises a first surface 112 that extends in a first plane and a second surface 114 that extends in a second plane. The first plane is offset from the second plane along the longitudinal axis 124 such that the first plane is not co-planar with the second plane. A tapered surface 116 extends between the first surface 112 and the second surface 114 and provides a transition therebetween. That is, the tapered surface 116 extends away from the first surface 112 such that the tapered surface 116 and the second surface 114 form a protrusion relative to the first surface 112. The second surface 114 comprises a plurality of needle apertures 118 through which the array of microneedles 108 extend.

[0159] In certain embodiments, the second surface 114 may not extend in the second plane. Instead, the second surface 114 may be non-planar such that the second surface 114 and the tapered surface 116 may be extensions of one another. In such embodiments, the plurality of needle apertures 118 through which the array of microneedles 108 extend may be disposed at the apex of the second surface 114. In this context, the apex of the 114 is the point or region of the second surface 114 that is maximally offset relative to the first surface 112 along the longitudinal axis 124.

[0160] In certain embodiments, the adhesive pad 122 may be affixed to the first surface 112 and optionally to at least part of the tapered surface 116 and further optionally to at least part of the second surface 114. The adhesive pad 122 may therefore be configured to conform to the first surface 112 (and optionally to the tapered surface 116 and the second surface 114). The adhesive pad 122 may have a removable cover layer that may be removed in order to expose an adhesive that may be used to affix the wearable sensing device 100 to the application surface.

[0161] In the non-limiting embodiment shown in FIG. 4, the first surface 112 is provided with a plurality of channels 126 which are recessed in the first surface 112. In use, the channels 126 may facilitate the escape of any moisture that builds up at the interface between the wearable sensing device 100 and the application surface. Consequently, the presence of the channels 126 mitigates issues associated with the build up of moisture, including but not limited to maceration of the skin, bacteria growth, and weakening of the adhesive bond due to prolonged water contact. In the non-limiting embodiment shown in FIG. 4 the channels 126 additionally extend across the tapered surface 116. However, in other embodiments, the channels 126 may exclusively extend across the first surface 112 (if they are present at all).

[0162] In certain embodiments the channels 126 may have a width (i.e. in a direction perpendicular to the longitudinal axis 124) of between 0.25 mm and 1.5 mm, or between 0.5 mm and 1.0 mm. In certain embodiments, the channels 126 may have a width of about 0.8 mm. In certain embodiments, the channels 126 may have a depth (i.e. in a direction parallel to the longitudinal axis 124) of between 0.05 mm and 0.75 mm, and between 0.1 mm and 0.5 mm. In certain embodiments, the channels 126 may have a depth of about 0.3 mm. In such embodiments, the channels 126 provide sufficient cross-sectional area for water vapour to passively diffuse away from the centre of the wearable sensing device 100 into ambient air, whilst avoiding unnecessarily using up useful space in the wearable sensing device 100 and reducing surface area for the adhesive, respectively.

[0163] The upstanding wall 110 comprises a first break line 400 and the channels 126 form a second break line 402 of the first body part 104. After use of the wearable sensing device 100, when the wearable sensing device 100 has been removed from the application surface, the first body part 104 may be broken along the first break line 400 and the second break line 402 so that the second body part 106 may be retrieved from the first body part 104 and optionally used in a replacement first body part 104 for subsequent use.

[0164] In the embodiment shown in FIG. 4, the plurality of channels 126 form hexagons (except for the channels 126 that define the second break line 402). Hexagons are advantageous in that they present no straight line of weakness across the first body part 104. Consequently, the first body part 104 is preferentially broken along the second break line 402 when a bending force is applied thereto.

[0165] FIG. 3 shows a top-down view of the wearable sensing device 100.

[0166] FIG. 5 shows a side view of the wearable sensing device 100 along direction A indicated on FIG. 3.

[0167] Similarly, FIG. 6 shows an end view of the wearable sensing device 100 along direction B indicated on FIG. 3. In each of FIG. 5 and FIG. 6, an offset distance 120 is indicated where the offset distance 120 is the magnitude of the offset between the first surface 112 and the second surface 114 along the longitudinal axis 124.

[0168] FIG. 7 shows a microneedle assembly 700 that may include the array of microneedles 108 in accordance with certain embodiments of the present invention. In other embodiments, the array of microneedles 108 may be otherwise provided. The microneedle assembly 700 shown in FIG. 7 and FIG. 8 comprises a substrate onto which various layers and / or coatings may be applied. Consequently, the dimensions discussed herein in respect of FIG. 7 and FIG. 8 relate to the dimensions of the substrate in the absence of such layers and / or coatings.

[0169]

[0170] The microneedle assembly 700 comprises a microneedle assembly bracket 702 from which the array of microneedles 108 extend. The microneedle assembly 700 also comprises connection piercing elements 704 that extend form the microneedle assembly bracket 702. In the non-limiting embodiment shown in FIG. 7, the connection piercing elements 704 are parallel to the microneedles 108 but the connection piercing elements 704 extend from the microneedle assembly bracket 702 in an opposing direction relative to the microneedles 108.

[0171] As described above, one or more of the microneedles 108 may comprise one or more electrodes that are each capable of generating an electrochemical response in the presence of at least one analyte. The connection piercing elements 704 may facilitate electrical connection of the array of microneedles 108 to one or more electrical components in the device body 102. In particular, each of the arrays of microneedles 108 may be electrically connected to at least one of the connection piercing elements 704 via electrical tracks that traverse at least part of the microneedle assembly bracket 702.

[0172] In the non-limiting embodiment shown in FIG. 7, the connection piercing elements 704 are configured to pierce an elastomeric (e.g. polymer) terminal of the device body 102 in order to establish a mechanical and an electrical connection thereto. As described further below, the elastomeric terminal is electrically conductive such that onward electrical connections may electrically connect the elastomeric terminal to one or more electronic components in the device body 102.

[0173] In the non-limiting embodiment shown in FIG. 7, each of the connection piercing elements 704 comprises a pair of barbs 706 that may improve the robustness of the mechanical engagement of the connection piercing element 704 with the elastomeric terminal and reduce the risk of inadvertent disengagement therebetween. In particular, the barbs 706 may facilitate satisfactory engagement without the need for adhesives. In alternative embodiments, one or more barbs 706 may be provided. In other embodiments, no barbs may be present.

[0174] The substrate of the microneedle assembly 700 is a substantially flat sheet as is evident from the side view of the microneedle assembly 700 shown in FIG. 8. Consequently, the substrate underlying each microneedle 108 has a first planar surface 714 and a second planar surface 716 opposing the first planar surface 714. The distance between the first planar surface 714 and the second planar surface 716 defines a thickness Tl. Since the array of microneedles 108 are formed on a common flat sheet, the substrate underlying each microneedle 108 of the microneedle assembly 700 has an identical thickness. In certain embodiments, Tl is 0.025 to 0.15 mm. In certain embodiments, Tl is 0.5 mm or less, 0.2 mm or less, ranges from 0.025 mm to 0.5 mm, ranges from 0.025 mm to 0.4 mm, ranges from 0.05 mm to 0.20 mm, or ranges from 0.075 mm and 0.100 mm. In certain preferable embodiments, Tl may be about 0.025 mm, 0.05 mm, 0.075 mm or 0.10 mm. Microneedles 108 having underlying substrates with such thicknesses are advantageous with regard to their function. In particular, thicknesses in these ranges reduce the cross-sectional area of skin that must be displaced or fractured in order for the needle to be inserted. Consequently, the work done required for insertion, and hence the overall resistive force on the microneedle 108, is reduced.

[0175] As a given microneedle 108 slides into the skin, the displaced skin resists the insertion by friction. This resistance is proportional to the amount by which the skin is elastically deformed. A thin microneedle 108 having a thickness in the ranges noted above reduces tissue trauma, the deformation of the skin, and hence reduces the overall (frictional) resistive force onthe microneedle 108. Reducing tissue trauma reduces inflammation, and less inflammation leads to greater signal accuracy when detecting the presence of analytes.

[0176] Moreover, reducing both the cross-sectional area and volume of matter that is inserted into the skin is understood to reduce the level of trauma experienced by the epidermis and dermis. This is a result of both minimising the amount and extent of displaced tissue, and also minimising the probability of a microneedle 108 interacting with nerve cells and superficial capillaries.

[0177] It is understood that the human or animal body generally responds negatively to the insertion of foreign objects. One parameter known to aggravate this response is stiffness. This is in part mitigated by the addition of a polymer outer layer that interfaces with the skin (which is described below). In addition to this, thinner microneedles 108 each having a thickness in the ranges described above results in a more flexible and compliant biosensor, which is understood to contribute to reducing the biological response towards the presence of the microneedles 108.

[0178] Additionally, microneedles 108 having underlying substrates with a thickness in the ranges described above are more favourable for accurate feature formation. For example, certain manufacturing processes (which may be used in the formation of functional microneedles 108) generally favour thinner substrates with regard to geometry accuracy. Such manufacturing processes include but are not limited to stamping, laser cutting, photochemical etching, and laser etching. In this case, the microneedle 108 tip sharpness is a key parameter that is preferably maintained, and this is better achieved with a thinner substrate.

[0179] Notwithstanding the above-described benefits of utilising thin microneedles 108, there are certain negative consequences associated with very thin microneedles 108. For example, microneedles 108 that are too thin will suffer bending and buckling during insertion into the application surface. Moreover, very thin microneedles 108 may be prone to snapping or breaking whilst inserted during wear. The thickness of the substrate of the microneedle assembly 700 also impacts the throughput, yield and ease of manufacturing (particularly as handling becomes difficult and requires specialist equipment at particularly low thicknesses).

[0180] The flat microneedles 108 described above having substrates with opposing first planar surfaces 714 and second planar surface 716 present an opportunity for each surface to host an electrode that is independent of the other. In order for this to be possible, there must be no electrical bridging between the first planar surface 714 and the second planar surface 716.When printing or otherwise applying conductive substances onto the first planar surface 714and second planar surface 716 in order to form electrically active features, the risk of bleeding over the edges of either the first planar surface 714 and the second planar surface 716 and electrically bridging the two surfaces increases with reduced thickness.

[0181] Considering such limitations of very thin microneedles 108, thicknesses in the abovedescribed ranges are found to provide optimal performance whilst accommodating negative consequences at an acceptable level.

[0182] In certain preferable embodiments, the substrate of the microneedle assembly 700 may comprise a metal. In certain embodiments, the metal may comprise a metal alloy. Suitable metals include but are not limited to 300 series stainless steel (e.g. 304, 316, 316L, 316 LVM). The temper may be at least half-hard. In certain embodiments the temper may be full hard. In certain embodiments, the metal may comprise a 400 stainless steel. In other embodiments, the metal may comprise titanium (e.g. grade 5 or grade 23). In certain embodiments, the substrate may comprise (or is formed from) metals (e.g., titanium, tungsten, silver, gold, copper, aluminium, steel (e.g., stainless steel), iron, platinum, tantalum, Nitinol, Elgiloy, or alloys thereof), carbon (e.g., graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre), plastics, liquid crystal polymers, silicon or composites (e.g. glass-filled, mineral-filled, or carbon-filled composites).

[0183] In certain embodiments, a passivation layer (discussed further below) may be provided between the substrate and other layers of each microneedle 108. The passivation layer may be non-conductive (e.g. a dielectric). In particular, the non-conductive passivation layer may provide electrical isolation between the substrate (which may itself be conductive) and the other layers provided thereon. In certain embodiments, the passivation layer may or may not be conformal around the substrate. In certain embodiments, the substrate may be entirely encapsulated by the passivation layer. In certain embodiments, the non-conductive passivation layer comprises insulating polymers (e.g., parylene (e.g., parylene-C, parylene-F or parylene- N), polyimide, polyvinylchloride, benzocylcobutene or acrylate) or metal oxides (e.g., titanium dioxide, silicon dioxide or aluminium oxide)

[0184] As described further below, each of the first planar surface 714 and the second planar surface 716 of each microneedle 108 may comprise an electrode. In the non-limiting embodiment shown in FIG. 8, the ratio of connection piercing elements 704 to microneedles 108 is 2: 1 (i.e. there are six connection piercing elements 704 and three microneedles 108). As such, each of the connection piercing elements 704 may facilitate the electrical connection ofone electrode from one of the first planar surface 714 and the second planar surface 716 of a respective microneedle 108.

[0185] In the embodiment shown in FIG. 7, the pitch Pl of the spaced microneedles 108 may range from 0.5 mm to 8.0 mm, or range from 0.5 mm to 5.0 mm, or range from 1.0 mm to 5.0 mm. In certain preferable embodiments, Pl may be about 3.0 mm or 4 mm.

[0186] Each microneedle 108 comprises a microneedle body 712 and an insertion tip 710 at a distal end thereof. When assembled in the wearable sensing device 100, an exposed portion of each microneedle 108 protrudes from device body 102. That is, the exposed portion of each microneedle 108 is the portion that is insertable into a user. The part of the substrate underlying this exposed portion has a length LI. In embodiments that include an adhesive pad 122 received on the first surface 112, the length LI is defined as the length of the substrate underlying the potion of each microneedle 108 that protrudes from the adhesive pad 122. That is, in any embodiment, the length LI is the length of the substrate that underlies the exposed portion of each microneedle 108 in the assembled wearable sensing device 100. In certain embodiments, LI may be 1.6 mm or less. In certain embodiments, LI may range from 0.4 mm to 2.0 mm, or range from 0.6 mm to 1.6 mm. In certain preferable embodiments, LI may be about 1.0 mm, 1.2 mm, or 1.4 mm. Each microneedle body 712 has a width W1 that, in certain embodiments, ranges from 0.05 mm to 0.4 mm, ranges from 0.1 mm to 0.4 mm, or ranges from 0.1 mm to 0.3 mm. In certain preferable embodiments, W1 may be about 0.2 mm, or 0.25 mm, or 0.3 mm.

[0187] In certain embodiments, each microneedle body comprises side walls extending between and perpendicularly relative to the first planar surface 714 and the second planar surface 716. In certain embodiments, edges of the first planar surface 714 are parallel relative to one another. In other embodiments, alternative arrangements may be provided.

[0188] Many of the factors described above in relation to the thickness of the microneedles 108 equally apply to their width.

[0189] Disposed between the microneedle body 712 of each microneedle 108 and the microneedle assembly bracket 702 is a shoulder 708 having width W2, where W2 > Wl. In certain embodiments, W2 ranges from 0.125 mm to 1.00 mm, from 0.20 mm to 0.80 mm, or from 0.25 mm to 0.8 mm. In certain preferable embodiments, W2 may be about 0.40 mm. The presence of the shoulder 708 (which resides on a part of each microneedle 108 that is notinserted into the application surface) reduces the risk of the respective microneedle 108 bending and buckling (e.g. during insertion).

[0190] The insertion tip 710 of each microneedle 108 extends from the respective 712 along a length L2. In certain embodiments, L2 ranges from 0.15 mm to 0.5 mm. In certain preferable embodiments, L2 may be about 0.3 mm.

[0191] As evident from the view of the non-limiting embodiment shown in FIG. 7, the insertion tip 710 of each microneedle 108 tapers, to a point, in the plane in which the first planar surface 714 extends. In certain embodiments, the insertion tip 710 of each microneedle 108 tapers symmetrically. Additionally, as evident from the side view shown in FIG. 8, the insertion tip 710 of each microneedle 108 includes a bevel across its thickness such that the thickness of the respective insertion tip 710 gradually reduces towards the distal end of the respective microneedle 108 along a bevel length. In certain embodiments, the bevel length may be approximately 0.01 mm to 0.40 mm, or from 0.02 mm to 0.20 mm, or from 0.15 mm to 0.20 mm and extend to the extreme distal tip of the microneedle 108. In some embodiments, the bevel length may be negligible.

[0192] In other embodiments, the insertion tip 710 may take other forms and / or have different dimensions.

[0193] The form of the insertion tip 710 of each microneedle 108 facilitates improved insertion of the respective microneedle 108 in the application surface.

[0194] FIG. 9 shows a microneedle assembly 700 according to an alternative embodiment. The microneedle assembly 700 of FIG. 9 is substantially identical to the microneedle assembly 700 of FIG. 7 save for the microneedle assembly 700 of FIG. 9 not having any barbs 706 or shoulders 708 and the pitch Pl differing between the two depicted embodiments.

[0195] The pitch P of the array of microneedles 108 is vital for achieving good insertion in the application surface. In general, a larger pitch is advantageous as it prevents a so-called “bed of nails” effect, whereby the force from multiple microneedles 108 is distributed on a local region of the application surface. Separating the needles reduces the interaction between microneedles 108 such that at the point of insertion, the local deformation of the application surface from one microneedle 108 does not propagate to neighbouring microneedles 108.

[0196] FIG. 10 is an optical coherence tomography (OCT) image of a blunt, polymer microneedle inserted in a polymer application surface to demonstrate an undesirable insertion. Blunt, non-penetrating microneedles increase “tenting” of the application surface, andpropagates deformation of the application surface towards neighbouring microneedles. FIG. 10 shows this tenting effect propagating laterally by approximately 1.50 mm. It follows that a pitch of 3.00 mm (in accordance with an embodiment of the present invention) will allow each microneedle to effectively be unaffected by adjacent microneedles. That is not to say that pitches smaller than 3.00 mm are precluded. Indeed, with other design considerations, pitches smaller than 3.00 mm may also avoid the “bed of nails” effect arising. However, a pitch of 3.00 mm provides a configuration that provides satisfactory (and safe) results notwithstanding several other design considerations.

[0197] FIG. 11 shows an OCT image of an array of microneedles 108 in accordance with an embodiment of the present invention during insertion into an application surface. The top left image of FIG. 11 shows a cross-sectional view of the inserted array of microneedles 108 where the array of microneedles 108 has a pitch along a given direction of 3 mm. The top right image of FIG. 11 shows the corresponding 2D distribution of the microneedles 108 where it can be seen that the array is dense with adjacent needles along other directions being spaced less than 3 mm.

[0198] The bottom left image of FIG. 11 shows a cross-sectional view of the inserted array of microneedles 108 where the array of microneedles 108 has a pitch along all directions of 3 mm. The bottom right image of FIG. 11 shows the corresponding 2D distribution of the microneedles 108 where it can be seen that the array is more sparse than the array of the top images.

[0199] FIG. 11 shows that an array of microneedles 108 with a pitch of 3 mm produces less of an air gap between the application surface and the underside of the wearable sensing device 100 (e.g. the second surface 114) when a sparser distribution of microneedles is provided. This is indicative of improved insertion performance.

[0200] Nevertheless, microneedles 108 formed in accordance with the embodiments described above permit denser arrangements without suffering the above-described disadvantages. In particular, the significantly thinner and sharper microneedle 108 geometry described above (compared with the geometries subject to the test of FIG. 11) reduces the degree of tenting on the application surface. Additionally, high speed penetration occurs before application surface deformation becomes significant. In certain non-limiting embodiments, penetration speed may be between 1 m / s and 15 m / s.

[0201] In general, a sharper insertion tip 710 will enable insertion with lower force. A ‘blade’ geometry can be superior to a ‘point’ geometry as it encourages the cutting of the skin over stretching of the skin, which would introduce resistive forces due to skin’s elasticity. In addition, vertical (i.e. straight and parallel) sides of the microneedle 108 (as opposed to triangular, pyramidal or conical sides) are beneficial as they reduce frictional force introduced by tissue pressure pushing the sides. The flat microneedle 108 geometries described above are found to demonstrate superior insertion performance, as well as improved manufacturability and easy, uniform deposition of substances on its surface (since they enable stamping, laser cutting, laser etching and photochemical etching from a flat sheet, and direct screen printing, spraying, droplet dispensing, or spin coating of layers (e.g. conductive layers) thereon).

[0202] Microneedles 108 in accordance with embodiments of the present invention allow a high percentage of successful insertions. It is found that thinner microneedles and faster velocities result in more complete insertion.

[0203] FIG. 12 shows preliminary results showing insertion success with measured microneedle thickness (including all layers, i.e. substrate and additional layers). The highlighted box indicates an area demonstrated to be relatively safe, with only a single case of partial insertion out of 150 otherwise successful insertions.

[0204] As described above, the array of microneedles 108 may comprise one or more electrodes. Each electrode may be one of a working electrode, a reference electrode or a counter electrode. In certain embodiments, the wearable sensing device 100 includes at least one working electrode, at least one reference electrode, and at least one counter electrode in accordance with known electrochemical sensors. In other embodiments, a single electrode may function as both a reference and a counter electrode and in such embodiments, the wearable sensing device 100 may include at least one such electrode and at least one working electrode.

[0205] FIG. 13 shows a microneedle 108 comprising a working electrode 1300 in accordance with an embodiment of the present invention. The microneedle 108 comprises a substrate 1302 upon which a conductive layer 1304 is provided. A dielectric layer 1306 covers a portion of the conductive layer 1304 whilst leaving another portion of the conductive layer 1304 exposed. The dielectric layer 1306 may comprise any electrically insulating material. On the exposed portion of the conductive layer 1304, several individual regions of a sensing layer 1308 are provided. Each region of the sensing layer 1308 may comprise a material that interacts with an analyte of interest and consequently generates an electrochemical response that may beelectrically transmitted along the conductive layer 1304 to one or more electronic components. Detection of the electrochemical response may be indicative of the presence and the concentration of the analyte of interest. The sensing layer 1308 allows the working electrode 1300 to detect and measure the concentration of the analyte by producing a detectable electrochemical response (also referred to as a current signal). The current signal is proportional to the concentration of the analyte and is relayed to the microneedle electrode. By measuring the current signal, the microneedle electrode can therefore measure the concentration of the analyte. In the non-limiting embodiment shown in FIG. 13, three separate sensing layers 1308 are shown disposed on the conductive layer 1304. In alternative embodiments, other numbers (i.e. one, two, or more than three) sensing layers 1308 may be provided.

[0206] The sensing layer 1308 may comprise: i) an enzyme or an ionophore; and ii) a third polymeric material. The enzyme or ionophore may be immobilized within the sensing layer (e.g., the enzyme or ionophore is located within the sensing layer with restricted movement). For example, the enzyme or ionophore may be covalently bound to the third polymeric material of the sensing layer. Suitably, the enzyme or ionophore (e.g., via functional amine groups) is covalently bound via a di-epoxy crosslinker to the functional groups of the third polymeric material of the sensing layer 1308 (e.g., amine or hydroxyl groups).

[0207] In some embodiments, the sensing layer 1308 comprises: i) an enzyme; and ii) a third polymeric material.

[0208] The enzyme may be selected from the group consisting of glucose oxidase, lactate oxidase, glucose dehydrogenase, diamine oxidase, P-hydroxybutyrate dehydrogenase and alcohol oxidase. Suitably, the enzyme is glucose oxidase.

[0209] The working electrode 1300 may additionally include an outer layer (not shown in FIG. 13). The outer layer may be applied by any suitable method including but not limited to spraying, dip coating, spin coating, and low volume dispensing (e.g. piezo-based dispensing).

[0210] The outer layer effects the specificity and ability of analytes to reach the sensing layer formed beneath the outer layer. The outer layer is semi-permeable and has greater permeability to some substances, but less permeability to other substances, thereby controlling the amount of certain substances reaching the sensing layer positioned underneath the outer layer.

[0211] In certain embodiments, the conductive layer 1304 may comprise (or is formed from) carbon (e.g., graphite, graphene, carbon nanotubes, pyrolytic carbon or carbon fibre), platinum,gold, rhodium, palladium, silver, silver-silver chloride, steel (e.g. stainless steel), copper, nickel, zinc, aluminium, tantalum or chromium.

[0212] In certain embodiments, the dielectric layer 1306 may comprise any suitable electrically insulating material. In certain embodiments, the dielectric layer 1306 may comprise (or is formed from) insulating polymers (e.g., parylene (e.g., parylene-C, parylene-F or parylene-N), polyimide, polyvinylchloride, benzocylcobutene or acrylate) or metal oxides (e.g., titanium dioxide, silicon dioxide or aluminium oxide).

[0213] With reference to the working electrode 1300, the width W1 and length LI of the microneedle 108 is preferably sufficient to dispense droplets of functional chemistry so that sufficient current may be achieved, whilst accounting for manufacturing tolerances.

[0214] FIG. 14 shows an alternative working electrode 1300 in accordance with another embodiment of the present invention. The working electrode 1300 of FIG. 14 has a single sensing layer 1308 in contrast to the working electrode 1300 of FIG. 13, but is otherwise identical.

[0215] FIG. 15 shows a cross-sectional view of the working electrode 1300 of FIG. 14 additionally including an outer layer 1310 enveloping the whole microneedle 108 and a passivation layer 1500 encapsulating the substrate 1302. As noted above, the outer layer 1310 may comprise a polymer and permit analytes of interest to pass therethrough so as to contact the sensing layer 1308. The outer layer 1310 (which may be semi-permeable) and the sensing layer 1308 may form a composite material. In particular, the composite material may comprise the semi-permeable outer layer and the sensing layer 1308 positioned underneath the semi- permeable outer layer 1310 that is capable of generating an electrochemical response in the presence of the analyte(s).

[0216] FIG. 20 shows calibration curves for five working electrodes 1300 according to embodiments of the present invention (referred to as sensors 1-5, prepared according to Example 1 A / Example IB set out below), all from the same manufacturing lot, indicating the stable current points relative to varying glucose concentration. The average gradient displays the sensitivity of the working electrode 1300 towards changing glucose concentration (nA / mM).

[0217] Example 1A

[0218] Sensing layer: redox polymer (10 mg / ml), glucose oxidase enzyme (11.5 mg / ml, 278 U / mg) and poly(ethylene glycol) diglycidyl ether (4.6 mg / ml, Mw 500) in HEPES solution (10 mM, pH 8).

[0219] Semi-permeable outer layer: outer layer polymer (110 mg / ml) and glycerol trigylcidyl ether (7.2 mg / ml) in 4:1 ethanol:HEPES solution (10 mM, pH 8).

[0220] The sensing layer solution was deposited onto a single microneedle electrode (i.e., the working microneedle electrode), and cured at 25 °C and 55% relative humidity (RH) for 24 hours. All of the microneedle electrodes (i.e., the working, reference and counter microneedle electrodes) were then dipped four times into the semi-permeable outer layer solution with a 7 minute wait in between coats. After dipping, the microneedle electrodes were stored at 25 °C and 55% RH for 24 hours. After this initial storage, the microneedle electrodes were cured at 48 °C and <10% RH for 60 hours.

[0221] Example IB

[0222] Sensing layer: redox polymer, glucose oxidase enzyme and poly(ethylene glycol) diglycidyl ether in buffered solution (pH 8).

[0223] Semi-permeable outer layer: outer layer polymer and glycerol trigylcidyl ether in 5:1 ethanol: buffer solution (pH 8).

[0224] The sensing layer solution was deposited onto a single microneedle electrode (i.e., the working microneedle electrode), and cured at room temperature and humidity for about 1 day. All of the microneedle electrodes (i.e., the working, reference and counter microneedle electrodes) were then dipped four times into the semi-permeable outer layer solution with about a 10 minute wait in between coats. After dipping, the microneedle electrodes were stored in controlled temperature and humidity for 24 hours. After this initial storage, the microneedle electrodes were cured at 45 - 55 °C and low humidity for about 3 days.

[0225] FIG. 16 shows a microneedle 108 comprising a counter electrode 1600 in accordance with an embodiment of the present invention. The microneedle 108 comprises a substrate 1302 upon which a conductive layer 1304 is provided. A dielectric layer 1306 covers a portion of the conductive layer 1304 whilst leaving another portion of the conductive layer 1304 exposed. The counter electrode 1600 may additionally include an outer layer (not shown).

[0226] With reference to the counter electrode 1600, it is preferable for the total surface area available for functionalisation to be sufficient to sink current without increasing the full cell potential beyond an acceptable range.

[0227] FIG. 17 shows a cross-sectional view of the counter electrode 1600 of FIG. 16 additionally including an outer layer 1310 enveloping the whole microneedle 108 and a passivation layer 1500 encapsulating the substrate 1302. As noted above, the outer layer 1310 may comprise a polymer.

[0228] FIG. 18 shows a microneedle 108 comprising a reference electrode 1800 in accordance with an embodiment of the present invention. The microneedle 108 comprises a substrate 1302 upon which a conductive layer 1304 is provided. A silver-silver chloride layer 1802 extends over the conductive layer 1304 and a protective layer extends over the silver-silver chloride layer 1802. In the non-limiting embodiment of FIG. 18, the protective layer comprises a dielectric layer 1306. The dielectric layer 1306 defines an aperture 1804 through which a portion of the silver-silver chloride layer 1802 is exposed (whilst, for the avoidance of doubt, the outer layer remains as a continuous outer layer of the microneedle 108). The presence of the dielectric layer 1306 and aperture 1804 may be referred to as a reference window. The reference electrode 1800 may additionally include an outer layer (not shown). Throughout the present specification, the term silver-silver chloride layer 1802 refers to a layer that comprises both silver and silver chloride.

[0229] In certain embodiments, the silver-silver chloride layer 1802 may not extend over the conductive layer 1304 across a region of the microneedle 108 that, in use, extends into the skin. In such embodiments, the silver-silver chloride layer 1802 may function to provide a currentcarrying path in that region and the silver-silver chloride layer 1802 and conductive layer 1304 may interface with one another in a region of the microneedle 108 that, in use, does not extend into the skin. In such embodiments, the dielectric layer 1306 still defines an aperture 1804 through which a portion of the silver-silver chloride layer 1802 is exposed. Furthermore, in such embodiments, in at least a portion of the microneedle 108, the silver-silver chloride layer 1802 may comprise the conductive layer 1304.

[0230] The presence of the dielectric layer 1306 over the majority of the silver-silver chloride layer 1802 reduces the exposed area of the silver-silver chloride layer 1802. This reduces the rate at which silver chloride passively diffuses away from the silver-silver chloride layer 1802 through the dielectric layer 1306 and into the polymer outer layer. That is, the dielectric layer1306 inhibits diffusion therethrough. Such diffusion depletes the silver-silver chloride layer 1802 and leads to reference instability, which is characterised by a noisy signal and eventually terminates the wear period of the wearable sensing device 100.

[0231] The size of the aperture 1804 may be limited by the resolution of the manufacturing method (e.g. screen printing, etching, spraying, dip coating, spin coating, and low volume dispensing (e.g. piezo-based dispensing)). In the non-limiting embodiment shown in FIG. 18, the aperture 1804 has an aperture length 1806 of 0.15 mm. In other embodiments, the aperture length 1806 may be between 0.1 mm and 0.5 mm. In other embodiments, the aperture 1804 may have a different aperture length 1806 but may still have a minimum dimension that is between 0.1 mm and 0.5 mm (e.g. width). In certain embodiments, the portion of the silversilver chloride layer 1802 that is exposed through the aperture 1804 has an area between 0.005 mm2and 0.15 mm2.

[0232] In certain embodiments, the protective (e.g. dielectric) layer 1306 may not include the aperture 1804 described above, but instead may comprise a porous protective layer (which in some embodiments may be a porous dielectric layer). In such embodiments, the pores of the porous protective layer may provide limited exposure of the silver-silver chloride layer 1802 beneath, whilst otherwise reducing the rate at which silver chloride passively diffuses away from the silver-silver chloride layer 1802 through the dielectric layer 1306 and into the polymer outer layer.

[0233] With reference to the reference electrode 1800 the ratio of volume of AgCl to Ag is preferably sufficient to enable a reference electrode 1800 lifetime of at least two weeks. A larger surface area enables this to be achieved without increasing the thickness of the silversilver chloride layer 1802 significantly. In certain embodiments, the ratio of AgCl to Ag in the silver-silver chloride layer 1802 may be between 1:4 and 4: 1. In certain embodiments, the ratio may be about 2:3.

[0234] In certain embodiments, the ink solid content by weight (i.e. the proportion of ink that is not solvent) of the silver-silver chloride layer 1802 may be between 60% and 90%. In certain embodiments, the ink solid content of the silver-silver chloride layer 1802 may be about 70% or 80%.

[0235] In certain embodiments, the ink solid content by weight (i.e. the proportion of ink that is not solvent) of the dielectric layer 1306 may be 100%.

[0236] In certain embodiments, the area covered by the dielectric layer 1306 may be between 0.05 mm2and 0.3 mm2. In certain embodiments, the area covered by the dielectric layer 1306 may be about 0.15 mm2.

[0237] In certain embodiments, the thickness of the dielectric layer 1306 may be between 1 m and 30 pm, or between 2 pm and 10 pm. In certain embodiments, the thickness of the dielectric layer 1306 may be 1 pm or less. In certain embodiments the thickness of the dielectric layer 1306 may be about 4 pm.

[0238] In another embodiment of the reference electrode 1800, no dielectric layer 1306 may be present. Instead, the silver-silver chloride layer 1802 may extend over the substrate, and the conductive layer 1304 may extend over the silver-silver chloride layer 1802 with one or more apertures provided so that the silver-silver chloride layer 1802 is exposed through the one or more apertures. In such embodiments, the conductive layer 1304 comprises the protective layer.

[0239] It is beneficial, in general, to reduce the number of layers on the microneedle substrate. This reduces overall thickness, which is a benefit for insertion and skin bio-interfacing. It also reduces the size of the tolerance stack, which is beneficial for manufacturing ease and yield.

[0240] It should be noted that in the various arrangements described above (particularly in relation to FIG. 13 to FIG. 19) the various layers may or may not extend across the entire width of the respective microneedle 108.

[0241] In accordance with embodiments of the present invention, electrodes may be provided on one or both of the first planar surface 714 and the second planar surface 716.

[0242] FIG. 19 shows a cross-sectional view of the reference electrode 1800 of FIG. 18 additionally including an outer layer 1310 enveloping the whole microneedle 108 and a passivation layer 1500 encapsulating the substrate 1302. As noted above, the outer layer 1310 may comprise a polymer.

[0243] In any embodiment, the outer layer 1310 may be semi-permeable. In any embodiment, the outer layer 1310 may comprise a polymeric material. In certain embodiments, the polymeric material may be a co-polymer (e.g., alternating, random or block co-polymer) comprising monomers A, B, C and D, wherein A, B, C and D are each independently selected from a monomer comprising a zwitterionic portion, a monomer comprising a pyridine portion, a monomer comprising a phenyl portion and a monomer comprising a hydrophilic portion.

[0244] FIG. 21 shows the open circuit potential (OCP) of multiple sensors with and without the reference window. “Uncovered reference” refers to a microneedle 108 having a silver-silver chloride layer 1802 but without any dielectric layer 1306 and aperture 1804. “Covered reference” refers to a microneedle 108 having a silver-silver chloride layer 1802 and a dielectric layer 1306 with the aperture 1804 (such as the microneedle 108 described above with reference to FIG. 18).

[0245] FIG. 21 shows the impact of the reference window on the functional lifetime of the counter electrode 1600 in an in-vitro setup. OCP is used as a proxy of the “health” of the counter electrode 1600. FIG. 21 shows that a fully exposed silver-silver chloride layer 1802 leads to a counter electrode 1600 lifetime of just 4-6 days. In contrast, the presence of the dielectric layer 1306 and the aperture 1804 provides a counter electrode 1600 lifetime in excess of 14 days.

[0246] FIG. 22 shows in-vivo data for the covered reference (a) and uncovered reference (b) microneedles. In particular the current and full cell potential is shown for each. As shown in FIG. 22, the covered reference microneedle 108 demonstrates a stable current and reflects the participant's glucose levels. In contrast, the uncovered reference microneedle 108 becomes unstable between 4 and 5 days, leading to unreliable readings. The full cell potential also drops below the expected range.

[0247] FIG. 23 shows a cross-sectional view of the wearable sensing device 100 in accordance with an embodiment of the present invention. The second body part 106 comprises a first casing 2300 and a second casing 2302 that are connectable to one another to enclose a number of internal components including one or more electronic components 2308 and a battery 2310. A series of electrically conductive and axially moveable pogo pins 2306 protrude through the second body part 106 and contact the one or more electronic components 2308. The one or more electronic components 2308 may include one or more processors and / or memory devices.

[0248] A gasket 2312 is seated in the first body part 104 and the gasket 2312 supports a plurality of elastomeric terminals 2304. The gasket 2312 may inhibit water ingress into the wearable sensing device 100. Each of the connection piercing elements 704 pierces and is embedded in one of the elastomeric terminals 2304 so as to form an electrical connection therebetween. Each elastomeric terminal 2304 is in electrical contact with one of the pogo pins 2306 such that each connection piercing element 704 may facilitate independent electricalcommunication between an electrode of one of the microneedles 108 and the one or more electronic components 2308.

[0249] The second body part 106 may be receivable in the first body part 104 and be retained therein. In assembling the second body part 106 in the first body part 104, the pogo pins 2306 make contact with the elastomeric terminals 2304 and the elastomeric terminals 2304 may deformto accommodate the presence of the pogo pins 2306.

[0250] As described above, the first body part 104 may be broken after use to subsequently remove the second body part 106 from the first body part 104. The second body part 106, which avoids any contact with any bodily fluids during normal use, may then be re-used in a new first body part 104 if desired.

[0251] FIG. 24 shows an exploded view that shows the gasket 2312 with elastomeric terminals 2304 alongside the first body part 104.

[0252] In alternative embodiments, no connection piercing elements 704 and / or elastomeric terminals 2304 may be provided. In such embodiments, protrusions of the microneedle assembly bracket 702 may abut the pogo pins 2306 to form the required electrical connection therebetween.

[0253] FIG. 25 shows a detailed cross-sectional view of a part of the wearable sensing device 100 in accordance with an embodiment of the present invention.

[0254] FIG. 26 shows part of the detailed cross-sectional view of FIG. 25 with additional features marked up. In particular, in the embodiment of FIG. 26, it can be seen that the second surface 114 is small in comparison to previously described embodiments. That is, only a small planar surface is offset from the first surface 112. The tapered surface 116 extends from a taper first end 2602 to a taper second end 2604, wherein the longitudinal spacing (i.e. the spacing along a direction parallel to the longitudinal axis 124) between the taper first end 2602 and the taper second end 2604 is equal to the offset distance 120. A taper first axis 2606 is defined as an axis that extends from the taper first end 2602 and is parallel to the longitudinal axis 124. Similarly, a taper second axis 2608 is defined as an axis that extends from the taper second end 2604 and is parallel to the longitudinal axis 124. A first distance 2600 is defined as extending between a microneedle axis 2612 of a given microneedle 108 (which is parallel to the longitudinal axis 124) and the taper first axis 2606 along a direction that is perpendicular to the longitudinal axis 124. A tapered surface length 2610 is defined as extending between the taperfirst axis 2606 and the taper second axis 2608 in a direction that is perpendicular to the longitudinal axis 124.

[0255] In certain embodiments, the first distance 2600 may be 3.0 mm or less. In certain embodiments, the first distance 2600 may be between 0 mm and 3.0 mm. In certain embodiments, the first distance 2600 is about 0.5 mm. In embodiments in which the first distance 2600 is 0 mm, the second surface 114 may not be present and the tapered surface 116 tapers upwards to an apex and tapers downward therefrom. In such embodiments, the taper first end 2602 coincides with the longitudinal axis 124 and the tapered surface length 2610 extends from the longitudinal axis 124 to the 2608.

[0256] Such arrangements ensure that the microneedles 108 are sufficiently close to the taper first end 2602 and so penetrate skin that is suitably tensioned by the presence of the offset second surface 114 when the wearable sensing device 100 is adhered to the skin. In arrangements in which there is a large distance between microneedles 108 and the taper first end 2602, the skin into which the microneedles penetrate may not be sufficiently tensioned. This may lead to suboptimal operating conditions including but not limited to unreliable insertion and poor maintenance of the microneedles 108 in the skin.

[0257] In certain embodiments, the tapered surface length 2610 may be between 2.0 mm and 5.0 mm. In certain embodiments, the tapered surface length 2610 may be about 2.0 mm.

[0258] In certain embodiments, the offset distance 120 may be between 0.5 mm and 2.0 mm. In certain embodiments, the offset distance 120 may be about 1.3 mm.

[0259] FIG. 27 shows the same cross-sectional view of FIG. 26 with different features marked up thereon. In particular, FIG. 27 shows a first angle 2700 of the wearable sensing device 100 that is defined as the angle between the taper first end 2602 and the taper second end 2604 across the offset distance 120. It should be noted that in the non-limiting embodiment shown in FIG. 27, the tapered surface 116 does not extend between the taper first end 2602 and the taper second end 2604 at the first angle 2700. However, in other embodiments, the tapered surface 116 may do so.

[0260] In certain embodiments, the first angle 2700 may be between 5° and 60° or between 20° and 40°. In certain embodiments, the first angle 2700 may be about 32°.

[0261] As described above, in certain embodiments, the wearable sensing device 100 additionally comprises an adhesive pad 122 received on at least part of the device body 102. For example, the adhesive pad 122 may be received on any one or more of the first surface 112,the second surface 114 or the tapered surface 116 of the first body part 104. In such embodiments, the adhesive pad 122 covers a part of the device body 102 such that the adhesive pad 122 itself becomes the exposed bottom surface of the wearable sensing device 100. In areas of the device body 102 that are not covered by the adhesive pad 122, the device body 102 remains as the exposed bottom surface of the wearable device 100 for that region. In such embodiments, an exposed one of the device body 102 and the adhesive pad 122 define a first surface 112’ (of the wearable sensing device 100) extending in a first plane and a second surface 114’ (of the wearable sensing device 100), wherein the first surface 112’ surrounds the second surface 114’ and the first surface 112’ is offset by an offset distance 120’ from the second surface 114’ along a longitudinal axis. Additionally, an exposed one of the device body 102 and the adhesive pad 122 further defines a tapered surface 116’ (of the wearable sensing device 100) extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface 112’ and the second surface 114’ such that the taper first end is adjacent to the second surface 114’ and the taper second end is adjacent to the first surface 112’.

[0262] The first surface 112’, second surface 114’, and tapered surface 116’ of the wearable sensing device 100 are analogous to the first surface 112, second surface 114, and tapered surface 116, respectively, of the first body 104 described above with reference to FIGs. 25 to 27, and all examples and relationships (numerical or otherwise) described above in relation to them are equally applicable to the first surface 112’, second surface 114’, and tapered surface 116’ of the wearable sensing device 100.

[0263] FIG. 32 shows an embodiment of the wearable sensing device 100 in which the adhesive pad 122 defines only the first surface 112’ of the wearable sensing device 100 and (the first body part 104 of) the device body 102 defines the second surface 114’ and the tapered surface 116’ of the wearable sensing device 100. The offset distance 120’ is shown. The length LI is also indicated (although the reader will appreciate that this length relates to the substrate within the microneedle 108).

[0264] FIG. 33 shows an embodiment of the wearable sensing device 100 in which the adhesive pad 122 defines each of the first surface 112’, the second surface 114’ and the tapered surface 116’ of the wearable sensing device 100. The offset distance 120’ is shown. The length LI is also indicated (although the reader will appreciate that this length relates to the substrate within the microneedle 108).

[0265] FIG. 28 shows an intermediate assembly 2800 according to an embodiment of the present invention. The intermediate assembly 2800 may be used during the manufacture of a wearable sensing device 100 according to embodiments of the present invention.

[0266] The intermediate assembly 2800 comprises a handling tab 2802 and a microneedle sub-assembly 2804 frangibly connected to the handling tab 2802 by a frangible connection point 2806. The microneedle sub-assembly 2804 comprises the array of microneedles 108. The frangible connection points 2806 are a narrowed, thinned or otherwise weakened point that preferentially breaks upon application of a force by a user. Any suitable frangible connection points 2806 may be utilised.

[0267] The handling tab 2802 is configured to facilitate manoeuvering of the microneedle sub-assembly 2804 such that the microneedle sub-assembly 2804 may be coated in a liquid to form the outer layer 1310 on the microneedles 108.

[0268] FIG. 29 shows an intermediate assembly 2800 according to another embodiment of the present invention. The intermediate assembly 2800 of FIG. 29 comprises a plurality of handling tabs 2802 that are frangibly connected to one another by frangible connection points 2806. That is, the frangible connection points 2806 may be broken in order to separate the plurality of handling tabs 2802. Each of the plurality of handling tabs 2802 is frangibly connected to a microneedle sub-assembly 2804 by further frangible connection points 2806 such that each microneedle sub-assembly 2804 may be broken off its respective handling tab 2802. Each of the microneedle sub-assemblies 2804 comprises a microneedle 108. In certain embodiments, each of the microneedle sub-assemblies 2804 may comprise more than one microneedle 108.

[0269] FIG. 30 shows a method 3000 according to an embodiment of the present invention. The method 3000 is a method of manufacturing a wearable sensing device 100. The method 3000 starts at block 3002 and at block 3004 comprises providing a first intermediate assembly that comprises one or more handling tabs 2802, and a plurality of microneedle sub-assemblies 2804, wherein each of the microneedle sub-assemblies 2804 is frangibly connected to the one or more handling tabs 2802.

[0270] The method 3000 further comprises at block 3006 providing a second intermediate assembly that comprises one or more handling tabs 2802, and a plurality of microneedle subassemblies 2804, wherein each of the microneedle sub-assemblies 2804 is frangibly connected to the one or more handling tabs 2802.

[0271] In certain embodiments, the first and / or second intermediate assembly may comprise the intermediate assembly 2800 of FIG. 29 or a variant thereof in which the handling tabs 2802 are not connected to one another.

[0272] The method 3000 further comprises at block 3008 manoeuvering the first intermediate assembly using the respective one or more handling tabs 2802 to coat the respective plurality of microneedle sub-assemblies 2804 with a first liquid to provide a first coating on the plurality of microneedle sub-assemblies 2804. The first coating comprises an outer layer 1310 on microneedles 108 of the microneedle sub-assemblies 2804 of the first intermediate assembly.

[0273] At block 3010, the method 3000 comprises manoeuvering the second intermediate assembly using the respective one or more handling tabs 2802 to coat the respective plurality of microneedle sub-assemblies 2804 with a second liquid to provide a second coating on the plurality of microneedle sub-assemblies 2804. The second coating comprises an outer layer 1310 on microneedles 108 of the microneedle sub-assemblies 2804 of the second intermediate assembly.

[0274] At block 3012 the method 3000 comprises separating the plurality of microneedle subassemblies 2804 on the first intermediate assembly from the one or more handling tabs 2802 by breaking the frangible connection points 2806 therebetween.

[0275] At block 3014 the method 3000 comprises separating the plurality of microneedle subassemblies 2804 on the second intermediate assembly from the one or more handling tabs 2802 by breaking the frangible connection points 2806 therebetween.

[0276] Finally, the method 3000 comprises at block 3016 assembling in a wearable sensing device 100 at least one of the separated plurality of microneedle sub-assemblies 2804 of the first intermediate assembly and at least one of the separated plurality of microneedle subassemblies 2804 of the second intermediate assembly, before the method 3000 ends at block 3018.

[0277] The assembled wearable sensing device 100 comprises both microneedles 108 that comprise an outer layer 1310 formed of the first coating and microneedles 108 that comprise an outer layer 1310 formed of the second coating.

[0278] In certain embodiments, additional intermediate assemblies may also be provided it the method 3000, such that additional microneedles 108 having outer layers 1310 formed of different coatings may be assembled in the wearable sensing device 100.

[0279] In certain embodiments, the outer layer 1310 may be optimised for a particular analyte that is intended to be sensed by the respective microneedle 108. The choice of first liquid and second liquid (and indeed any additional liquids) and the conditions under which they are applied may determine the properties of the respective outer layers 1310. In certain embodiments, the outer layer 1310 may comprise a polymer. The outer layer 1310 may be semi-permeable. The microneedles 108 may be provided with different combinations of outer layer 1310 and sensing layers in accordance with embodiments of the present invention. The outer layers 1310 provided by the coatings may form outermost layers of the respective microneedles 108.

[0280] FIG. 31 shows a method 3100 according to another embodiment of the present invention. The method 3100 is a method of manufacturing a wearable sensing device 100. The method 3100 starts at block 3102 and at block 3104 comprises providing an intermediate assembly comprising a plurality of handling tabs 2802 frangibly connected to one another, and a plurality of microneedle sub-assemblies 2804, wherein each of the microneedle subassemblies 2804 is frangibly connected to the one of the plurality of handling tabs 2802. The intermediate assembly may comprise the intermediate assembly 2800 described above.

[0281] At block 3106, the method 3100 comprises separating the plurality of handling tabs 2802 from one another by breaking the frangible connection points 2806 therebetween.

[0282] At block 3108, the method 3100 comprises manoeuvring each of the plurality of microneedle sub-assemblies 2804 using the respective handling tab 2802 to apply a coating on the respective microneedle sub-assembly 2804. The coating comprises an outer layer 1310 on microneedles 108 of the microneedle sub-assemblies 2804 of the intermediate assembly. The separated microneedle sub-assemblies 2804 may be coated with different coatings, and / or with the same coating material but under different application conditions ("process parameters").

[0283] At block 3110, the method 3100 comprises assembling in a wearable sensing device 100 at least one of the coated microneedle sub-assemblies 2804.

[0284] In method 3000 or method 3100, in addition to the choice of the liquid, other properties that may differ when applying the outer layer 1310 to different intermediate assemblies or microneedle sub-assemblies 2804 may include the thickness of the outer layer 1310, the hydrophilicity of the outer layer 1310, the porosity or diffusivity of the outer layer 1310 to an analyte of interest, and the diffusivity of interferent molecules. In particular, in certain embodiments, an identical liquid may be utilised for successive (or parallel) coatings,but the resulting coatings may differ from one another by virtue of different process parameters being used.

[0285] Increasing the thickness of the outer layer 1310 may provide a higher linearity albeit with a slower response time.

[0286] Increasing the hydrophilicity may provide more rapid hydration resulting in a faster break-in time.

[0287] Increasing the porosity or diffusivity to the analyte of interest improves sensitivity.

[0288] Reducing the diffusivity of interferent molecules increases accuracy.

[0289] Additionally, process parameters of the liquid to be coated that may be varied individually or in any combination include: the viscosity of the liquid, the number of coats, the bath temperature (of a bath of the liquid), chamber / environment temperature surrounding the liquid, entry speed of the intermediate assembly in the liquid, exit speed of the intermediate assembly from the liquid, duration between dips of the intermediate assembly in the liquid, the time in humidity, the time in desiccation, addition of additives and / or enzymes to the liquid, and utilisation of multiple differing outer layers.

[0290] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0291] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanyingclaims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0292] The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

Claims

CLAIMS1. A wearable sensing device for detecting at least one analyte, comprising: a device body comprising a first surface extending in a first plane and a second surface, wherein the first surface surrounds the second surface and the first surface is offset by an offset distance from the second surface along a longitudinal axis, the first surface being configured to receive adhesive means for affixing the device body to an application surface of a user, the device body further comprising a tapered surface extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface and the second surface such that the taper first end is adjacent to the second surface and the taper second end is adjacent to the first surface; and an array of microneedles each extending along a microneedle axis that is parallel to the longitudinal axis, each microneedle extending through apertures in the second surface and comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; wherein a taper first axis extends from the taper first end and is parallel to the longitudinal axis, and a first distance for each microneedle is defined as extending between the respective microneedle axis and the taper first axis in a direction perpendicular to the longitudinal axis; and wherein the first distance is 3.0 mm or less.

2. A wearable sensing device for detecting at least one analyte, comprising: a device body and an adhesive pad received on at least part of the device body, wherein an exposed one of the device body and the adhesive pad define a first surface extending in a first plane and a second surface, wherein the first surface surrounds the second surface and the first surface is offset by an offset distance from the second surface along a longitudinal axis, and an exposed one of the device body and the adhesive pad further defines a tapered surface extending between a taper first end and a taper second end, wherein the tapered surface adjoins the first surface and the second surface such that the taper first end is adjacent to the second surface and the taper second end is adjacent to the first surface; andan array of microneedles each extending along a microneedle axis that is parallel to the longitudinal axis, each microneedle extending through apertures in the second surface and comprising at least one electrode that is capable of generating an electrochemical response in the presence of at least one analyte; wherein a taper first axis extends from the taper first end and is parallel to the longitudinal axis, and a first distance for each microneedle is defined as extending between the respective microneedle axis and the taper first axis in a direction perpendicular to the longitudinal axis; and wherein the first distance is 3.0 mm or less.

3. A wearable sensing device according to claim 1 or 2, wherein the first distance is about 0.5 mm.

4. A wearable sensing device according to any preceding claim, wherein a taper second axis extends from the taper second end and is parallel to the longitudinal axis, and a tapered surface length is defined as extending between the taper first axis and the taper second axis in a direction perpendicular to the longitudinal axis, wherein the tapered surface length is between 2.0 mm and 5.0 mm.

5. A wearable sensing device according to claim 4, wherein the tapered surface length is about 2.0 mm.

6. A wearable sensing device according to any preceding claim, wherein the offset distance is between 0.5 mm and 2.0 mm.

7. Awearable sensing device according to claim 6, wherein the offset distance is about 1.3 mm.

8. A wearable device according to any preceding claim, wherein a first angle is defined between the taper first end and the taper second end across the offset distance, wherein the first angle is between 5° and 60°.

9. A wearable device according to claim 8, wherein the first angle is between 20° and 40°.

10. A wearable device according to claim 9, wherein the first angle is about 32°.

11. A wearable sensing device according to claim 1 or any of claims 3 to 10 when dependent on claim 1, wherein each microneedle has an exposed portion that protrudes from the device body, wherein a substrate underlying the exposed portion has a length LI that is 2.0 mm or less.

12. A wearable sensing device according to claim 2 or any of claims 3 to 10 when dependent on claim 2, wherein each microneedle has an exposed portion that protrudes from the adhesive pad, wherein a substrate underlying the exposed portion has a length LI that is 2.0 mm or less.

13. A wearable sensing device according to claim 11 or 12, wherein LI is between 0.4 mm and 2.0 mm, or between 0.6 mm and 1.6 mm, and is optionally about 1.0 mm, 1.2 mm, or 1.4 mm.

14. A wearable sensing device according to any preceding claim, wherein each microneedle has an insertion tip, and a microneedle body disposed between the insertion tip and the device body, and wherein a substrate underlying each microneedle body has a width W1 that is between 0.05 mm and 0.4 mm, or between 0.1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm, and is optionally about 0.2 mm, 0.25 mm or 0.3 mm.

15. A wearable sensing device according to claim 14, wherein each microneedle comprises a shoulder disposed between the microneedle body and the device body.

16. A wearable sensing device according to claim 15, wherein a substrate underlying the shoulder has a width W2 between 0.125 mm and 1.00 mm, or between 0.20 mm and 0.80 mm, or between 0.25 mm and 0.8 mm, and is optionally about 0.40 mm.

17. A wearable sensing device according to any of claims 14 to 16, wherein a susbtrate underlying each insertion tip has a length L2 that is between 0.15 mm and 0.5 mm, and is optionally about 0.3 mm.

18. Awearable sensing device according to claim 1 or any of claims 3 to 17 when dependent on claim 1, comprising a plurality of channels recessed in the first surface.

19. Awearable sensing device according to claim 18, wherein the plurality of channels have a width of between 0.25 mm and 1.5 mm, or between 0.5 mm and 1.0 mm, or about 0.8 mm.

20. Awearable sensing device according to claim 18 or 19, wherein the plurality of channels have a depth of between 0.05 mm and 0.75 mm, or between 0.1 mm and 0.5 mm, or about 0.3 mm.

21. Awearable sensing device according to any of claims 18 to 20, wherein the plurality of channels extends into the tapered surface.

22. Awearable sensing device according to claim 21, wherein the plurality of channels extends into the second surface.

23. A wearable sensing device according to any preceding claim, wherein the second surface extends in a second plane.

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