Long-term wearable micro-needle device

Abstract

A wearable device is disclosed for maintaining contact between a microneedle or other type of skin-penetrating protrusion and interstitial fluid of the skin. The device has a movable portion that supports the microneedle and a skin contact portion. The microneedle is initially in a retracted state and is biased into the skin by movement of the movable portion along a non-linear or arcuate path. The device has a low profile when held on the skin and is thus less invasive for long-term wear applications such as continuous specimen monitoring and sustained drug delivery.

Description

Technical Field

[0001] The present invention generally relates to an apparatus useful for introducing microneedles into a subject's skin and even more useful for retaining the microneedles in place over an extended period of time. The apparatus is configured to be simple, lightweight, and have a low profile so as to be relatively unobtrusive to the subject.

Background Art

[0002] Advances in microfabrication technology in the 1990s enabled the mass production of microneedle devices for medical use.

[0003] A single microneedle typically has a length of 150 - 1500 μm, a width of 50 - 250 μm, and a tapered tip with a thickness of 1 - 25 μm. Microneedles can be manufactured from metal, silicon, polymer, glass, or ceramic, and the base of the microneedle is typically attached to a base substrate to form an array. The microneedle base substrate may include an adhesive to improve engagement with the skin.

[0004] Solid microneedles coated with therapeutic substances are used to deliver pharmaceutical actives directly to the epidermis and dermis, thereby overcoming the troublesome barrier of the upper layer of the skin. Another scheme for delivering therapeutic agents uses soluble polymer microneedles with encapsulated active substances, which gradually release the active substances into the skin over time. Hollow microneedles may be used to deliver liquid drug compositions to the skin via the needle lumen.

[0005] Sampling of interstitial fluid for subsequent analysis may also be accomplished by aspirating fluid from the body via the needle lumen.

[0006] Conductive microneedles may be coated with redox-modified aptamers to sense specific analytes in interstitial fluid.

[0007] The prior art discloses numerous devices for inserting microneedles into the skin of a subject. Such devices are typically configured to facilitate the application of microneedles by the subject in a non-clinical environment such as at home. Ease of use and reproducibility are the main objectives of these devices.

[0008] Some devices are dedicated to the application of microneedles only, and once the task is completed, the device is removed together with the microneedle. Other prior art applicator devices are configured to be separated from the microneedle, thereby allowing the microneedle to remain in place within the skin for a period of time after introduction. While in the skin, the microneedle may gradually release an active substance or, alternatively, may sense increases and decreases in the concentration of an analyte in the interstitial fluid.

[0009] Yet another type of prior art device is configured to introduce a microneedle, and the device and the microneedle remain in place on the subject for a period of time. These devices provide simplicity for the subject using the device, but nevertheless, they pose many problems.

[0010] One problem is that such devices are generally very conspicuous and easily recognizable by the subject. The device may catch on clothing or any other nearby object and may come off completely or partially. These devices may need to be worn overnight, and significant discomfort may occur when the subject rolls over on the device.

[0011] A further problem is that prior art devices are complex with a large number of individual components. This increases the cost of the device and also increases the tendency to fail. The large number of components also increases the weight of the device, thereby increasing its visibility to the subject. It has been found that the discomfort associated with the weight of the device increases in proportion to the duration for which the device is worn. In some applications (such as hormone monitoring), continuous real-time data may be required over a period of weeks. The device is likely to be changed several times over that period, but the problem remains of the subject having to wear a heavy device for a long time.

[0012] A further problem is that it is uncertain whether the microneedle was properly inserted into the skin in the first instance and further whether the microneedle remains properly embedded in the skin over time. Prior art devices typically include a housing, the lower surface of which lies flat on the surface of the skin. It is difficult, if not impossible, for the subject to check for proper microneedle embedding while looking at the surface of the skin, assuming the presence of the housing. If there is doubt, the device may be removed and a new device applied to the skin. If the microneedle was actually properly inserted, the replacement of the device is wasteful.

[0013] One aspect of the present invention is to provide an improvement to prior art microneedle applicator devices that remain in place for an extended period of time. The improvement may be any one or more of visibility, size, weight, complexity, cost, and the ability to monitor inaccurate embedding. The improvement may be provided only by one embodiment of the present invention. In certain situations, the present invention may not provide any improvement and instead may only provide a useful alternative to prior art devices.

[0014] Discussions of documents, acts, materials, devices, articles, etc. are included herein only for the purpose of providing a context for the present invention. It is not suggested or represented that any or all of these matters formed part of the prior art base existing prior to the priority date of each claim of the present application or were common general knowledge in the field of the present invention. Summary of the Invention

[0015] In a first aspect, which is not necessarily the broadest aspect, the present invention provides an apparatus for bringing one or more protrusions into contact with a subject's skin over a long period of time, the apparatus comprising: one or more protrusions configured such that each protrusion penetrates the skin; a skin contact portion that defines a skin contact surface and one or more spaces that allow at least one of the one or more protrusions to extend therethrough; a movable portion configured to move the one or more protrusions from a first position behind the skin contact surface to a second position where the skin contact surface protrudes; a holding portion configured to hold the skin contact surface in contact with the skin during use; The movable portion is configured to move from the first position to the second position in a non-linear path.

[0016] In one embodiment of the first aspect, the non-linear path is generally an arcuate path.

[0017] In one embodiment of the first aspect, the movable portion has a connecting end and a free end.

[0018] In one embodiment of the first aspect, the free end moves a greater distance than the connecting end.

[0019] In one embodiment of the first aspect, the non-linear path is depicted by reference to the free end.

[0020] In one embodiment of the first aspect, the non-linear path is less than about 10 mm, less than 9 mm, less than 8 mm, less than 7 mm, less than 6 mm, less than 5 mm, less than 4 mm, or less than 3 mm.

[0021] In one embodiment of the first aspect, the angular measurement of the arc is less than about 45°, less than 40°, less than 35°, less than 30°, less than 25°, less than 20°, less than 15°, less than 14°, less than 13°, less than 12°, less than 11°, less than 10°, less than 9°, less than 8°, less than 7°, less than 6°, or less than 5°.

[0022] In one embodiment of the first aspect, the movable part has a pivoting portion, a hinging portion, a flexing portion, or an attaching portion.

[0023] In one embodiment of the first aspect, the movable part is associated with an attachment part.

[0024] In one embodiment of the first aspect, during use, the attachment part is stationary and the movable part is movable relative to the attachment part.

[0025] In one embodiment of the first aspect, the attachment part includes a portion that enables the movable part to pivot, hinge, bend, or attach.

[0026] In one embodiment of the first aspect, the attachment part is in a fixed spaced relationship relative to the skin contact surface

[0027] In one embodiment of the first aspect, the attachment part is spaced from the skin contact surface by less than about 10 mm, less than 9 mm, less than 8 mm, less than 7 mm, less than 6 mm, less than 5 mm, less than 4 mm, less than 3 mm, or less than 2 mm.

[0028] In one embodiment of the first aspect, the attachment part is generally transverse to the movable part.

[0029] In one embodiment of the first aspect, the device further includes a user-actuable release portion, and the release portion is configured to hold the movable portion in the first position until the user actuates the release portion, at which point the movable portion is released and enabled to move to the second position.

[0030] In one embodiment of the first aspect, the device further includes a locking portion configured to lock the movable portion when in the second position.

[0031] In one embodiment of the first aspect, the device is configured such that movement of the movable portion from the first position to the second position requires a motive force generated either internally and / or externally to the device.

[0032] In one embodiment of the first aspect, the internal motive force generated to the device results from a spring, an elastically deformable member, a shape memory member, or other biasing means, and the external motive force generated to the device results from the user.

[0033] In one embodiment of the first aspect, the device does not have an internal motive force generator configured to move the movable portion from the first position to the second position.

[0034] In one embodiment of the first aspect, the holding portion is a dermatologically acceptable composition disposed on or around the skin contact surface, or includes a dermatologically acceptable composition disposed on or around the skin contact surface.

[0035] In one embodiment of the first aspect, the dermatologically acceptable composition is an adhesive or a function equivalent to an adhesive.

[0036] In one embodiment of the first aspect, the holding portion is configured to mechanically hold the skin contact surface in contact with the skin.

[0037] In one embodiment of the first aspect, the holding part is selected from any one or more of a strap, a band, a belt, a clamp, a grip, a necktie, a clasp, a sleeve, a stocking, a sock, a glove, a cap without a brim, a hat with a brim, an undergarment, a singlet, a shirt, a bra, a top, trousers, a scarf, a ring, glasses, and a choker.

[0038] In one embodiment of the first aspect, one or more protruding parts are mechanically connected to the movable part directly or indirectly.

[0039] In one embodiment of the first aspect, one or more protruding parts are a wire, a needle, and / or a micro-needle.

[0040] In one embodiment of the first aspect, one or more protruding parts form an array.

[0041] In one embodiment of the first aspect, one or more protruding parts are of a sufficient length to be capable of contacting the epidermis, dermis, or hypodermis of the subject.

[0042] In one embodiment of the first aspect, one or more protruding parts are configured to function to transmit an electric current to the skin, transmit an electric current from the skin, transmit an electric current through the skin, transmit a sound wave to the skin, transmit a sound wave from the skin, transmit a sound wave through the skin, transmit light to the skin, transmit light from the skin, transmit light through the skin, transmit heat to the skin, transmit heat from the skin, transmit heat through the skin, sample a fluid or tissue from the skin, deliver a biologically active substance to the skin, or introduce an analyte sensing substance to the skin during use.

[0043] In one embodiment of the first aspect, each of the one or more protruding portions is conductive, and the device further includes a circuit having an audio, visual, or tactile indicator, the circuit being configured to activate the indicator when the one or more protruding portions come into contact with a conductive fluid naturally present on the skin.

[0044] In one embodiment of the first aspect, the circuit includes at least two protruding portions, and the circuit is configured to be completed by at least two protruding portions that come into contact with a conductive fluid naturally present on the skin so as to activate the indicator.

[0045] In one embodiment of the first aspect, the circuit includes one protruding portion and at least one conductive pad disposed against the skin, and the circuit is configured to be completed by the pad and the protruding portion that are in electrical communication with a conductive fluid naturally present on the skin so as to activate the indicator.

[0046] In one embodiment of the first aspect, when the device is applied to the skin, the movable part is in the second position, and any part of each of the one or more protruding portions where the skin contact surface protrudes is embedded in the skin, the housing includes a housing dimensioned to extend above the skin by about 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm or less for most or substantially all parts.

[0047] In one embodiment of the first aspect, a long period is longer than about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, or 96 hours

[0048] In one embodiment of the first aspect, one or more protruding portions are configured to be non-detachable from the device or non-detachable from the device without the assistance of a tool.

[0049] In one embodiment of the first aspect, the movable part and the mounting part are integral.

[0050] In one embodiment of the first aspect, the integral movable part and mounting part are made of an elastically deformable material.

[0051] In one embodiment of the first aspect, the integral movable part and mounting part are part of the circuit board of the device.

[0052] In one embodiment of the first aspect, until the release member is actuated such that the movable part is released and enabled to move to the second position, the movable part is biased towards the second position and maintained in the first position against the biasing by the user-actuable release portion.

[0053] In one embodiment of the first aspect, the user-actuable release portion is a ledge configured to hold the movable part in the first position, and the motive force provided by the user deforms the ledge and / or the movable part such that the movable part is released from the ledge and enabled to move to the second position.

[0054] In one embodiment of the first aspect, the movable part is in a hinged association with the skin contact part.

[0055] In one embodiment of the first aspect, the hinge is disposed around or towards the peripheral region of the movable part and the skin contact part.

[0056] In one embodiment of the first aspect, the release portion includes a member configured to be removable or deformable by a user so as to maintain the movable portion in the first position while allowing the movable portion to move to the second position.

[0057] In one embodiment of the first aspect, the member is removable by sliding generally across the skin contact portion.

[0058] In one embodiment of the first aspect, the member is generally wedge-shaped, and the device includes a hinge that associates the movable portion with the skin contact portion, with the thin portion of the wedge being disposed proximal to the hinge and the thick portion of the wedge being disposed distal to the hinge.

[0059] In one embodiment of the first aspect, the release portion is removable from the device and includes a gripping portion that facilitates removal by hand.

[0060] In the second aspect, the present invention provides a method of contacting a protrusion with a subject's skin, the method including providing an apparatus of any embodiment of the first aspect, contacting the skin contact surface of the apparatus with the subject, and moving the movable portion from the first position to the second position in a non-linear path or enabling the movable portion to move from the first position to the second position in a non-linear path.

[0061] In one embodiment of the second aspect, the apparatus remains applied to the skin for a period longer than about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, or 96 hours.

[0062] In the third aspect, the present invention provides an apparatus for contacting one or more protrusions with a subject's skin, the apparatus including one or more protruding portions configured such that each protruding portion penetrates the skin, A skin contact portion that determines a skin contact surface and one or more spaces that allow one or more skin contact portions to extend therethrough, A movable portion configured to move one or more protruding portions from a first position behind the skin to a second position where the skin contact surface protrudes, A holding portion configured to hold the skin contact surface in contact with the skin during use, A user-actuable release portion configured to hold the movable portion in the first position until a user actuation of the release portion, at which point the movable portion is released and is moved or is enabled to move to the second position.

[0063] In one embodiment of the third aspect, the release portion includes a member configured to maintain the movable portion in the first position but removable or deformable by the user such that the movable portion is capable of moving to the second position.

[0064] In one embodiment of the third aspect, the member is removable by sliding generally across the skin contact portion.

[0065] In one embodiment of the third aspect, the member is generally wedge-shaped, and the device includes a hinge that associates the movable portion with the skin contact portion, with the thin portion of the wedge being disposed proximal to the hinge and the thick portion of the wedge being disposed distal to the hinge.

[0066] In one embodiment of the third aspect, the release portion is removable from the device and includes a gripping portion that facilitates removal by hand.

[0067] In a fourth aspect, the present invention provides a method of contacting projections with the skin, the method comprising providing an apparatus according to any embodiment of the third aspect, contacting the skin contact surface of the apparatus with a subject, and actuating a user-activatable release portion to move the movable portion from a first position to a second position or to enable the movable portion to move from the first position to the second position. BRIEF DESCRIPTION OF THE DRAWINGS

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Figure 1

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Figure 2A

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Figure 2B

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Figure 3A

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Figure 3B

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Figure 4

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Figure 5A

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Figure 5B

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Figure 6

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Figure 7

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Figure 8

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Figure 9

[0080] Unless otherwise indicated herein, the configurations of the drawings labeled with the same numbers are considered to be the same configuration or at least functionally similar configurations when used across different drawings.

[0081] The drawings are not made to any specific scale or dimension and are not presented as a perfectly accurate representation of various embodiments.

[0082] After considering this description, it will be apparent to those skilled in the art how the present invention may be implemented in various alternative embodiments and alternative applications. However, while various embodiments of the present invention are described herein, these embodiments are presented by way of example and not limitation. Thus, this description of various alternative embodiments should not be construed as limiting the scope or breadth of the present invention. Further, the description of advantages or other aspects applies to specific exemplary embodiments and not necessarily to all embodiments, and in fact applies to any embodiment covered by the claims.

[0083] Throughout this description and the claims of this specification, the term "comprise" and variations of that term such as "comprising" and "comprises" are not intended to exclude other additives, components, integers or steps.

[0084] References to "one embodiment" or "an embodiment" throughout this specification mean that a particular configuration, structure, or feature described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places in this specification are not necessarily all referring to the same embodiment, although they may be.

[0085] As used herein, positional terms such as "lateral", "across", "above", "over", "below", "higher", "lower", "upward", "downward", "plan view", etc. should be considered with reference to the apparatus of the present invention when applied to an area facing upward of the subject's skin, such as the upper surface of a human thigh when a human is sitting on a chair. The apparatus can be applied to skin regions having different orientations with respect to the upright direction, and in this case, one of ordinary skill in the art can adequately reconfigure the aforementioned positional terms.

[0086] The term "subject" is used to refer to an animal (including humans and non - human animals) to which the present apparatus may be applied. The term "user" is used to refer to a human who applies the apparatus to a human or non - human animal. The subject and the user may be the same human subject, but they do not necessarily have to be.

[0087] Various separate embodiments of the present invention are disclosed herein (whether by drawings or by written description), and the embodiments have one or more configurations disclosed in the context of this specification. It will be understood that there is no intention to limit the application of a particular configuration or combination of configurations to its use in the disclosed embodiments. For example, a first embodiment may be disclosed as including configurations A and B, and a second embodiment may be disclosed as including configurations C and D. The intention is to include within the scope of the present invention embodiments having any one, two, three, or four of configurations A, B, C, and D in any available combination.

[0088] However, it may be apparent to those skilled in the art that a particular combination is not so preferable or is actually contraindicated. For example, if configuration B requires configuration A to operate, an embodiment including the combination of configurations B, C, and D may not be operable.

[0089] The present invention is based, at least in part, on the discovery that an improved or alternative long-term wearable micro-needle device is provided when a movable portion that biases a micro-needle against a subject's skin moves along a non-linear path. Moreover, the non-linear path may be of limited length, and the path may be arcuate on a limited scale. With this configuration, the main movable portion of the device requires only a limited range of motion in the vertical direction to attach and insert the micro-needle into the subject's skin. The limited range of motion allows the housing of the device to take a relatively low profile when viewed laterally. Thus, the device rises to a relatively small height on the skin and is therefore less obtrusive to the subject.

[0090] Moreover, the non-linear path of the movable part allows for the use of a simplified mechanism. For example, the movable part may move by a simple bending mechanism or a hinge mechanism. These mechanisms require a relatively small number of components, enabling the development of a device that is overall smaller, lighter, simpler, more reliable, and less expensive.

[0091] Certain embodiments of the present invention have additional configurations that provide further advantages or further useful alternatives to the prior art when used alone or in combination with other configurations. Such embodiments are described in more detail by reference to the non-limiting preferred embodiments described below.

[0092] Refer to FIG. 1, which shows a basic form of the device (10) having a micro-needle array (one micro-needle is marked 15) attached to a movable part that is an elastically deformable arm (20) in this embodiment. The arm (20) is biased to take a linear configuration (20b), but initially, as shown by the dashed representation (20a), the arm is bent and curved upward and presented to the user.

[0093] The device (10) includes a rigid housing (25) having a skin contact portion (30) defining a downward-facing skin contact surface (35) on its lower side. The surface (35) is placed on the subject's skin and held therein by areas of dermatologically acceptable adhesives (40a, 40b). Suitable adhesives can typically withstand water to allow the subject to bathe normally. The adhesives typically have sufficient adhesiveness to suppress peeling that may occur during the course of daily activities such as dressing, undressing, sleeping, performing work at home, mild to moderate intensity sports activities, and brushing against objects while walking. The level of the adhesive is typically not so high as to cause any difficulty, discomfort, pain, irritation, or skin damage when removing the device.

[0094] Exemplary adhesives are synthetic rubber adhesives or pressure-sensitive acrylic adhesives of the type used in medical tapes. A double-sided medical tape such as 3M TM TM 1577 tape may be used, with one side adhering to the device and the other side adhering to the subject's skin.

[0095] The skin contact portion (30) includes a space (45), the margins of which are marked (45a) and (45b). The space (45) provides respective passages through which the microneedles (15) pass, enabling the distal region of the microneedles to penetrate and be embedded in the underlying skin (50) when the arm (20) is in the straight position (20b).

[0096] The arm (20) is held in its bent state by a ledge (shelf) (55) that functions as a release means. When the user desires to insert the microneedles (15) into the skin (50), the user depresses the button (60) as indicated by the arrow. The lower surface of the button (60) supports the ledge (50), and since the ledge (55) (manufactured from a rubbery material or formed, for example, from flexible protrusions on the inner surface of the housing (10)) has a certain degree of deformability, the ledge bends downward under the force to release the edge of the arm (20a). The elastic nature of the arm (20a) rapidly returns the arm (20a) to its biased straight position (20b), thereby pushing the microneedles (15) into the underlying skin (50). The ledge (55) is configured to exhibit sufficient elasticity to resist the biasing force within the arm (20a), but its elasticity is not sufficient to resist the downward force applied by the button (55) when depressed.

[0097] In the embodiment of FIG. 1, the arm (20) is fixed to one end of the housing (25) by a fastener (63). The arm (20) is flexible, but the flexibility is not so high that it easily moves away from the position (20b) when at a predetermined location on the skin (50) of the subject. As will be understood, any movement of the arm (20) away from the position (20b) pulls the microneedle (15) out of the skin (50). Considering the bias of the arm (20) towards the position (20b), there is no need for a locking mechanism to maintain the arm in the predetermined position (20b). However, if required, a suitable locking mechanism for the embodiment of FIG. 2A will be described below.

[0098] FIG. 2A shows an alternative basic form of the device (200) in which the arm (205) is rigid and is hingedly connected (hinged) to the housing (25) via a hinge pin (210). The embodiment of FIG. 2A operates in the same manner as the embodiment of FIG. 1 as long as the ledge (55) acts as the release means. However, in the embodiment of FIG. 2A, the button (215) acts on the rigid arm (205a). The rigid arm (205) transmits the force of the button to the deformable ledge (55), causing the ledge (55) to bend and thus releasing the free end of the arm (205a). The button (215) is continuously depressed by the user until the arm takes the position (205b), at which position the microneedle (215) is embedded in the skin (50). Again, the point on the free end of the arm (205a) travels along a non-linear path, which in this embodiment is an arc that is a segment of a circle, and the origin of the circle is at the hinge pin (210).

[0099] It will be appreciated that the hinge-connected configuration of FIG. 2A does not resist the arm (205) moving away from the position (205b) while the device is worn. Thus, while in place, there is a risk that the microneedle (15) will be pulled out of the skin (50). Accordingly, a locking mechanism is provided to maintain the arm in a predetermined position (205b). The locking mechanism includes a deformable latch (220) made, for example, from a material having some flexibility or from an internal protrusion formed from the housing (25) material. The latch (220) has an inclined upper surface and when in contact with the rigid arm (205), the entire latch (220) is forced to bend to the left (as shown) under the force applied by the user via the button (215) and the inclined upper surface. Once the end of the arm (205) clears the lower corner of the inclined upper surface, the latch (220) assumes its normal upright position and the free end of the arm (205b) seats firmly within a recess in the base of the latch (220).

[0100] An alternative to the embodiment of FIG. 2A is shown in FIG. 2B. In FIG. 2B, the device (200) lacks an upper housing. The arm (205a) is maintained in a predetermined position by release means (55) which, in this embodiment, are removable by the user when the device (200) is applied to the subject. After removal of the release means (55), the arm (205a) is pushed downward by the user to assume a second position (205b).

[0101] In the embodiments of FIGS. 1, 2A and 2B, it should be noted that when released from the ledge (55), the free end of the arm (20 or 205) moves non-linearly as it returns to its biased position (20b). If a single point on the free end of the arm (20 or 205) is considered, that point travels along a non-linear path that describes an arc. In the context of the present invention, the terms "arc", "arcuate" and similar terms refer to a curve connecting any two points. The term "arc" should not be construed narrowly to mean only a segment of a circle, but in some embodiments it is a segment of a circle (see, for example, the embodiment of FIG. 2A).

[0102] As is apparent from the basic embodiments of both FIGS. 1, 2A, and 2B, in each case, the arm (20 or 205) moves a relatively small distance when transitioning from the first position to the second position. In practice, in these embodiments (and certain other embodiments), the device is intentionally configured such that the arm cannot move along any path that is outside the path between the first and second positions. In other words, the device may be configured such that the arm cannot move along any path that is outside the shortest distance between the first and second positions.

[0103] By imposing a limit on the path along which the arm may move, advantages are provided as long as the height of the device (in the vertical direction, as shown) is also limited. Thus, the device may take on a low profile that extends a relatively short distance (in the sense of dimensions) over the skin of the subject.

[0104] Next, referring to FIGS. 3A and 3B, a preferred apparatus is shown that is constructed generally in accordance with the embodiment of FIG. 1 and is operable in substantial conformity with the embodiment of FIG. 1. The arm (20) is formed integrally with a PCB (65) that carries various electronic components necessary for the operation of the apparatus. The PCB material is elastically deformable such that the arm (having micron needles attached to the terminals) can bend downward as shown to position the arm in a first position, but when released, assumes a second position due to a natural bias toward the second position.

[0105] The arm (20) is maintained in the first position by the end of the arm (20) being on the ledge (55), as most clearly shown in FIG. 1A. In this position, the micron needles (15) are held within the apparatus and there is no portion extending through the space (45). This is the configuration in which the apparatus is provided for use and in which the apparatus is applied to the skin of a subject.

[0106] The arm (20) is connected to a micron needle mounting block (70) that supports the micron needles. The micron needle mounting block (70) also includes a conduit (not shown) for passing current from each of the micron needles (15) to one of a number of connection points (75) on the PCB (65). With this configuration, electrical signals may be transmitted at and / or from the micron needles embedded in the skin of the subject. For example, the apparatus may be configured as a sensor having micron needles configured to contact a biological fluid within the body of the subject and detect an analyte (analytical substance) therein. The biological fluid may be, but is not limited to, interstitial fluid, blood, or a mixture thereof. Electrical signals from the micron needles are transmitted to the PCB for amplification, filtering, encoding, analysis, transmission, or any other electrical or electronic process.

[0107] In this embodiment, the PCB serves a dual function of holding the electronics of the device and also functions as the driving means for moving the microneedles from an internal position of the device to an external position. The PCB material has been found to be suitable for providing a limited movable range suitable for the arm of the present device. This configuration reduces the number of components within the device.

[0108] The upper surface of the housing (25) presents the operating surface of a button (215) that can be depressed by the user's finger. The button (215) is biased upward (as shown) by a spring or because the button is integrally formed with the housing (25) material. In the latter form of bias, the button (215) may be attached to an arm that is integral with the housing material and may be biased such that the upper surface of the button (215) is in the same plane as the housing (25).

[0109] The depression of the button (215) releases the ledge (55) and the lower portion (not visible) of the button (215) is supported on the upper surface of the arm (20) so as to bias the arm (20) downward to assume a second position, the upper surface of which is the rear surface of the PCB (65). In the second position, it will be understood that the microneedles extend through their respective spaces (45) and are embedded in the underlying skin (e.g., the epidermis, dermis, or hypodermis of a subject).

[0110] The natural bias of the PCB (65) material towards the second position is strong enough to keep the arm (20) in the second position and does not require means to lock the arm in the second position. Thus, the microneedles (15) can remain embedded in the subject's skin over a long period of time.

[0111] In an alternative embodiment, the arm (20) has a curved configuration when in the second position and is naturally biased to move away from the second position. In another embodiment, the bias of the arm (20) towards the second position is not strong enough to prevent any movement away from the second position. In such embodiments (and other embodiments), a locking mechanism may be provided to prevent movement of the arm away from the second position so that the microneedle (15) does not retract into the device and remains embedded in the skin. A suitable locking mechanism is a latch mechanism as disclosed in connection with other embodiments herein. Other locking mechanisms will be apparent to those skilled in the art having the benefit of this disclosure.

[0112] The housing (25) includes opposing recesses (80) to facilitate gripping between the user's thumb and second finger and holding the device against the skin surface. The user's first finger is free to operate the button (215) to embed the microneedle (15) into the skin located therebelow.

[0113] The skin contact surface (35) may have a dermatologically acceptable adhesive layer (not shown) applied to the skin contact surface to maintain the device in place on the subject's skin over an extended period of time. The adhesive layer can cover a portion or substantially all of the skin contact surface (35). As described for other embodiments of the device described herein, a manually releasable flexible layer may cover the adhesive until the device is applied to the skin.

[0114] Next, referring to FIGS. 4, 5A, 5B, 6, and 7, a preferred device is shown that is constructed generally in accordance with the embodiment of FIG. 2B and operable generally in accordance with the embodiment of FIG. 2.

[0115] The embodiment includes an upper housing portion (25) and a skin contact portion (30). A removable flexible layer (90) that can be grasped via a tab (95) is also provided, and removal of the flexible layer exposes a dermatologically acceptable adhesive on the skin contact surface (35). As described above, the adhesive is for holding the device on the subject's skin over a long period of time. The flexible layer (90) functions to prevent curing or drying of the adhesive and to prevent contamination of the adhesive layer prior to use and / or premature attachment of the adhesive to the packaging or other surfaces. In a particularly preferred embodiment, in addition to covering the adhesive layer, the flexible layer (90) extends to cover the space (45) to prevent contamination of the microneedles (15) and to help prevent unintentional needle sticks to the user.

[0116] The device may have a holding portion that functions to hold the device on the skin such that the protruding portion remains in contact with the biological fluid of the subject. The holding portion may be dedicated to that function or may perform another function.

[0117] In many situations, a dermatologically acceptable adhesive or a holding portion that includes a dermatologically acceptable adhesive will be useful. The adhesive allows for simplicity in application of the device by the user, often only requiring removal of a protective backing sheet to expose the adhesive and then contacting the exposed adhesive with the skin. This method of application is similar to the application of a sticking plaster and is thus already a familiar method to the user.

[0118] Instead of using an adhesive, the holding portion may be any mechanical means for maintaining the device in a desired position on the skin. For example, the device may include a dedicated strap that engages around a limb that can be adjusted to hold the device in place for secure application to the subject. Alternatively, the device may be incorporated into a wearable item such as a glove or shirt, or a jewelry item such as a ring that functions to hold the device in a predetermined position. The device may be configured to engage (e.g., by complementary hook and loop means) with a separate wearable item, or may have a wearable item integrated therewith.

[0119] In some embodiments, the device is simply held by a wearable item that drapes over the housing. For example, the holding portion may be a snug-fitting elasticised glove that is worn over the device.

[0120] In some embodiments, the holding portion is any surface or part of the device that contacts the subject's skin, and the configuration of the subject is at least partially responsible for maintaining the device in a predetermined location on the subject. For example, the device may be configured to be held in a close position between two parts of the body or within an existing anatomical structure. The device may be shaped and / or sized to be held between toes, between buttocks, within the groin, within the mouth, within the nostrils, within the ear canal, or within the umbilical cavity.

[0121] In other embodiments, the device housing is shaped and / or sized to fit snugly over a digit, toe, or ear, for example. The device housing may be elastically deformable and may be composed of, for example, a rubberized material, and may be configured to stretch over any anatomical part (such as a finger).

[0122] Each of the foregoing embodiments is considered to be a holding portion in the context of the present invention.

[0123] The device further includes a release member (100) having a gripping portion (105) and a wedge portion (110), and their functions are more fully described below.

[0124] Referring next to the exploded views of FIGS. 5A and 5B, components (elements) similar to the components of the foregoing figures immediately become apparent.

[0125] In this embodiment, the motive force that moves the arm (205) and thereby biases the microneedle (15) against the underlying skin is provided by the user. During use, the user places a finger on the upper housing 25 and presses downward. Further, the arm (205) is movable by a hinge configuration.

[0126] The hinge configuration is provided by opposing lugs (115) extending from the skin contact portion (30), each lug including a hole. The arm (205) includes opposing laterally extending disks (120), each disk being positioned within the hole of a lug (115). It will be apparent that the arm (205) can hinge relative to the skin contact portion (30) to enable movement from a first position to a second position.

[0127] The arm (205) is presented to the user with the arm in a first position. The arm (205) is maintained in the first position by the wedge portion (110) of the release member (100). Prior to removal of the release member (100), the wedge portion is inserted between the skin contact portion (30) and the arm (205), thereby holding the microneedle within the device.

[0128] When attempting to apply the device to the subject's skin, the user pulls on the tab (95) to remove the flexible layer (90) and expose the adhesive layer on the skin contact surface (35). The device is then applied to the skin and the adhesive is maintained in place over a long period of time.

[0129] Once the device is applied to the skin, the user grasps the gripping portion (105) and pulls it horizontally to the left (as shown in the figure) to completely remove the release member (100). The release member (100) has no further function and is discarded at this point. By removing the release member (100), the arm (205) is released from the first position and is allowed to move to the second position (under the downward force applied by the user), whereby the lower surface of the arm (205) contacts the upper surface of the skin contact portion (30). In the second position, the microneedle (15) extends into the skin located below through the space (45).

[0130] As will be appreciated, the release member (100) may be configured to prevent the upper housing (25) of the device from closing against the skin contact portion (30) when not intended by the user. The release member (100) is inserted or otherwise or juxtaposed between the upper housing (25) and the skin contact portion (30) to prevent the closing of the upper housing (25) towards the skin contact portion (30) sufficient to allow the tip of the microneedle (i.e., the protruding portion) to protrude from the base of the hole in the skin contact portion (30). Preventing the closing also prevents the movement of the arm (205) from the first position to the second position. Thus, when the release member (100) is in place, the tip of the microneedle cannot be inadvertently accessed, causing contamination or damage to the microneedle. When using the device, the user removes the release member (100) as a step in the usage process. In a preferred embodiment of using the device, the user first adheres the device to the subject's skin and then removes the release member (100) before pushing the upper housing (25) to insert the microneedle into the skin.

[0131] Before removal by the user, the release member (100) can be held in place by any one of a variety of configurations. In one example, the release member (100) includes a protrusion that fits into a recess in the upper housing (25), a recess in the skin contact portion (30), or recesses in both the upper housing (25) and the skin contact portion (30) to help hold the release member in place until it is intentionally removed. In another example, the release member (100) is designed to be slidably assembled to the skin contact portion (30) or the upper housing (25) such that friction between the release member (100) and either the upper housing (25) or the skin contact portion (30) helps hold the release member in place until it is intentionally removed. In yet another example, magnetic force may be used to help hold the release member (100) in place. In one embodiment of the present invention, a magnet mounted within the release member (100) is positioned to be close to a Hall effect sensor positioned in either the upper housing (25) or the skin contact portion (30) when the release member (100) is in place. According to this embodiment, when the release member (100) is removed by the user, the Hall effect sensor detects the removal of the magnet and causes the device to perform some operation, such as powering on an electronic circuit that is in a usable state and converting the electronic circuit from sleep mode to active mode. The above are examples of possible ways to help hold the release member (100) in place before intentional removal, which may be used alone or in combination, and it should be understood that other methods known in the art may also be used alone or in combination with a given example.

[0132] In some embodiments of the present invention, the release member (100) can also function as a cover element used to cover the microneedle after the device is removed from the subject. In a preferred example of this embodiment, the locking element is disposed on the upper housing (25) and extends downwardly towards the skin contact portion (30). The release member (100) includes a groove that allows the release member (100) to slide over the locking element when the release member (100) is pulled out of the device, while continuously holding the surface of the release member (100) that faces the upper surface of the skin contact portion (30). During use, the release member (100) according to this preferred embodiment is removed and held by the user before pressing the upper housing (25) to insert the microneedle into the subject's skin. After the device is removed from the subject after use, the user is instructed to adhere the release member (100) to the adhesive layer on the lower surface of the skin contact portion (30) to cover the protruding microneedle. In another example of this embodiment, the release member (100) remains attached to the device even after being pulled out by the user, and is repositioned to cover the protruding microneedle after the device is removed from the subject after use, such that the release member (100) is flexibly attached to the device. In yet another example of this embodiment, the release member (100) and the upper housing (25) are designed such that the release member (100) can be slidably or otherwise engaged with the upper housing (25) after the release member (100) is removed, where the release member (100) is intended to be stored while the device is in use and removed to be used as a covering element after the device is removed from the subject.

[0133] In some embodiments, the device is configured to facilitate removal of the device from the subject by the user. As will be appreciated, the use of an adhesive layer can sometimes cause difficulties in removing the device from the skin. An example of such a configuration includes leaving a portion of the skin contact surface (35) uncoated with adhesive such that a gap exists between the skin of the test animal and the surface (35), and the user uses the gap as a leverage point to help pull the device away from the skin by breaking the bond of the adhesive. In another example, a leverage mechanism that is not located on the skin contact surface is incorporated to allow a gap that is higher than the gap created by the absence of adhesive on a portion of the skin contact surface. In yet another example, a tab that extends beyond at least one edge of the skin contact portion (30) and is attached to the adhesive layer can be incorporated, and the user stretches and yields the adhesive layer and then pulls on the tab with sufficient force to peel the adhesive from the skin contact surface (35) and the skin.

[0134] In some embodiments of the present invention, the device is designed such that the release member (100) is locked in place at a predetermined location prior to use of the device unless pressure is applied to the upper housing (25). This embodiment is intended to further improve the risk that the release member (100) is prematurely withdrawn. In an example of this embodiment, there is a configuration in which the release member (100) is lockably engaged with at least one of the upper housing (25) and the skin contact portion (30) when the upper housing (25) is not being pushed. When the upper housing (25) is pushed down, a configuration in at least one of the upper housing (25) and the skin contact portion (30) is distorted such that the release member (100) is disengaged and enabled to be pulled out.

[0135] In yet other embodiments, the release member (100) need not be removed from the device by the user. According to these embodiments, since the release member (100) includes a flexible element with a sufficiently high rigidity, the release member, when exposed to the closing forces that may exist on the device during manufacturing, storage, and while in the user's hand, before application to the subject, does not substantially deflect, but is sufficiently flexible so that when the device is applied to the subject's skin and the user intentionally applies a closing force to the device, it deflects. When bending in such a manner, the release member (100) deflects to allow the upper housing (25) to approach the skin contact portion (30). In these embodiments, the release member (100) can also function as a locking element, or the release member (100) can be separated from the locking portion. In some of these embodiments, the configuration labeled as (220) in FIGS. 5A, 5B, and 7 forms the release member (100).

[0136] Each space (45) of the device is dimensioned such that the microneedles can clearly extend therethrough, and at least the tapered portion of the microneedles does not impact the side of the hole during insertion. In some embodiments, the hole may have a sufficient cross-section such that no portion of the microneedles contacts the side of the space during insertion. In other embodiments, at least a portion of the hole along its length has a cross-section such that a portion of the length of the microneedles contacts the side of the hole during insertion. According to this embodiment, the hole functions to help support a portion of the length of the microneedles to help prevent bending of the microneedles when they are inserted.

[0137] In some embodiments of the device, the skin contact portion (30) includes an additional space or recess configured to receive a protrusion on the release member to assist in holding the release member until it is removed by the user. Additionally or alternatively, the skin contact portion (30) includes a protrusion designed to be received in a recess in the release member to assist in holding the release member in place until intentional removal by the user.

[0138] The embodiments shown in FIGS. 4, 5A, 5B, 6, and 7 include a locking portion in the form of a latch (220) that permanently locks the arm (205) in a second position and prevents the arm (205) from any hinging movement. In the illustrated embodiment, the latch (220) can deflect in response to movement of the arm (205) toward the closed position but can return to its original position when the arm (205) is in the second position (205b), thereby locking the arm (205) in place, and is a simple integral member.

[0139] The locking portion may act on another component of the device rather than on the arm (205), and that component then locks the arm in place. For example, the locking portion acts on the upper housing (25), and the upper housing (25) then holds the arm (205) in the second position. Further alternatively, the locking portion acts on the PCB (65), and the PCB (65) then holds the arm (205) in the second position.

[0140] In other embodiments, the locking portion includes a recess into which a protrusion on the upper housing (25) is inserted to lock the upper housing (25) in the closed position (i.e., the arm (205) in the second position). In one embodiment, the housing (25) is enabled to close relative to the skin contact portion (30), such that once the upper housing (25) is closed, the locking portion is enabled to move to lock the upper housing (25) in place in the closed position. The locking portion includes a flexible element designed to enable the locking portion to move when the upper housing (25) hits. In one embodiment, the device includes a protrusion on the upper housing (25) designed to be inserted into a recess in the locking portion, the protrusion including a flexible element that enables the protrusion to move, enabling the upper housing (25) to close relative to the skin contact portion (30), and then the housing (25) closes relative to the skin contact portion (30) and the protrusion moves to be inserted into a recess in the locking portion to lock the upper housing (25) in the closed position. The flexible element may include a shaft deformable enough to enable the upper housing (25) to close without yielding the shaft, so the flexible element attempts to return to its original position after the upper housing (25) is closed. Although less preferred, in a functional embodiment nonetheless, the flexible element includes a coil spring.

[0141] The flexible element of the locking portion may be manufactured from any suitable material having the required rigidity and yield point. Examples of suitable materials include amorphous plastics, crystalline plastics, spring steel, spring-loaded steel, stainless steel, or other materials known in the art having suitable mechanical properties.

[0142] In a preferred embodiment of the present invention, the locking portion is manufactured from the same material as the skin contact portion (30) to facilitate the manufacture of a skin contact portion having an integral locking portion.

[0143] In a particularly preferred embodiment of the present invention, the force required to deflect the flexible element or otherwise move it is designed to be large enough so that the pressure the user needs to supply to deform the flexible element and thus bring the upper housing (25) closer to the skin contact portion is sufficient to insert the microneedles into the skin. According to this embodiment, the flexible element of the locking portion is used to set the force required to close the device (thereby causing the arm to assume a second position), and to ensure that that force is sufficient to insert the microneedles into their intended positions where they are to be embedded in the skin.

[0144] In other embodiments, the locking portion includes at least one adhesive region located on at least one of the lower surface of the upper housing (25) and the upper surface of the skin contact surface (35). When the device is closed, the one or more adhesive regions adhere the upper housing (25) to the skin contact portion (30) to lock the device in the closed position.

[0145] In another embodiment of the present invention, the locking portion can take three different stable states. In the first state, the locking portion is in a disengaged configuration before the upper housing (25) is pushed downward toward the skin contact portion (30) to close the device. In the second state, the locking portion is in a first engagement position. When the locking portion is in the first engagement position, the locking portion serves to lock the microneedles (15) in the skin embedding position (i.e., the arm (205) is in the second position). In the third state, the locking portion is in a second engagement position. In this state, the locking portion locks the device in the open position (i.e., the arm (205) is in the first position), and the microneedles are retracted into the device to improve the possibility of needle stick injuries due to microneedle protrusion after use of the device. In an example of this embodiment, the locking portion includes a user engagement portion that can be grasped by the user or engaged in another way, such that the user can deflect the flexible portion of the locking portion, for example, by engaging a fingernail under the protruding ledge. According to this example, to close the device, the user presses the upper housing (25) to lock the upper housing in place, as in other embodiments disclosed herein. When it is desirable to remove the device from the subject, the upper housing (25) is released from the skin contact portion (25), and then the locking portion is deflected in a second direction to lock the device in the open position (i.e., the arm is in the first position), and the microneedles are in the retracted position. The user engages the locking portion and deflects the locking portion in a first direction. In a preferred embodiment of this example, in the first direction, the locking portion is moved away from the body of the device, and in the second direction, toward the body of the device. When sufficiently deflected in the second direction, the locking portion is designed to stably engage within a recess, for example, to prevent unintentional closure of the device.

[0146] In some embodiments of the present invention, the downward force on the microneedles when inserted into the skin is provided via a flexible element of a locking portion that applies a downward force when the device is locked in the closed position (i.e., the movable arm is in the second position). In some embodiments, effective locking of the movable arm in the second position is provided by a dedicated spring or other suitable biasing means. In other embodiments, the spring or other biasing means is not dedicated to the locking function and may also act, for example, as the driving force in the movement of the arm from the first position to the second position. For example, a torsion spring may apply a closing torque at the pivot point (if present). In yet another example, a flat disk or coil spring is attached to the rear of the microneedle such that when the device is closed, the spring is distorted or compressed to apply a downward force on the microneedle when the device is closed.

[0147] Although not an essential configuration of the present invention, a PCB (65) is required for many applications where the microneedles conduct current to, from, or through the skin. In this regard, the PCB may support a microprocessor and / or volatile electronic memory (such as RAM) and / or non-volatile electronic memory (such as ROM) and / or a wireless network module (such as a Bluetooth module). The device typically includes, of course, a power source by a button cell. TM The device typically includes, of course, a power source by a button cell.

[0148] The embodiment shown in FIG. 3A further includes a light-emitting diode (LED) (120) visible to the user. One function of the LED (120) may be for the user and / or subject to confirm that the microneedles are properly embedded in the skin at the time of application and remain properly embedded over a long period of wear.

[0149] The LED is electrically connected to the PCB (65), and then the PCB (65) is electrically connected to the microneedle (15). The proper embedding of the microneedle can be determined by referring to one or more of the current between two microneedles, the resistance to the current, or the impedance.

[0150] Alternatively, the proper embedding of a single microneedle can be determined by referring to one or more of the current, the resistance to the current, or the impedance between the single microneedle and some other electrical contact of the device with the skin. As an example, a conductive pad can be placed against the surface of the skin, and in some examples, the conductive pad is placed on the surface of the housing that contacts the skin. This conductive pad that cooperates with at least one of the microneedles completes an electrical circuit when the microneedle is inserted into the skin. The completion of this circuit is used to indicate the correct insertion of the microneedle.

[0151] The electronic device (electronics) involved can be simple, and any example of its biological fluid of the skin, such as the interstitial fluid (which is naturally conductive), acts to complete the circuit including the LED. Assuming that the proper embedding is indicated by the simple contact of the microneedle with the biological fluid. The LED is illuminated where the microneedle contacts the biological fluid (or vice versa), thereby providing a visual indication of the correct embedding.

[0152] To provide a higher level of assurance of correct micro-needle embedding, a more sophisticated electronic configuration may be required. For example, it may be necessary to consider whether the minimum length of the micro-needle is embedded, thereby providing assurance of insertion of the micro-needle to a specific minimum depth. The device may include electronic means for measuring a quantum of a parameter such as a current flow, and a higher current flow indicates a more complete embedding of the micro-needle. Program instructions executed by an on-board processor or otherwise associated with the device may use a parameter such as a current flow (optionally along with other physiological or environmental parameters) as an input to provide an indication of the degree of micro-needle embedding.

[0153] A further function of the LED may be to provide other information such as the battery charge level. For example, the LED may be connected to a microprocessor that can monitor the battery voltage, and the microprocessor may cause the LED to blink red when the voltage drops below a predetermined threshold. The value may be a voltage that is somewhat above the minimum operating voltage that allows the subject time to access a replacement battery (or replacement device if the battery is not user-serviceable) before the device becomes inoperable.

[0154] In other embodiments, the LED may generate an output indication of the data connection status. For example, the LED may alternately blink red and green light to warn of an interruption in a wireless data connection with a remote device such as a smartphone. The smartphone may be involved in processing the sensor output and warning the subject by audible output when a threshold (such as a glucose concentration) is breached. In such embodiments, the LED and the device networking module may be connected to a microprocessor, which monitors the connection status of the module and causes an output to be generated to the LED when the connection is made and / or when the connection is lost. The smartphone application software may be configured to warn the user of a loss of data connection, but the smartphone may lose power (e.g., by running out of charge), in which case the only means by which the subject is warned is the device itself.

[0155] A similar output function to the LED may be provided by a buzzer or miniature speaker that provides an audible output understandable by the subject. The output may be, for example, a tone, a series of tones, or synthesized voice.

[0156] Next, refer to an alternative embodiment of the device shown in FIG. 9, which is a modified version of the embodiment shown in FIGS. 4 - 8. The embodiment of FIG. 8 includes a temperature sensor (300) that extends through a space (305) in the skin contact portion (30) during operation so as to contact the surface of the subject's skin. The temperature sensor (300) may be, for example, a thermocouple or a thermistor operably connected to a microprocessor on a PCB (65). The temperature sensor may be in direct contact with the skin or may be separated from the skin via a thermally conductive material.

[0157] The temperature sensor may be disposed within a pocket or other formation sized to receive the temperature sensor. The pocket may be made of a thin sheet-like material of plastic, such as a thermally conductive plastic having a metal or other filler, to facilitate the transfer of thermal energy from the underlying skin to the temperature sensor. The temperature sensor may be surrounded by a thermally conductive paste to facilitate the transfer of thermal energy from the pocket wall to the temperature sensor.

[0158] The floor of the pocket may extend outwardly from the device such that when the device is applied to the skin surface, the floor of the pocket is gently pressed against the skin surface, thereby facilitating the transfer of thermal energy from the skin to the temperature sensor. It will be appreciated that pressing the floor of the pocket too hard against the skin surface will push blood out of the skin capillaries, thereby artificially cooling the skin surface.

[0159] Preferably, only the floor of the pocket is made of a thermally conductive material and the remainder is made of a low thermal conductivity material. Such a configuration prevents thermal energy from escaping from the temperature sensor.

[0160] The insulating material may form the ceiling of the pocket to ensure that thermal energy is retained around the temperature sensor and not lost to the interior cavity of the housing.

[0161] The pocket may include a space extending through the floor such that the temperature sensor can be in direct contact with the skin surface. Given that no thermal energy is required to cross any intervening material, a temperature close to the actual skin temperature is expected.

[0162] In a further modification, the temperature sensor may be an infrared sensor module, in which case at least the material of the pocket floor must not substantially interfere with its operation. It is contemplated that a space may be formed in the floor to allow the infrared sensor module to be directly exposed to the skin surface to enable an accurate reading of the skin temperature.

[0163] The signal output from the temperature sensor (300) may be used in calculations performed by a microprocessor (or a remote microprocessor) to more accurately determine the concentration of the target analyte. For example, the microprocessor may have access to a stored set of calibration curves, each curve being performed at a given temperature. Based on the output of the temperature sensor (300), an appropriate calibration curve may be selected, and thus a more accurate analyte concentration may be determined.

[0164] The embodiment of FIG. 9 includes a release member (100) having paired protrusions (the first protrusion is marked 310, and the paired second protrusion is obscured by the first protrusion). The protrusion (310) extends downwardly through a space (315) in the skin contact portion (30). The function of the protrusion (310) is to prevent lateral movement of the release member (100) until the lower surface of the skin contact portion (30) is pressed against the skin. The act of pressing against the skin causes the protrusion (310) to project vertically out of the space (315) so as to allow the release member (100) to be laterally pulled away by the subject. This mechanism prevents the release member (30) from being inadvertently removed before the device is properly applied to the skin surface. Without such a mechanism, the microneedles (15) may prematurely extend through the space (45) and become contaminated by contact with air or objects, or may be physically damaged, for example, by snagging on clothing.

[0165] Some embodiments of the device may require the upper region of the microneedles to be electrically insulated in order to avoid the wet surface of the skin that forms a conduction path between the microneedles (separate from the biological fluid thereunder).

[0166] As another means of controlling moisture, the absorbent material may be positioned on the microneedle attachment portion proximate to the microneedle tip. In embodiments of the device for sensing applications, the material absorbs any excess fluid that may be generated by the insertion of the microneedles into the skin, improving the subject's experience and ameliorating any problems that fluid contact with other parts of the device, such as electronic circuitry or electrical contacts, may cause. In embodiments of the device for fluid extraction applications, the material acts as a wicking agent for transporting fluid from the microneedle site to a desired final site on the device or to the exterior of the device. In some embodiments, the absorbent material is in the form of a sheet. In embodiments where it is desirable to prevent contamination or damage to the microneedles prior to insertion, the sheet includes holes through which the microneedles pass, the holes being sized large enough to prevent the absorbent material from contacting the microneedles during the microneedle insertion process, but small enough to allow excess fluid to exude from the access penetration points created by the microneedles and contact and be absorbed by the material. In other embodiments, such as when the device is used for fluid extraction, the sheet of absorbent material has no holes or the holes are sized such that the absorbent material contacts the microneedles during and after insertion to assist its wicking action. In embodiments where the sheet has no holes, the microneedles form holes as they pass through the sheet as part of the insertion process.

[0167] The device may be configured for and / or used for use in any suitable application where it is necessary for the microneedles to be implanted in the subject's skin over an extended period of time.

[0168] Such uses include electrochemical aptamer-based sensing in which a target analyte in a biological fluid is detected by binding to a capture entity, such as an aptamer, that includes a redox reporter. The capture entity may be covalently or non-covalently attached to the micro-needle, and the redox reporter causes an electrical signal to be transmitted by the micro-needle after binding of the target analyte. The target analyte may be a drug or other exogenous species, or an endogenous species such as a hormone or metabolite.

[0169] When the micro-needle functions as an electrode to detect an analyte present in a layer of skin, the device may include circuitry and components for electrically exciting the electrode, receiving, measuring, and processing the electrical signal resulting from the electrical excitation. According to this embodiment, the micro-needle may include a tip, a shaft, and a base, in which case the electrical signal is generated by an electrode coated on or integrated into the surface of the micro-needle and transmitted along the shaft of the micro-needle to the base of the micro-needle, in which case electrical connections are made to the base or shaft of the micro-needle to transmit the electrical signal to and from the electrode to the electronic circuitry. The electrode can be formed proximate to the tip of the micro-needle, on at least a portion of the shaft of the micro-needle remote from the tip of the micro-needle, or on at least a portion of the shaft of the micro-needle proximate to the tip of the micro-needle.

[0170] The microneedles may be connected to an electronic circuit configuration by various methods known in the art, such as soldering, wire wrapping, or spring-loaded load pins. In one embodiment, the microneedles are attached to pass through a plate or a block of dielectric material, and the connection portion of the microneedles is positioned on or above the surface of the plate or block distal to the microneedle tip. A zebra strip connection may be used to connect the microneedles to an electronic circuit configuration to facilitate a robust connection without the need to precisely align a zebra connector with the microneedle ends in at least one dimension.

[0171] Another potentially useful application is the delivery of active substances to the skin. The substances may mostly remain in the skin or may enter the systemic circulation. In such applications, the microneedles may be hollow and the substances are delivered through the needle lumen. Alternatively, the microneedles may be coated with an active substance such that the substance is instantaneously released into the biological fluid or is gradually released over a long time frame. As a further alternative, the microneedles themselves may be soluble in a biological fluid such that the active substance is released as the microneedles dissolve and may contain the active substance within their bulk. The active substance may be a pharmaceutical composition (e.g., a small molecule, protein, peptide, or nucleic acid) or an immunologically active composition (e.g., a collection of proteins) for use as a vaccine.

[0172] A further potential application is the delivery of an electric current to the skin for the purpose of muscle stimulation or for the stimulation or inhibition of a biological process of a subject. Similarly, the device may be used to detect an electric current in the skin of a subject, for example, to detect nerve conductance.

[0173] In any of the above applications, the microneedles may be solid or hollow, as required or desired.

[0174] The length of the microneedle may be selected according to a particular application. Typically, the microneedle is required to extend at least beneath the stratum corneum. The depth of the stratum corneum varies according to location; for example, the layer is relatively thick on the sole of the foot and relatively thin on the back of the hand. Accordingly, the length of the microneedle extending beyond the housing may be adjusted according to the intended application site.

[0175] In some cases, the microneedle may be required to extend well below the stratum corneum and into the underlying layer of the epidermis, the dermis, and even into the hypodermis, including the subcutaneous tissue. Again, the length of the microneedle extending beyond the device may be correspondingly set.

[0176] One of ordinary skill in the art will also understand the possible need to set the length of the microneedle according to the intended subject. For example, relatively short microneedles are generally required to effect contact with the subcutaneous tissue of neonatal subjects, while for the same site, adult subjects require longer microneedles.

[0177] It may be desirable in some applications for one microneedle to penetrate the skin deeper than another microneedle. Accordingly, the two microneedles may terminate at different distances from the skin surface or at different distances from the microneedle attachment portion. In some embodiments, the two microneedles are of different lengths. In other embodiments, the microneedles are of the same length and the attachment portion is configured to axially displace one microneedle relative to the other. For example, the attachment portion may include a first electrode extending from a first level and a second electrode extending from a second level to be multi-level.

[0178] For typical applications, the microneedles may extend outwardly from the device over a distance between about 10 μm and about 5000 μm. For many applications, a distance between about 500 μm and about 4000 μm is useful.

[0179] Those skilled in the art will understand that the invention described herein is susceptible to further variations and modifications other than those specifically described.

[0180] For example, the movable arm may be moved by the user constricting or pushing in the flexible portion of the device housing, by the actuation of a rotary lever, or by sliding an element along an inclined one for biasing the arm downward.

[0181] The skin contact portion of the device is depicted as being precisely planar at its lower surface (skin contact surface), but in some embodiments, the skin contact portion may be curved to conform to the surface of a body part such as a finger, wrist, heel, or ear. The skin contact portion may have some flexibility (in at least one direction) so as to be conformable to the surface of the body part.

[0182] The space through which the microneedles extend is generally shown as a hole, but other types of spaces are contemplated. In some embodiments, the space is not a hole, and one such embodiment has microneedles that extend through the space peripheral to the skin contact portion.

[0183] It will be understood that the present invention includes all the foregoing variations and modifications that fall within the spirit and scope of the present invention, and in fact includes further variations and modifications.

[0184] Accordingly, the spirit and scope of the present invention should not be limited by the foregoing examples, but should be understood in the broadest sense permitted by law.

Claims

1. An apparatus for contacting one or more protrusions with the skin of a subject over a long period of time, one or more protrusions configured such that each protruding portion penetrates the skin, a skin contact portion that defines a skin contact surface and one or more spaces that allow the at least one or more protruding portions to extend therethrough, a movable portion configured to move the one or more protruding portions from a first position behind the skin contact surface to a second position where the skin contact surface protrudes, a holding portion configured to hold the skin contact surface in contact with the skin during use, and comprising: the movable portion is configured to move from the first position to the second position in a non-linear path, device.

2. The apparatus according to claim 1, wherein the non-linear path is generally an arcuate path.

3. The apparatus according to claim 1 or 2, wherein the movable portion has a connection end and a free end.

4. The apparatus according to claim 3, wherein the free end moves a greater distance than the connection end.

5. The apparatus according to any one of claims 1 to 4, wherein the non-linear path is drawn by referring to the free end.

6. The apparatus according to any one of claims 1 to 5, wherein the non-linear path is less than about 10 mm, less than 9 mm, less than 8 mm, less than 7 mm, less than 6 mm, less than 5 mm, less than 4 mm, or less than 3 mm.

7. The apparatus according to any one of claims 1 to 6, wherein the angular measurement of the arc is less than about 45°, less than 40°, less than 35°, less than 30°, less than 25°, less than 20°, less than 15°, less than 14°, less than 13°, less than 12°, less than 11°, less than 10°, less than 9°, less than 8°, less than 7°, less than 6°, or less than 5°.

8. The apparatus according to any one of claims 1 to 7, wherein the movable portion has a pivoting portion, a hinge portion, a bending portion, or an attachment portion.

9. The apparatus according to any one of claims 1 to 8, wherein the movable portion is associated with a mounting portion.

10. The apparatus according to claim 9, wherein the mounting portion is stationary during use and the movable portion is movable relative to the mounting portion.

11. The apparatus according to claim 9 or 10, wherein the mounting portion includes a portion that allows the movable portion to pivot, hinge, bend, or attach.

12. The attachment portion is in a fixed spaced relationship with respect to the skin contact surface, the device according to any one of claims 9 to 11.

13. The attachment portion is spaced from the skin contact surface by less than about 10 mm, less than 9 mm, less than 8 mm, less than 7 mm, less than 6 mm, less than 5 mm, less than 4 mm, less than 3 mm, or less than 2 mm, the device according to any one of claims 9 to 12.

14. The attachment portion is generally transverse to the movable portion, the device according to any one of claims 9 to 13.

15. Further comprising a user-actuable release portion, the release portion being configured to hold the movable portion in the first position until user actuation of the release portion, at which point the movable portion is released and is movable to the second position, the device according to any one of claims 9 to 14.

16. Further comprising a locking portion configured to lock the movable portion when in the second position, the device according to any one of claims 9 to 15.

17. The movement of the movable portion from the first position to the second position is configured to require a motive force generated internally and / or externally to the device, the device according to any one of claims 9 to 16.

18. The internal motive force to the device is generated from a spring, an elastically deformable member, a shape memory member, or other biasing means, and the external motive force to the device is generated from a user, the device according to claim 17.

19. There is no internal motive force generator configured to move the movable portion from the first position to the second position, the device according to any one of claims 1 to 18.

20. The holding portion is a dermatologically acceptable composition disposed on or around the skin contact surface, or comprises a dermatologically acceptable composition disposed on or around the skin contact surface, the device according to any one of claims 1 to 19.

21. The dermatologically acceptable composition is an adhesive or a function equivalent to an adhesive, the device according to claim 20.

22. The holding portion is configured to mechanically hold the skin contact surface in contact with the skin, the device according to any one of claims 1 to 21.

23. The holding portion is the device according to claim 22, selected from any one or more of a strap, a band, a belt, a clamp, a grip, a necktie, a clasp, a sleeve, a stocking, a sock, a glove, a brimless hat, a brimmed hat, an undershort, a singlet, a shirt, a bra, a top, trousers, a scarf, a ring, glasses, and a highlighter.

24. The device according to any one of claims 1 to 23, wherein the one or more protruding portions are mechanically connected directly or indirectly to the movable portion.

25. The device according to any one of claims 1 to 24, wherein the one or more protruding portions are a wire, a needle, and / or a microneedle.

26. The device according to claim 25, wherein the one or more protruding portions form an array.

27. The device according to any one of claims 1 to 26, wherein the one or more protruding portions are of a sufficient length to be capable of contacting the epidermis, dermis, or hypodermis of the subject.

28. The device according to any one of claims 1 to 27, wherein the one or more protruding portions are configured to transmit current to, from, or through the skin, transmit sound waves to, from, or through the skin, transmit light to, from, or through the skin, transmit heat to, from, or through the skin, sample fluid or tissue from the skin, deliver a biologically active substance to the skin, or introduce an analyte sensing substance into the skin during use.

29. The one or more protruding portions are each conductive, and the device further includes a circuit having an audio, visual, or tactile indicator, the circuit being configured to activate the audio, visual, or tactile indicator when the one or more protruding portions contact a conductive fluid naturally present on the skin. The device according to any one of claims 1 to 28.

30. The circuit includes at least two protruding portions, and the circuit is configured to be completed by the at least two protruding portions that contact the conductive fluid naturally present on the skin so as to activate the audio, visual, or tactile indicator. The device according to claim 29.

31. The circuit includes one protruding portion and at least one conductive pad disposed against the skin, and the circuit is configured to be completed by the conductive pad and the protruding portion that are in electrical communication with the conductive fluid naturally present in the skin so as to activate the audio, visual, or tactile indicator, the apparatus according to claim 29.

32. The apparatus includes a housing, and when the apparatus is applied to the skin, the movable part is in the second position, and any part of each protruding portion of the one or more protruding portions where the skin contact surface protrudes is embedded in the skin, the housing has dimensions such that for most or substantially all parts, it extends above the skin by about 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm or less, the apparatus according to any one of claims 1 to 28.

33. The long period is longer than about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, or 96 hours, the apparatus according to any one of claims 1 to 32.

34. The one or more protruding portions are configured to be inseparable from the apparatus or not separable from the apparatus without the assistance of a tool, the apparatus according to any one of claims 1 to 33.

35. The movable part and the mounting part are integral, the apparatus according to any one of claims 1 to 34.

36. The integral movable part and mounting part are manufactured from an elastically deformable material, the apparatus according to claim 35.

37. The integral movable part and mounting part are part of the circuit board of the apparatus, the apparatus according to claim 35 or 36.

38. Until the actuating of the release part that enables the movable part to be released and move to the second position, the movable part is biased towards the second position and is maintained in the first position against the biasing by the user-actuable release part, the apparatus according to any one of claims 15 to 37.

39. The user-actuable release portion is a ledge configured to hold the movable portion in the first position, and the motive force provided by the user deforms the ledge and / or the movable portion so as to enable the movable portion to be released from the ledge and move to the second position. The device according to any one of claims 15 to 37.

40. The movable portion is in a hinged relationship with the skin contact portion. The device according to any one of claims 15 to 33.

41. The hinge is disposed in or towards a peripheral region of the movable portion and the skin contact portion. The device according to claim 40.

42. The release portion includes a member configured to maintain the movable portion in the first position but removable or deformable by the user so as to enable the movable portion to move to the second position. The device according to any one of claims 15 to 41.

43. The member is removable by sliding substantially across the skin contact portion. The device according to claim 42.

44. The member is generally wedge-shaped, and the device includes a hinge associating the movable portion with the skin contact portion. A thin portion of the wedge is disposed proximal to the hinge, and a thick portion of the wedge is disposed distal to the hinge. The device according to claim 42 or 43.

45. The release portion is removable from the device and includes a gripping portion facilitating manual removal. The device according to any one of claims 42 to 44.

46. A method of contacting a protrusion with the skin of a subject, comprising: providing a device according to any one of claims 1 to 45; contacting the skin contact surface of the device with the skin; moving the movable portion from the first position to the second position along a non-linear path or enabling the movable portion to move from the first position to the second position along a non-linear path. Method.

47. The method according to claim 46, wherein the device remains applied to the skin for a period longer than about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, or 96 hours.

48. A device for contacting one or more protrusions with the skin of a subject, comprising: one or more protruding portions configured such that each protruding portion penetrates the skin; a skin contact portion that defines a skin contact surface and one or more spaces that allow the one or more skin contact portions to extend therethrough; a movable portion configured to move the one or more protruding portions from a first position behind the skin to a second position where the skin contact surface protrudes; a holding portion configured to hold the skin contact surface in contact with the skin during use; a user-actuable release portion, wherein the release portion is configured to hold the movable portion in the first position until user actuation of the release portion, at which point the movable portion is released and is able to move to or be moved to the second position. Device.

49. The device according to claim 48, wherein the release portion includes a member configured to maintain the movable portion in the first position but removable or deformable by a user such that the movable portion is able to move to the second position.

50. The device according to claim 49, wherein the member is removable by sliding generally across the skin contact portion.

51. The member is generally wedge-shaped, and the device includes a hinge that associates the movable portion with the skin contact portion, wherein the thin portion of the wedge is disposed proximal to the hinge and the thick portion of the wedge is disposed distal to the hinge. The device according to claim 49 or 50.

52. The device according to any one of claims 48 to 51, wherein the release portion is removable from the device and includes a gripping portion that facilitates removal by hand.

53. A method of contacting a protrusion with the skin, comprising: providing a device according to any one of claims 48 to 52; contacting the skin contact surface of the device with a subject. Actuating the user-actuable release portion to move the movable portion from the first position to the second position or to enable the movable portion to move from the first position to the second position, Method.

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